A radiographic image imaging device is provided. The device includes: an acquisition component that acquires battery remaining power amount information representing an amount of power remaining in a battery, which is incorporated in a portable radiographic image imaging device and supplies power to the portable radiographic image imaging device, the portable radiographic image imaging device detecting radiation irradiated at a subject of imaging and generating a radiographic image; a calculation component that calculates a possible standby duration of the portable radiographic image imaging device on the basis of the battery remaining power amount information acquired by the acquisition component and a number of images of the portable radiographic image imaging device; and a display component that displays the number of images and the possible standby duration.

1. Field of the Invention
The present invention relates to a radiographic image imaging device, a radiographic image imaging method and a storage medium storing a radiographic image imaging program, and particularly relates to a radiographic image imaging device, radiographic image imaging method and a storage medium storing radiographic image imaging program that image radiographic images represented by radiation that has been emitted from a radiation source and passed through a subject of examination.
2. Description of the Related Art
In recent years, radiographic detectors such as flat panel detectors (FPDs) in which radiation-sensitive layers are disposed on thin film transistor (TFT) active matrix substrates, and that detect irradiated radiation such as X-rays or the like and output electronic signals representing radiographic images represented by the detected radiation, have become practical. These radiographic detectors have advantages over related art imaging plates in that images can be checked immediately and video images can be checked.
Portable radiographic imaging devices (hereinafter also referred to as electronic cassettes) that incorporate these radiation detectors and memorize radiographic image data outputted from the radiation detectors have also become practical. These electronic cassettes have excellent portability, so may image patients who have simply been placed on stretchers, beds and the like. Moreover, adjustment of imaging locations is easy, by changing positions of the electronic cassettes. Therefore, even imaging of patients who cannot move may be administered with flexibility.
Electronic cassettes are commonly driven by batteries. Remaining charge amounts in the batteries need to be properly managed.
Therefore, in Japanese Patent Application Laid-Open (JP-A) No. 2006-95020, a technology is disclosed that calculates a possible number of images for a radiation detector on the basis of a charged amount of a battery and displays the number of possible images at a display. Specifically, a technology is disclosed in which an expected number of images is registered in advance in a mode such as an imaging menu, and a result of comparison between the calculated number of possible images and the expected number of images is displayed at the display.
JP-A No. 2005-6888 has disclosed a technology that calculates a number of possible images for an X-ray detector on the basis of the remaining capacity of a battery, and carries out appropriate processing in accordance with the number of possible images.
JP-A No. 2006-43191 has disclosed a technology that, on the basis of a maximum number of images per individual subject to be imaged (per patient) when an imaging device is used in a hospital or the like, determines a fixed limit relating to remaining charge amounts that represents a replacement period of a battery.
The electrical power that is consumed by an electronic cassette is not just the power that is consumed by imaging but also includes power that is consumed during standby, when imaging is not being performed. Moreover, if, for example, imaging is carried out a plural number of times for different locations of a single patient with different postures and the like, then standby durations between images and durations that vary with, for example, posture differ between patients. Therefore, the power that is consumed in a single examination differs between patients.
However, in the related art technologies described above, no account is taken of the power that is consumed during standby. Therefore, what amount of time standby is possible for is not known, and there is a risk that a battery may run short of charge in the middle of an examination.

Radiographic image imaging device, radiographic image imaging method and storage medium storing radiographic image imaging program


An event management system is disclosed. The event management system includes a memory, a computer display, an event creation component, a conversion mapping component that maps passenger data from a user format into an application specific format; a group scheduling component that categorizes passengers into groups, a passenger management component, a vehicle management component, a staff management component, a versioning component, an invoicing component, and a data visualization component. Also disclosed is a computerized method for event planning.

An event or group movement includes the forecasting and management of a group of people that will arrive from numerous domestic and/or international locations at various times on various days via commercial flights, private jet aviation, train, bus, car service, or personal transportation. Upon the arrival of the entire group it is very common that corporate events will occur that require the logistical coordination of transporting the group to and from each planned event. Once the event has ended each person will require coordination to return to their destination city; this can take place over a period of days or within a few hours on the same day.
One of the problems encountered by the corporate travel and event management industries with regard to large events is the coordination and management of the ground transportation and greeting services for the event. For a large event such as a company meeting or a company retreat numerous individuals from various geographical locations travel to the city in which the event will take place. In many instances, there is more than one airport which may service the event location. For each of these airports there are usually many airline carriers and multiple terminals in which travelers may arrive. In order for greeters to be scheduled to meet travelers at the time of arrival at the gate for the particular terminal and for travelers to be met by a chauffeur in a scheduled vehicle provided by a ground transportation company, someone must coordinate and solve the problem of hundreds of travelers arriving and departing at different terminals at both scheduled and unscheduled times. Typically the variables involved with solving this problem are the particular airport they will arrive or depart from, terminal of arrival or departure, scheduled time of arrival or departure, any change in scheduled flight time, number of individuals arriving at or departing from a particular terminal during that particular time period, and the number of travelers a greeter or a ground transportation vehicle can accommodate. With hundreds of travelers, multiple airport arrivals and departures at various terminals, flight delays, it is difficult for someone to schedule ground transportation vehicles and greeters.
An example of such an event and scenario would be as follows: an event is located in the Washington, D.C. area, hundreds of travelers would be traveling by air to three different airports (i.e., the Baltimore Washington Airport, Dulles Airport and National Airport), each of these airports have multiple terminals for planes to arrive. The ground transportation which will move the travelers from each of the three airports to the event location which may be in a hotel in downtown Washington, D.C., could be accomplished with various types of vehicles including sedans, limousines, SUV's, vans, minibuses, and motor coaches. Each of these vehicle types has a different capacity for carrying passengers. In order to assess which vehicle type would be used for a given pick-up at a particular terminal at a particular airport the scheduler needs to identify and group passengers that are arriving at approximately the same time in the same terminal. The scheduling is exasperated by the fact that planes may arrive early or later than scheduled, and certain vehicle types may be unavailable if stuck in traffic or still handling a previous pick-up. Other variables may also complicate solving the transportation problem such as certain passengers being VIPs and requiring separate cars or special vehicles for their transportation.
Additional challenges occur when people are arriving and departing at the same time on scheduled domestic and customs flights that require check in two hours prior to departure and an undetermined amount of time to go through customs on arrivals.
Similar issues exists with the scheduling of greeters to meet passengers on their arrival at airport terminals and direct passengers to baggage claims and vehicles. For example, depending upon the number of passengers arriving at a particular time in a particular terminal, multiple greeters may be necessary to direct the passengers to the appropriate vehicles for transportation to the event and location. Determining if a flight is arriving as a customs flight will also complicate the process and requires additional scheduling.
Assigning and managing the ground transportation can be considerably complex especially if there is a limited fleet of vehicles that are being used to transport the passengers. Determining the most efficient or optimal way to assign the vehicles and move the passengers can be difficult given all the variables that are involved in scheduling.
When a company plans a company event they may have an internal person or department responsible for managing the event, they may outsource the event to a corporate travel company or utilize the services offered by a destination management company (DMC). These people or departments will be referred to as the "Travel Manager". Depending upon the number of attendees and geographic locations selected the Travel Manager will provide a rough ballpark estimate of the costs of the event. Typically ground transportation services are estimated as a percentage of the total cost for the event. e.g., 10%. Sometimes, the ground transportation service costs are estimated based upon the ground transportation cost for a prior event or an event which occurred in a prior year. A detailed calculation of the actual cost of the ground transportation is not typically done because it requires too many hours of manual labor by the Travel Manager.
Once the decision to have an event is made, the planning generally progresses to the next step, and the company event's person will generate a manifest of passenger attendees along with information about arrival and departure times and airlines for those passengers as well as any activities, events or dine-arounds that will require transporting the group during the event days. This manifest list is provided to the Travel Manager for their use in estimating the cost of the ground transportation. Upon receipt of the manifest the Travel Manager will typically begin a very labor intensive process of reformatting the spreadsheet to identify what days and times people are scheduled to arrive and depart and from what airport and terminal and begin a very crude grouping or assignment of passengers to vehicles. This process usually takes at least several hours and does not verify or validate information or account for any changes. Once the travel manager has completed the initial forecasted manifest, the travel manager will forward it to the local ground transportation provider which will then estimate the ground transportation costs. Typically this is a very rough cost and does not account for invalid information, changes, or optimized grouping calculations. Due to the overwhelming amount of changes and grouping variations it is very common that the quote is completely different than the actual cost. This can result in a lost opportunity to win the business or illustrate the opportunity to optimize the groupings and decrease ground transportation cost.
In addition to the ground transportation portion of the event management, the hotels involved in the event management do not have detailed information about arrival time of guests at the hotel or check out times for guests departing from the hotel.
Organizing the movement of passengers from one location to another is a complicated, time-consuming and error-prone process. There are many instruction manuals, help guides, books, time management software and seminars that provide event planning guidance. However, these tools amount to little more than common sense organizational techniques and a laundry list of "to-do" checklists.
There is a strong need to have an event management system for automating the repetitive and labor-intensive parts of the event management process, validating, verifying and automatically correcting passenger information, providing real-time pricing for rapid invoice forecasting, and automating grouping of passengers into vehicles based upon a multitude of user and system defined factors. A system for allowing better scheduling of ground transportation and providing hotels with better information of travelers arrival times is needed.


