Methods and devices for providing a haptic responses to a haptic feedback device may include receiving, by an application providing a virtual environment executing on a computer device, physical movement input based at least on movement of the haptic feedback device that corresponds to a virtual movement interaction with a virtual object in the virtual environment. The methods and devices may include accessing a haptic signature associated with the virtual object. The methods and devices may include determining a haptic response based at least upon the haptic signature to identify the virtual object through the haptic response. The methods and devices may include transmitting the haptic response to the haptic feedback device.

The present disclosure relates to computer graphics systems, and more particularly, to virtual environments.
Interactions with virtual objects in mixed reality and/or virtual reality environments may lack immersion. Individuals perceive experiences through all five senses in the natural world. Most of these experiences are visually led, resulting in a perception gap when interacting in virtual environments. For example, since most interactions in virtual environments are visual, users have to solely rely on visual cues to access information. Moreover, interactions with virtual environments may need specialized controllers which have limited interaction abilities. For example, previous solutions that replicate some of the interactivity include virtual environment hand controllers that users hold in their hands. These controllers need to be grasped and hence limit the ability to allow gestures and natural interactions.
Thus, there is a need in the art for improvements in interactions with virtual environments.

Natural interactions with virtual objects and data through touch


A battery connector adapted for being electrically connected with a printed circuit board includes an insulating housing defining a plurality of terminal passageways, a plurality of fixing members fastened in the insulating housing and stretching beyond a top surface of the insulating housing for being soldered to the printed circuit board, and a plurality of electrical terminals disposed in the corresponding terminal passageways and each having a fixing board, a first contact portion stretching out of a bottom surface of the insulating housing and a substantially lying-V shaped second elastic portion extended from a top of the fixing board. A free end of the second elastic portion stretches out of the top surface of the insulating housing and is arched upward to form a second contact portion capable of elastically abutting against the printed circuit board.

1. Field of the Invention
The present invention generally relates to a battery connector, and more particularly to a battery connector capable of making terminals and a printed circuit board electrically connected with each other steadily.
2. The Related Art
It is well known that mobile phones or other portable electronic devices often use rechargeable batteries as power sources. Traditionally, the mobile phone and the electronic device need a battery connector mounted therein for electrically connecting the rechargeable battery with a printed circuit board mounted in the mobile phone and the electronic device. The battery connector is connected with the printed circuit board by soldering terminals thereof to the printed circuit board by means of a SMT method. However, when the terminals are not coplanar due to the inaccurate manufacturing, some terminals near the printed circuit board are easily soldered to the printed circuit board while other terminals apart from the printed circuit board are difficultly soldered to the printed circuit board. It results in a bad electrical connection between the terminals and the printed circuit board. Thus a battery connector which can make the terminals and the printed circuit board electrically connected with each other steadily is required.


The engine misfire detection process according to one aspect of the invention first makes tentative detection on the occurrence or the non-occurrence of an engine misfire in execution of both vibration control and rotation speed control. In response to the tentative detection of an engine misfire, the engine misfire detection process subsequently makes final detection on the occurrence or the non-occurrence of an engine misfire. In the event of no final detection of an engine misfire, the engine misfire detection process makes tentative detection and final detection on the occurrence or the non-occurrence of an engine misfire in prohibition of the vibration control. In the event of still no final detection of an engine misfire, the engine misfire detection process makes tentative detection and final detection on the occurrence or the non-occurrence of an engine misfire in further prohibition of the rotation speed control. Even in the event of no final detection of an engine misfire in execution of both the vibration control and the rotation speed control, the procedure of the invention makes final detection on the occurrence or the non-occurrence of an engine misfire in prohibition of execution of the vibration control and further the rotation speed control. This arrangement desirably increases the detection frequency of engine misfires.

One proposed structure of the engine misfire detection apparatus includes an internal combustion engine and a motor generator connected to an output shaft of the internal combustion engine. In the failure of accurate detection of misfires of the internal combustion engine according to a driving condition of a vehicle, this prior art engine misfire detection apparatus restricts or prohibits the detection of misfires of the internal combustion engine (see Patent Document 1). The restriction or prohibition of the detection of misfires in the internal combustion engine in the event of failed detection of the engine misfires with high accuracy according to the driving condition of the vehicle aims to prevent wrong detection of misfires in the internal combustion engine.    Patent Document 1: Japanese Patent Laid-Open No. 2001-317402

Engine misfire detection apparatus for internal combustion engine and engine misfire detection method


A phosphor protection film for protecting phosphors contained in a phosphor layer. The phosphor protection film includes a functional layer, a bulking layer that has a single-layer structure or a laminated structure, and a first vapor deposited layer (gas barrier layer) that has gas barrier properties in this order from outside to inside. The clearance between the functional layer and the first vapor deposited layer in the thickness direction of the phosphor protection film is 45 to 280 μm.

In light-emitting units, such as backlight units of liquid crystal displays and electroluminescent light-emitting units, phosphors contained in a phosphor layer may come into contact with oxygen or moisture and their performance may thereby be reduced over time. In order to prevent this reduction, these light-emitting units often employ a structure in which a film having gas barrier properties is provided on one or both surfaces of a phosphor layer. For example, PTL 1 discloses a color conversion member having a structure in which both surfaces of each of two color conversion layers containing different types of phosphors are sandwiched between barrier films.

