The ingredient feeder for automated cooking apparatus, covered in the present invention, is a horizontally oriented dispensing apparatus, having a variety of shapes and dimensions, constructed from different materials, thus optimized for a wide range of ingredients. Individually controlled, the feeders accurately and precisely dispense ingredients, while their positioning and orientation utilize space. Easy ingredient changes and refill by quick ingredient container replacement, enables a non-stop operation. A simple construction is aiming for operability and quick setup.

With increased modernization steadily creeping in personal lifestyle, kitchen gadgets are becoming increasingly popular and efficient, all over the world. In that line, automatic cooking machines are increasingly becoming popular as these saves time as well as energy, considered core aspects of efficiency in a busy world.
Despite the progress of such automatic machines smoothing out cooking process considerably, still a considerable degree of limitation of these is quite palpable. While automatic cooking mechanism is primarily focused on undertaking various cooking modes, e.g., stir frying, stewing, deep frying, boiling, steaming, pan frying, roasting braise, little progress in automation had occurred in feeding the inputs. An existing prior art in this respect are as follows:
In US20150238046A1 titled, "Automatic ingredient feeding apparatus applicable in a fully automated cooking machine" An automatic ingredient feeding apparatus comprises a machine frame, a feeder mechanism, a flipping mechanism and a plurality of compartment door control mechanisms. The feeder mechanism comprises a shell, the shell is provided therein with a receiving space for receiving a multi-compartment container and is provided therein with a multi-compartment ingredient-dropping chamber facing the receiving space. The flipping mechanism is used for mounting the feeder mechanism on the machine frame and for controlling the feeder mechanism to implement a 180-degree flip. Each of the plurality of compartment door control mechanisms controls an opening/closing of a compartment door of the individual compartment of the multi-compartment ingredient-dropping chamber. The flipping mechanism and the plurality of compartment door control mechanisms are all connected to a master control device.
However, the ingredient feeder talked about has the disadvantage of insufficient ingredient space and lack of adaptability to various cooking ingredients required for a plurality of cooking, thus limiting the capability of the automatic cooking apparatus substantially. Such insufficiency of space for the ingredients as well as adapting the feeder to a plurality of raw cooking inputs of various shapes and sizes are tried to be taken care of, in the present invention.

Ingredients feeder for an automated cooking apparatus


The invention concerns a water resistant portable object such as a diving watch including a sound generator device (12) and a microprocessor (1), characterized in that it emits acoustic signals at two different frequencies (f1) and (f2) as a function of the medium, air or water, in which the wearer of the watch is situated.

Human beings do not perceive sounds in the same way in the air and in water. However for obvious reasons of safety, the wearer of the watch must be able to be warned in an optimum manner whatever medium (air or water) he is in. This is particularly true when the wearer of the watch makes a submarine dive. It is vital that the diver is warned in sufficient time that his dive time is running out or that he has reached his maximum dive depth.
Diving watches are known from Japanese Patent Nos. JP 60-001588 and JP 07-333359 in the name of Seiko and JP 57-101786 in the name of Casio.
The electronic watch disclosed in JP Patent No. 60-001588 is capable of generating an acoustic time alarm and an acoustic depth alarm. The audible signal frequency is the same for both alarms. However, the features of the alarm (repetition frequency, sound length) are different depending upon whether it is the time alarm or the depth alarm.
The electronic watch disclosed in JP Patent No. 57-101786 includes a device that indicates the depth reached and generates an acoustic signal when this depth reaches a predetermined value.
The electronic watch disclosed in JP Patent No. 07-333359 includes means that detect whether the depth measurement has reached a predetermined value. An acoustic alarm is then produced and a hand is actuated.
The three aforecited documents all provide the possibility of producing an acoustic alarm when the wearer is making a submarine dive. However, none of these three documents discloses or suggests adapting the frequency of the alarm as a function of the medium (air or water) in which the user is located. It has been observed that the medium (air or water) in which the acoustic signal propagates and the auditory apparatus (external/internal ear or the bones of the cranial cavity in the case of submarine perception) act like filters as regards the signal. They form what is currently called a perception filter. An empirical curve can be obtained, which, depending upon the medium in which one is situated, indicates, for a given frequency, the difference between the acoustic power emitted and the acoustic power as it is perceived by the user. It will thus be noted that in the air, the sound perceived by the user is only very slightly attenuated by the perception filter in a broad frequency range comprised between 1 and 10 kHz. In water, sound transmission seems optimal at a frequency of the order of 800-1000 Hz with attenuation of the order of 40 dB. However, at a frequency two times higher, attenuation is greater than 60 dB.
It is thus an object of the present invention to provide a portable object such as a diving watch including a sound generator device which provides the user thereof with optimum sound perception whatever the medium in which the user is situated.

Water resistant portable object including a sound generator


A semiconductor device is described. In one embodiment, the device includes a Group-III nitride channel layer and a Group-III nitride barrier layer on the Group-III nitride channel layer, wherein the Group-III nitride barrier layer includes a first portion and a second portion, the first portion having a thickness less than the second portion. A p-doped Group-III nitride gate layer section is arranged at least on the first portion of the Group-III nitride barrier layer and a gate contact formed on the p-doped Group-III nitride gate layer.

Common power devices on the basis of GaN (gallium nitride) are mainly lateral HEMTs using a 2-dimensional electron gas (2-DEG) which is formed at the heterojunction between undoped GaN and undoped AlGaN (aluminium gallium nitride). Such devices are typically normally-on devices.
Approaches to form normally-off-devices, i.e. enhancement devices, include a p-doped AlGaN or p-doped GaN barrier layer between the gate and the undoped barrier layer to raise the conductivity band of the barrier layer such that the threshold voltage of the device is shifted to positive values. In order to obtain functional devices, the undoped barrier layer should not produce a too high density of the 2-dimensional electron gas, which counteracts the threshold voltage rise. However, reducing the density of the 2-DEG also reduces the conductivity of the drift region between source and drain.
Another approach is to form a recessed-gate-structure with a reduced barrier thickness below the gate formed by a Schottky metal. Manufacturing of such structures is complicated and not always reproducible.
For these and other reasons there is a need for the present invention.


A window-integrated antenna for LMS and FM reception in mobile motor vehicles in which the window pane of the motor vehicle, in conjunction with the line structures of the antenna and the metallic frame enclosing the window pane, is used as the antenna for the reception of LMS and USW signals, the connection points of the line structures being situated in the region of one of the corners formed by the metallic frame, in proximity to which the mechanical component used as the USW/LMS antenna unit is also positioned. The first conductor section of the antenna, which is positioned perpendicularly to the upper horizontal frame part of the metallic frame, is adjoined by a second long conductor section forming an angle preferably of 90° or forming a radius which is preferably implemented as a quarter circle having a small radius, the second conductor section running parallel to the upper horizontal frame part and extending over the largest part of the width of the window pane; and in proximity to the second lateral frame part, the second conductor section is adjoined by a third, likewise short conductor section forming an angle preferably of 90° or forming a radius which is preferably implemented as a quarter circle having a small radius, the third conductor section extending in the direction of the upper horizontal frame part and being connected to a fourth conductor section, forming the loop; the fourth conductor section, forming with the third conductor section an angle preferably of 90° or forming a radius which is preferably implemented as a quarter circle having a small radius, is positioned at a relatively small distance to the upper horizontal frame part and is shorter than the second conductor section of the antenna.

A window-integrated antenna of this type is described in German Patent No. DE 36 19 704, for example, in regard to a diversitary antenna arrangement, in which the window pane of the motor vehicle is used in conjunction with one or more line structures and the metallic frame surrounding the window pane, as the antenna for the reception of LMS and USW signals. In that case, two antenna conductors are positioned on the window pane of the motor vehicle, of which the one antenna conductor includes three conductor sections. The connection points of the two antenna conductors are situated in a corner of the window pane, in proximity to which the connecting network is also positioned, which has three inputs. Two of the inputs are each connected to one of the connection points of the two antenna conductors. The third input is assigned to the ground point of the metallic frame. The inputs connected to the connection points of the antenna conductors, together with the ground point, in each case form a monopole connection.
A disadvantage of the conventional window-integrated antenna is that the line structures of the antenna conductor which are used are optimized either for LMS reception or for USW reception. In this case, very long line structures are frequently used for the LMS reception, which have no resonance response for USW frequencies. Line structures whose length corresponds to ¼ of the operating wavelength in the USW range and which act in this context as the monopole are used for USW reception. However, these are again subject to the disadvantage that they do not have adequate reception response for LMS frequencies. If the line structures of the antenna conductors are integrated into a windshield made of laminated safety glass, they also always have an interfering effect, since they are in the visible area.
A further window-integrated antenna for motor vehicles is described in German Patent No. DE 92 17 173. Provided therein is an antenna structure which does not visually interfere in the window pane of the motor vehicle and which considers monopoles exclusively for the reception of LMS and diversitary USW signals, but it has been shown that the reception of LMS signals is nonetheless inadequate using antenna structures of this type. In order to allow reliable reception of LMS signals, antennas which may be positioned as a separate antenna on a different spatial point of the motor vehicle, on the bumper or on the spoiler, for example, are therefore frequently additionally used in motor vehicles.
However, the conventional window-integrated antennas frequently have the disadvantage that by taking the reception of different radio signals into consideration, the line structures which are used have at least two line ends such that, based on the requirement for a connection point, an electrical connection must be established in the region of the window pane of the motor vehicle. While this may be performed in a simple manner for a window pane made of single-layer safety glass, it is not possible to electrically connect multiple separate antenna conductors in a window pane made of laminated safety glass, since the manufacturing reliability of the window pane is no longer ensured because of possible air inclusions.