The present invention relates to cleaning compositions, including laundry, dishwashing, hard surface cleaner, oral/dental cleaning compositions, comprising a proteinic substrate based oxygenase, which provide effective and efficient cleaning of proteic based stains and/or soils such as protein containing food stains/soils and everyday body soils and provide sanitisation of the treated surfaces. Furthermore, the cleaning compositions of the present invention provide fabric realistic items cleaning and whitening performance when formulated as a laundry detergent composition.

Performance of a cleaning product, for use in washing or cleaning method, is judged by a number of factors, including the ability to remove soils, and the ability to prevent the redeposition of the soils, or the breakdown products of the soils on the articles in the wash.
Many consumer relevant stains contain proteinic components and are difficult to remove from the washed surfaces. Food stains originating from dairy products as such, like milk or egg, or processed within food or drink products, are particularly challenging to remove.
In addition, the complex nature of everyday "body" soils typically found on pillow cases, T-shirts, collars and socks, provides a continuous thorough cleaning challenge for detergents. These soils are difficult to remove completely and often residues build up on fabric leading to dinginess and yellowing. Moreover, body fluids stains, such as blood and menstrual fluids, are often difficult to remove effectively from a soiled item, especially when the stains have been ageing. Everyday body soils are also found on sanitary and kitchen surfaces such as bathtubs, toilet bowl and dishware.
The items can be fabrics, hard surfaces, dishware such as plasticware, glassware or chinaware, teeth and mouth.
Traditionally, protease enzymes and/or high levels of bleaching compounds, optionally with bleach precursors and/or bleach enhancers, are incorporated in cleaning compositions. Bleaching agents are compounds which are precursors of hydrogen peroxide which is formed in the course of the washing procedure. Perborates and percarbonates are the most important examples of such hydrogen peroxide precursors.
In view of the above, there exits clearly a continuous need to provide cleaning compositions which have an excellent detergency performance. Accordingly it is an object of the present invention to provide a cleaning composition which provides effective and efficient cleaning of proteic based stains and/or soils such as protein containing food stains/soils and everyday body soils. It is a further object to provide a cleaning composition which provides fabric realistic items cleaning and whitening.
The above objective has been met by formulating cleaning compositions comprising a proteinic substrate based oxygenase.
It has been surprisingly found that an enzymatic bleach system based on a proteinic substrate based oxygenase delivers in a cleaning composition, bleach-like benefits in an unexpected broad range of performance areas such as dingy cleaning, whiteness maintenance and stain removal. It has also been found that the cleaning compositions of the present invention provide sanitisation of the treated surfaces.
It has been further found that the performance of the cleaning compositions of the present invention is improved by the addition of another enzymatic bleach system, a conventional activated bleach system, a metallo catalyst based bleach system and/or another detergent enzyme, especially a protease.
In a preferred embodiment, the present invention relates to a laundry composition comprising a proteinic substrate based oxygenase, further providing fabric realistic items cleaning and whitening. In a second embodiment, the present invention relates to dishwashing or household cleaning compositions comprising a proteinic substrate based oxygenase and in a third embodiment, the present invention relates to oral/dental care compositions comprising a proteinic substrate based oxygenase.
The use of a proteinic substrate based oxygenase in a cleaning composition for substantive removal of proteic based stains/soils such as protein containing food stains/soils and everyday body soils and for sanitisation, has never been previously recognised. Nor have been recognised the substantive fabric realistic items cleaning and whitening performance when the proteinic substrate based oxygenase is used within a laundry detergent composition.

Cleaning compositions comprising a specific oxygenase


A thermally conductive sheet, which contains: a binder; carbon fibers; and an inorganic filler, wherein the thermally conductive sheet is to be sandwiched between a heat source and a heat dissipation member of a semiconductor device, wherein the carbon fibers have an average fiber length of 50 μm to 250 μm, wherein thermal resistance of the thermally conductive sheet is less than 0.17 K·cm2/W, as measured in accordance with ASTM-D5470 with a load of 7.5 kgf/cm2, and wherein the thermally conductive sheet has an average thickness of 500 μm or less.

Semiconductor elements have been improved to have high density and to be highly mounted, along further improvement in quality of electronic devices. It is important to more efficiently radiate heat generated from an electronic part constituting an electronic device because of the aforementioned trends. In order to efficiently radiate heat, a semiconductor element is mounted to a heat sink, such as a radiating fin, and a heat sink plate. As for a thermally conductive sheet, a thermally conductive sheet, in which filler (thermally conductive filler), such as inorganic filler, is dispersed in silicone, has been widely used. Examples of the inorganic filler include alumina, aluminum nitride, and aluminum hydroxide.
Various researches have been conducted on the thermally conductive sheet for the purpose of achieving high thermal conductivity.
For example, it has been attempted to increase a filling rate of the inorganic filler blended in a matrix. If the filling rate of the inorganic filler is increased, however, a flexibility of a resulting thermally conductive sheet may be impaired, or powdering may occur due to the high filling rate of the inorganic filler. Therefore, there is a limitation in a method for increasing the filling rate of the inorganic filler.
Moreover, proposed are techniques for adding boron nitride (BN), flaky particles, such as graphite, or carbon fiber in a matrix (for example, see PTL 1 and PTL 2). These proposed techniques are those utilizing anisotropy of thermal conductivity, which the flaky particles or the like have. In case of carbon fiber, for example, there is thermal conductivity of about 600 W/m·K to about 1,200 W/m·K in a direction of alignment of the fiber. In case of boron nitride, there is thermal conductivity of about 110 W/m·K in the in-plane direction, and about 2 W/m·K in a direction vertical to the in-plane direction. These materials have been known to have anisotropy.
In recent years, high density and highly dense mounting of a semiconductor element are significantly advanced. Therefore, even higher thermal conductivity of a thermally conductive sheet has been required. Moreover, it is desired to achieve high thermal conductivity with a thin sheet.
Use of the carbon fiber can provide a thermally conductive sheet, which realizes both excellent high thermal conductivity and flexibility (for example, see PTL 3). However, use of a thin sheet (for example, the average thickness being 500 μm or less) increases thermal resistance at an interface. Therefore, it has not yet provided a thermally conductive sheet, which realizes both excellent high thermal conductivity that is required recently, and excellent flexibility.
Accordingly, there are currently needs for a thermally conductive sheet, which can achieve both excellent high thermal conductivity, and excellent flexibility with a small thickness, a production method thereof, and a semiconductor device using the thermally conductive sheet.

Thermally conductive sheet, method for producing same, and semiconductor device


Glycidyl esters are prepared by reacting a compound containing one or more ethylenically unsaturated ester groups with hydrogen peroxide in the presence of an alkali metal or alkaline earth metal salt of tungstic acid, phosphoric acid and a phase transfer catalyst, optionally in the presence of one or more solvents.

Glycidyl esters, particularly polyglycidyl esters have been generally prepared by reacting carboxylic acids or di- or polycarboxylic acids with an epihalohydrin followed by dehydrohalogenation of the intermediate halohydrin product. In this method, often the product is oligomerized during the dehydrohalogenation step resulting in the product having a viscosity as well as an epoxide equivalent weight much higher than that desired. It would be desirable to have available a process for preparing glycidyl esters, particularly di- and polyglycidyl esters which have epoxide equivalent weight values substantially equivalent to the theoretical epoxide equivalent weight.