Phosphor protection film, wavelength conversion sheet, and light-emitting unit


The present invention relates to a method of controlling a re-emission interval of an asynchronous transfer mode interval controller using a theoretical departure time. The present invention controls the generation of CDV in a controller of the current RDT similarly to the existing RDT method for controlling the intervals of ATM cells by processing the time which a cell is outputted from an interval controller as a theoretical departure time and registering by a little earlier time in CSQ compensating for the queuing delay of OQ, and solves the problem of the queuing delay accumulation in the existing RDT method.

1. Field of the Invention
The present invention generally relates to a method of controlling a re-emission interval of an asynchronous transfer mode interval controller and, more particularly, a method of controlling a re-emission interval using a theoretical departure time.
2. Description of the Prior Art
Generally, in developing public telecommunication network, a user requires gradually increased speed, a wide-band, and multiple functions, and increased intelligence regarding service such as multimedia, etc. Today, B-ISDN has been developed for wide band communication. Since international standard organization such as ITU-T and ATM-Forum have recommended ATM as a wide band communication mode, an ATM switching system is being devloped.
However, traffic control is essential in using an ATM system because the user information therein is transferred in an ATM cell and an asynchronous method is utilized. To maintain the quality of service for the connected calls, there is call admission control for determining whether a new call is accepted, priority control for recognizing a sensibility degree for transfer delay and cell loss among various kinds of cells and preferentially transferring and discarding calls, congestion control for controlling flow so that a blocking state is not maintained for a long time when congestion occurs and for preventing congestion in network node, Usage Parameter Control(UPC)/Network Parameter Control(NPC) for protecting a network source by monitoring a traffic characteristic agreed upon between a user and a network and discarding a cell when the agreement is violated, and a cell interval control for efficiently using the network resource by controlling cell interval and equalizing burst traffic.
There are conventional cell interval control methods such as an Arrival Re-emission Time(ART) method based on the input time in an interval controller, and a Recent Departure Time(RTD) method based on the output time from an interval controller.
The ART method described above have a simple buffer control dealing with multiplexing in an interval controller but having an effect on a multiplexed cell stream in output traffic by taking the input state into consideration without taking output state from the interval controller into consideration. Delay which is generated between every cell varies because of the multiplexing of the interval controller, as indicated by cell delay variation(CDV). Accordingly, in an ART mode, there is declined performance of an interval control function due to the multiplexing of the interval controller. The multiplexing output cell stream in the interval controller is affected by the utilization of link and, consequently in the context of network resource management, stable interval control is difficult. On the other hand, the Recent Departure Time(RDT) method performs control based on the output time of the interval controller. By including CDV generated from the interval controller, it is possible to control a distinctive cell interval. However, in RDT method, when counting the expectation departure time, the actual departure time of the previous cell is used at the interval controller. After this registered cell with the scheduled departure time has a little queuing delay, it departs from the interval controller later than the scheduled time. As such the departure time is used for determining the scheduled departure time of the next input cell, the queuing delay is accumulated according to sequential cell processing. Therefore, this requires theoretically unlimited buffers.
Accordingly, the present invention suggests a method of controlling a cell interval in order to reduce delay from the interval controller, which has stable characteristics for the connecting number and the utilization of a link and is unsensitive to CDV by applying the advantage of RDT mode and compensating for the shortage thereof, and therefore uses a Theoretical Departure Time(TDT) for controlling the cell re-emission interval.

Method for controlling a re-emission interval in an asynchronous transfer mode interval controller

Electronics and Telecommunications Research Institute


In a shade guide, a plurality of shade tabs whose colors are mutually different are arranged regularly based on the colors. The arrangement of the plurality of shade tabs is an arrangement determined based on: S values and V values that are determined according to to which areas, from among areas partitioned by a plurality of straight lines in an L*-C* plane, the coordinates of the colors of the shade tabs belong, and H values that are determined according to to which areas, from among areas partitioned by a plurality of straight lines in an a*-b* plane, the coordinates belong. S groups, each of which is a shade tab group having a common S value, are arranged in the shade guide. V rows, each of which is a shade tab group having a common V value, are arranged in each S group. In each V row, the plurality of shade tabs have mutually different H values and are aligned in an order that is in accordance with the H values. Using this shade guide enables precisely and easily discriminating the color of an evaluation target tooth.