Window-integrated antenna for LMS and diversitary FM reception in mobile motor vehicles


A method of generating a linked client master mind map. Client actions and documents are linked to a client master mind map to generate a linked client master mind map. The linked client master mind map and a client relationship management program are reviewed and packaged.

Field of the Invention
The present invention generally relates to a method and apparatus for creating a process around front facing use of "mind maps" for communication to clients and customers.
Description of the Related Art
A connected set of lists organized by similar categories is conventionally referred to as a "mind map." Whereas a list is linear, a mind map is connected horizontally rather than vertically (in linear fashion). As the brain is divided into two halves, the left for logical, step-by-step linear analytical processes, and the right for the big picture and creative thought, one thinks both vertically and horizontally. One uses both sides of the brain.
Mind maps are thinking tools that reflect externally what goes on inside a person's head. Mind maps allow people to make associations result in connections; connections that feed to memory and to thinking. The brain is radiant. That is, it thinks centrally (holistically) and explodes (radiates) out in all directions.
Step One—Mind Download
FIG. 8 illustrates a conventional method 800 of creating a client master mind map which may include five steps. Referring to FIG. 8, in an exemplary first step, Step 810, one would perform a mind download, also referred to as a "mind burst" or a "mind dump." A first technique would be to take a piece of paper and spend ten minutes writing down all the major open items being worked on for the client. Typically, after ten minutes, 80% of everything related to the client will have been written down. If there are client relationship management (CRM) program activities or other information, then it is usually best to slowly perform this very important initial process.
Typically, retrieving information from a person's brain requires use of different parts of the brain: the big picture (more of the right side) and individual activities (more of the left side). Many find it difficult to do both seamlessly. Certainly, if a person were to type directly into a word processing file or e-mail, then the typing function may be automatic. But moving around a mind map program requires more brain attention. It is preferable that a team member other than the advisor builds and updates the mind maps.
Step Two—1st Revision & Reconstruction
Next, in Step 820, the list created in Step One is now entered into the client master mind map. This may be done by opening up the client master mind map template with the 15-branch titles, entering each item on the list under the appropriate branch, and placing the items that are difficult to enter under the "To Be Sorted" branch.
Next, the mind map should be printed out and an advisor should go through and make corrections, and enter the corrections by revising and reconstruction. Reconstruction is the process by which an item is moved from one branch to another.
Step Three—Incubation
Next, in Step 830, the mind map is put aside for one to three days. After the waiting period, the mind map is printed out for a second revision and reconstruction. By such "incubating," new connections may have been discovered or remembered after allowing a few days of incubation.
Step Four—2nd Revision/Reconstruction
In Step 840, changes are made to the client master mind map. The changes may then be entered into the program, and then the client master mind map is printed out for a final review.
Step Five—Decide/Conclude
In Step 850, it is exemplarily determined if the client master mind map is complete and accurate, and the branches and items are reviewed for presentation to the client.
To illustrate a conventional method of creating a mind map, assume that a customer that has never entered a grocery store and is not familiar with the layout, but nevertheless can identify all the products contained within the store.
In this example, FIG. 9 illustrates a list of items to be purchased in the grocery store by the customer. The order of the items on the grocery list is not related to other items on the list or how these items are arranged in the grocery store. However, all items will be found in the grocery store.
At the grocery store, without proper organization, one unfamiliar with the grocery store would walk in the front door, grab a cart, and continue into the store. If a first item on the list is milk, the visitor to the store would look for the dairy aisle, and go to the dairy aisle. At the dairy aisle, the customer would get the milk and move on to the next item on the list.
The next item on the list is Cheerios®. The customer may recall passing Aisle 5 and that the cereal is located on that aisle. The customer would then proceed to Aisle 5 for the Cheerios®. The next item on the list is eggs, so the customer would return to the dairy aisle.
Since the customer is unfamiliar with the layout, there will be a lot of repeated trips down the same aisles. Of course, most people do not behave this way at store. But, in terms of more complicated areas of life, such as financial services the grocery store story may be an apt analogy for the conduct of conventional businesses.
Of course, a far better way to grocery-shop would be to organize items on the list exactly as the grocery store is laid out. In this case, the items on the list may be connected to each aisle in list format, as illustrated in FIG. 10. That is, FIG. 10 illustrates an exemplary mind map for a customer's use.
A variety of behavioral theories have been postulated about how people behave in different settings. One thing people are sure of is that one's behavior changes over time. These changes are both intentional and unintentional. One purposefully changes one's habits, attitudes and outlook, which results in a different way of operating. People also are affected by outside forces as well as by health, jobs, family and a variety of other factors. One such behavioral theory is the Transtheoretical Model of Behavior. The Transtheoretical Model of Behavior 1100 is broken down into five steps as illustrated in FIG. 11: a precontemplation step 1112 followed by a contemplation step 1120, a preparation step 1130, an action step 1140, and, finally, a maintenance step 1150.
Precontemplation happens when various thoughts and ideas arise in a person's head. There is no action; just musings and wonderings.
The second step is Contemplation. In Contemplation, a person may be considering offering a new service or purchasing a new program. Many ideas and thoughts might be eliminated at this time, while a few will make it through to the third step, Preparation. During the Preparation stage, information is gathered, research is completed, and consideration takes place on how to integrate the new product or service into an existing business and team. At some point during this period, the moment of truth arrives. A "go" or "no go" decision is made. To "go" means to take action, the fourth step. The implementation of delivering the new product or service takes place. Finally, after Action is taken, this new behavior needs to be Maintained, the fifth step.
It is important to note that at any point during the five steps, one may move backwards or forwards. One's complex world, one's limited time and one's confusing business landscape do not allow many pre-contemplated ideas to survive, be fleshed out, acted upon and then maintained as part of one's already established business behaviors.
The present inventor has recognized that conventional methods of dealing with clients and customers have a number of problems including the conventional back-facing, opaque use of mind maps. The present invention overcomes the conventional difficulties by creating a "front-facing" use of mind maps for clients and customers.


An image recognition method, a terminal, and a storage medium are provided. The method includes: performing feature extraction on a to-be-recognized image by using an encoder, to obtain a feature vector and a first annotation vector set; performing initialization processing on the feature vector, to obtain first initial input data; and generating first guiding information based on the first annotation vector set by using a first guiding network model. The first guiding network model is configured to generate guiding information according to an annotation vector set of any image. The method also includes determining a descriptive statement of the image based on the first guiding information, the first annotation vector set, and the first initial input data by using a decoder.

With development of science and technologies and requirements of people for convenient man-machine interactive manners, machine learning has been widely applied to the image recognition field. For example, in scenarios such as early children education, image retrieval, and navigation for the blind, people usually expect machines to automatically recognize images and provide descriptive statements that can accurately describe image content, that is, translate the images into a natural language, so as to quickly understand the images or classify the images by using the natural language.
At present, an image recognition system framework usually includes an encoder and a decoder. Based on the system framework, the related technology provides an image recognition method that uses extracted image features and guiding information to obtain a descriptive statement of the image. However, existing methods only uses manually-extracted features as guiding information, which are not automatically learned. Such procedure requires manual labor and cannot be self-adaptive to individual image recognition tasks.

Image recognition method, terminal, and storage medium

TENCENT TECHNOLOGY (SHENZHEN) COMPANY LIMITED


In one illustrative example, a mobile device includes one or more processors, memory coupled to the one or more processors, a wireless transceiver coupled to the one or more processors, and a user interface which includes a visual display and a plurality of keys. The one or more processors are operative to identify whether a radio frequency (RF) out-of-coverage condition exists between the mobile device and a wireless communication network within a predetermined time period from a date and time of an appointment associated with a calendar application of the mobile device. In response to identifying such condition, the one or more processors cause an RF out-of-coverage warning indication to be produced at the user interface in association with the appointment. Otherwise, the one or more processors refrain from causing this RF out-of-coverage warning indication to be produced. The indication may be or include a message which instructs a user of the mobile device to relocate the mobile device for removing the out-of-coverage condition for the appointment. At the date and time of the appointment, the one or more processors also cause a calendar reminder indication for the appointment to be produced at the user interface, as a reminder of the appointment.