A apparatus for classifying a seed as inbred or hybrid comprises a terahertz signal source for emitting a terahertz signal towards the seed, a detector for detecting at least part of the terahertz signal having interacted with the seed, a scanner for moving the support relative to the terahertz signal to provide a scan of the seed, a data processing device for forming an image data from the detected terahertz signal as obtained for a plurality of positions during the scan of the seed, and a decision support system for providing a classification from the image data. In an embodiment, the terahertz signal source is arranged for emitting a continuous or pulse wave signal, and wherein the detector is arranged for detecting an amplitude and a phase of the terahertz signal having interacted with the seed. A signal representing an outcome of the classification may control a separator to separate seeds according to their classification.

In crop production, high yields are desired so as to obtain a large amount of crop per acre of land. Thereby, many factors, such as climate, composition of the soil, nutrition, etc. play a role. A quality of the seed from which the crop is grown, plays a relevant factor also, as genetic properties of the plant have a substantial impact on the quality and quantity of crop grow, as well as on susceptibility for diseases, hardness to withstand a certain climate, etc. A relevant factor is a genetic purity of the seed so as to be able to maintain desired genetic properties of the seed.
It is known that certain crops, such as rice are self-pollinated. Self pollination may result in seeds with low genetic diversity. The low genetic diversity in turn may lead to segregation of traits, lower yields and genetic deterioration of varieties.
Thus, there is a strong need for a distinguishing of a genetic purity of a seed, in order to enable to quickly and precisely select hybrid seeds from inbred seeds, for example to provide a selection of high level genetic purity hybrid seeds to farmers for commercial cultivation. Estimating the genotypic difference of a seed has been performed in various ways. These ways include destructive methods, such as morphological, biochemical, DNA markers (DNA fingerprinting) methods:                morphological markers are influenced by the environmental conditions, are labor intensive and time consuming;        biochemical markers such as isozyme and protein patterns are least influenced by the environment however exhibit limited polymorphism and often do not allow discrimination between closely related inbred lines;        DNA markers (e.g. SSR markers) are still time consuming.
Furthermore, some non-destructive methods are known. An example is making use of near infrared radiation.                The seed is illuminated by light of a pre-defined NIR spectrum and the spectral features of the reflected/transmitted light are measured.        NIR reflection spectroscopy is an important technique that is widely used for the analysis of grain and seed samples. The spectral information obtained for the seeds samples under investigation can be further examined to provide quantitative information on vital composition parameters, such as protein, carbohydrate, fat, moisture and sugar content by means of chemometrics and appropriate calibration models.
NIR is a secondary technique, and therefore an accuracy of NIR instruments depends on an accuracy of calibration as well as on a similarity of a composition of a calibration sample to a sample to be analyzed. Furthermore, variations in environmental factors, such as humidity and temperature, may have an effect on the spectral information obtained from the sample, thereby potentially influencing an accuracy of the NIR technique. In addition, NIR radiation penetrates only into a surface layer of the seed tissue which limits the body and amount of genetic material to be sampled.

Method and apparatus for classifying a seed as inbred or hybrid


A dispersion compensating optical fiber is disclosed which is highly dispersive and which has a low effective area. The dispersion compensating optical fiber is suited for use with transmission optical fiber such as conventional single mode fiber. An optical transmission fiber and optical transmission system are also disclosed.

1. Field of the Invention
The present invention relates generally to optical fiber, and particularly to dispersion compensating optical fibers and systems employing same.
2. Technical Background
While some optical transmission systems can tolerate fairly large amounts of residual dispersion at 10 Gbit/second, these systems can tolerate only small amounts of residual dispersion at higher transmission rates of about 40 Gbit/second without causing unwanted signal distortion. Dispersion in such high bit-rate optical transmission systems needs to be controlled at the wavelength, or wavelengths, or interest. Various solutions have been proposed to achieve dispersion, and dispersion slope, values required for compensating transmission fibers. One approach involves housing a dispersion compensating fiber in a dispersion compensating module wherein the dispersion compensating fiber compensates for the accumulated dispersion of the transmission fiber at a location where the fiber end is accessible. Such modules include a length of dispersion compensating fiber wound onto a spool or reel.
Wavelength division multiplexing (WDM) systems have operated around the 1550 nm wavelength region, defined herein as including the C-band, which includes wavelengths between about 1525 nm to about 1565, and the L-band, which includes wavelengths between about 1565 nm to about 1625 nm

Highly dispersive dispersion compensating fiber for transmission fiber and transmission system utilizing same


A method and apparatus are provided. The apparatus includes a plurality of central processing units, a plurality of core input/output units, a plurality of last level cache memory banks, an interconnect network comprising multiple instantiations of dedicated data channels, wherein each dedicated data channel is dedicated to a memory transaction type, each instantiation of dedicated data channels includes arbitration multiplexors, and each dedicated data channel operates independently of other data channels.

A last level cache (LLC) in a central processing unit (CPU) is generally sized to hold a few megabytes of data or instruction lines of recent memory accesses to lower the latency of requests from the CPU as compared to memory accesses of dynamic random access memory (DRAM). A cache that stores megabytes of data requires a large physical area and integrated circuit floor planning resources to provide maximum capacity at minimum response latency. In a multi-CPU and multi-LLC memory bank shared cache system, an interconnect network, sometimes referred to as a network-on-chip (NoC), is capable of high bandwidth between a master CPU and LLC memory banks but exponentially expands wire, power, timing, and area requirements for each instantiation of CPU and LLC memory bank.
An integrated circuit system design may prefer blocks such as CPUs or LLC memory banks to be as uniform and "tile-able" as possible, meaning by designing one module and repeating instantiations or tiling several identical copies adjacent to the original resulting in a desired configuration. For large LLC memory systems, a tile-able or modular LLC memory bank design may be incorporated in multiple product configurations with minimum re-design if the LLC's memory protocol is also tile-able and modular.
Common solutions may include full ring busses, meshes and direct end-to-end wires, where each solution balances system complexity, power consumption, die area, wire cost, scalability, and selective memory coherence requirements. While high-end server systems have high-complexity, high-power solutions (e.g., rings, meshes, and switches) and low-end designs have low-complexity, non-scalable solutions (e.g., end-to-end dedicated connections), there is a need for a solution for CPU systems for mobile devices (e.g., in a mid-range of 1 to 8 nodes (CPUs)) with low-power consumption, mid-range complexity, and mid-range bandwidth requirements while achieving tile-ability.

Non-uniform bus (NUB) interconnect protocol for tiled last level caches


There is provided a digital-analog converter capable of easily extending the resolution that can easily extend the resolution by a simple circuit implementation when a 10-bit digital-analog converter is configured on the basis of an 8-bit digital-analog converter used in a display driving IC, and prevent an increase in area of the display driving IC. A digital-analog converter capable of easily extending the resolution according to an aspect of the invention includes a voltage dividing unit including a plurality of resistors connected in series with each other between operating voltage terminals to divide operating voltages into a plurality of voltages at connection nodes of the plurality of resistors, a decoder unit providing a plurality of switching signals including a first switching signal for selecting a voltage and a second switching signal for controlling the current, a switch unit selecting two voltages from the plurality of voltages divided by the voltage dividing unit according to the first switching signal, a comparing unit comparing the two voltages with each other selected by the switching unit to output a reference current corresponding to a difference between the two voltages, a current control unit controlling a feedback current according to the second switching signal of the decoder unit, and an adding unit transmitting the feedback current to the current control unit and adding one voltage between the two voltages selected by the switch unit and a feedback voltage determined according to the feedback current.