People who have beautiful teeth tend to have a favorable impression on others. Demand for aesthetics with respect to teeth has therefore being increasing year by year. In medical treatment and cosmetic treatment in dentistry, when providing a patient's teeth with a prosthetic such as a denture or a crown restoration, the color of the prosthetic is preferably the same color as the adjacently located teeth. It is therefore required in the manufacturing of the prosthetic to precisely discriminate the color of a patient's tooth and manufacture the prosthetic based on the discriminated color. Note that discriminating the color of a tooth in this way is sometimes called tooth-color evaluation (shade taking).
Conventionally, shade guides have been used as color samples for discriminating the color of teeth. A shade guide has a plurality of shade tabs that are a plurality of colors and are arranged according to the colors. Each shade tab is, for example, formed from plastic and shaped as a tooth. Also, each shade tab has been assigned a number for specifying the color of the shade tab.
For example, an observer brings at least one of the shade tabs close to the patient's tooth, and compares the color of the patient's tooth and the color of the shade tab. As a result of the comparison, the observer selects the shade tab whose color is felt to be the closest to the patient's tooth, and discriminates the color of such shade tab as the color of the patient's tooth. Thereafter, for example, the observer notifies a prosthetics manufacturer of the number that specifies the color of the selected shade tab. The prosthetics manufacturer manufactures a prosthesis using materials that give off the same color as the color specified by the number.
In this way, the discrimination of the color of a tooth includes a subjective evaluation by an observer. Subjective evaluations by observers are different from individual to individual, and vary according to the environment at the time of observation. The reliability of the tooth color discrimination result is prone to being low. There is desire for a shade guide that, in order to improve the reliability of the discrimination result, enables a precise discrimination of the color of a tooth by an observer.
The range of colors of shade tabs in conventional shade guides has not covered the range of colors observed for natural teeth. For this reason, there have been cases in which a color close to the color of a tooth targeted for evaluation cannot be found in the shade guide. In order to address this problem, there has been a proposal for a shade guide in which shade tabs whose colors correspond to the distribution range of the colors of natural teeth specified in a color space are arranged (e.g., see Japanese Patent No. 3100809).
However, the above-described conventional shade guide does not take into account visual sensitivity in the actual perception of colors by humans. This shade guide is therefore insufficient for precisely and easily visually discriminating the color of a tooth targeted for evaluation.

Shade guide, method for discriminating tooth colors, artificial tooth manufacturing method


A process for producing benzene and xylenes comprising introducing hydrocarbon liquid stream to hydroprocessor to yield first gas stream and hydrocarbon product (C5+); optionally introducing hydrocarbon product to first aromatics separating unit to produce saturated hydrocarbons (C5+) and first aromatics stream (C6+); feeding hydrocarbon product and/or saturated hydrocarbons to reformer to produce reformer product, second gas stream, and hydrogen stream; introducing reformer product to second aromatics separating unit to produce a non-aromatics recycle stream and second aromatics stream comprising C6+ aromatics; recycling non-aromatics recycle stream to reformer; introducing first aromatics stream and/or second aromatics stream to third aromatics separating unit to produce first C6 aromatics (benzene), C7 aromatics (toluene), C8 aromatics (xylenes&ethylbenzene), C9 aromatics, C10 aromatics, and C11+ aromatics; introducing C7 aromatics, C9 aromatics, C10 aromatics, or combinations thereof to disproportionation and transalkylation unit to yield third aromatics stream (benzene and xylenes); and conveying C11+ aromatics to hydroprocessor.

Benzene and xylenes are important chemicals, with applications ranging from chemical intermediates to solvents. Benzene is a natural constituent of crude oil and it is used primarily as a precursor for manufacturing chemicals with more complex structure, such as ethylbenzene, cumene, cyclohexane, nitrobenzene, and alkylbenzenes. Benzene also has a high octane number, and as such is an important component of gasoline. Benzene can also be used for making some types of rubbers, lubricants, dyes, detergents, drugs, explosives, and pesticides.
While xylenes occur in small concentrations in crude oil, xylenes are produced mainly as part of the BTX aromatics (benzene, toluene, and xylenes) extracted from the product of catalytic reforming known as "reformate." Xylenes are primarily used as solvents in various applications, such as in printing, rubber, and leather industries; and are a common component of ink, rubber, adhesives, thinning paints, varnishes, and cleaning agents (e.g., for steel, silicon wafers, integrated circuits). However, there is concern over the depletion of finite reserves of crude oil. Thus, there is an ongoing need to develop methods for producing aromatic hydrocarbons such as benzene and xylenes from feedstocks other than crude oil, for example from feedstocks derived from waste plastics.

This patent is subject to a terminal disclaimer.

Conversion of waste plastic through pyrolysis to high value products like benzene and xylenes


A furnace plant including at least one furnace vessel comprising side walls, a bottom and a roof. At least one heater is configured to heat metal in the furnace vessel. A compartment includes sidewalls lined with refractory material. The compartment forms an extension of the furnace vessel. At least one electromagnetic stirrer is arranged outside and adjacent to the compartment. A refractory plate is arranged inside the compartment. The refractory plate includes an upper edge configured to be positioned below a meniscus of molten metal and includes a lower edge positioned spaced apart from a bottom of the compartment. The plate is arranged such that a gap between the plate and a wall of the compartment increases toward the bottom of the compartment.

Typically, when metal is melted for casting, material floats to the surface of the molten metal and is oxidized. Oxidized material acts as a contaminant in the subsequently cast metal, having such side effects as weakening the metal and providing the case metal with other unfavorable characteristics. To address this issue, special furnaces and mechanical stirrers have been developed.

Device for submerging material into liquid metal by an electromagnetic stirrer


Described is a system for open doorway detection for autonomous robot exploration, the system includes an onboard range sensor that is operable for constructing a three-dimensional (3D) point cloud of a scene. One or more processors that receive the 3D point cloud from the range sensor. The 3D point cloud is then filtered and downsampled to remove cloud points outside of a predefined range and reduce a size of the point cloud and, in doing so, generate a filtered and downsampled 3D point cloud. Vertical planes are extracted from the filtered and downsampled 3D point cloud. Finally, open doorways are identified from each extracted vertical plane.