1. Field of the Technology
The present disclosure relates generally to mobile stations which operate in wireless communication networks, and more particularly to alert methods and apparatus for call appointments in a calendar application based on communication conditions of a mobile station.
2. Description of the Related Art
Mobile communication devices, such as cellular telephones or mobile electronic mail (e-mail) devices, sometimes experience poor or no service under certain degraded radio frequency (RF) coverage conditions. In these conditions, a user of the mobile device may be unaware of the poor or no service and unwittingly attempt to initiate a voice call from the mobile device. In this situation, the voice call request will be denied. The user may not immediately be aware when service has been restored and, in some cases, the user may forget to reattempt the voice call even when service has been restored.
A related problem is associated with pre-established calendar appointments made via a calendar application of the mobile device. Such calendar appointments are stored in memory of the mobile device and are typically associated with calendar information which includes a date, time, and/or time period of the appointment. The calendar information of the calendar application may be automatically synchronized with a corresponding calendar application on a computer (e.g. a PC) of a local area network (LAN) via the wireless communication network. The calendar appointment may or may not be for an anticipated scheduled voice call (e.g. a conference call) utilizing the mobile device. If the calendar appointment is for such a scheduled call, wireless coverage is required for the mobile device. That is, at the date and time of the appointment, the mobile device must be located within RF coverage range of the wireless communication network to make or receive the call for the appointment. If not, the user may miss or be late for the scheduled call. Note that the user may not be aware of any RF coverage problem until the calendar application reminds the user of the appointment, at or near the date and time of the appointment.
A further problem is associated with scanning operations of a mobile device when voice calls are anticipated based on calendar appointments or call reminders. If a calendar appointment is for a scheduled call, then wireless coverage is required for the mobile device. That is, at the date and time of the appointment, the mobile device must be located within RF coverage range of the wireless communication network to make or receive the call for the appointment. If not, the user may miss or be late for the scheduled call. When the mobile device initially goes out-of-coverage, the mobile device performs scanning operations at a relatively fast scan rate in attempt to identify any available wireless networks within RF coverage range. Over time, however, when no networks are found, the scan rate is decreased to a relatively slow scan rate. This is done in order to reduce power consumption of the mobile device, as scanning operations consume a significant amount of battery power. Currently, however, scanning operations and scan rates are functionally disconnected from stored calendar appointments which may be for voice calls or otherwise require wireless service for the mobile device.
Accordingly, it would be advantageous to provide techniques to facilitate anticipated voice calls for convenience and ease-of-use so as to overcome the deficiencies in the prior art.

This patent is subject to a terminal disclaimer.

Alert methods and apparatus for call appointments in a calendar application based on communication conditions of a mobile station


An image processing apparatus which is equipped with card slots can cope with plural kinds of memory cards acting as media, and a recording apparatus does not occur a malfunction in its card reader due to a lack of a current to be supplied to the medium even when the plural media are respectively inserted in the card reader. To do so, when the media are initially inserted in the plural card slots, the slot in which the medium is first inserted is set to be available, and the remaining slots are set to be unavailable. Besides, power is not supplied to the slots which have been set to be unavailable.

1. Field of the Invention
The present invention relates to an image processing apparatus which is equipped with plural card slots, a control method for the image processing apparatus, and a program for executing the control method.
Moreover, the present invention relates to a recording apparatus which is equipped with a multislot card reader corresponding to plural kinds of media, a control method for the image processing apparatus, and a program for executing the control method.
2. Related Background Art
A conventional image processing apparatus which is equipped with a card slot, e.g., a memory card slot, includes only one card slot.
For example, the conventional image processing apparatus has only one PC (personal computer) card slot (also called a PC card reader) which includes only a PCMCIA (Personal Computer Memory Card International Association) interface, as the memory card slot.
However, when a medium (i.e., a memory card such as an MS (memory stick), an SD/MMC (secure digital/multimedia card), an SM (SmartMedia™), a CF (CompactFlash™) or the like) other than the PC card (i.e., the memory card based on a PCMCIA interface standard) is used for the PC card reader, it is necessary to connect the medium in question to the PC card reader through a conversion adapter. For this reason, the medium which is accessible from the PC card reader is always only one.
As just described, there is a problem that the conventional image processing apparatus which includes only one card slot cannot cope with the plural kinds of memory cards (e.g., the MS, the SD/MMC, the SM, the CF and the like) when there is no conversion adapter.
Incidentally, an image processing apparatus which includes plural card slots becomes available in recent years. In the image processing apparatus of this type, an operator selects a functional card slot by using a slide switch.
However, in this case, when the operator selects the functional card slot by using the slide switch, the operator has to adequately handle the slide switch according to the kind of memory card which the operator wishes to use, whereby there is a problem that the handling of the slide switch is complicated.
Moreover, in another image processing apparatus which becomes available in recent years and includes plural card slots, when a card is inserted into the card slot, the functional card slot is automatically selected and changed if necessary. In this case, even when the card slot has been automatically changed to the functional card slot, the image processing apparatus does not notify an external apparatus (e.g., a personal computer) accessibly connected to the card slot in question that the card slot has been changed. Therefore, when the card slot has been automatically changed to the functional card slot, an operator and the external apparatus accessibly connected to the card slot in question cannot discriminate and confirm such a fact. Thus, when the memory card inserted in the card slot is removed therefrom and then another memory card is inserted in this card slot, the external apparatus accesses the newly inserted memory card on the premise that the memory card is not changed, whereby there is a fear that the data stored in the inserted memory card is damaged.
That is, in the above image processing apparatus, the card is inserted in and removed from the card slot as the power supply of the apparatus is being on, and the functional card slot is automatically and arbitrarily changed against the user's intention, whereby there is a problem that the operator may be confused.
Moreover, in the image processing apparatus of this type, there is a fear that a malfunction occurs in a connected external processing apparatus such as a personal computer or the like due to the above automatic change of the card slot.
Furthermore, there is a fear that, when the malfunction occurs in the external processing apparatus such as the personal computer or the like connected to the image processing apparatus, the data stored in the memory card inserted in the card slot of the image processing apparatus is damaged.
In regard to the above problems, in the case where the image processing apparatus is equipped with the multislot card reader, there is a possibility that the card reader accesses the media of which the number corresponds to the number of the provided card slots. However, even in such a case, any problem does not occur if the card reader can simultaneously access the plural media of which the number is the same as that of the card slots.
Incidentally, an MFP (multifunctional printer) is known as an example of the recent image processing apparatus which includes plural card readers. In the MFP, the card reader and the main body of the MFP are connected to each other through a USB (universal serial bus), and power is supplied to the card reader through a Vbus of the USB. Here, it should be noted that, according to the USB standard, the upper limit of the current capable of being supplied through the Vbus is set to 500 mA.
Therefore, in case of simultaneously accessing the media in all the card slots, because the current may become insufficient with respect to some kinds of media, there is a fear that a malfunction occurs in the card reader.
That is, in the conventional recording apparatus which is equipped with the multislot card reader, there is a problem that, when the plural media are respectively inserted in the plural card slots, the malfunction occurs in the card reader due to a lack of the current to be supplied to the inserted medium.
Moreover, for example, in a case where the medium is accessed from a PC which operates based on Windows™ 2000, because only one end point can merely be set for the USB according to the specification of a Windows™ standard file system, the medium in only one of the plural card slots can be accessed according to the standard file system. Thus, there is a problem that it is highly complicated to effectually inform the PC of the accessible and inaccessible media.
That is, in the conventional recording apparatus which is equipped with the multislot card reader, when the plural media are respectively inserted in the plural card slots, the medium in only one of the plural card slots can be accessed according to the standard file system, and it is thus complicated to effectually inform the PC of the accessible and inaccessible media. In other words, there is a problem that an intermediary process between the card reader and the PC is complicated.


A method and an apparatus for detecting a background noise of a sensor, relating to the technical field of electronics, are provided. The method for detecting a background noise of a sensor includes: receiving a sampling value output by the sensor and judging whether the sampling value falls within a background noise acceptable range; selecting the sampling value as a current background noise sampling value when the sampling value falls within the background noise acceptable range; and calculating a current background noise of the sensor according to a previous background noise and the current background noise sampling value of the sensor. Also provided is an apparatus for detecting a background noise of a sensor.

With the continuous development of sensor technology, sensors are universally applied to various industries, and moreover, various novel sensors continuously emerge to provide convenience for people to acquire external information. A sensor converts, by means of an own physical property, a signal to another signal.
Usually, an output quantity of a sensor may be considered as superposition of two output components. An output component changes along with change of a valid input quantity, and can reflect the change of the valid input quantity. The other output component is referred to as a background noise of the sensor, which does not change along with the change of the valid input quantity; even when the valid input quantity is zero, this output component is not zero (namely the background noise is not zero), and the background noise will change along with the change of environment factors such as temperature, humidity and own material fatigue of the sensor. In the existing technology, a background noise of a sensor is normally measured by using a return-to-zero method. That is, a value, which is measured under the condition that a valid input quantity is zero, is taken as a background noise.
However, the return-to-zero method for measuring a background noise of a sensor is merely applicable to an input-controllable sensor that works in a relatively fixed environment during a working period. When the sensor works under an environment slowly changing (or rapidly changing) frequently, the sensor needs to be continuously calibrated to remove influence of the background noise. Apparently, it is difficult to apply the return-to-zero method to the sensor under this working environment. For example, various sensors in a mobile phone cannot be calibrated by isolation of an external input quantity, and these sensors need to continuously work, so that the return-to-zero method is inapplicable to measure the background noise of the sensors.

