A method includes receiving location area-related information, associating the location area-related information with a neighbor cell information to determine if a cell belongs to a forbidden location area, and avoiding selection of the cell if the cell is determined to belong to the forbidden location area. Embodiments described include a UE, network element, computer program product, and integrated circuit.

The following abbreviations are defined as follows:
2GSecond generation mobile system, such as GSM3GThird generation mobile system, such as UTRANCCCHCommon Control ChannelCNCore NetworkCS domainCircuit Switched domain, typically normal call trafficGSMGroupe Special Mobile, global mobile communication systemLALocation AreaLAILocation Area Identity, PLMN identifier + LA identifierLRLocation Registration, CS location update/PS routing area update, or combinedPBCCHPacket Broadcast Common ChannelPCCCHPacket Common Control ChannelPLMNPublic Land Mobile NetworkPSI3-seriesPacket System Information Type 3PS domainPacket Switched domain, connectionless trafficRANRadio Access NetworkRATRadio Access TechnologySISystem InformationUEUser Equipment, (e.g., mobile terminal or mobile station)UTRANUniversal Terrestrial Radio Access NetworkWCDMAWideband Code Division Multiple Access
A problem can arise when a 3G network operator, who does not control a 2G network, has established a national roaming agreement to provide service for network subscribers outside the coverage of the network operator's 3G coverage. The roaming partner may also provide 3G service. The 3G service, though, may not be available for national roaming. Similarly a dual mode network operator may allow international roaming only on the 2G network. Another similar case can occur when only specific home network customers have access to the 3G network. Roaming subscribers (generally those who do not have permission to use 3G service) should not use the 3G service when there are 3G cells within a location area. On the other hand, as 3G neighbor cells are broadcast on the 2G network, the roaming subscriber will also receive this information and use it as defined. This means that roaming subscribers may possibly reselect to the 3G cells. The network operator may assure that the roaming subscriber does not obtain 3G service by concentrating the 3G cells in location area(s) which are different from the 2G location area(s), and then by rejecting a location update request into a 3G location area for those subscribers who are not permitted to use 3G cells (with an appropriate cause value). The subscriber is then forced to leave the 3G cell, but stay in the same network when the reject cause is, for example, one specified as #15 ("no suitable cells in this location area").
A similar (non-roaming) scenario may also occur in the user's 2G- and 3G-capable home network when the user, by subscription, is allowed to operate only in the 2G portion of the home network and not in 3G portion of the home network
In general, this means that if an attempted LR procedure ends in rejection by the network, then the behavior of the UE is governed by the cause value that the network included in the message indicating rejection of the request. In some cases the reject cause values are meaningful across all cells in the same Location Area (LA). As an example, cause value #15 ("no suitable cells in this location area") denies access for the UE to all cells in the same LA. The location area reject forces the UE to add the location area to the list of forbidden location areas that are not accessible by the UE for a certain amount of time (such as 12 hours).
A future cell re-selection procedure will then exclude all cells of the serving Public Land Mobile Network (PLMN) that indicate the same LA, so in practice the UE is commanded by the network to search a cell of another LA in the same PLMN.
One problem with the current approach is that when the UE has re-selected back to a GSM cell, the only knowledge it has concerning WCDMA neighbor cells, based on the system information messages, is the radio frequency and scrambling code. In addition, the 2G to 3G reselection follows a principle that the suitability criteria of the target cell need not be checked before the reselection attempt is initiated. In some cases this is not possible without compromising the operation at the serving cell.
This means that the UE may, after a short time, try reselection to the same or another 3G cell. The outcome from this reselection would be a failure, as the location area is listed on the list of forbidden location areas. This though is not known unless the UE reselects to the cell or reads the 3G cell location area information (e.g. prior to the cell change). This approach is time consuming, increases power consumption and, in a worst case, the user may experience an inferior connection, as a service interrupt is generated when an unsuccessful (unnecessary) reselection attempt is performed during GPRS packet transfer mode (when NC0 or NC1 mode is applied for cell reselection). In this case, data transfer may be significantly degraded (depending on the frequency of "unnecessary" reselection attempts), a page can be lost, or the entire connection can be lost.
On the 2G side, the UE when camped on a CCCH is expected to read SI3/4 before reselection is possible. The information received in this SI (which may also be referred to as System Information) message contains information about the neighbor cell's location area. Thereby the UE can evaluate, before the cell change, whether the cell is listed on a list of forbidden location areas. If this is the case, the UE can prevent a cell change towards that cell.
In the situation of 2G-3G inter-working the same approach is not possible in most cases. The only currently specified solution for the UE is to attempt to perform cell re-selection as described above. This trial and error mechanism is not very efficient. The failure may continuously repeat even if the UE attempts multiple cell re-selections towards the same 3G cell.
In case of reselection towards a 3G cell, the UE needs to read the system information of the 3G cell in order to obtain the location area information of that cell. However in order to do this while there is an ongoing GPRS data transfer connection, the MS needs to interrupt the data transfer, which may cause the data throughput to be reduced.
It can be noted that a similar situation exists also on the 2G side when the UE or mobile station (MS) is camped on the PCCCH. In this case the UE receives the neighbor cell(s) parameters regarding cell reselection from the current serving cell's broadcast PSI3-series on the PBCCH. This means that the MS does not need to read the neighbor cell's SI3/4 information in order to obtain the parameters affecting cell reselection, so the MS will not know the LAI of the neighbor cell, thereby introducing the same situation as in 2G-3G inter-working cell reselection.

Apparatus, method and computer program product providing inclusion of local area information in broadcast messages and maintenance of radio access network black list


The present disclosure relates to attempting to monitor and control memory access and, more specifically, to attempting to limit memory access to a specific registered software agent.