(1) Field of the Invention
The present invention relates to a navigation system and, more particularly, to a system for detecting the location and orientation of open doorways for autonomous robot exploration.
(2) Discussion of Related Art
Exploration is a fundamental problem for autonomous mobile robots operating in unknown or dynamic environments. Exploration is related to the well-known problem of path planning. However, unlike the original problem, where complete knowledge of the environment is given, exploring an unknown environment is usually performed in a step-by-step greedy fashion. Instead of planning in advance the entire trajectory of the mobile robot, a greedy exploration strategy only plans one step (or a few steps) ahead based on the information about the environment acquired by the sensor(s) mounted on the robot. Determining where the robot moves next can be a problematic task.
Over the last decade, a developmental shift has occurred from ground-based robot platforms to mobile aerial robots (e.g., UAV), as the latter provides more agility and speed. While outdoors, UAVs can easily navigate the airspace. However, navigating indoors requires development of a system for small UAVs to navigate in indoor environments (e.g., corridor, warehouses). In such settings, the next candidate positions to explore typically refer to where the open spaces (e.g., open doors) are. Thus, the problem is then reduced to finding open doorways in such an environment.
Many visual doorway detection algorithms have been proposed in the past, as it is of great importance for both navigation and manipulation tasks. Most of the earlier works focused on extracting two-dimensional (2D) appearance and shape features to recognize doors. For example, A. C. Murillo, J. Kosecka, J. J. Guerrero, and C. Sagues, in "Visual Door Detection Integrating Appearance and Shape Cues", Journal of Robotics and Autonomous Systems, 2008, proposed a probabilistic approach by defining the likelihood of generating the door configurations with various features. In other work, Zhichao Chen and Stanley Birchfield, in "Visual Detection of Lintel-Occluded Doors from a single image, Workshop on Visual Localization from Mobile Platforms, CVPR 2008, proposed a Adaboost based approach along with two geometric features, concavity and bottom-edge intensity, to model the door explicitly. In yet other work, Yingli Tian, Xiaodong Yang, and Aries Arditi, in "ComputerVision-based Door Detection for Accessibility of Unfamiliar Environments to Blind Persons," ICCHP (2) 2010, further proposed a more generic geometric based approach to detect doors based on stable features such as edges and corners. However, as in most 2D vision algorithms, these works are sensitive to common factors such as illumination changes, occlusion, clutter, and perspective distortion.
As noted above, many approaches toward indoor robot navigation and exploration have been developed in the past. One of the major categories among these approaches focus on addressing the SLAM (Simultaneous Localization and Mapping) problem, where the goal is to integrate the information collected during navigation into an accurate map possible. In other words, SLAM aims to localize the robot and reconstruct the map from its trajectory. Many recent works in this category has started to utilize 3D range sensor in conjunction with point cloud alignment mechanisms for autonomous UAV navigation. An example of such work is that by Shaojie Shen, Nathan Michael, and Vijay Kumar, in "Autonomous Multi-Floor Indoor Navigation with a Computationally Constrained MAV", ICRA 2011. However, this line of work does not address the important question of where the robot should go next.
Another related area falls into obstacle avoidance. Due to the growing interests in smaller UAV flying in indoor and other GPS denied environments, quite a few research works have been developed to utilize onboard visual sensors to ensure safe maneuver in such conditions. Techniques focusing on monocular sensors have long been the main studied area. This includes the optical flow based approach by Zigg et al. (i.e., Simon Zigg, Davide Scaramuzza, Stephan Weiss, Roland Siegwart, "MAV Navigation through Indoor Corridors Using Optical Flow", ICRA 2010) and the imitation learning based approach by Ross (i.e., Stephane Ross et al., "Learning Monocular Reactive UAV Control in Cluttered Natural Environments", CoRR abs/1211.1690, 2012). Similar to the SLAM community, researchers also started to investigate the areas of utilizing Lidar or other RGB-D sensors for obstacle avoidance (e.g., Allen Ferrick, Jesse Fish, Edward Venator, Gregory S. Lee, "UAV Obstacle Avoidance Using image Processing Techniques", Technologies for Practical Robot Applications, 2012). However, regardless of monocular vision or 3D vision, a common theme across most works on obstacle avoidance is the reactive action control for UAVs. This means that the control system will react and prevent the UAV from colliding with an obstacle when it is close by. However, it does not plan ahead for opportunity spaces which are further away to be explored.
In Lange's work (i.e., Sven Lange, Niko Sunderhauf Peer Neubert, Sebastian Drews, Peter Protzel, "Autonomous Corridor Flight of a UAV Using a Low-Cost and Light-Weight RGB-D Camera", Advances in Autonomous Mini Robots, 2012), a 3D algorithm is proposed to process a point cloud captured by a Kinect sensor mounted on a UAV. The UAV is assumed to navigate and explore in an indoor corridor environment. The algorithm simply detects 4 major planes from the point cloud: two walls, a ground and a ceiling. Then, the distances between the UAV and each of the four planes are computed. Subsequently, the position of the UAV is adjusted and maintained in the center of the four planes. This implementation is very straight forward in a corridor setting. While the system of Lange allows the UAV to move in straight line, it does not extend beyond that in that it does not identify the exact location and orientation of open doors which are suitable for navigation.
Another related work is that of Derry et al. (i.e., Matthew Derry, Brenna Argall, "Automated Doorway Detection for Assistive Shared-Control Wheelchairs", ICRA 2013), in which a 3D based algorithm is proposed to detect doors for assistive wheelchairs. The work of Lange is not appropriate for a UAV in that it operates on a ground plane and also imposes strong assumptions on the geometry of the point cloud (e.g., the input point cloud contains mostly front facing walls, the viewing angle between the sensor and a wall is unchanged in y-axis etc.).
Thus, a continuing need exists for a system that provides fast and efficient detection of open doorways using only 3D point cloud data and, in doing so, provides detection of the location and orientation of doorways through which an autonomous UAV can navigate.