Method and apparatus for detecting background noise of sensor


One aspect of the invention relates to a method for the purification of cadaverine from an aqueous cadaverine composition comprising one or more involatile impurities, the method comprising obtaining cadaverine from evaporation or distillation of the aqueous cadaverine composition wherein one or more solvents are added to the evaporation/distillation system before the evaporation/distillation starts, during the evaporation/distillation and/or after the evaporation/distillation substantially stops when no more evaporation/distillation is observed; wherein the one or more solvents comprise at least one or more high boiling point (HBP) solvents. In certain embodiments, cadaverine may be evaporated/distilled at an unexpectedly lower heating temperature for an unexpectedly shorter heating time to provide a desired yield. Because cadaverine may decompose at high temperature, the unexpectedly lower heating temperature and unexpectedly shorter heating time decrease the undesired cadaverine decomposition. The methods disclosed herein provides unexpected high recovery rate (˜100%) in the evaporation/distillation of cadaverine at a larger scale at a lower heating temperature compared to conventional distillation methods. Thus, the method disclosed herein will be highly appreciated in the industrial production of cadaverine.

Bio-based cadaverine is a valuable platform chemical involved in the production of partially or fully bio-based products, such as partially or fully bio-based Nylon 56 and Nylon 510. Bio-based cadaverine can be synthesized via lysine decarboxylation of lysine in microorganisms. One way to separate and purify cadaverine from the bio-based production includes evaporation/distillation of cadaverine from an aqueous cadaverine composition. However, the cadaverine fermentation broth or enzymatic conversion solution may comprise involatile impurities that interfere with the cadaverine evaporation/distillation. Thus, the cadaverine evaporation/distillation may require high heating temperature and long evaporation/distillation time, while the cadaverine recovery yield is still relatively low and may contain undesired contaminations.
Thus, there is a need to provide a purification method of cadaverine (e.g. bio-based cadaverine) in the presence of involatile impurities with improved recovery yield and cadaverine quality.

Purification of cadaverine using high boiling point solvent


Provided herein are catalysts useful in non-enzymatic saccharification processes. The catalysts can be polymeric catalysts or solid-supported catalysts with acidic and ionic moieties. Provided are also methods for hydrolyzing cellulosic materials into monosaccharides and/or oligosaccharides using the catalysts described herein.

Saccharification of cellulosic materials, such as biomass waste products of agriculture, forestry and waste treatment are of great economic and environmental relevance. As part of biomass energy utilization, attempts have been made to obtain ethanol (bioethanol) by hydrolyzing cellulose or hemicellulose, which are major constituents of plants. The hydrolysis products, which include sugars and simple carbohydrates, can then be subjected to further biological and/or chemical conversion to produce fuels or other commodity chemicals. For example, ethanol is utilized as a fuel or mixed into a fuel such as gasoline. Major constituents of plants include, for example, cellulose (a polymer glucose, which is a six-carbon sugar), hemicellulose (a branched polymer of five- and six-carbon sugars), lignin, and starch. Current methods for liberating sugars from lignocellulosic materials, however, are inefficient on a commercial scale based on yields, as well as the water and energy used.
Work from the 1980's on the hydrolysis of β-glycosidic bonds using perfluorinated solid superacid microporous resins, such as Dupont Nafion®, attempted to develop catalytic methods for use in digesting cellulose. Batch reactors and continuous-flow fixed-bed tube reactors were used to demonstrate hydrolysis of cello-oligosaccharides to monomeric sugars; however, these processes were unable to achieve appreciable digestion of cellulose or hemicellulose, and notably, the crystalline domains of cellulose.
As such, there is an ongoing need for new methods using catalysts that can efficiently generate sugar and sugar-containing products from biomass on a commercially-viable scale.

Methods of producing sugars from biomass feedstocks


An example method for facilitating policy-driven storage in a microserver computing environment is provided and includes receiving, at an input/output (I/O) adapter in a microserver chassis having a plurality of compute nodes and a shared storage resource, policy contexts prescribing storage access parameters of respective compute nodes and enforcing the respective policy contexts on I/O operations by the compute nodes, in which respect a particular I/O operation by any compute node is not executed if the respective policy context does not allow the particular I/O operation. The method further includes allocating tokens to command descriptors associated with I/O operations for accessing the shared storage resource, identifying a violation of any policy context of any compute node based on availability of the tokens, and throttling I/O operations by other compute nodes until the violation disappears.

Microservers are an emerging trend of servers for processing lightweight, scale out workloads for hyper-scale data centers with large numbers of relatively lightweight server nodes. The microserver represents a new server architecture characterized by many (e.g., tens or even hundreds) lightweight server nodes bundled together in a shared chassis infrastructure, for example, sharing power, cooling fans, and input/output components, eliminating space and power consumption demands of duplicate infrastructure components. The microserver topology facilitates density, lower power per node, reduced costs, and increased operational efficiency. Microservers are generally based on small form-factor, system-on-a-chip (SoC) boards, which pack processing capability, memory, and system input/output onto a single integrated circuit.

Policy-driven storage in a microserver computing environment


A polymeric electrolyte comprising: a polymeric material and an electrolyte salt; or a polymeric material, a solvent and an electrolyte salt, wherein a copolymer composed of 50 to 99 mol % of an ethylenically unsaturated compound and 1 to 50 mol % of carbon monoxide comprises 66.7 to 100 wt % of the polymeric material.