1. Field
The present disclosure relates to attempting to monitor and control memory access and, more specifically, to attempting to limit memory access to a specific registered software agent.
2. Background Information
A typical computer or processing system is controlled by an operating system that allows the execution of various programs. A kernel or kernel mode program is often referred to as the core of an operating system; the portion of the system that manages memory, files, and peripheral devices; maintains the time and date; launches applications; and allocates system resources. In this context a "computer" refers to any device with a processing unit and is a term not limited to the traditional PC or laptop.
It is typically desirable that kernel level software, the state of the software, and software's configuration information be protected from unintended alteration or access. With the increase is sophistication of computer worms, viruses, and other malware and the complexity of monolithic operating systems (e.g. Windows and Linux) this protection has become increasingly difficult.
Typically used memory protection schemes enforce course-grain access control. These schemes often control memory access based upon a privilege level assigned to the accessing software. Typically, programs are assigned one of only two possible privilege levels. These two privilege levels may often be referred to as kernel mode and application/user mode. These schemes do not offer any protection against memory access from other software running within the same privilege level in the monolithic operating system.
This implies that on a typical system, a kernel mode program is typically allowed unbounded access to all memory pages on the system. The kernel mode program may intentionally or accidentally corrupt data or reconfigure other programs, possibly to execute malicious code
Furthermore, standard processor protection mechanisms are often operating system enforced. As such, these protection mechanisms may be overridden by malicious code that has kernel level privileges. For example, a malicious kernel level program can change the memory page table protection bits corresponding to a valid driver to allow tampering. A need therefore exists, to detect and control access to memory.

Memory protection within a virtual partition


An optical device with a quantum well is provided. The optical device includes an active layer made of a Group III-V semiconductor compound and having a quantum well of a bandgap grading structure in which conduction band energy and valence band energy change linearly with a slope with the content change of predetermined components while an energy bandgap between the conduction band energy and the valence band energy is maintained at a predetermined value; and two barrier layers, one of which is positioned on an upper surface of the active layer and the other is positioned on a lower surface of the active layer, and which are made of a Group III-V semiconductor compound and have higher conduction band energy and lower valence band energy than the active layer. A driving voltage is decreased and luminous efficiency and reliability are enhanced.

This application claims the priority of Korean Patent Application No. 2003-1609, filed on Jan. 10, 2003, in the Korean Intellectual Property Office, the disclosure of which is incorporated herein in its entirety by reference.
1. Field of the Disclosure
The present disclosure relates to an optical device with a quantum well, and more particularly, to an optical device with a quantum well with improved luminous efficiency and reliability.
2. Description of the Related Art
A quantum well is a structure formed by inserting between two different semiconductor layers a thin semiconductor layer having an energy bandgap much smaller than those of the two semiconductor layers. Carriers such as electrons or holes are confined in the quantum well by energy barriers. Studies on the quantum well have been actively conducted because an optical device with the quantum well can generate a large amount of light even at a small driving voltage.
FIGS. 1A and 1B are diagrams of a quantum well structure in a conventional optical device before and after applying a driving voltage, respectively.
Referring to FIG. 1A, an optical device comprises first and second barrier layers D and D′ having high conduction band energy and low valence band energy, and an active layer E formed between the first and second barrier layers D and D′ and having lower conduction band energy and higher valence band energy than the first and second barrier layers D and D′. Before applying a driving voltage, the conduction band energy of the active layer E corresponding to the bottom of the quantum well structure exhibits a constant energy level.
When driving voltage is applied, electrons and holes are rearranged so that the quantum well structure has an asymmetrical distribution of electrons and holes, as shown in FIG. 1B. Referring to FIG. 1B, the conduction band energy and the valence band energy of the active layer E change linearly with a slope. In this case, most electrons and holes are respectively distributed in the conduction band quantum well and the valence band quantum well in such a way to face each other diagonally, thereby decreasing the recombination efficiency of electrons and holes.
In particular, in an optical device in which an active layer having a quantum well structure is made of a GainNAs semiconductor material, N and In do not easily grow into a crystal due to unstable combination. Also, due to the addition of N, luminous efficiency and lifetime may be lowered.


Each of the panoramic images corresponding to a plurality of positions of a viewpoint is compressed and stored as partial images obtained by dividing each panoramic image by a predetermined field of view. The panoramic image has a field of view wider than a display field of view of an image to be displayed on a display unit. A partial image containing an image to be reproduced is selected based on the information about the position and the direction of a viewpoint and the display field of view, and an image corresponding to the position and the direction of a viewpoint is generated and displayed from the selected partial image. Thus, when virtual space in the walk-through system is designed using the IBR technology, stored image data can be efficiently reproduced.