Fast open doorway detection for autonomous robot exploration


Significance of biological pathway in disease state is predicted by (a) providing expression level data for a plurality of biomolecules differentially expressed in a disease state, compared with same biomolecules expressed in a non-diseased state: (b) determining presence probability of the biomolecules in disease state; (c) determining effect of each biomolecule from the plurality of biomolecules on the expression of different downstream biomolecules within pathway to provide perturbation factor for each biomolecule in the pathway; (d) combining statistical significance of differentially expressed biomolecules present in the disease state, with a sum of perturbation factors for all of the biomolecules, generating an impact factor; (e) calculating statistical significance of impact factor based upon determined probability of having statistical significant presence of differentially expressed biomolecules in step (b) and the sum of perturbation factors in step (c); and (f) outputting statistical significance of impact factor for the pathway relevant to the disease.

This section provides background information related to the present disclosure which is not necessarily prior art.
Together with the ability of generating a large amount of data per experiment, high throughput technologies also brought the challenge of translating such data into a better understanding of the underlying biological phenomena. Independent of the platform and the analysis methods used, the result of a high-throughput experiment is, in many cases, a list of differentially expressed genes. The common challenge faced by all researchers is to translate such lists of differentially expressed genes into a better understanding of the underlying biological phenomena and in particular, to put this in the context of the whole organism as a complex system. A computerized analysis approach using the Gene Ontology (GO) was proposed to deal with this issue. This approach takes a list of differentially expressed genes and uses a statistical analysis to identify the GO categories (e.g. biological processes, etc.) that are over- or under-represented in the condition under study. Given a set of differentially expressed genes, this approach compares the number of differentially expressed genes found in each category of interest with the number of genes expected to be found in the given category just by chance. If the observed number is substantially different from the one expected just by chance, the category is reported as significant. A statistical model (e.g. hypergeometric) can be used to calculate the probability of observing the actual number of genes just by chance, i.e., a p-value. Currently, there are over 20 tools using this over-representation approach (ORA). In spite of its wide adoption, this approach has a number of limitations related to the type, quality, and structure of the annotations available. An alternative approach considers the distribution of the pathway genes in the entire list of genes and performs a functional class scoring (FCS) which also allows adjustments for gene correlations. Arguably the state-of-the-art in the FCS category, the Gene Set Enrichment Analysis (GSEA), ranks all genes based on the correlation between their expression and the given phenotypes, and calculates a score that reflects the degree to which a given pathway P is represented at the extremes of the entire ranked list. The score is calculated by walking down the list of genes ordered by expression change. The score is increased for every gene that belongs to P and decreased for every gene that does not. Statistical significance is established with respect to a null distribution constructed by permutations.
Both ORA and FCS techniques currently used are limited by the fact that each functional category is analyzed independently without a unifying analysis at a pathway or system level. This approach is not well suited for a systems biology approach that aims to account for system level dependencies and interactions, as well as identify perturbations and modifications at the pathway or organism level. Several pathway databases such as KEGG, BioCarta, and Reactome, currently describe metabolic pathway and gene signaling networks offering the potential for a more complex and useful analysis. A recent technique, ScorePage, has been developed in an attempt to take advantage of this type of data for the analysis of metabolic pathways. Unfortunately, no such technique currently exists for the analysis of gene signaling networks. All pathway analysis tools currently available use one of the ORA approaches above and fail to take advantage of the much richer data contained in these resources. GenMAPP/MAPPfinder and GeneSifter use a standardized Z-score. PathwayProcessor, PathMAPA, Cytoscape and PathwayMiner use Fisher's exact test. MetaCore uses a hypergeometric model, while ArrayXPath offers both fisher's exact test and a false discovery rate (FDR). Finally, VitaPad and Pathway Studio focus on visualization alone and do not offer any analysis.
The approaches currently available for the analysis of gene signaling networks share a number of important limitations. Firstly, these approaches consider only the set of genes on any given pathway and ignore their position in those pathways. This may be unsatisfactory from a biological point of view. If a pathway is triggered by a single gene product or activated through a single receptor and if that particular protein is not produced, the pathway will be greatly impacted, probably completely shut off. If the insulin receptor (INSR) is not present, the entire pathway is shut off. Conversely, if several genes are involved in a pathway but they only appear somewhere downstream, changes in their expression levels may not affect the given pathway as much.
Secondly, some genes have multiple functions and are involved in several pathways but with different roles. For instance, the above INSR is also involved in the adherens junction pathway as one of the many receptor protein tyrosine kinases. However, if the expression of INSR changes, this pathway is not likely to be heavily perturbed because INSR is just one of many receptors on this pathway. Once again, all these aspects are not considered by any of the existing approaches.
Probably the most important challenge today is that the knowledge embedded in these pathways about how various genes interact with each other is not currently exploited. The very purpose of these pathway diagrams is to capture some of our knowledge about how genes interact and regulate each other. However, the existing analysis approaches consider only the sets of genes involved on these pathways, without taking into consideration their topology. In fact, our understanding of various pathways is expected to improve as more data is gathered. Pathways will be modified by adding, removing or re-directing links on the pathway diagrams. Most existing techniques are completely unable to even sense such changes. Thus, these techniques will provide identical results as long as the pathway diagram involves the same genes, even if the interactions between them are completely re-defined over time.
Finally, up to now the expression changes measured in these high throughput experiments have been used only to identify differentially expressed genes (ORA approaches) or to rank the genes (FCS methods), but not to estimate the impact of such changes on specific pathways. Thus, ORA techniques will see no difference between a situation in which a subset of genes is differentially expressed just above the detection threshold (e.g., 2 fold) and the situation in which the same genes are changing by many orders of magnitude (e.g., 100 fold). Similarly, FCS techniques can provide the same rankings for entire ranges of expression values, if the correlations between the genes and the phenotypes remain similar. Even though analyzing this type of information in a pathway and system context would be extremely meaningful from a biological perspective, currently there is no technique or tool able to do this.
We propose a radically different approach for pathway analysis that attempts to capture all aspects above. An impact factor (IF) is calculated for each pathway incorporating parameters such as the normalized fold change of the differentially expressed genes, the statistical significance of the set of pathway genes, and the topology of the signaling pathway. We show on a number of real data sets that the intrinsic limitations of the classical analysis produce both false positives and false negatives while the impact analysis provides biologically meaningful results.