As portable information devices such as a laptop computer and a cellular phone have become popular, a demand for electrochemical devices such as a primary battery, a secondary battery and an electric double layer capacitor used as power supplies for the devices has rapidly increased. It is particularly required for these electrochemical devices to be compact and light, and from into a thin film, and simultaneously improvement of reliability is also expected. In recent years, in addition to power supplies for portable information devices new applications such as power supplies for a hybrid electric car and energy storage have been developed, and thus have been required to further improve the reliability.
An electrolyte solution in which an electrolyte salt is dissolved in a solvent is generally used in an electrochemical device, and when leakage liquid and further an electrolyte solution are non-aqueous electrolyte solutions, troubles such as catching fire and setting fire are caused, which make a major factor in impairing the reliability. Accordingly, these problems can be solved by using a solid electrolyte in place of an electrolyte solution. Particularly, a polymer electrolyte is easy to form a thin film and has excellent mechanical properties and flexibility, and therefore is a highly promising material.
From such viewpoints, many investigations with respect to a polymer electrolyte have been made over the years and there have been many proposals since it was firstly reported that ionic conductivity was produced by composite formation of a certain kind of alkali metal salt with a poly(ethylene oxide)-based high polymer (see Non-Patent Document 1).
Patent Document 1 proposes semi-solid gel-type polymer electrolytes comprising methyl polymethacrylate, electrolyte salts such as LiClO4 or LiBF4, and organic solvent.
Patent Document 2 proposes an electrochemical generator using an all solid-type polymer electrolyte in which an electrolyte salt is solid-solubilized in a high polymer containing a heteroatom such as oxygen or nitrogen, and poly(ethylene oxide) and a polyamine, are shown as examples of a polymer material in the document.
Patent Document 3 proposes a gel-type polymer electrolyte composition in which an electrolyte salt is dissolved in a mixture of a high polymer having a dielectric constant of 4 or more and an organic solvent having a dielectric constant of 10 or more, and shows that examples of a polymer material satisfying such a requirement include nitrocellulose, a phenol resin, polyvinylidene fluoride, polyacrylonitrile and chlorosulfonated polyethylene.
Patent Document 4 discloses a lithium solid electrolyte cell using metal lithium as a negative electrode and metal chalcogenide as a positive electrode, and shows that examples of the solid electrolyte include polymer electrolytes using a vinylidene fluoride copolymer, polyvinyl chloride, polyvinyl acetate, polyvinyl pyrrolidone or the like.
Patent Document 5 proposes an ionic conductive solid composition using a polymer material and discloses polysiloxane as an excellent polymer material.
Patent Document 6 discloses a hybrid ion conductor using an oxyethylene (meth)acrylate polymer.
Further, Patent Document 7 discloses an ionic conductive crosslinking-type resin composition based on an aliphatic epoxy resin, Patent Document 8 discloses a polymer electrolyte based on polyphosphazene, Patent Document 9 discloses an ionic conductive polymer complex comprising polyalkylene carbonate, metal salts and organic solvent, Patent Document 10 discloses a polymer solid electrolyte and a polymer solid electrolyte cell using polyurethane, and Patent Document 11 discloses, for example, an ionic conductive composition based on polyvinyl alcohol.
As described above, with respect to a polymer electrolyte, two kinds of polymer materials of an all solid-type polymer electrolyte comprising a polymer material and an electrolyte salt and a gel-type polymer electrolyte mixed with a polymer material and an electrolyte salt, and further a solvent have been proposed, but the following significant problem still remains.
That is, no material achieving practically satisfying ionic conductivity was proposed for an all solid-type polymer electrolyte. Further, a large amount of solvent had to be mixed to obtain practical ionic conductivity in the case of a gel-type polymer electrolyte. Therefore, from the viewpoint of reliability, reliability of each of these electrolytes is only a level better than that of an electrochemical device using a conventional liquid electrolyte, and thus high reliability originally expected for a polymer electrolyte was not achieved.
Thereafter, keeping in line with commercialization of a lithium ion secondary battery, it was proposed to apply a polymer electrolyte to a lithium ion secondary battery (see Patent Document 12). Thereby, research of a polymer electrolyte has been actively conducted and a lithium ion secondary battery using a gel-type polymer electrolyte was commercialized. However, as described above, this gel-type polymer electrolyte contained a large amount of solvent, and high reliability originally expected for a polymer electrolyte was not obtained. As a result, in a lithium ion secondary battery market, most of the product is occupied by the one using a liquid electrolyte and the market share of a lithium ion secondary battery using a gel-type polymer electrolyte is extremely small. In order to solve this problem, various polymer materials have been investigated since then, and Patent Document 13 proposes an ionic conductive polymer electrolyte comprising a polymer A having a carbonyl group (1 to 40% by weight), a poly(vinylidene fluoride)-based polymer B (20 to 70% by weight), a metal salt C (1 to 50% by weight) and an organic solvent D (20 to 85% by weight). Herein, preferable examples of the polymer A having a carbonyl group include polyesters, polycarbonates and polyester carbonates, and the other examples thereof further include polyamides, polypeptides, polyurethanes and polyketones. However, this system also contains a large amount of organic solvent, and the ionic conductivity is not always satisfying.
As described above, although a lithium ion secondary battery using a gel-type polymer electrolyte is put into practical use for only partial application of compact consumer batteries, major problems still remain in development of a polymer electrolyte in the present situation.
Patent Document 1: JP-A-54-104541
Patent Document 2: JP-A-55-098480
Patent Document 3: JP-A-57-143356
Patent Document 4: JP-A-58-075779
Patent Document 5: JP-A-59-230058
Patent Document 6: JP-A-60-031555
Patent Document 7: JP-A-60-248724
Patent Document 8: JP-A-61-254626
Patent Document 9: JP-A-62-030147
Patent Document 10: JP-A-01-197974
Patent Document 11: JP-A-01-284508
Patent Document 12: JP-A-01-241767
Patent Document 13: JP-A-11-060870
Non-Patent Document 1: P. V. Wright, Polymer, 14, 589 (1973)

Polymeric electrolyte, method for production thereof, and electrochemical element


An electrical interconnect to block light for use with an array of micro electromechanical machines separated by the first breaks includes a layer of an electrically conductive and an electrically isolated portions separated by second breaks configured to cross the first breaks on multiple sides of one of the micro electromechanical machines.

Many electronic devices include an array of micro electromechanical machines or MEMs which are controlled by an underlying circuitry layer which may or may not include one or more semi-conductor switching mechanisms such as transistors. In particular devices, such as displays, the underlying circuitry layers may be exposed to high levels of illumination. This illumination may cause the circuitry layer and the electronic device to not perform as intended.

Hewlett-Packard Development Company, L.P.


A method is disclosed for operating a mobile station (10) to obtain service from a cellular system, as is a mobile station that operates in accordance with the method. The method includes the steps of (a) scanning a set of dedicated control channels and tuning to the strongest dedicated control channel; (b) receiving a first control message (SPOM) from the dedicated control channel; (c) storing a first System Identification (SID) from the first SPOM; (d) determining if the channel number of the strongest dedicated control channel is equal to a system boundary channel number; and if yes, (e) tuning to a second strongest dedicated control channel; (f) receiving a second SPOM from the second strongest dedicated control channel and storing a second SID from the second SPOM; and (g) comparing the first SID to the second SID and if they are not equal, entering an IDLE task while remaining tuned to the second strongest dedicated control channel, else if the first SID is equal to the second SID, (h) re-tuning to the strongest dedicated control channel and entering the IDLE task while remaining tuned to the strongest dedicated control channel.

In U.S. Pat. No. 5,020,091 there is described a cellular telephone communications system that includes multiple cells covering a geographical area, such as a metropolitan area. To the base station of each cell a number of frequencies are assigned, with some of the assigned frequencies being specified as control channels used for reciprocal identification between the telephones and the system. The location of the dedicated control channels in the cell's frequency spectrum identifies the type of cellular system, A or B (see, for example, EIA/TIA-553). A metropolitan area typically has one of each type of system.
In a cellular system of most interest to this invention the channel from a base station to the mobile station is referred to as the forward channel, i.e., the forward control channel and the forward voice channel. The channel from the mobile station to the base station is referred to as the reverse channel, i.e., the reverse control channel and the reverse voice channel.
The mobile station's transmitting channels are, by example, from 824.040 to 848.970 MHz and the receiving channels are, by example, from 869.040 MHz to 893.970 MHz. Further by example, the frequency 844.980 MHz is channel 666 for the mobile station's transmitter, and the frequency 889.980 MHz is channel 666 for the mobile station's receiver. When a system allocates a voice channel to the mobile station (e.g., channel 666), it allocates a frequency pair for receiving and transmitting. The frequency pair is referred to simply as channel 666. The receiving and transmitting frequencies of a given channel are always spaced apart by 45 MHz from one other.
Voice channels and access channels use both the forward and reverse channels. The system may have one or more forward control channels used for paging purposes only, and the mobile station is not allowed to transmit on the corresponding reverse channel (i.e., 45 MHz below the paging channel frequency). The forward paging channel is used only for receiving pages and orders from the base station.
However, in most cases the access channel set and the paging channel set are the same, and may comprise 21 channels (i.e., 42 frequencies). In this case the mobile station is allowed to transmit on the reverse control channels, while the corresponding forward control channels are used for paging and also for sending orders to the mobile station. In this case the orders can also include messages from the base station to the mobile station, which are related to system access, e.g. registration confirmation or initial voice channel designation (in the case of a page response).
In greater detail, and referring to FIG. 5A, there is shown an exemplary mobile station transmit (TX or reverse) frequency band and an exemplary mobile station receive (RX or forward) frequency band. The depiction of FIG. 5A is based on the EIA/TIA-553 frequency band allocation (mandatory). Each band is divided into 666 frequency channels, with half of the frequency channels being assigned to the A system and the remaining half to the B system. Although not illustrated in FIG. 5A, it should be realized that additional or extended frequency bands, also described in EIA/TIA-553, could also be allocated. The total width of the mandatory band is 20 MHz+20 MHz.
Each band includes a set of dedicated control channels (e.g., 21 control channels) for the A system, and a corresponding set of dedicated control channels for the B system. The dedicated control channels are used to send information to the mobile station so that it can proceed to the paging channel selection task. The dedicated control channel set is identical across North America (i.e., channels 334-354 for the B system and channels 333-313 for the A system).
In the illustrated case there is a 45 MHz separation between the TX and RX channels. That is, the TX channel number 1 is 45 MHz below the RX channel 1, the TX channel number 2 is 45 MHz below the RX channel 2, etc. As such, it is useful to think of frequency channel pairs, wherein a given mobile station, when assigned to a voice channel (e.g., channel 22), would receive from the base station at a frequency of n MHz, and would transmit to the base station at a frequency of (n-45) MHz. For the dedicated control channels, and by example, dedicated control channel 1 of the B system (i.e., channel 334) could be received by the mobile station from the base station at frequency n, and the mobile station may transmit to the base station at frequency (n-45) MHz.
In most if not all current systems each dedicated control channel is also a combined paging and access (P/A) channel, wherein paging messages and system access information are transmitted to the mobile station on a forward dedicated control channel, and wherein the mobile station transmits access requests (e.g., call origination messages) and other information to the base station on the corresponding reverse channel of the P/A channel pair.
The base stations frequently transmit an Overhead Message Train (OMT). The OMT includes a System Parameter Overhead Message (SPOM) that consists of two words. The SPOM always contains System Identification (SID) information. The SID is unique for each cellular system. The use of the SID enables the cellular phone to determine whether it is using its home system or whether it is roaming.
According to current standards (e.g., EIA/TIA-553), the SPOM is transmitted every 800.+-.300 ms. The OMT may contain additional words, such as the REGID, which in some systems is sent in, by example, every tenth OMT.
As is depicted in FIG. 1, a typical cellular network is divided into a number of regions (e.g., SID1-SID5) each having contiguous radio cells (shown nominally as hexagons). One region or SID may also include one or more paging areas, each encompassing one or more radio cells.
Referring to FIG. 2, when the mobile station is powered on, or after a re-scan timer has expired, the mobile station enters a task where it scans the dedicated control channel set, determines the received signal strength indicator (RSSI) for each channel, and tunes to the strongest channel. The mobile station must receive a SPOM message within three seconds of tuning to the strongest control channel. If the mobile station is not able to complete this task, it either tunes to the second strongest channel, or it continues the channel selection process until the mobile station is able to lock onto one of the dedicated control channels.
Each cell site (or sector) usually has one control channel and several voice channels. Control channels and voice channels are selected according to the network frequency plan, but they include the channels 333 and 334 which, as is shown in FIG. 5B, are adjacent channels of different cellular systems (i.e., System A and System B).
A problem that is addressed by the teaching of this invention results from the use of a 10 kbits/second continuous data stream on the forward control channel. The spectrum of this signal is wider than the channel spacing (30 kHz), which means that some of the signal's energy appears also on adjacent channels (one channel above or below the channel). In the example of FIG. 5B, energy from channel 334 (System B) is shown as leaking into channel 333 (System A).
As was indicated above, when the cellular phone is powered on, performs a re-scan, or accesses the system, it first selects the serving system. If System A is selected, the cellular phone scans channels 333 . . . 313, measures the RSSI of each channel, and tunes to the best channel (strongest RSSI). The cellular phone must then receive message words within predetermined period of time before it can lock onto the channel and/or proceed to other tasks.
The problem arises when the cellular phone selects, by example, System A, and the cellular phone is located too near to a cell site which belongs to System B and which has the control channel of 334. Because of the presence of a large signal level on channel 334, the channel scan and RSSI measurement task can inadvertently determine that the adjacent channel 333 is the strongest control channel in the System A, when actually channel 331 (for example) is the strongest control channel. In this case the cellular phone may tune to channel 333 and then go to the Idle mode or task. The problem is that channel 333 is not a valid channel, at this location, for serving system A. Instead, the cellular phone is actually monitoring the "ghost" of the System B control channel 334. Since the cellular phone cannot normally receive any orders (page messages etc.) from the System B (assuming that System A is the phone's serving system), the cellular phone is essentially cut-off from service in its home system.
Problems also exist with call originations and terminations, since the cellular phone is normally not allowed to make calls in the System B when registered in System A (and vice-versa).
Another problem is that the cellular phone may illuminate its roaming indicator, even though the user expects that he or she is actually in the home system. A system selection feature, such as "A-only", is of no help, since the cellular phone remains tuned to the control channel set associated with the desired system.