1. Field of the Invention
The present invention relates to a digital-analog converter capable of easily extending the resolution, and more particularly, to a digital-analog converter capable of easily extending the resolution that can easily extend the resolution by a simple circuit implementation when a 10-bit digital-analog converter is configured on the basis of an 8-bit digital-analog converter used in a display driving IC, and prevent an increase in area of the display driving IC.
2. Description of the Related Art
In recent years, the market for display devices, especially, digital TVs has grown. In order to achieve high display quality, high output resolution of driving ICs of the display devices has been required.
In general, bit extension of the digital-analog converter used in the driving IC is performed to increase the output resolution of the driving IC.
FIG. 1A is a configuration view illustrating an example of a digital-analog converter according to the related art.
Referring to FIG. 1A, a digital-analog converter 10 according to the related art includes a first resistor array 11 that divides voltages by a plurality of resistors, a first switch array 12 that has a plurality of switches for selecting the divided voltages, a first buffer unit 13 that buffers the two voltages selected by the first switch array 12, a second resistor array 14 that divides the voltages buffered by the first buffer unit 13 by a plurality of resistors, a second switch array 15 that selects the voltages divided by the second resistor array 14, a decoder unit 16 that controls the operation of selecting the voltages by each of the first switch array 12 and the second switch array 15, and a second buffer unit 17 that buffers the voltages selected by the second switch array 15 to output a final output voltage.
The above-described digital-analog converter 10 according to the related art is obtained by adding the first buffer unit 13, the second resistor array 14, and the second switch array 15 to a converter with 8-bit resolution. However, problems occur with the bit extension in that an increase in the number of resistors and switches results in an increase of chip area, and an off-set voltage of the buffer unit is applied to the final output voltage to cause deterioration in off-set characteristics of the entire system.
FIG. 1B is a configuration view illustrating another example of a digital-analog converter according to the related art.
Referring to FIG. 1B, a digital-analog converter 20 according to the related art includes a first resistor array 21 that divides voltages by a plurality of resistors, a first switch array 22 that selects the voltages divided by the first resistor array 21 by a plurality of switches, a second resistor array 23 that divides the voltages divided by a plurality of resistors, a second switch array 24 that selects the voltages divided by the second resistor array 23 by a plurality of switches, a decoder unit 25 that controls the operation of selecting the voltages by the first switch array 22 and the second switch array 24, and a buffer unit 26 that buffers the voltages selected by the second switch array 24.
When compared with the digital-analog converter 10 according to the related art, which is shown in FIG. 1A, the digital-analog converter 20 according to the related art increases a plurality of resistances of the plurality of resistors that are included in the second resistor array 23 to thereby remove the first buffer unit 13. However, the second resistor array 23 and the second switch array 24 are added to extend the resolution of the digital-analog converter with 8-bit resolution. The addition of the second resistor array 23 and the second switch array 24 results in an increase in the number of resistors and switches. This increase results in an increase of chip area. Further, since the resistances of the resistors included in the second resistor array 23 are increased, a current loss may occur to reduce uniformity between output channels.

Digital-analog converter capable of easily extending resolution


A controller for indicating whether a previously-detected, acceleration-sensor malfunction no longer exists. The controller includes an electronic memory and an electronic processing unit connected to the electronic memory. The electronic processing module includes a malfunction monitoring module, a failure handling module, and a signal checking module. The signal checking module performs a signal check after the malfunction monitoring module generates the fault signal. The signal check includes executing a signal check function with a longitudinal acceleration signal. Also disclosed is a vehicle including the controller, and a method executed by the controller.

Today's vehicles include a large number of systems for controlling aspects of the vehicle including engine emissions, anti-lock braking, passenger restraints, and much more. Each of these systems requires information in order to function, such as wheel speed data, or vehicle acceleration data. This information is generally obtained from sensors located throughout the vehicle. To ensure the integrity of the information, controllers perform failure analysis and testing on the sensors and the signals or data the sensors provide. If an error is detected in the information transmitted from the sensor, a controller can implement an alternate operating state for the vehicle control module. The alternate operating state may ignore the faulty sensor or may turn off the vehicle control module entirely. The controller may also generate an error signal (e.g., a tell-tale indicator such as a "check engine" warning light) to inform the operator of the vehicle of the malfunction.

Good checking for vehicle longitudinal acceleration sensor


A front wheel stabilizing device includes a mount adapted to be secured to a main frame of an electric motor-driven wheeled vehicle, and an axle disposed between two side plates of the mount. A wheel mounting member has a tubular head which is rotatably sleeved on the axle, and a cantilever arm which extends from the tubular head forwardly to terminate at a wheel-carrying end for mounting a stabilizing wheel thereon. The stabilizing wheel can yield under a jolting force that arises as a result of movement of the stabilizing wheel over an uneven ground so as to displace from a more tractive position to a less tractive position. A torsion spring has a coiled segment which is wound on the tubular head, and two urging ends which abut against the mount and the cantilever arm, respectively, so as to bias the stabilizing wheel downwardly, thereby restoring the stabilizing wheel from the less tractive position back to the more tractive position.

1. Field of the Invention
This invention relates to a front wheel stabilizing device for an electric motor-driven wheeled vehicle, more particularly to a front wheel stabilizing device to prevent tipping of the wheeled vehicle.
2. Description of the Related Art
A conventional electric motor-driven wheelchair is generally provided with a front wheel stabilizing device to improve tracking upon undulating or irregular surfaces and to provide anti-tip stability. FIGS. 1 and 2 show an electric power wheelchair 10 disclosed in Taiwanese patent publication No. 370866. The wheelchair 10 includes a main frame 11, two front drive wheels 12 mounted proximate to a front side of the main frame 11, two rear caster wheels 13 mounted on a rear aide of the main frame 11, and a footrest 14 and two front stabilizing devices 15 mounted on the front side of the main frame 11.
Each of the front stabilizing devices 15 includes a support rod 151 which extends through an insert hole 112 formed in a front upright post 111 of the main frame 11 and which is secured to the front upright post 111 by means of screw fasteners 16 that extend through lock holes 113 formed in the front upright post 111, a cantilever arm 152 which is pivotally mounted on the front upright post 111, a stabilizing wheel 153 which is mounted on the cantilever arm 152, and a compression spring 154 which is disposed between a front segment 1511 of the support rod 151 and the cantilever arm 152.
Due to the provision of the front stabilizing devices 15, when the wheelchair 10 travels over undulating or irregular surfaces, the compression springs 487 provide a damper effect to the cantilever arms 152 and the stabilizing wheels 153 so as to improve anti-tip stability. However, the upright posts 111 need to be formed with the insert holes 112 for passage of the support rods 151, and the lock holes 113 for securing the support rods 151 to the upright posts 111, thereby resulting in weakening of the structure of the main frame 11 and complicating the manufacturing process. Moreover, as the front segments 1511 of the support rods 151 extend forwardly of the main frame 11 for the compression springs 154 to be mounted thereon, they are liable to be damaged as well as unsightly.
U.S. Pat. Nos. 5,848,658 and 6,460,641 also disclose electric power wheelchairs, which, however, suffer from the aforesaid drawbacks as well.

Front wheel stabilizing device for an electric motor-driven wheeled vehicle


Disclosed embodiments provide systems and methods related to automatically assigning temporary delivery workers to a delivery task. A method for automatically assigning temporary delivery workers to a delivery task comprises receiving a request to determine delivery tasks for temporary delivery workers from a user device, retrieving delivery tasks needing assignments from a database, each delivery task associated with a delivery location and a volume of parcels, and determining a number of permanent delivery workers needed based on a volume of parcels associated with each delivery task. The method further comprises retrieving permanent delivery workers and temporary delivery workers needing assignments from the database, each delivery worker associated with a feasible volume of delivery parcels, assigning the retrieved permanent delivery workers to the retrieved delivery tasks, assigning the retrieved temporary delivery workers to the retrieved delivery tasks needing assignments after the permanent delivery worker assignments.

Fulfillment centers (FCs) encounter more than millions of products daily as they operate to fulfill consumer orders as soon as the orders are placed and enable delivery workers to pick up shipments. Operations for enabling delivery workers to pick up shipments may include assigning a delivery worker to a delivery task. Although currently existing FCs and systems for assigning workers are configured to handle large volumes of delivery tasks, a common issue arises when a FC receives orders that cannot be handled by delivery workers associated with the FC.
To mitigate such problems, conventional delivery assignment systems may assign temporary delivery workers, for example, workers delivering on an as-needed basis (e.g., seasonally), to perform delivery tasks. While these computerized systems attempt to assign delivery tasks in an efficient manner, the systems relied upon a human user to review a table of expected and actual workload values and determine assignments of temporary delivery workers to a delivery task. For example, a manager in charge of assigning delivery tasks may review an electronic document listing expected and actual workload of delivery tasks, including a volume of parcels for each delivery task, and determine whether or not a temporary delivery worker is required. The manager may then manually assign temporary delivery workers to unassigned tasks.
Therefore, there is a need for improved methods and systems for an automatic delivery task assignment of temporary delivery workers.