Technology of capturing real space using a capture device mounted on a moving object, and representing the captured real space as virtual space using a computer based on the captured image data (for example, 'Building Image-Based Cybercities by Using Vehicle-Mounted Cameras' by Endoh, Katayama, Tamura, Hirose, Watanabe, and Tanigawa (published by Shingaku Society, PA-3–4, pp. 276–277, in 1997), 'Building Image-Based Cybercities by Using Vehicle-Mounted Cameras (2)—Generation of Wide-Range Virtual Environment by Using Photorealistic Images—' by Hirose, Watanabe, Tanigawa, Endoh, Katayama, and Tamura (published in Proceedings of the Virtual Reality Society of Japan Second Annual Conference, pp. 67–70, in 1997), etc.
A method for representing real space captured as virtual space based on the captured image data captured by the capture device mounted on a moving object can be a method of reconstructing a geometric model of real space based on captured image data, and representing it in the conventional CG technology. However, the technology is limited in correctness, precision, reality, etc. of a model. On the other hand, the image-based rendering (IBR) technology of representing virtual space using a captured image without using a model has recently attracted attention. The IBR technology produces an image from any viewpoint based on a plurality of captured images. Since the IBR technology uses captured images, realistic virtual space can be represented.
To produce walk-through system of virtual space using the above mentioned IBR technology, it is necessary to produce and present an image depending on the position in the virtual space of a user. In this type of system, each frame of captured image data is associated and stored with the position in the virtual space, the corresponding frame is obtained based on the position and the view direction of the user in the virtual space, thereby reproducing the frames.
As a common method of obtaining the position data in the real space, the position measurement system using an artificial satellite represented by the GPS (Global Positioning System) which is also used for a car navigation system, etc. A method of associating the position data obtained in the GPS with the captured image data can use a time code (Japanese Patent Application laid-open No. 11-168754). In this method, each frame of captured image data can be associated with position data by associating the time data contained in the position data with the time code added to each frame of captured image data.
In the walk-through presentation in the above mentioned virtual space, a user can see a desired direction from his or her viewpoint. Therefore, an image at each viewpoint is stored as a panoramic image covering a range wider than an image to be reproduced, a partial image to be reproduced is cut out and displayed from the panoramic image based on the position and the direction of the viewpoint of the user in the virtual space.
However, an image actually displayed in the walk-through system is a part of a panoramic image. Although the other portions are not used, it is necessary to read data or perform a decoding process on the entire panoramic image, thereby performing an inefficient process. That is, to display an image, it is necessary to read the entire panoramic image depending on the position of a user, decode the entire panoramic image when it is compressed, cut out a partial image from the obtained image data depending on the direction of the view of the user, and then display the image. Although the reading and decoding processes are performed on the entire panoramic image, only a part of it is practically used for display, and other portions are wastefully processed.
Especially when a full round image or a full sky image is used as a panoramic image, most of the processes of reading and decoding the panoramic image at each viewpoint position are not required and wasteful when the image is actually displayed. That is, the computer is excessively loaded, thereby disabling the walk-through system in reproducing and displaying images in real time.

Storing and processing partial images obtained from a panoramic image


The present invention provides an OLED array substrate, a manufacturing method of the same, a display panel, and a display device, and relates to the field of active matrix organic light-emitting diode (AMOLED) display technology. The present invention can solve the problem that turn-on and turn-off of a switching thin film transistor and grayscale control cannot be performed effectively because the switching thin film transistor and a driving thin film transistor are manufactured as thin film transistors having same performance parameters in an existing OLED array substrate. The OLED array substrate according to the present invention includes a switching thin film transistor and a driving thin film transistor, wherein, an S factor of the switching thin film transistor is less than that of the driving thin film transistor.

As compared with a thin film transistor-liquid crystal display (TFT-LCD) which is the mainstream of existing display technologies, an organic light-emitting diode (OLED) display has advantages of wide viewing angle, high brightness, high contrast, low power consumption, smaller volume and lighter weight, and the like, and is the focus of attention among current flat panel display technologies.
Driving methods of organic light-emitting diode displays are classified into two types of passive matrix (PM) and active matrix (AM). As compared with passive matrix driving, active matrix driving has advantages of large amount of display information, low power consumption, long service life of a device, high contrast screen, and the like. At present, an active matrix organic light-emitting diode (AMOLED) display mainly uses a low temperature polysilicon-thin film transistor (LTPS-TFT) to drive an OLED to emit light. As shown in FIG. 1, an active matrix organic light-emitting diode display device generally includes a switching thin film transistor 2, a driving thin film transistor 1, and an organic light-emitting diode (OLED) 3. A gate of the switching thin film transistor 2 is connected to a scan line 4. A drain (or source) of the switching thin film transistor 2 is connected to a data line 5, and a source (or drain) of the switching thin film transistor 2 is connected to a gate of the driving thin film transistor 1. A source (or drain) of the driving thin film transistor 1 is connected to a power line 6, and a drain (or source) of the driving thin film transistor 1 is connected to an anode of the OLED 3. A cathode of the OLED 3 is grounded, and a storage capacitor 7 is connected between the source (or drain) and the gate of the driving thin film transistor 1. Generally, the switching thin film transistor 2 is required to have a small S factor (subthreshold swing) such that an electric current changes with a voltage greatly, whereas the driving thin film transistor 1 is required to have a large S factor such that an electric current changes with a voltage slightly. Thus, it can be ensured that the switching thin film transistor 2 has a better switching performance, which facilitates grayscale control. However, in the prior art, the switching thin film transistor 2 and the driving thin film transistor 1 are manufactured as thin film transistors having the same performance parameters, which is not helpful for effective turn-on and turn-off of the switching thin film transistor and the grayscale control.


A system that can store electronic program guide information using 3D graphics is disclosed. In a particular embodiment, a data filter and a text-to-image converter are used for converting filtered data into a set of digital images that are defined as a set of texture maps. In order to apply those texture maps, a memory analyzer analyzes the set-top box layout and indicates available memory types. The memory analyzer controls a memory distributor for distributing texture maps into the appropriate types of memory.