Method for analyzing biological networks


A self magnetizing motor and a compressor having the same is configured to require a lower starting voltage and to deliver superior performance. In the self magnetizing motor, a magnetic material on an exterior of the rotor is magnetized when power is supplied to a magnetizing unit of the stator. A plurality of conductive bars are inserted on the outer circumference of the rotor core. A spacing distance between outer portions of the conductive bars and inner circumference of the magnetizable material is longer than an air gap between the stator and the rotor. As a result, a magnetic strength of the magnetic material may be increased.

1. Field
The present application discloses a self magnetizing motor and a compressor having the same.
2. Background
In general, a motor is a device for converting electrical energy into kinetic energy. Motors may be divided in direct current (DC) motors and alternating current (AC) motors according to a power source to be used. AC motors include induction motors, synchronous motors and commutator motors. The induction motors may be classified into a single-phase induction motor and a three-phase induction motor.
The single-phase induction motor has a relatively simple structure. Also, it is relatively easy to obtain a single-phase power source for such a motor. As a result, single phase induction motors are widely used in all sorts of electrical devices and appliances for domestic, office, industry and architecture. The single-phase induction motor cannot start rotating using just its main coil. For this reason, in addition to the main coil, these motors include a sub coil which receives current having a phase which is approximately 90 degrees out of phase with the current supplied to the main coil. The current applied to the sub-coil generates a starting torque. The main and sub coils are wound on a stator using a predetermined winding method.
In the related art single-phase induction motor, when an AC power source is supplied to the main coil and the sub coil during the initial starting procedure, a rotating magnetic field is generated. Once the rotor begins to rotate, the current supplied to the sub coil is stopped by a current cut-off device. Current is then only supplied to the main coil. Also, as the rotor rotates, an induction current is generated in conductive bars of the rotor.
The AC current applied to the main coil generates a rotating magnetic field which rotates at a predetermined speed which depends on the physical configuration of the motor. However, in related art motors, the rotor will rotate at less than the speed of the rotating magnetic field. The difference between the rotational speed of the rotating magnetic field and the rotating speed of the rotor is typically called "slip."

Self-magnetizing motor and compressor having the same


The present invention relates to methods and compositions for modulating mannosylation profile of recombinant proteins expressed by mammalian host cells during the cell culture process, using a polyether ionophore.