This patent is subject to a terminal disclaimer.

Systems and methods for automatic assignment of flexible delivery work


A bin holding device includes two vertical side elements spaced to accommodate a storage bin between the two vertical side elements. Each side element is provided with a bin supporting assembly including a bin support and an actuator. The bin support includes an upper bin interacting part arranged to interact with the storage bin when the storage bin is accommodated in the bin holding device, such that a top edge of the accommodated storage bin is held at a predetermined level. The actuator is operably connected to the bin support and includes a lower bin interacting part arranged to interact with the storage bin during introduction of the storage bin into the bin holding device in a downward vertical direction, such that the upper bin interacting part is moved to interact with the storage bin.

The Applicant's already known AutoStore system is a storage system comprising a three-dimensional storage grid structure wherein storage bins/containers are stacked on top of each other to a certain height. Such a prior art system is shown in FIG. 1a.
The storage system is disclosed in detail in for instance NO317366 and WO 2014/090684 A1.
The storage system 10 comprises a grid structure 20 constructed as aluminium columns interconnected by top rails. Between the columns, vertical compartments are defined, in which the storage bins 30 may be stacked vertically above each other. A number of vehicles 40, or robot vehicles, are arranged on the top rails and may move horizontally on top of the storage grid.
Each vehicle is equipped with a lifting device for picking up, carrying, and placing storage bins 30 that are stored in the storage grid.
The system also comprises picking and/or supply stations 60, where one or several product items are picked out from the storage bin 30 or where one or several product items are placed into the storage bin 30.
When a product item stored in a storage bin is to be picked from the storage grid, the robot vehicle is arranged to pick up the storage bin containing that product type and then transport it to a bin lift 50. The bin lift transports the storage bin to the picking and/or supply station 60, where the item of the product type is retrieved from the storage bin. The storage bin with the remaining product items is thereafter returned to the storage grid by means of a bin lift and a robot vehicle. The picking and/or supply station 60 illustrated in FIG. 1a is only shown schematically as a simple table upon which the storage bin is arranged. A more advanced prior art picking and/or supply station 60 illustrated in FIG. 1b.
The same procedure is used for supplying product items into the storage grid. First, items are supplied into a storage bin at a picking and/or supply station. The bin lift then lifts the storage bin up to the upper level where a robot vehicle transports the storage bin to its correct position within the storage grid.
A storage control and communication system is used to monitor inventory, to keep track of the location of respective storage bins (within storage grid and/or during transport), the content of each storage bins etc. Further, the storage control and communication system may also comprise, or may be provided in communication with, a control system for controlling the robot vehicles to pick a desired storage bin and to deliver it at the desired location at the desired time—without colliding with other vehicles.
The storage bins 30 have the same footprint and in most prior art systems are of the same height. To allow for increased storage flexibility it is desirable to have a storage system, wherein the storage bins may have different heights.
However, prior art picking and/or supply stations, also called work stations, designed for storage bins having a specific height, see FIG. 1b, are not suitable for use with a storage system comprising storage bins of different heights. Such stations comprise an opening 1 for operator access to the storage bin 30. The top edge of the storage bin is arranged below the opening at substantially the same level to minimize any gap between said top edge and the circumference of the opening. This provides the operator with an ergonomic work position, keeping the bottom of the storage bin as close to the operator as possible, minimizes exposure of the station interior and minimizes the operator risk of squeeze/crush injuries.
An example of a prior art picking/supply station is disclosed in WO 2012/026824 A1. The exemplary prior art picking/supply station comprises box-shaped holding devices for receiving storage bins from a storage system. The holding devices are disclosed having stop devices to prevent a storage bin from sliding through the holding device. The stop devices are not further defined; however, from the drawings they appear to be multiple inclined arms interacting with corresponding recesses extending from the bottom of the storage bin.
The purpose of the present invention is to provide a picking/supply station suitable for storage bins of different heights.


Systems and/or methods are disclosed herein to identify a user interacting with a content presentation system, adaptively learn, in a passive manner, a user's pattern of accessing content over time, and globally store the user's identifying and use information. Specifically, disclosed are systems and/or methods for switching from a first signal provided to a second signal, including identifying a user of a first content presentation system, creating a first preferred channel list which includes channel information for each of select ones of plural signals, where the preferred channel list is created based on the identity of the user and based on channel use information for the user during a recurring first time period, presenting substantially simultaneously to the user a first signal of the select ones of plural signals in a first frame and a second signal of the select ones of plural signals in a second frame.

There is a vast and growing industry dedicated to gathering, organizing, and presenting media content to consumers (viewers and/or users) of information such as news, entertainment, sports, emergency alerts, advertisements, and other subject matter. This industry is supplying information to consumers at an ever-increasing rate. This overabundance of information will soon surpass the standard methods consumers use to sift through the information to access the information that is desired. For example, serially switching channels on a television from one channel number to the next highest (or lowest) channel number is inefficient, frustrating, and time-consuming. The problem becomes exacerbated as the number of available television channels increases. The typical television viewer normally is not interested in viewing any but a small fraction of the available channels and the need to "surf" through a huge number of channels to reach a desired channel makes the viewing experience less than optimal. Even jumping to a particular channel (e.g., by entering the channel number into a remote control device) becomes problematic since the viewer must remember the channel number, manage the rearrangement of channels which may change from time-to-time as distributors rearrange their channel assignments to accommodate new programming and/or remove old programming, and associate desired content with completely different channel numbers if the viewer travels to a different geographic location. This problem is in no way limited to television viewing as is evident by the increase in the number of terrestrial radio stations as well as the advent of satellite radio "stations" with their large number of channels dedicated to particular musical, informational, or "talk radio" content. Similarly, for example, media content presented to consumers via the internet is continually expanding and the consumer is presented with comparable problems. A further example is a music-playing device, such as a personal portable music player for which the consumer can add/delete content at will. There are also other means of communication for which the need to manage the flow of information is becoming necessary.
Furthermore, current systems for interfacing with a content presentation system (e.g., a television, a radio, an internet-connected device, a music playing device, a portable entertainment device, a personal digital assistant, a cellular phone/information system, and combinations thereof) may not have the means to identify the user nor present content for which the identified user is most likely seeking access. Those systems that do require that the user actively input information into the system. Additionally, current interfacing systems do not share their information with other interfacing systems but rather are slaved to a particular content presentation system.
The present disclosure overcomes the above-mentioned limitations in existing systems by disclosing, among other things, systems and/or methods to identify a user interacting with a content presentation system, adaptively learn, in a passive manner, a user's pattern of accessing content over time, and globally store the user's identifying and use information.
According to one embodiment, the present disclosure relates to a novel method for switching from a first signal provided by a content provider to a second signal provided by the content provider, including identifying a user of a first content presentation system that is operatively connected to the content provider, where the content provider provides a plurality of signals to the first content presentation system, creating a first preferred channel list which includes channel information for each of select ones of the plural signals, where the preferred channel list is created based on the identity of the user and based on channel use information for the user during a recurring first time period, presenting substantially simultaneously to the user via the first content presentation system a first signal of the select ones of plural signals in a first frame and a second signal of the select ones of plural signals in a second frame, where the first frame is larger than the second frame, and switching the content presentation system so that the second signal is presented in a third frame that is larger than the second frame.
Furthermore, the above embodiment may include creating a second preferred channel list based on the identity of the user and based on previously determined information for the user wherein the information is determined for a recurring second time period, associating the second preferred channel list with a first actuator operable by the user for interacting with the first content presentation system, and operating the first actuator to thereby switch the first content presentation system from presenting a third signal provided by the content provider to presenting a fourth signal provided by the content provider.
According to another embodiment, the present disclosure relates to a novel system for switching from a first signal provided by a content provider to a second signal provided by the content provider, including a first content presentation system, circuitry for determining an identity of a user of the first content presentation system that is operatively connected to the content provider, where the content provider provides a plurality of signals to the first content presentation system, circuitry for creating a first preferred channel list which includes channel information for each of select ones of the plural signals, where the preferred channel list is created based on the identity of the user and based on channel use information for the user during a recurring first time period, circuitry for presenting substantially simultaneously to the user via the first content presentation system a first signal of the select ones of plural signals in a first frame and a second signal of the select ones of plural signals in a second frame, where the first frame is larger than the second frame, and circuitry for switching the content presentation system so that the second signal is presented in a third frame that is larger than the second frame.
Additionally, the above-described embodiment may further include circuitry for creating a second preferred channel list based on the identity of the user and based on previously determined information for the user where the information is determined for a recurring second time period, a first portable device including a first actuator which is operable by the user for interacting with the first content presentation system, and circuitry for associating the second preferred channel list with the first actuator operable by the user for interacting with the first content presentation system, where operating the first actuator switches the first content presentation system from presenting a third signal provided by the content provider to presenting a fourth signal provided by the content provider.
These and many other advantages of the present disclosure will be readily apparent to one skilled in the art to which the disclosure pertains from a perusal of the claims, the appended drawings, and the following detailed description.