1. Field of the Invention
The invention relates to television electronic programming guides ("EPGs"). More particularly, it relates to a method and apparatus for cost-effective memory management.
2. Description of the Related Art
Prior art EPGs provide television viewers with on-screen television schedule information presented, e.g., in a convenient, regular or non-regular rectangular grid format. One type of EPG is used in conjunction with an analog television system. That type of EPG sometimes is called a passive programming guide ("PPG"). In such a system, one of the cable channels is reserved for displaying programming information. The programming information is displayed in a grid pattern. The first column lists the various channels of the cable broadcast system. Additional columns, e.g., columns two, three and four, display program information for what is showing on the channels listed in the first column, in half-hour increments. For example, suppose that a person tunes to an EPG at 10:35 p.m., the second column would display program information for 10:00–10:30 p.m., the third column would display program information for 10:30–11:00 p.m., and the fourth column would display program information for 11:00 p.m. 11:30 p.m. A row at mid-screen displays the time slots relating to the second, third and fourth columns. A portion of the television ("TV") screen typically provides continuous advertisements.
Cable TV systems typically provide more television channels than there is space for rows in a useable grid pattern. A grid is typically used that scrolls at a pre-selected slow rate, so that a viewer can see what is showing on all of the channels. In the case of satellite broadcasts, the situation becomes even more complex. Digital satellite TV systems may provide 1,000 TV channels with various TV programs and services.
The program schedule information contained in an analog EPG is typically broadcast by an operator on a dedicated one of the channels of the cable TV system. However, most digital EPGs operate in a different way. In a digital EPG, program schedule information and sometimes applications and/or systems software is transmitted to equipment located on the viewer's premises (e.g., a digital set-top box) by way of broadcast, cable, direct satellite or other suitable form of transmission. A digital set-top box ("STB") serves to deliver compressed digital video, data and audio signals in real time usable form to one or more TV sets. The STB, which is basically a dedicated computing device, contains memory allowing the program schedule information to be stored for later viewing. The program schedule information stored in the STB is periodically updated, e.g., on a continuous, daily, weekly, or biweekly basis or any other useful pattern. A microprocessor within the STB utilizes the viewer's TV set to display the stored program schedule information and to implement other functions of the EPG in response to user-generated signals. The functions available to the viewer vary depending on the sophistication of the particular EPG and hardware capabilities.
Digital EPGs are often used in an interactive television system and are sometimes called interactive programming guides ("IPGs"). In an interactive television system EPG, a user may browse schedule information in any order, select programs from on-screen menus for current or future viewing, and order pay-per-view programming on demand. Some (advanced) EPGs permit other functions, e.g., an e-mail function, or a function that permits a user to block certain kinds of programs, such as adult or violent programs, and choose favorite channels. Prior art digital EPGs, however, collectively fail to provide viewing capabilities that realistically address the viewing habits of the users of these systems.
As mentioned above, an analog TV EPG is viewed on a TV screen as a continuously scrolling rectangular table. This solution does not allow any user interaction and is suitable only for the passive television viewer. This is a poor solution for interactive TV, because:    1. The scrolling speed is set upfront (it is not necessarily constant) and cannot be adjusted by user's request.    2. In an analog EPG system, the user cannot switch to the channel of choice immediately from the EPG (e.g., by clicking on a display of a channel number on the EPG). Instead, the user must input the channel number with a remote controller.    3. The analog EPG scrolling table is completely sequential (providing information in an order depending upon channel number and designer's chosen style) and the user cannot pre-sort schedule data or otherwise personalize the EPG.
A more sophisticated solution is the interactive EPG or ("IPG"). Unfortunately existing solutions have their own problems. For example, interactive EPG systems provide drop-down menus that require multiple steps in order to interact with the EPG, which can lead to user frustration when a search for a desired program is unsuccessful or simply too complicated. As known today, interactive EPGs are inflexible in terms of menu design, because the menu itself is a set of regular two-dimensional grids.
Additional problems with the prior art electronic programming guides are listed below.    1. Program Description Truncation. When displaying schedule information in grid format, i.e., columns representing time slots and rows representing channels, program titles are generally truncated to fit into the cells of the grid. The width of a grid cell varies with the program duration. Since a 30-minute program is allotted only a small space for the program title and description, titles and/or descriptions for half- and even full-hour programs often must be truncated to fit in the allotted space. Some systems simply cut off the description of a program without abbreviating it in any way, such that the user cannot determine the subject matter of the program. While some systems partially alleviate this problem by providing two lines of text in each grid cell, this is a less than ideal solution because program descriptions may still be truncated.    2. Inability to Create a Program Itinerary While Viewing a TV Program. Prior art EPGs lack a method for a user to create a program itinerary, electronically, concurrently while the user views a program on the TV screen. Thus, when a user views a program on a particular channel, he or she cannot electronically set up a sequence of other channels to surf.    3. Inability to Simultaneously Channel Surf and View EPG. Prior EPGs leave much guess work for the user as he or she navigates through a sequence of channels. When skimming through channels and trying to determine what program is being displayed on a channel, commonly known as "channel surfing," the user must guess which program is currently being aired from the video segment encountered during channel surfing. Since up to thirty percent of the programming appearing on a channel at any given time is advertising, the user is not provided with any clues as to what program is showing on a selected channel at a given time. Hence, the user often has no choice but to wait until an advertisement or commercial ends before learning what program is showing on the selected channel. Existing solutions allow user to go to the channel and find more information by using a special button of remote control, i.e., "info" button. Thus, a need exists for an EPG that displays current program schedule information for each channel at the same time that the user surfs through the channels.    4. Text Size. Unfortunately, existing EPGs allow for only one font size. However, human beings do not all have the same acuity of vision. As a result, two problems appear: some viewers may have difficulty or even be unable to read the information in the EPG and some viewers want to see more information using smaller font.    5. Specular Highlighting. Existing EPGs provide only a very rudimentary lighting capability. For example, existing EPGs do not have an adequate means to adjust the brightness of the EPG. This detracts from the utility of the EPG.
Thus, methods and apparatus for generating a two-dimensional ("2D") TV graphical user interface ("GUI") for providing TV program guides on a TV screen are known in the art. A conventional TV GUI uses a single layer of on-screen display graphics to present TV program information and, typically, multiple menus are provided to enable users to navigate through the presented information. For example, an apparatus that generates a main menu of a program guide, which includes program source information and program event information for a plurality of program sources, and further generates navigation menus for allowing a viewer to modify the program guide is disclosed in U.S. Pat. No. 5,694,176, issued Dec. 2, 1997 to Bruette et al. A system and a process in which a program listing is displayed as a grid of two-dimensionally arranged adjacent irregular cells, which vary in length corresponding to time duration of the programs, with a title of a program being displayed in each of said irregular cells, said grid having a plurality of channels listed in a first dimension and time listed in a second dimension, is disclosed in U.S. Pat. No. 5,809,204, issued Sep. 15, 1998 to Young.
A multi-layered TV GUI that uses a memory for storing graphics data that is capable of storing two graphics planes that represent upper and lower layers of graphics displayable on a TV screen, and that uses a graphics accelerator to combine the graphics planes to produce various graphical effects on the screen is disclosed in U.S. Pat. No. 6,016,144, issued Jan. 18, 2000 to Blonstein et al. (hereinafter "Blonstein '144"). One advantage of a multi-layered TV GUI that produces multiple layers of graphics on a TV screen is that it eliminates the need for a multi-menu hierarchical system. (A hierarchical menu system often causes confusion when the user loses track of the menu that he or she came from and how to get back.) A variety of other TV GUI are disclosed in the following additional issued patents: U.S. Pat. No. 4,706,121, issued Nov. 10, 1987 to Young (hereinafter "Young '121"); U.S. Pat. No. 5,781,246, issued Jul. 14, 1998 to Alten et al.; U.S. Pat. No. 5,986,650, issued Nov. 16, 1999 to Ellis et al.
In Young '121, the multi-layered TV GUI provides a TV GUI that adjusts graphical presentation in a matrix of text to expose a predetermined portion of a lower layer of graphics. In Blonstein '144, electronic program schedule data is stored in a system memory and, during the rendering process, converted into a set of bit-maps (one bitmap for each single layer) and stored in a graphics accelerator buffer memory. However, while prior art EPGS, such as Young '121 and Blonstein '144 relate generally to graphical displays and in particular to navigation within a 2D graphical display space, they do not approach the advantages of a 3D graphical display.
What is clearly needed is a method and system for cost-effective optimal storing of electronic program schedule data using a combination of on-chip memory and system memory for 3D-enabled EPGs.