Method to prevent cellular phone from receiving control channel of wrong system


A single instance, multi-tenant procurement system, includes an access module to provide access to a plurality of end users associated with an organization to their respective accounts, each account being customized by a super user of the organization, a search engine to execute searches for products offered by one or more suppliers, a transaction module to process and track one or more requisitions generated by the plurality of end users, a business rules module to apply business rules established between the organization and the one or more suppliers to process the requisitions, and a data repository to store data generated on the system.

Current e-commerce systems and methods provide consumers and businesses the ability to browse product lines and consummate sales transactions. However, current e-commerce systems do not allow for easy customization of the needed functionality to facilitate the transaction. While current systems can be customized for a specific business or customer, the customization is a time consuming and complicated task. These customizations must generally be hard coded into the application by the developers, thereby incurring increases in costs, delay in implementation, and loss of productivity. In the field of procurement, for example, an organization in need of a product or service generally has contractual relationships with multiple vendors to provide the desired product or service. The contractual relationship may define such terms as price, lot size, form of delivery, amount of discount, and other business rules. These rules may become complex as one term may influence other terms, such as different levels of discounts based on the number of items ordered.
Procurement systems also generally require order authorization from a procurement officer of the organization or someone in charge of reviewing the orders for compliance with internal policies of the organization, in addition to the contractual relationships with the vendors. These orders must be processed and tracked as the orders progress through the approval process such that the individuals placing orders are notified of whether the order was approved or denied, as well as for internal audit purposes.
Furthermore, procurement system also do not currently provide features that would allow users to: create new items that may not already be available to them for ordering, and permit such new items to be ordered by other users of the organization as well; create new user-customized forms for accessing items and, specifically, for searching for items and ordering; define new user-customized searchable item attributes; and, dynamically manage procurement contracts when amendments are made after contract execution, or certain contractual events (e.g., rebates or price reductions) occur that the parties (e.g., buyer organization and supplier) should be notified about. Therefore, there is a need for a system and method that can provide an efficient and simple procurement process that is easily customizable for multiple organizations and multiple vendors with simple and complex business terms, and can also provide a single point-of-access for both businesses and consumers to interface, interact, and implement and execute transactions, in accordance with existing or newly defined relationships, using a custom and configurable methodology for realizing their requirements.

Form management in an electronic procurement system


A method of treating acute myeloid leukemia (AML), including the steps of (i) measuring a density of blast cells in the peripheral blood and the bone marrow of a subject with AML; (ii) administering to the subject a CXCR4 antagonist; and (iii) administering to the subject a therapeutically effective amount of the CXCR4 antagonist and a therapeutically effective amount of a chemotherapeutic agent, if the blast cell density in the peripheral blood is less than 10% of the total peripheral white blood cells, or at least five-fold lower than the blast cell density in the bone marrow, or at least two-fold higher one day or more following step (ii).

The present invention, in some embodiments thereof, relates to methods of treating acute myeloid leukemia (AML) and, more particularly but not exclusively, to selectively treating AML patients identified for being potentially responsive to a CXCR4 antagonist.
Acute myeloid leukemia is a heterogeneous group of diseases characterized by the uncontrolled proliferation of hematopoietic stem cells and progenitors (blasts) with a reduced capacity to differentiate into mature cells (Estey et al., Lancet 368:1894-1907, 2006). Despite sensitivity to chemotherapeutic, long-term disease-free survival for AML patients remains low and the majority eventually relapse from minimal residual disease (MRD; Matsunaga et al., Nat Med. 9:1158-65, 2003). Bone marrow (BM) is the major site for MRD where adhesion of AML cells to bone marrow components may provide protection from the drugs (Estey et al., Lancet 368:1894-1907, 2006). The chemokine receptor CXCR4 and its ligand stromal derived factor-1 (SDF-1/CXCL12) are important players involved in the cross-talk between leukemia cells and the BM microenvironment (J. A. Burger and A. Peled, Leukemia 23:43-52, 2009).
The bicyclam drug termed AMD3100, originally discovered as an anti-HIV compound, specifically interacts with CXCR4 in an antagonistic manner. Blocking CXCR4 receptor with AMD3100 results in the mobilization of hematopoietic progenitor cells. WO 2007/022523 discloses the use of CXCR4 agonists such as AMD3100 for enhancing the effectiveness of chemotherapeutic methods in subjects afflicted with myeloid or hematopoietic malignancies.
T-140 is a 14-residue synthetic peptide developed as a specific CXCR4 antagonist that suppress HIV-1 (X4-HIV-1) entry to T cells through specific binding to CXCR4 (Tamamura et al., Biochem. Biophys. Res. Commun. 253(3): 877-882, 1998). Subsequently, peptide analogs of T-140 were developed as specific CXCR4-antagonisic peptides with inhibitory activity at nanomolar levels [Tamamura et al. (Org. Biomol. Chem. 1: 3663-3669, 2003), WO 2002/020561, WO 2004/020462, WO 2004/087068, WO 00/09152, US 2002/0156034, and WO 2004/024178].
WO 2004/087068 discloses antagonists of chemokine receptors, particularly the CXCR4 receptor, and methods of their use, for example, in the treatment, prevention or diagnosis of cancer. The '068 publication discloses that exemplary CXCR4 peptide antagonists include T140 and derivatives of T140, and that the pathology includes cancer such as breast, brain, pancreatic, ovarian, prostate, kidney, and non-small lung cancer.
WO 00/09152 discloses a variety of therapeutic uses for CXCR4 antagonists such as in the treatment of cancer.
WO 2004/024178 discloses the use of a chemokine receptor antagonist as a ligand for the CXCR4 receptor for the apoptosis-inducing treatment and/or the prevention of the metastatic spread of cancer cells in a patient.
U.S. Publication No. 2002/0156034 discloses the use of CXCR4 antagonists for the treatment of hematopoietic cells such as in cancer.
WO 2002/020561 discloses peptide analogs and derivatives of T-140. The 561 publication demonstrates that the claimed peptides are potent CXCR4 inhibitors, manifesting high anti-HIV virus activity and low cytotoxicity.
Recently, a comparative study between the CXCR4 antagonists TN140 and AMD3100 suggested that TN140 is more effective than AMD3100 as a monotherapy in AML. TN140 and to a lesser extend AMD3100 induced regression of human CXCR4-expressing AML cells and targeted the NOD/Shi-scid/IL-2Rγnull (NOG) leukemia-initiating cells (LICs) (Y. Zhang et al., Cell Death and Disease, 2012).
WO 2004/020462 discloses additional novel peptide analogs and derivatives of T-140, including 4F-benzoyl-TN14003. The '462 publication further discloses preventive and therapeutic compositions and methods of using same utilizing T-140 analogs for the treatment of cancer, such as T-Cell leukemia.
Beider et al. (Exp. Hematol. 39:282-92, 2011) reported that 4F-benzoyl-TN14003 exhibits a CXCR4-dependent preferential cytotoxicity toward malignant cells of hematopoietic origin including AML. In vivo, subcutaneous injections of 4F-benzoyl-TN14003 significantly reduced the growth of human AML xenografts.
WO 2014/155376 discloses the use of 4F-benzoyl-TN14003 combined with a chemotherapeutic agent in the treatment of AML.
WO 2015/063768 discloses the use of 4F-benzoyl-TN14003 in the treatment of AML with FLT3 mutation.
Uy et al. (Blood 119: 3917-2924, 2012) describes the use of the CXCR4 antagonist prelixafor (AMD3100) in the treatment of relapsed or refractory AML patients.