System and method for picture-in-picture assisted time-adaptive surfing for a content presentation system


The invention relates to the electrolysis of aqueous electrolyte solutions containing GeO2; hydroxide and water with metal alloy electrodes, such as, copper or tin rich alloy electrodes with alloying elements such as Sn, Pb, Zn, Cu etc, to generate Germane (GeH4). Cu-rich alloy electrodes have been demonstrated to increase the GeH4 current efficiency by almost 20% compared to Cu metal electrodes. Germanium deposition has been found to be either absent or minimal by using Cu-rich alloy electrodes. Several different methods for maintaining the cell performance or restoring the cell performance after a reduction in current efficiency over time, have been identified. A titration-based method for the analysis of the electrolyte, to obtain the concentration of GeO2 and the concentration of hydroxide has also been disclosed.

The present invention relates to electrode materials for the electrochemical synthesis of germane (GeH4). Several electrode materials have been previously reported in literature, which include Ni, Cu, Pb, Sn, Cd, Zn, Pt, Al, Ge, Graphite, Fe and Hg.
SU1732697A1, RU2071993 and RU2230830 taught the use of a Ni electrode to electrochemically generate germane with current efficiencies estimated at 15-20% when operating at optimal conditions in a flow-through cell with cross mixing of anolyte and catholyte. The patents focused on the process of cross-mixing the anode and cathode electrolytes and not on, the electrode material itself.
U.S. Pat. No. 5,158,656 alleged the use of a germanium electrode to generate germane at current efficiencies of 30%. However, this result is in contrast to that reported in a journal publication (Green et. al., J. Electrochem. Soc., v106, n3, p253) which showed that germanium electrodes do not generate germane efficiently.
Djurkovic et. al. (Glanik Hem. Drustva, Beograd, v25/26 (8-10), 1961, p469) studied several different metals (Al, Fe, Pb, Cu, Zn and Hg) as electrodes.
Tomilov et. al. (Inorganic Materials, 2008, v44, n10, p1081) evaluated several different metals as electrodes in a filter-press electrolyzer with the catholyte circulated by a centrifugal pump and concluded that copper and cadmium were optimal electrode materials with current efficiencies of 32-34%. The authors' also reported that the current efficiencies decreased over a period of time due to the deposition of Germanium on the electrode surface.
Thus, there is still a need in the art to provide effective means for the electrochemical synthesis of germane, especially, with stable performance.

Electrodes for electrolytic germane process


Disclosed are novel multi-functional hematopoietic receptor agonist proteins, DNAs which encode the multi-functional hematopoietic receptor agonists proteins, methods of making the multi-functional hematopoietic receptor agonists proteins and methods of using the multi-functional hematopoietic receptor agonists proteins.