Method and system for optimal usage of memory for storing scheduling and guiding data in 3D-enabled EPG


The embodiments of the present disclosure relate to antigens of β-coronaviruses, preparation methods and uses thereof. The amino acid sequence of the antigen of the β-coronavirus includes an amino acid sequence arranged in a (A-B)-(A-B) pattern or an amino acid sequence arranged in a (A-B)-C-(A-B) pattern or an amino acid sequence arranged in a (A-B)-(A-B′) pattern or an amino acid sequence arranged in a (A-B)-C-(A-B′) pattern. The antigen of the β-coronavirus has a single-chain dimer structure. A single-chain dirtier expressed according to examples of the present disclosure is stable in content and has excellent immunogenicity as an antigen of a β-coronavirus, and a vaccine prepared by using the single-chain dimer as an antigen of a β-coronavirus can elicit high-titer neutralizing antibodies in mice.

Coronaviruses, belonging to the coronavirus genera of the family Coronaviriciae, are positive-strand enveloped RNA viruses, the genome of which is the largest among all RNA viruses. Both animals and humans can be hosts of coronaviruses. Coronaviruses mainly infect the respiratory tracts and digestive tracts of mammals and birds, and seven kinds of coronaviruses are currently known to infect humans, including four (HCoV-229E, HCoV-NL63, OC43 and HKU1) that may cause a mild cold. Globally, there are three kinds of coronaviruses imposing the greatest threats to public health, namely severe acute respiratory syndrome coronavirus (SARS-CoV) that broke out in 2002-2003, Middle East respiratory syndrome coronavirus (MERS-COV) that erupted in 2012 and persisted to date, and a novel coronavirus that broke out in 2019 (2019-nCoV), all of which are β-coronaviruses.
Middle East Respiratory Syndrome (MERS) is a disease caused by Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection. In June 2012, the first MERS case was found in Saudi Arabia, and a novel coronavirus was isolated from a sputum sample of the case. This virus was subsequently named MERS-CoV by the coronavirus group of the International Committee on Taxonomy of Viruses. The virus spread in the Middle East and spread to Asia, Africa, Europe and North America. According to WHO statistics, as of Oct. 6, 2015, there were 1,589 infections and 567 deaths worldwide, with a mortality rate of 35.6% In particular, the MERS epidemic imported from the Middle East to South Korea in May and June 2015 resulted in 186 infections and 36 deaths. Even one MERS case was imported into China. It brought a serious threat to the global public health system. MERS-CoV virus and SARS virus broke out in 2003 belong to (β-Coronavirus subgenus, but they have a higher lethality rate than SARS-CoV. MERS-CoV may spread in the form of aerosol, and thus is difficult to prevent and control. Neutralizing antibodies to MERS-CoV can be detected in the serum of dromedarycamels in many countries in the Middle East, suggesting that dromedary camel, which is an important vehicle in Middle East countries, is an intermediate host for MERS-CoV. Therefore, the sporadic MERS-CoV infection of humans in the Middle East has happened frequently since the discovery of MERS-CoV in 2012. As a result, with the increasing frequency of international communications, the risk of MERS spreading around the world has always existed. At present, there are still no vaccines and effective treatments in the world. Thus, it is urgent and important to develop a safe and effective vaccine against MERS-CoV.
In 2019, there was a case of pneumonia of unknown cause, which was identified as a coronavirus by using an electron microscope, and was temporarily named 2019 novel coronavirus (2019-nCoV), and later named SARS-CoV-2. The novel coronavirus can be transmitted from person to person through respiratory tracts and droplets, as well as through the air and digestive tracts. The source of infection is mainly patients infected with the novel coronavirus, but it is not ruled out that the asymptomatic cases are also the source of transmission. The disease may not occur immediately after infection of the virus, and the incubation period of the virus is relatively long, 1-14 days, which makes it difficult to prevent and control the disease. After entering a human body, the novel coronavirus, enters cells through angiotensin converting enzyme 2 (ACE 2) to infect the human body, causing the patient to have clinical symptoms such as fever, dry cough and muscle pain. Besides, a few of patients may have symptoms such as nasal obstruction, pharyngalgia and diarrhea and severe symptoms in some patients may rapidly progress to acute respiratory distress syndrome, septic shock, metabolic acidosis which is difficult to correct, and coagulation dysfunction, causing life danger. There is no specific drug or vaccine for the moment to prevent this virus, and only symptomatic support treatment is available.
In addition, some other coronaviruses also cause many serious animal diseases, especially posing a serious threat to agricultural livestock and pets. For instance, transmissible gastroenteritis virus (TGEV) can cause severe diarrhea in pigs with extremely high mortality, and its deletion mutant virus porcine respiratory coronavirus (PRCV) can cause severe respiratory diseases in pigs; feline infectious peritonitis virus (FIPV) can cause peritonitis and ascites aggregation in cats with high mortality; canine coronavirus (CCoV) can cause gastroenteritis symptoms in dogs to varying degrees, which spreads quickly and is difficult to control, and porcine epidemic diarrhea virus (PEDV) causes intestinal diseases such as porcine epidemic diarrhea, which is easy to spread in pigs with high mortality rate. There are also murine, bovine and other coronaviruses. These coronaviruses pose a serious threat to human and animal health. Therefore, it is of great significance to develop vaccines against coronaviruses.