Methods of treating acute myeloid leukemia


Substantially random interpolymers comprising (1) ethylene, (2) one or more aromatic vinylidene monomers or hindered aliphatic or cycloaliphatic vinylidene monomers, and (3) one or more olefinic monomers having from 3 to about 20 carbon atoms. These interpolymers find utility as film, or as sheet or as a component of a multilayered structure, as fabricated articles, as foams, fibers or emulsions and as adhesives, in adhesive formulations and in sealant compositions.

The generic class of materials covered by .alpha.-olefin/hindered vinylidene monomer substantially random interpolymers and including materials such as ethylene/vinyl aromatic monomer interpolymers are known in the art. For example, substantially random ethylene/styrene interpolymers, including pseudo-random interpolymers as described in EP 415815 A, offer a range of material structures and properties which makes them useful for varied applications, including the compatibilization of blends of polyethylene and polystyrene as described in U.S. Pat. No. 5,460,818. Random copolymers of aromatic vinyl monomer and an .alpha.-olefin having 4 to 12 carbon atoms are described in U.S. Pat. No. 5,244,996. Limited generic reference can be found to terpolymers of ethylene/styrene/.alpha.-olefin materials, but to date no evidence has been found which describes the effective incorporation of monomers into a copolymer, with examples in JP 07,278,230 limited to 2 mole percent or less incorporation of styrene in ethylene/.alpha.-olefin copolymers.
Although of utility in their own right, Industry is constantly seeking to further expand the applicability of these generic interpolymers, and especially those based on .alpha.-olefin/vinylidene aromatic monomers, such as ethylene/styrene interpolymers. Desired improved or superior performance characteristics to current state of the art materials can include, but are not limited to, an extended temperature range of application and low temperature performance, desirable mechanical properties and melt processability. The interpolymers of this invention provide an effective technology to address such needs.

Interpolymers of ethylene, olefinic monomers, and aromatic vinylidene or hindered aliphatic or cycloaliphatic vinylidene monomers


A process for the production of compacted bodies of powdered medicament is disclosed, the process comprising the steps of:. a) positioning expansible means along the longitudinal axis of the mold; PA1 b) placing loose powdered medicament in the mold; and PA1 c) expanding the expansible means perpendicularly to the longitudinal axis of the mold. An apparatus for use in the process according to the invention and medicament compacts formed by the process are also disclosed.