The present invention relates to multi-functional hematopoietic receptor agonists.
Colony stimulating factors (CSFs) which stimulate the differentiation and/or proliferation of bone marrow cells have generated much interest because of their therapeutic potential for restoring depressed levels of hematopoietic stem cell-derived cells. CSFs in both human and murine systems have been identified and distinguished according to their activities. For example, granulocyte-CSF (G-CSF) and macrophage-CSF (M-CSF) stimulate the in vitro formation of neutrophilic granulocyte and macrophage colonies, respectively, while GM-CSF and interleukin-3 (IL-3) have broader activities and stimulate the formation of both macrophage, neutrophilic and eosinophilic granulocyte colonies. IL-3 also stimulates the formation of mast, megakaryocyte and pure and mixed erythroid colonies.
U.S. Pat. No. 4,877,729 and U.S. Pat. No. 4,959,455 disclose human IL-3 and gibbon IL-3 cDNAs and the protein sequences for which they code. The hIL-3 disclosed has serine rather than proline at position 8 in the protein sequence. International Patent Application (PCT) WO 88/00598 discloses gibbon- and human-like IL-3. The hIL-3 contains a Ser8xe2x86x92Pro8 replacement. Suggestions are made to replace Cys by Ser, thereby breaking the disulfide bridge, and to replace one or more amino acids at the glycosylation sites.
U.S. Pat. No. 4,810,643 discloses the DNA sequence encoding human G-CSF.
WO 91/02754 discloses a fusion protein comprised of GM-CSF and IL-3 which has increased biological activity compared to GM-CSF or IL-3 alone. Also disclosed are nonglycosylated IL-3 and GM-CSF analog proteins as components of the multi-functional hematopoietic receptor agonist.
WO 92/04455 discloses fusion proteins composed of IL-3 fused to a lymphokine selected from the group consisting of IL-3, IL-6, IL-7, IL-9, IL-11, EPO and G-CSF.
WO 95/21197 and WO 95/21254 disclose fusion proteins capable of broad multi-functional hematopoietic properties.
GB 2,285,446 relates to the c-mpl ligand (thrombopoietin) and various forms of thrombopoietin which are shown to influence the replication, differentiation and maturation of megakaryocytes and megakaryocytes progenitors which may be used for the treatment of thrombocytopenia.
EP 675,201 A1 relates to the c-mpl ligand (Megakaryocyte growth and development factor (MGDF), allelic variations of c-mpl ligand and c-mpl ligand attached to water soluble polymers such as polyethylene glycol.
WO 95/21920 provides the murine and human c-mpl ligand and polypeptide fragments thereof. The proteins are useful for in vivo and ex vivo therapy for stimulating platelet production.
In evolution, rearrangements of DNA sequences serve an important role in generating a diversity of protein structure and function. Gene duplication and exon shuffling provide an important mechanism to rapidly generate diversity and thereby provide organisms with a competitive advantage, especially since the basal mutation rate is low (Doolittle, Protein Science 1:191-200, 1992).
The development of recombinant DNA methods has made it possible to study the effects of sequence transposition on protein folding, structure and function. The approach used in creating new sequences resembles that of naturally occurring pairs of proteins that are related by linear reorganization of their amino acid sequences (Cunningham, et al., Proc. Natl. Acad. Sci. U.S.A. 76:3218-3222, 1979; Teather and Erfle, J. Bacteriol. 172: 3837-3841, 1990; Schimming et al., Eur. J. Biochem. 204: 13-19, 1992; Yamiuchi and Minamikawa, FEBS Lett. 260:127-130, 1991; MacGregor et al., FEBS Lett. 378:263-266). The first in vitro application of this type of rearrangement to proteins was described by Goldenberg and Creighton (J. Mol. Biol. 165:407-413, 1983). A new N-terminus is selected at an internal site (breakpoint) of the original sequence, the new sequence having the same order of amino acids as the original from the breakpoint until it reaches an amino acid that is at or near the original C-terminus. At this point the new sequence is joined, either directly or through an additional portion of sequence (linker), to an amino acid that is at or near the original N-terminus, and the new sequence continues with the same sequence as the original until it reaches a point that is at or near the amino acid that was N-terminal to the breakpoint site of the original sequence, this residue forming the new C-terminus of the chain.
This approach has been applied to proteins which range in size from 58 to 462 amino acids (Goldenberg and Creighton, J. Mol. Biol. 165:407-413, 1983; Li and Coffino, Mol. Cell. Biol. 13:2377-2383, 1993). The proteins examined have represented a broad range of structural classes, including proteins that contain predominantly xcex1-helix (interleukin-4; Kreitman et al., Cytokine 7:311-318, 1995), xcex2-sheet (interleukin-1; Horlick et al., Protein Eng. 5:427-431, 1992), or mixtures of the two (yeast phosphoribosyl anthranilate isomerase; Luger et al., Science 243:206-210, 1989). Broad categories of protein function are represented in these sequence reorganization studies:
The results of these studies have been highly variable. In many cases substantially lower activity, solubility or thermodynamic stability were observed (E. coli dihydrofolate reductase, aspartate transcarbamoylase, phosphoribosyl anthranilate isomerase, glyceraldehyde-3-phosphate dehydrogenase, ornithine decarboxylase, omp A, yeast phosphoglycerate dehydrogenase). In other cases, the sequence rearranged protein appeared to have many nearly identical properties as its natural counterpart (basic pancreatic trypsin inhibitor, T4 lysozyme, ribonuclease T1, Bacillus xcex2-glucanase, interleukin-1xcex2, xcex1-spectrin SH3 domain, pepsinogen, interleukin-4). In exceptional cases, an unexpected improvement over some properties of the natural sequence was observed, e.g., the solubility and refolding rate for rearranged xcex1-spectrin SH3 domain sequences, and the receptor affinity and anti-tumor activity of transposed interleukin-4-Pseudomonas exotoxin fusion molecule (Kreitman et al., Proc. Natl. Acad. Sci. U.S.A. 91:6889-6893, 1994; Kreitman et al., Cancer Res. 55:3357-3363, 1995).
The primary motivation for these types of studies has been to study the role of short-range and long-range interactions in protein folding and stability. Sequence rearrangements of this type convert a subset of interactions that are long-range in the original sequence into short-range interactions in the new sequence, and vice versa. The fact that many of these sequence rearrangements are able to attain a conformation with at least some activity is persuasive evidence that protein folding occurs by multiple folding pathways (Viguera, et al., J. Mol. Biol. 247:670-681, 1995). In the case of the SH3 domain of xcex1-spectrin, choosing new termini at locations that corresponded to xcex2-hairpin turns resulted in proteins with slightly less stability, but which were nevertheless able to fold.
The positions of the internal breakpoints used in the studies cited here are found exclusively on the surface of proteins, and are distributed throughout the linear sequence without any obvious bias towards the ends or the middle (the variation in the relative distance from the original N-terminus to the breakpoint is ca. 10 to 80% of the total sequence length). The linkers connecting the original N- and C-termini in these studies have ranged from 0 to 9 residues. In one case (Yang and Schachman, Proc. Natl. Acad. Sci. U.S.A. 90:11980-11984, 1993), a portion of sequence has been deleted from the original C-terminal segment, and the connection made from the truncated C-terminus to the original N-terminus. Flexible hydrophilic residues such as Gly and Ser are frequently used in the linkers. Viguera, et al. (J. Mol. Biol. 247:670-681, 1995) compared joining the original N- and C-termini with 3- or 4-residue linkers; the 3-residue linker was less thermodynamically stable. Protasova et al. (Protein Eng. 7:1373-1377, 1994) used 3- or 5-residue linkers in connecting the original N-termini of E. coli dihydrofolate reductase; only the 3-residue linker produced protein in good yield.
Novel hematopoietic proteins of this invention are represented by the formulas:
R1xe2x80x94L1xe2x80x94R2, R2xe2x80x94L1xe2x80x94R1, R1xe2x80x94R2, or R2xe2x80x94R1
wherein R1 and R2 are independently selected from the group consisting of;
(I) A polypeptide comprising; a modified human G-CSF amino acid sequence of the formula:
wherein
Xaa at position 1 is Thr, Ser, Arg, Tyr or Gly;
Xaa at position 2 is Pro or Leu;
Xaa at position 3 is Leu, Arg, Tyr or Ser;
Xaa at position 13 is Phe, Ser, His, Thr or Pro;
Xaa at position 16 is Lys, Pro, Ser, Thr or His;
Xaa at position 17 is Cys, Ser, Gly, Ala, Ile, Tyr or Arg;
Xaa at position 18 is Leu, Thr, Pro, His, Ile or Cys;
Xaa at position 22 is Arg, Tyr, Ser, Thr or Ala;
Xaa at position 24 is Ile, Pro, Tyr or Leu;
Xaa at position 27 is Asp, or Gly;
Xaa at position 30 is Ala, Ile, Leu or Gly;
Xaa at position 34 is Lys or Ser;
Xaa at position 36 is Cys or Ser;
Xaa at position 42 is Cys or Ser;
Xaa at position 43 is His, Thr, Gly, Val, Lys, Trp, Ala, Arg, Cys, or Leu;
Xaa at position 44 is Pro, Gly, Arg, Asp, Val, Ala, His, Trp, Gln, or Thr;
Xaa at position 46 is Glu, Arg, Phe, Arg, Ile or Ala;
Xaa at position 47 is Leu or Thr;
Xaa at position 49 is Leu, Phe, Arg or Ser;
Xaa at position 50 is Leu, Ile, His, Pro or Tyr;
Xaa at position 54 is Leu or His;
Xaa at position 64 is Cys or Ser;
Xaa at position 67 is Gln, Lys, Leu or Cys;
Xaa at position 70 is Gln, Pro, Leu, Arg or Ser;
Xaa at position 74 is Cys or Ser;
Xaa at position 104 is Asp, Gly or Val;
Xaa at position 108 is Leu, Ala, Val, Arg, Trp, Gln or Gly;
Xaa at position 115 is Thr, His, Leu or Ala;
Xaa at position 120 is Gln, Gly, Arg, Lys or His
Xaa at position 123 is Glu, Arg, Phe or Thr
Xaa at position 144 is Phe, His, Arg, Pro, Leu, Gln or Glu;
Xaa at position 146 is Arg or Gln;
Xaa at position 147 is Arg or Gln;
Xaa at position 156 is His, Gly or Ser;
Xaa at position 159 is Ser, Arg, Thr, Tyr, Val or Gly;
Xaa at position 162 is Glu, Leu, Gly or Trp;
Xaa at position 163 is Val, Gly, Arg or Ala;
Xaa at position 169 is Arg, Ser, Leu, Arg or Cys;
Xaa at position 170 is His, Arg or Ser;
wherein optionally 1-11 amino acids from the N-terminus and 1-5 from the C-terminus can be deleted; and
wherein the N-terminus is joined to the C-terminus directly or through a linker capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids;
(II) A polypeptide comprising; a modified hIL-3 amino acid sequence of the formula:
wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg;
Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
Xaa at position 36 is Asp, Leu, or Val;
Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
Xaa at position 38 is Asn, or Ala;
Xaa at position 40 is Leu, Trp, or Arg;
Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
Xaa at position 57 is Asn or Gly;
Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg;
Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser. Ala, Tyr, Phe, Ile, Met or Val;
Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
Xaa at position 85 is Leu, Asn, Val, or Gln;
Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
Xaa at position 87 is Leu, Ser, Trp, or Gly;
Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln;
Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
Xaa at position 103 is Asp, or Ser;
Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gin, His, Ser, Ala or Pro;
Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp;
Xaa at position 111 is Leu, Ile, Arg, Asp, or Met;
Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile;
Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln;
Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
wherein optionally from 1 to 14 amino acids can be deleted from the N-terminus and/or from 1 to 15 amino acids can be deleted from the C-terminus; and wherein from 0 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; and
wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids;
or
(III) A polypeptide comprising; a modified human c-mpl ligand amino acid sequence of the formula:
wherein;
Xaa at position 112 is deleted or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met;
Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
Xaa at position 115 is deleted or Gln, Gly, Ser, Thr, Tyr, or Asn; and
wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids;
or
(IV) A polypeptide comprising; a modified hIL-3 amino acid sequence of the formula: Thr Thr Ser Leu Lys Thr Ser Trp Val Asn
wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg;
Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
Xaa at position 36 is Asp, Leu, or Val;
Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
Xaa at position 38 is Asn, or Ala;
Xaa at position 40 is Leu, Trp, or Arg;
Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or
Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
Xaa at position 57 is Asn or Gly;
Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg;
Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
Xaa at position 85 is Leu, Asn, Val, or Gln;
Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
Xaa at position 87 is Leu, Ser, Trp, or Gly;
Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;
Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;
Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;
Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;
Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln;
Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;
Xaa at position 103 is Asp, or Ser;
Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;
Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;
Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp;
Xaa at position 111 is Leu, Ile, Arg, Asp, or Met;
Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;
Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gin, or Ile;
Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;
Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;
Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;
Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln;
Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
wherein optionally from 1 to 14 amino acids can be deleted from the N-terminus and/or from 1 to 15 amino acids can be deleted from the C-terminus; and wherein from 1 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3;
or
(V) a colony stimulating factor;
and wherein L1 is a linker capable of linking R1 to R2;
with the proviso that at least R1 or R2 is selected from the polypeptide of formula (I), (II), or (III); and
said hematopoietic protein can optionally be immediately preceded by (methioninexe2x88x921), (alaninexe2x88x921) or (methioninexe2x88x922, alaninexe2x88x921).
The more preferred breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (I) above are; 38-39, 39-40, 40-41, 41-42, 48-49, 53-54, 54-55, 55-56, 56-57, 57-58, 58-59, 59-60, 60-61, 61-62, 62-63, 64-65, 65-66, 66-67, 67-68, 68-69, 69-70, 96-97, 125-126, 126-127, 127-128, 128-129, 129-130, 130-131, 131-132, 132-133, 133-134, 134-135, 135-136, 136-137, 137-138, 138-139, 139-140, 140-141 and 141-142.
The most preferred breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (I) above are; 38-39, 48-49, 96-97, 125-126, 132-133 and 141-142.
The more preferred breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (II) above are; 28-29, 29-30, 30-31, 31-32, 32-33, 33-34, 34-35, 35-36, 36-37, 37-38, 38-39, 39-40, 66-67, 67-68, 68-69, 69-70, 70-71, 84-85, 85-86, 86-87, 87-88, 88-89, 89-90, 90-91, 98-99, 99-100, 100-101 and 101-102.
The most preferred breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (II) above are; 34-35, 69-70 and 90-91.
The more preferred breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (III) above or the amino acid sequence of (SEQ ID NO:256) are; 80-81, 81-82, 82-83, 83-84, 84-85, 85-86, 86-87, 108-109, 109-110, 110-111, 111-112, 112-113, 113-114, 114-115, 115-116, 116-117, 117-118, 118-119, 119-120, 120-121, 121-122, 122-123, 123-124, 124-125, 125-126 and 126-127.
The most preferred breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (III) above or the amino acid sequence of (SEQ ID NO:256) are; 81-82, 108-109, 115-116, 119-120, 122-123 and 125-126.
The invention is also intended to include multifunctional receptor agonist which comprises a sequence rearranged c-mpl receptor agonist in which the cysteine at position 7 and/or 151 are substituted with another amino acid. Preferably, the substitution at position 7 and 151 is Ser, Ala, Gly, His, Asn, Asp, Thr, Phe or Thr. More preferably, the substitution at position 7 and 151 is Ser, Ala, Gly, His or Asn.
The multifunctional receptor agonist of the present invention can also be represented by the following formula:
(T1)a-(L1)b-X1-(L)c-X2-(L2)d-(T2)e
X1-(L)c-X2-(L)-Y1-(L)c-Y2
in which:
X1 is a peptide comprising an amino acid sequence corresponding to the sequence of residues n+1 through J of the original protein having amino acids residues numbered sequentially 1 through J with an amino terminus at residue 1;
L is an optional linker;
X2 is a peptide comprising an amino acid sequence of residues 1 through n of the original protein;
Y1 is a peptide comprising an amino acid sequence corresponding to the sequence of residues n=1 through K of the original protein having amino acids residues numbered sequentially 1 through K with an amino terminus at residue 1;
Y2 is a peptide comprising an amino acid sequence of residues 1 through n of the original protein;
L1 and L2 are optional peptide spacers:
n is an integer ranging from 1 to Jxe2x88x921;
b, c, and d are each independently 0 or 1;
a and e are either 0 or 1, provided that both a and e cannot both be 0; and
T1 and T2 are proteins.
Additionally, the present invention relates to recombinant expression vectors comprising nucleotide sequences encoding the multi-functional hematopoietic receptor agonists, related microbial expression systems, and processes for making the multi-functional hematopoietic receptor agonists. The invention also relates to pharmaceutical compositions containing the multi-functional hematopoietic receptor agonists, and methods for using the multi-functional hematopoietic receptor agonists.
In addition to the use of the multi-functional hematopoietic receptor agonists of the present invention in vivo, it is envisioned that in vitro uses would include the ability to stimulate bone marrow and blood cell activation and growth before infusion into patients.