The surface spike protein (S protein) is the major neutralizing antigen of a coronavirus. The receptor binding domains (RBD) of the spike proteins (S proteins) of HERS-CoV, SARS-CoV and 2019-nCoV are considered as the most important antigen target domains to induce a body to produce neutralizing antibodies. The RBDs, as vaccines, can focus the neutralizing antibodies generated by body stimulation on the receptor binding of viruses, which can improve the immunogenicity and immune efficiency of the vaccines. MERS-CoV invades a cell by RBD binding to the host cell's receptor (CD26, also known as DPP4). in addition, both SARS-CoV and 2019-nCoV were found to enter a cell via their RBD binding to the host cell. receptor hACE2.
The information disclosed herein is merely intended to provide a better understanding of the general background of the present disclosure and should not be construed as an acknowledgement or an implication in any form that the information constitutes the prior art that is already known to a person skilled in the art.

Antigens of β-coronaviruses, preparation methods and uses thereof

INSTITUTE OF MICROBIOLOGY, CHINESE ACADEMY OF SCIENCES


The invention concerns a method and a system for ensuring the operation of the safety circuit of an elevator or escalator, said safety circuit containing safety contacts (10, 12, 14) connected in series with a contactor (16). In the method, the largest bypass current coming to the contactor in a fault situation is defined, a testing device (202) is connected in series with the safety circuit, said testing device containing at least one resistor (26), which is used to produce a desired test current that is larger than the largest bypass current, and the neutral point (18) of the safety circuit is shifted if the contactor (16) remains energized by the aforesaid test current.

It is of primary importance to the operation of an elevator system that the elevator system should function faultlessly and above all in a predictable manner. Especially in situations where various systems, e.g. remote monitoring systems, are connected to the safety circuits of already existing elevators, it is necessary to make sure that the operation of the safety circuits of the elevator system will meet the required safety standard even after the connection of said systems.
Elevator systems employ various monitoring devices and methods to ensure the safety of the elevator. One of these is the so-called electric safety circuit. The safety circuit consists of safety device contactors connected in series. If any one of the safety devices breaks the safety circuit, then the elevator will stop or will not start moving. The safety circuit monitors e.g. the car doors, hoistway doors, locks, etc. If e.g. the elevator car doors are open, then the safety circuit is open.
FIG. 1a presents an example of the structure of a safety circuit. In FIG. 1a, there are three safety contactors 10, 12, 14 connected in series. The safety circuit is connected to main contactors 16 and a monitoring card 106, which is presented as a highly simplified resistance circuit. The main contactors 16 and the monitoring card 106 are connected to common ground 18 (neutral ground). The worst fault situation that may be caused by the monitoring card is illustrated in FIG. 1b, where the neutral conductor connected to neutral ground 18 is broken (110). In this situation it is possible that the fault causes a current to flow through the main contactors that will be sufficient to keep the main contactors energized "while the safety circuit is open".
Let us assume that each one of the resistances 100, 102, 104 has a magnitude of 300 k•. In this case, the smallest over-bridging resistance has a magnitude of 450 k•. In other words, two parallel 300k• resistances are in series with a third 300 k• resistance. FIG. 1c presents a circuit corresponding to the circuit in FIG. 1b. The resistance 112 has a magnitude of 450 k•. If the safety circuit voltage (Umax) is 230Vac, then the largest possible fault current will be about 0.5 A.
On the basis of the above-mentioned factors, it is possible that the fault current produced in a fault situation will be sufficient to keep the main contactors energized. If the main contactors remain energized even if the safety circuit is open, then the elevator does not meet the safety regulations.
Elevator safety regulations recommend that the neutral ground of the safety circuit should be connected via an analyzing card, such as e.g. a remote monitoring card, to neutral ground. The recommendations given by elevator regulations define the safest way of implementing the connection of an analyzing card to the safety circuits. If a deviation from this is opted for, then a corresponding safety level has to be proved via a risk analysis. The normal recommendation for a circuit to avoid a bypass current situation is to take the return current from the main contactors via the neutral conductor of the analyzing card to neutral ground, thus making it impossible for the safety circuit to be incorrectly bypassed in a fault situation. Such a circuit is presented in FIG. 1d. However, in many existing elevator control systems it is often difficult to change the connections afterwards.