The glycosylation profile of a protein, such as a therapeutic protein or an antibody, is an important characteristic that influences biological activity of the protein through changes in half-life and affinity due to effects for instance on folding, stability and antibody-dependent cellular cytotoxicity (ADCC, one of the mechanism responsible for the therapeutic effect of antibodies)(Eon-Duval et al., 2012). Glycosylation is highly dependent on the cell line that is used for the production of the protein of interest, as well as on the cell culture processes (pH, temperature, cell culture media composition, raw material lot-to-lot variation, medium filtration material, air, etc.).
ADCC activity is influenced by the amount of fucose and/or mannose linked to the oligosaccharides of the Fc region, with enhanced activity seen with a reduction in fucose and/or an increase in mannose. Indeed, for instance, compared to fucosylated IgGs, non-fucosylated forms exhibit dramatically enhanced ADCC due to the enhancement of FcyRllla binding capacity without any detectable change in complement-dependent cytotoxicity (CDC) or antigen binding capability (Yamane-Ohnuki and Satoh, 2009). Similarly, antibodies exhibiting high level of mannose-5 glycans also presented higher ADCC (Yu et al., 2012). Thus, where the ADCC response is the principle therapeutic mechanism of antibody activity, the provision of methods for the preparation of recombinant therapeutic protein with a glycosylation profile characterized by decreased fucosylation and/or increased mannosylation, are beneficial. The advantages of highly mannosylated antibodies also include achieving therapeutic efficacy at low doses.
Modulation of protein glycosylation, such as mannosylation, is of particular relevance for marketed therapeutic proteins or antibodies as glycosylation (such as mannosylation) can impact therapeutic utility and safety. Further, in the frame of biosimilar compounds, control of the glycosylation profile of a recombinant protein is crucial, as the glycosylation profile of said recombinant protein has to be comparable to the glycosylation profile of the reference product. Some compounds have been reported as having an impact on mannosylation of proteins produced recombinantly: for instance, WO2014151878 and WO2014159259 disclose the use of oligosaccharides such as sucrose to increase mannosylation levels, WO2015105609 relates to the use of arginase inhibitor and WO2015066357 suggests the use of monensine.
However, there still remain a need for culture conditions and production methods that allow controlling the glycosylation profile, such as mannosylation profiles, of a recombinant protein, while not impacting the performance of the cells in culture or the recombinant protein yield. The present invention addresses this need by providing methods and compositions for modulating recombinant protein glycosylation, such as recombinant protein mannosylation, while keeping acceptable production yield/conditions.

Methods for modulating protein mannosylation profiles using maduramycin, narasin, or salinomycin


A diffracting x-ray optic for accepting and redirecting x-rays. The optic includes at least two layers, the layers having a similar or differing material composition and similar or differing crystalline orientation. Each of the layers exhibits a diffractive effect, and their collective effect provides a diffractive effect on the received x-rays. In one embodiment, the layers are silicon, and are bonded together using a silicon-on-insulator bonding technique. In another embodiment, an adhesive bonding technique may be used. The optic may be a curved, monochromating optic.

In x-ray analysis systems, high x-ray beam intensity and small beam spot sizes are important to reduce sample exposure times, increase spatial resolution, and consequently, improve the signal-to-background ratio and overall quality of x-ray analysis measurements. In the past, expensive and powerful x-ray sources, such as rotating anode x-ray tubes or synchrotrons, were the only options available to produce high-intensity x-ray beams. Recently, the development of x-ray optic devices has made it possible to collect the diverging radiation from an x-ray source by focusing the x-rays. A combination of x-ray focusing optics and small, low-power x-ray sources can produce x-ray beams with intensities comparable to those achieved with more expensive devices. As a result, systems based on a combination of small, inexpensive x-ray sources, excitation optics, and collection optics have greatly expanded the availability and capabilities of x-ray analysis equipment in, for example, small laboratories and in the field.
Monochromatization of x-ray beams in the excitation and/or detection paths is also useful, as discussed above. One existing x-ray monochromatization technology is based on diffraction of x-rays on optical crystals, for example, germanium (Ge) or silicon (Si) crystals. Curved crystals can provide deflection of diverging radiation from an x-ray source onto a target, as well as providing monochromatization of photons reaching the target. Two common types of curved crystals are known as singly-curved crystals and doubly-curved crystals (DCCs). Using what is known in the art as Rowland circle geometry, singly-curved crystals provide focusing in two dimensions, leaving x-ray radiation unfocused in the third or orthogonal plane. Doubly-curved crystals provide focusing of x-rays from the source to a point target in all three dimensions. This three-dimensional focusing is referred to in the art as "point-to-point" focusing.
Commonly-assigned U.S. Pat. Nos. 6,285,506 and 7,035,374 disclose various configurations of curved x-ray optics for x-ray focusing and monochromatization. In general, these patents disclose a flexible layer of material (e.g., Si) formed into curved optic elements. The monochromating function, and the transmission efficiency of the optic are determined by the crystal structure of the optic. The present invention provides certain improvements in the formation of curved crystal optics, offering important performance advantages.

X-ray focusing optic having multiple layers with respective crystal orientations


This invention discloses a DMOS planar power device having a plurality of transistor cells formed in a semiconductor substrate with a drain region of a first conductivity type disposed at a bottom surface of the substrate. Each of the DMOS transistor cells includes a polysilicon segment constituting a gate supported on a top surface of the substrate wherein the gate being disposed substantially in a center portion of the transistor cell. The DMOS transistor cell further includes a source region of the first conductivity type disposed in the substrate surrounding edges of the gate with a portion extends underneath the gate. The DMOS transistor cell further includes a body region doped with a body dopant of a second conductivity type disposed in the substrate encompassing the source region. The body region has a portion extending underneath the gate having a under-the-gate distance less than a lateral diffusion of the body dopant and the body region having outer edges extending outwardly to neighboring transistor cells. The DMOS transistor cell further includes a shallow low-concentration first-conductivity-type region under the gate wherein the shallow low-concentration first-conductivity-type region having a depth shallower than a depth of the source region.