Fused G-CSF and IL-3 proteins and uses thereof


A chip dispensing kiosk including a vault for holding casino chips, a dispensing assembly for dispensing selected numbers of casino chips and security and input systems to allow a pit manager to access the kiosk and have the kiosk dispense selected numbers of chips. These chips may be dispensed individually, in stacks or automatically loaded into a table chip tray back module. The kiosk is interactive with the casino's accounting system so as to report the dispensing of casino chips or receipt of casino chips. One preferred embodiment consists of a casino back room, cage, or Pit area chip tray management device that can be utilized by casino personnel to physically accept and count dumped gaming chips, communicate information with an ICT Intelligent Chip Tray Module, and automatically reload the chip tray per computer controlled specifications for any given table ID or chip loading requirement.

1. Field of the Invention
The present invention is generally directed to the field of casino management and in particular to a device and process whereby casino chips can be automatically sorted and loaded into trays to provide a supply of casino chip trays to gaming stations within a select area of the casino. In one embodiment, the invention contemplates a sorting, stacking and loading device that loads a chip tray to exact specifications corresponding to various programmable or selectable chip denomination configurations.
2. General Background and State of the Art
Modern casinos have evolved to incorporate hundreds or thousands of slot machines or other types of coin or ticket operated gaming machines. However, gaming tables where players can play blackjack, poker games, roulette or craps remain as a mainstay of the casino design. Generally, the slot machines are placed around one or more gaming table pit areas. A single pit area may include such gaming tables such as blackjack or poker tables, roulette tables and crap tables. The pit areas are generally positioned in a central portion of an open area within the casino. Each pit area is overseen by a pit manager, responsible for a significant number of oversight functions including security, detecting improper play, and table money and chip management.
Each gaming table includes a chip tray for continually organizing and storing the bank of chips used for play on that table during its operation. The dealer, croupier, or operator collects the chips from lost player bets and places them in the tray and in turn pays chips for winning bets from this tray to the winning player. Depending on the number of players and the magnitude of their game wagers, the value of the chip bank stacked in the table chip tray at any given time will significantly change on a continuous basis during a shift or operational period of the table game. In large modern casinos ICT or Intelligent Chip Tracking systems provide the ability to monitor this chip bank value or level on a continuous basis on each table by various electronic means. However, a precise accounting of the physical chips contained in the tray at given intervals such as at shift start and end may be required to independently verify such chip tray inventory starting and ending values. And in smaller less automated casinos it becomes vital to meet regulatory auditing requirements of table game revenues by performing periodic physical counts of the chip tray bank inventory. Such independent physical verifications can be time consuming and labor intensive.
Additionally most US casinos do not return the table chip trays to a standard chip tray bank value and/or chip denomination configuration upon opening or starting such a table's period of operation due to the time and labor required for reloading the chip tray to such a standard. The chip denomination configuration is comprised of such components as the number of different chip denominations in the tray, the values of the chip denominations in the tray, the number of chips of each different denomination in the tray, and the channel locations and quantities of each chip denomination in the tray. Such standards would of course vary by type of table game, and minimum bet denomination set for play in a specific table game.
Casinos also include an accounting cage and/or a back room area, which is discreetly and securely located away from the center of activity within a casino. In many casino environments when open a gaming table, it is necessary for the casino to arrange to have casino chips delivered from a caged vault area across the casino floor to the gaming table located in a particular pit area or grouping of gaming tables. Restocking of a gaming table chip tray during the course of play may be necessary if patrons have several wins and additional chips are necessary. Restocking a gaming table during the course of play can be distracting to the players and cause the casinos to lose revenue if an impatient player must wait for additional casino chips to be delivered to the gaming table.
Accordingly, it would be beneficial to have the ability to restock a gaming table with casino chips from a position located proximate to the pit area. However, since the casino chips can be utilized as money within the casino, and have values from one dollar to several thousand dollars, precise accounting for the casino chips within the accounting system is mandatory at all times. Whether these table chip trays are counted and reloaded in the pit area or in a more secure gage or back room area, it would be desirable to automate the physical counting, sorting and reloading process to provide accuracy, controllability, flexibility, simplicity and speed.
Although devices currently exist with the capacity to count and sort gaming table chips into columns of similar colors or denomination values. These existing devices do not automatically load a gaming table chip tray with a specified bank value and/or chip denomination configuration as previously described.