The present disclosure relates to the use of nucleic acid (e.g., mRNA) combination therapies for the treatment of cancer. The disclosure provides compositions, and methods for their preparation, manufacture, and therapeutic use, wherein those compositions comprise at least two polynucleotides (e.g., mRNAs) in combination wherein the at least two polynucleotides are selected from the group consisting of (i) a polynucleotide encoding an immune response primer (e.g., IL23), (ii) a polynucleotide encoding an immune response co-stimulatory signal (e.g., OX40L), (iii) a polynucleotide encoding a checkpoint inhibitor (e.g., an anti CTLA-4 antibody), and, (iv) a combination thereof. The therapeutic methods disclosed herein comprise, e.g., the administration of a combination therapy disclosed herein for the treatment of cancer, e.g., by reducing the size of a tumor or inhibiting the growth of a tumor, in a subject in need thereof. In some aspects, the combination therapies disclosed herein disclosed are administered intratumorally.

Cancer is a disease characterized by uncontrolled cell division and growth within the body. In the United States, roughly a third of all women and half of all men will experience cancer in their lifetime. Polypeptides are involved in every aspect of the disease including cancer cell biology (carcinogenesis, cell cycle suppression, DNA repair and angiogenesis), treatment (immunotherapy, hormone manipulation, enzymatic inhibition), diagnosis and determination of cancer type (molecular markers for breast, prostate, colon and cervical cancer for example). With the host of undesired consequences brought about by standard treatments such as chemotherapy and radiotherapy used today, genetic therapy for the manipulation of disease-related peptides and their functions provides a more targeted approach to disease diagnosis, treatment and management. However, gene therapy poses multiple challenges including undesirable immune response and safety concern due to the incorporation of the gene at random locations within the genome.
Various methods of treating cancer are under development. For example, dendritic cell (DC) vaccines have been studied as a possible anti-cancer therapy. However, DC vaccines require multiple steps of isolating DCs from a subject, ex vivo manipulation of DCs to prime the cells for tumor antigen presentation, and subsequent administration of the manipulated DCs back into the subject. Further, it is reported that the overall clinical response rates for DC vaccines remain low and the ability of DC vaccines to induce cancer regression remains low. See, e.g., Kalkinski et al., "Dendritic cell-based therapeutic cancer vaccines: what we have and what we need," Future Oncol. 5(3):379-390 (2009).
Important goals for the field of immuno-oncology are to improve the response rate and increase the number of tumor indications that respond to immunotherapy, without increasing adverse side effects. One approach to achieve these goals is to use tumor-directed immunotherapy, i.e., to focus the immune activation to the most relevant part of the immune system. This may improve anti-tumor efficacy as well as reduce immune-related adverse events. Tumor-directed immune activation can be achieved by local injections of immune modulators directly into the tumor or into the tumor area. Therapies focused on targeting checkpoint inhibitors and co-stimulatory receptors can generate tumor-specific T cell responses through localized immune activation.
In recent years, the introduction of immune checkpoint inhibitors for therapeutic purposes has revolutionized cancer treatment. Of interest are therapies featuring combinations of checkpoint inhibitors with other costimulatory or inhibitory molecules.
T cell regulation, i.e., activation or inhibition is mediated via co-stimulatory or co-inhibitory signals. This interaction is exerted via ligand/receptor interaction. T cells harbor a myriad of both activating receptors, such as OX40, and inhibitory receptors (i.e., immune checkpoints) such as programmed death receptor 1 (PD-1) or cytotoxic T lymphocyte-associated protein 4 (CTLA-4) (Mellman et al. 2011 Nature; 480:480-489). Activation of this immune checkpoints results in T cell deactivation and commandeering these pathways by tumor cells contributes to their successful immune escape.
Immune checkpoint inhibitors such as pembrolizumab or nivolumab, which target the interaction between programmed death receptor 1/programmed death ligand 1 (PD-1/PD-L1) and PD-L2, have been recently approved for the treatment of various malignancies and are currently being investigated in clinical trials for cancers including melanoma, head and neck squamous cell carcinoma (HNSCC). Data available from these trials indicate substantial activity accompanied by a favorable safety and toxicity profile in these patient populations.
For example, checkpoint inhibitors have been tested in clinical trials for the treatment of melanoma. In particular, phase III clinical trials have revealed that therapies such as ipilimumab and pembrolizumab, which target the CTLA-4 and PD-1 immune checkpoints, respectively, have raised the three-year survival of patients with melanoma to ˜70%, and overall survival (>5 years) to ˜30%.
Likewise, checkpoint inhibitors have been tested in clinical trials for the treatment of head and neck cancer. In preclinical studies, it had been shown that that 45-80% of HNSCC tumors express programmed death ligand 1 (PD-L1) (Zandberg et al. (2014) Oral Oncol. 50:627-632). Currently there are dozens of clinical trials evaluating the efficacy and safety of immune checkpoint inhibitors as monotherapy or in combination regimens in HNSCC. For example, clinical trials with PD 1, PD-L1, and CTLA-4 inhibitors are being tested in HNSCC. Data that the PD-1 antibody pembrolizumab might be effective in metastatic/recurrent (R/M) HNSCC patients were generated in the phase 1b Keynote-012 phase I/II trial (Cheng. ASCO 2015, oral presentation). More recently the data of the randomized CheckMate-141 phase III clinical trial were presented (Gillison. AACR 2016, oral presentation). This study investigated the efficacy of the monoclonal PD-1 antibody nivolumab given every 2 weeks in platinum-refractory R/M HNSCC patients. The study was stopped early due to superiority of the nivolumab arm of the study.
Most immunotherapies available or under development rely on antibodies, which are cumbersome to manufacture, and being foreign proteins frequently lead to the development of anti-drug antibody neutralizing antibodies (ADA nAB). See, e.g., Krishna & Nadler (2016) "Immunogenicity to Biotherapeutic—The role of Anti-drug Immune Complexes" Frontiers in Immunology 7:21; Schellekwn (2010) "The immunogenicity of therapeutic proteins" Discov. Med, 9:560-4. Thus, there is still a need of effective immunotherapies for the treatment of cancer.