The administration by inhalation of medicaments in dry powder form is well known. Devices for the metering and dispensing of measured doses of medicament from a reservoir have also been described previously, for example, in UK Patent No. 2041763 and U.S. Pat. No. 2587215. Such devices typically comprise a medicament reservoir and a metering chamber with a volume chosen such that, when filled, the chamber contains the desired weight of medicament for one dose. Filling of the metering chamber is generally accomplished under the influence of gravity, the chamber typically being located at the bottom of the reservoir. Such devices have the disadvantage that variations in the density of the metered powder can easily occur is resulting in inaccurate or inconsistent dosing. The packing density of the powder may also depend on the weight of powder remaining in the reservoir, leading to a gradual reduction in the dose delivered by the device. In addition, the dose metered is strongly dependent on the orientation of the device.
European Patent Application 407028 discloses a device which overcomes the disadvantages of other dry powder devices by the use of a metering means which relies not on gravitational force to fill a metering chamber, but on abrasion of a compacted body of powdered medicament. This application contemplated the use of hydraulic presses and the like in the production of the medicament compacts, by which pressure would be applied in the direction of a longitudinal axis of a sample of powdered medicament. Although this is satisfactory in many cases, in others there is a variation in the density of the medicament compact from point to point. Since the device of European Patent Application No. 407028 (in which the medicament compacts are adapted for use) functions by abrading a fixed volume of the medicament compact, it is important that the density of medicament throughout the compact is as uniform as possible. If the density is uniform then slices of medicament of the same thickness abraded from the compact will contain the same amount of medicament, thus ensuring that the correct dosage of medicament is consistently administered to a patient.
We have now found a novel process for the production of medicament compacts which overcomes or substantially mitigates the problems encountered in processes known from the prior art.
According to the present invention, there is provided a process for the production of a medicament compact, which comprises the steps of:
a) positioning expansible means along the longitudinal axis of a mould; PA1 b) placing loose powdered medicament in the mould; and PA1 c) expanding the expansible means perpendicularly to the longitudinal axis of the mould. PA1 a) a mould having a longitudinal axis adapted to receive loose powdered medicament, PA1 b) expansible means adapted to be positioned along the longitudinal axis of the mould, and PA1 c) means for expanding the expansible means perpendicularly to the longitudinal axis of the mould. PA1 a) positioning expansible means along the longitudinal axis of a mould; PA1 b) placing loose powdered medicament in the mould; and PA1 c) expanding the expansible means perpendicularly to the longitudinal axis of the mould.
Steps a) and b) may be performed in either order or simultaneously, however, we prefer them to be performed in the order shown above.
The powdered medicament is preferably metered into the mould, e.g. by weighing the desired amount of medicament. Alternatively, medicament compacts of the desired total mass may be produced by cutting to the appropriate length.
After performing steps a) and b), or during step b), it is preferable to vibrate the mould assembly and/or action a levelling device. This ensures that the medicament has settled to a level height i.e. that the top surface of the medicament is even, and is of known volume prior to compaction. Vibration of the mould assembly may achieved using the base unit of a vibratory bowl feeder, this provides axial vibration of adjustable amplitude.
During vibration of the mould assembly it is desirable that any loose parts of the assembly should be held in position, this may be accomplished by using a vacuum to hold such parts in place.
Suitable expansible means for use in the process according to the invention include an expansible mandrel, for example, a cylindrical mandrel capable of radial expansion. The cylindrical mandrel may comprise a plurality of segments capable of radial movement, in the retracted state the segments form a complete cylinder and in the expanded state gaps are present between the segments. The mandrel preferably has from 2 to 12, for example, 6 segments. When the medicament compact is to be administered from a device according to European Patent Application 407028 which, for a single dose, abrades a cylindrical compact for a predetermined angle of less than 360.degree. around the longitudinal axis, then the mandrel preferably has the same number of segments as there are doses in a 360.degree. rotation about the longitudinal axis of the compact. For example if the device abrades the compact for 60.degree. about the longitudinal axis for a single dose then the expanding mandrel preferably has 6 segments. This minimises the effects of any irregularities in the internal configuration of the compact.
Outward radial movement of the segments may be produced by a wedging action using e.g. pistons and/or by inflation of a bag placed at the centre of the mandrel. Inflation of the bag may be achieved using compressed gas, e.g. air; or hydraulically.
The degree of expansion of the mandrel will depend upon the desired size and density of the medicament compact, for example, the mandrel may expand from a diameter of 16 mm to 20 mm.
The outer surface of the mandrel is preferably covered by an elastomeric sleeve. The sleeve prevents ingress of powder into the expansible means. The elastomeric sleeve may be made of any material which exhibits a suitable degree of elasticity, e.g. vulcanised rubber. In addition to a suitable degree of elasticity, the elastomeric material should be non-toxic and preferably has a high degree of tear resistance and is easily moulded. The elastomeric material is preferably a vulcanised elastomer suitable for is drug contact, for example, a natural rubber or silicone rubber compound.
As the elastomeric sleeve expands radially it's thickness reduces and there may be a tendency for it to shorten in length. It is desirable for the sleeve to remain a constant length, so it is preferable that the ends of the sleeve turn inwards towards the longitudinal axis of the mandrel. This may help to prevent axial shortening in two ways, firstly, it grips onto the ends of the mandrel segments, thus restricting shrinkage by shear forces; secondly, as it expands and its outer diameter increases, radial tension is generated which tries to pull the cylinder edges in towards the axis.
As the mandrel expands the elastomeric sleeve may tend to flatten across the gaps which open up between the segments. This effect may be reduced by applying a pressure, e.g. of 5 bar, to the interior of the elastoineric sleeve, thus allowing it to be inflated relative to the expansible means. At other times it is desirable to maintain a lower pressure, e.g. 0.5 bar, within the elastomeric sleeve, this pressure helps to prevent the ingress of powder into the expansible mandrel.
Other expansible means which may be mentioned include inflatable means such as inflatable bags, inflation of the bag may be achieved using compressed gas, e.g. air; or hydraulically.
The pressure exerted by the expansible means will depend upon the desired density of medicament in the compact (by density of medicament we mean the mass of medicament per unit volume). However, the expansible means typically exerts a pressure of from 60.times.10.sup.3 to 2000.times.10.sup.3 N.m.sup.-2, for example 900.times.10.sup.3 N.m.sup.-2.
The density of the medicament in the compacts produced according to the invention will depend inter alia upon medicament used. However, a typical compact may have a density of from 0.1 to 1.5 g/cm.sup.3, preferably from 0.4 to 0.8 g/cm.sup.3. The density of the medicament compacts produced according to the invention may be determined by weighing a fixed volume of medicament abraded from the compact.
We prefer the medicament compact to be formed in a mould which subsequently forms all or part of the medicament reservoir of a medicament inhalation device. Thus, after compaction the compact and mould are in a form suitable for direct transfer to the inhalation device. By obviating the need to remove the compact from the mould prior to its insertion in the device, handling of the medicament compact, and hence the risk of contamination or loss of medicament through premature abrasion, is reduced.
After production the compact may be transferred directly to the inhalation device from which it is to be administered, alternatively the compacts may be packaged separately thus providing replacement indictment reservoirs for the device from which they are to be administered.
According to a second aspect, the invention provides the novel apparatus described herein for carrying out the first aspect of the invention.
Therefore we provide an apparatus for the production of a medicament compact from loose powdered medicament which comprises:
The process according to the invention may further be combined with the axial compaction process envisaged in European Patent Application 407028, thus allowing the formation of compacted annuli one on top of the other. When axial compaction is used the process must also include rotation of the compact relative to the expansible means of the mould in order to release the compact from the mould.
The process of the invention has the advantage that it produces medicament compacts having a more uniform density than compacts produced by prior art processes. In particular the density of the material at a given radius from the longitudinal axis of the compact will be the same throughout the compact, although the density at different radii need not be the same, such medicament compacts are novel. Medicament compacts having such a density distribution are advantageous in that sequential volumes of medicament abraded from the compact, e.g. by the device disclosed in European Patent Application 407028, will have similar masses, thus resulting in improved uniformity of dose administered to the patient.
The process is also advantageous in that it allows medicament compacts to be produced in a single rather than a multi-step compaction procedure, it also allows the production of longer compacts having a more uniform density distribution. The process also ensures good adhesion of the medicament to the wall of the powder chamber, this is advantageous when the medicament is formed in a mould which subsequently form all or part of the medicament reservoir of an inhalation device since it prevents the compact slipping during abrasion.
According to further aspect of the invention we provide a compact of powdered inhalation medicament characterised in that the density at all points at a given radius from the longitudinal axis of the compact is substantially the same.
Furthermore, we provide a compact of powdered inhalation medicament, obtainable by a process comprising the steps of:
Medicament compacts according to these further aspects of the invention will usually be annular, i.e. cylindrical with a cylindrical inner space. The radial thickness of the medicament in such a medicament compact is preferably in the range of 0.2 to 20 mm, more preferably 0.5 to 5 mm, for example 2 mm. The cylindrical inner space preferably has a diameter of more than 10 mm and preferably less than 100 mm, for example 20 mm.
The length of the medicament compact will depend on its intended use and the number of doses of active ingredient it contains. For administration from a device as disclosed in European Patent Application No. 407028, a suitable length will be in the range 5 to 50 mm, e.g. 20 mm.
Active ingredients which may be incorporated in compacts according to the invention include any active ingredients which are conventionally administered by inhalation in powdered form. Such active ingredients include drugs for use in the prophylactic or remedial treatment of reversible obstructive airways disease. Specific active ingredients which may be mentioned include salts of cromoglycic acid, e.g. sodium cromoglycate; salts of nedocromil, e.g. nedocromil sodium; inhaled steroids such as beclomethasone dipropionate, tipredane, budesonide and fluticasone; anticholinergic agents such as ipratropium bromide; bronchodilators, e.g. salmeterol, salbutamol, reproterol, terbutaline, isoprenaline and fenoterol, and salts thereof. If desired a mixture of active ingredients, for example, al mixture of sodium cromoglycate and a bronchodilator, such as salbutamol, reproterol, isoprenaline, terbutaline, fenoterol or a salt of any one thereof, may be used.
Other active ingredients that may be mentioned include antihistamines, e.g. clemastine, pentamidine and salts thereof, acetyl-.beta.-methylcholine bromide; peptide hormones, e.g. insulin and amylin; bradykinin antagonists; PLA.sub.2 inhibitors; PAF antagonists; lipoxygenase inhibitors; leukotriene antagonists; CNS active drugs, e.g. NMDA antagonists, glutamate antagonists, CCK agonists and antagonists; macrolide compounds, e.g. FK 506, rapamycini, cyclosporin ind structurally related compounds; vitamins; vaccines, e.g. MMR vaccine and polio vaccine; and vectors for gene therapy, e.g. plasmids containing genes intended to correct genetic disorders such as cystic fibrosis.
The particles of active ingredient incorporated into the medicament compacts according to the invention preferably have a mass median diameter in the range 0.01 to 15 .mu.m. We prefer that at least 80% w/w and preferably at least 90% w/w of the particles of active ingredient are less than 20 .mu.m, more preferably less than 10 .mu.m, especially less than 7 .mu.m in diameter. The proportion of particles of active ingredient having a diameter in the range 2 to 15 .mu.m is preferably more than 80% w/w.
The particulate active ingredient may be prepared by any suitable technique, as will be known to those skilled in the art. Suitable techniques include milling, e.g. using a hammer or fluid energy mill, micronisation, spray drying and freeze drying.
The medicaments to be compacted according to the invention may comprise a solid pharmaceutically acceptable carrier substance in addition to an active ingredient. The carrier preferably has an effective particle size of from 10 to 100 .mu.m.
The term "effective particle size" is used to denote the apparent particle size of a body without distinction as to the number of individual particles which go to make up that body i.e. no distinction is made between a single particle of given size and an agglomerate of the same size which is composed of finer individual particles.
The solid pharmaceutically acceptable carrier in the medicament will generally be a non-toxic material chemically inert to the active ingredient but may, if so desired, also comprise larger particles of the active ingredient. Examples of carriers which may be used in the medicament compacts include dextrans, glucose, mannitol and lactose. A particularly preferred carrier is crystalline lactose.
The particulate carrier may be prepared by grinding the carrier and subsequently separating out the desired fraction by conventional methods, e.g. by air classification and sieving.
The medicament may be prepared by mixing the ingredients together in a mixer, e.g. a planetary or other stirred mixer, prior to formation of the compact according to the process of the invention.
When the medicament comprises a solid carrier, we prefer the proportion of active ingredient to be from 0.1 to 70% w/w, more preferably from 0.1 to 55% w/w, and especially from 5 to 50% w/w of the medicament.
The medicament compacts according to the invention may also contain other ingredients such as flavouring agents, sweetening agents or colourants.
Any conventional pharmaceutically acceptable flavouring agents may be used, particular flavouring agents which may be mentioned include volatile oils, e.g. peppermint oil; and menthol. The proprietary product known by the tradename Dentomint, which contains both peppermint oil and menthol, may also be used. We prefer the flavouring agent to be peppermint oil BP/Ph. Eur.
We prefer the flavouring agent to be a polysaccharide entrapped flavouring agent such as those disclosed in Internationail Patent Application No. PCT/GB93/00503. Polysaccharide entrapped flavouring agents are advantageous for use in the compacts produced according to the invention since they are sufficiently resilient to sustain the compression forces required to produce the medicament compacts without releasing the flavouring agent entrapped therein to any significant extent.
Sweetening agents which may be used include any conventional sweetening agents, particular sweetening agents which may be mentioned include saccharin sodium, mannitol, aspartame, cyclamates and sugar.
The medicament compacts produced according to the invention preferably contain a plurality of doses of active ingredient. The actual number of doses incorporated into the compacts will depend inter alia upon the length of the compact, the nature of the active ingredient and the device from which it is to be administered. However, the compacts will typically comprises from 20 to 250, e.g. 112 doses of active ingredient.

Process for production of medicament formulations