MRNA combination therapy for the treatment of cancer


A bulk product filling device 10 comprises a fill channel 39 having a fill pening 17 associated with a processing region 13 through which a bulk product to be handled can be introduced into the processing region 13 and a suitable liquid inlet device 38 disposed in the vicinity of the fill channel 39 for the introduction of liquids. The liquid inlet device 38 has at least one inlet opening (gap 36) integrated in the wall region 42 of the fill channel 39 which leads, at the edge of the free fill opening cross-section 31, into the fill opening 17. The liquid inlet device 38 is therefore configured in such a fashion and disposed on the bulk product filling device 10 in such a manner that an even and homogeneous moistening of the bulk product can be achieved.

The invention concerns a bulk product filling device having a fill channel with a fill opening associated with a processing region by means of which a bulk product which is to be processed can be introduced into the processing region and with a liquid inlet device disposed in the vicinity of the fill channel and suitable for the introduction of liquids.
A bulk product filling device of this kind is e.g. known in the art through the figure on page 89 of the text book "Granulation", published by Heyden Publishing Company 1981, ISBN 0-85501-177-7
A bulk product can be introduced into a processing region of a mixing device or a reactor by means of a bulk product filling device. Mixing tools are displaced along a horizontal shaft to rotate within the mixing device. The size, number, disposition, geometrical shape, and rotational velocity of the mixing tools are mutually adjusted to bring the product introduced into the container into three-dimensional motion. The mixing process is carried out using the centrifugal and swirling method and can be executed continuously or in batches. The mixing process leads to a crossing of the individual travel paths of the bulk product. The bulk product is frequently thrown against the wall of the housing of the mixing device, reflected, and once more captured and accelerated by the mixing tools. For this reason, good mixing is achieved.
For certain mixing processes, liquid components must be introduced into the bulk product. This can, in particular, be necessary when the bulk product tends to produce dust and/or is a granular-type product. One should prevent excessive compression of the bulk product during processing with the mixing tools within the mixing device. The bulk product should behave properly within the mixing device and tend to agglomerate but not to bond and to build structures having a small diameter so that, at the end of the mixing procedure, the product has the proper consistency. Deposition of the bulk product on the walls of the mixing device during mixing is equally undesirable as is the formation of clumps and clusters.
When equipping a bulk product filling device with a liquid inlet device, the following problems result:
In prior art, one part of the liquid inlet device projects into the fill channel to introduce the liquid into the bulk product. The part of the liquid inlet device disposed in the fill channel limits the free cross-section of the fill opening. Filled bulk product therefore cannot stream unhindered into the processing region. The bulk product collides against portions of the liquid inlet device to prevent optimized functioning of the liquid inlet. The liquid can only reach parts of the incoming bulk product. Bulk product can stick to the liquid inlet device and reduce the size of inlet openings of the liquid inlet device or even block them.
In other conventional mixing devices, the liquid inlet device is not disposed in the vicinity of the inlet channel, rather has direct access to the processing region. In this case, the liquid inlet device must be passed through the wall of the mixing device. This kind of feed-through is difficult to effect, since the mixing device is usually surrounded by a jacket of flowing cooling water, a hot water heater or a steam heater. In addition, an insulating layer can also be provided for. A plurality of liquid inlet devices may be necessary for introducing the liquid into the bulk product so that the jacket surrounding the mixing device has to be penetrated a plurality of times. This interferes with the function of this jacket.
The conventional liquid inlet devices provided on the bulk product fill device only lead to moistening of a portion of the bulk product.

Gerbruder Lodige Maschinenbau-Gesellschaft mit beschrankter Haftung


System and computer-implemented method for license management of virtual appliances in a computing system uses an activated virtual appliance in the computing system to forward an activation license from a license server on behalf of an unactivated virtual appliance in the computing system.

License management in a computing system typically involves distributing activation licenses from at least one license sever to components of the computing system. In some implementations, the components of the computing system and the corresponding license server are located in different networks within the computing system. For example, in a hybrid cloud system, a license server may be deployed in a public network while components of the computing system may be deployed in a private enterprise network.
In some license management schemes, an end user in a multi-tier provider space trying to activate a component only has access to a tier above and does not have access to the root tier of the multi-tier provider space. In such license management schemes, each tier in the multi-tier provider space needs to implement a user interface to distribute license information to the following tier of the multi-tier provider space, which can increase the cost for license management implementation.

System and method for license management of virtual appliances in a computing system