1. Field of the Invention
This invention relates generally to the structure and fabrication process of planar DMOS power devices. More particularly, this invention relates to a novel and improved DMOS device structure and fabrication process. Specially configured body mask is employed to laterally shift the body regions such that the body regions are spaced farther away from each other. The size of the DMOS can be reduced by reducing the gate-width without unduly increasing the JFET resistance. This is achieved by maintaining substantially a constant distance between the body regions when the gate-width is reduced. Furthermore, specially configured gapped-gates are formed to reduce the gate capacitance such that the speed of the MOSFET device is increased. Simplified manufacture processes are applied to maintain a low production cost and to improve the device reliability.
2. Description of the Prior Art
Conventional structure and processing steps for fabricating a power metal oxide silicon field effect transistor (MOSFET) power device are limited by several technical difficulties. Specifically, conventional planar cellular structure of power MOSFETs, such as square, circular, and hexagonal topologies are limited by the difficulty that the on-resistance is decreased when the polysilicon space is reduced to achieve higher cell density by shrinking unit cell areas. However, the surface area occupied by the polysilicon gate electrode limits a further increase of cell density for the planar DMOS. Additional reduction in the size of the gate electrode exacerbates the parasitic JFET pinching effect, leading to higher device on-resistance at a small cell pitch. Conversely, if the polysilicon gate dimension is held constant to avoid the pinching effect, and the size of the source/body region, i.e., the opening in the polysilicon, is reduced instead, the specific on-resistance still increases at high cell densities. This is caused by the transistor gate width per unit area decreases. With such electrical and geometric restrictions, the cell density is limited to 6.5 million cells/inch.sup.2. For a person of ordinary skill in the art, further increases in planar DMOS cell density is unwarranted and likely to be detrimental to performance. The pinching effect caused by cell pitch reduction has to be eliminated to significantly benefit power MOSFET specific on-resistance. Additionally, the JFET resistance can be reduced with a shallower body junction. However, the breakdown voltage of the device is degraded with shallower body junctions. The tradeoffs of these performance characteristics become designer's dilemmas, which cannot be easily resolved with conventional planar structures and current state of the art manufacturing technology.
FIG. 1 shows a typical vertical double diffused MOS (VDMOS) device which uses a double diffusion technique to control the channel length L. Two successive diffusions are performed with first a p diffusion using boron, then a n diffusion using either arsenic or phosphorus, to produce two closely spaced pn junctions at different depths below the silicon surface. With this pn-junction, as shown in FIG. 1, the VDMOS supports the drain voltage vertically in the N-epitaxial layer. The current flows laterally from the source through the channel parallel to the surface of the silicon. The current flow then turns through a right angle to flow vertically down through the drain epitaxial layer to the substrate and to the drain contact. The p-type "body" region in which the channel is formed when a sufficient positive voltage is applied, and the n+ source contact regions are diffused successively through the same window etched in the oxide layer. The channel length can be controlled through the processing steps. Because of the relative doping concentrations in the diffused.
As discussed above, when the width of the gates is reduced to increase the cell density, the body regions are pulled together. The JFET regions between the body regions are pinched and resulting in a higher JFET resistance, i.e., a higher R-JFET. Typically, for a body dopant such as boron, there is a ratio of lateral diffusion to vertical of approximately 0.8. Therefore, if the depth of the body is b, generally the body regions extend lateral from the edges of the gate with a distance of about 0.8b into a region under the gate. Referring to FIG. 1B, where a conventional MOSFET device is shown with the body regions formed by implanting the body dopant ions, which are blocked by the polysilicon gates. The body regions are then formed by carrying out a body diffusion. The body regions as shown have a depth of b and a lateral diffusion length .lambda. of 0.8b measured from the edges of the gate. If the width of the gate is G, then the distance J between the body regions is approximately: EQU J=G-2.lambda.=G-2(0.8b)
As the width of the gate G is reduced, the distance J between the body regions is also reduced which causes the JFET resistance to increase. It appears, from Equation (1), that a longer distance of J may be maintained by keep a shallow P-body with reduced value of b. However, a shallow body would create several problems, e.g., device punch through, lower breakdown voltage and reduced device ruggedness. For these reasons, in a conventional MOSFET power device, it is difficult to maintain a same JFET resistance when the cell size is reduced.
In addition to above limitations, it is also difficult to improve the switching speed and meanwhile reducing the production cost of the DMOS power device. This is particularly true when the power DMOS devices become more complicate both in cell structure and in device topology. In the meantime, in order to achieve higher switching speed, it is desirable to reduce the gate-to-drain capacitance. However, a device structure capable of providing such performance improvement typically involves the application of more complex fabrication processes. As the fabrication processes become more complex and increased number of masks are required, longer manufacture time cycles become necessary, which leads to higher production costs. Complex fabrication processes with increased number of masks introduce further concerns. As more masks and processing steps are applied, more uncertainties of production yield and product reliability are introduced. The production costs are further impacted due to these undesirable factors. For these reasons, many technical improvements are attempted to improve the device performance to achieve higher switching speed while reducing the number of masks employed for MOSFET fabrication. Several MOSFET device structures and manufacture techniques are also disclosed in U.S. Patents.
In a U.S. Pat. No. 5,273,922, entitled "High Speed Low Gate/Drain Capacitance DMOS Device", (issued on Dec. 28, 1993), as that shown in FIG. 2, Tsoi discloses a DMOS device. Tsoi's device includes a field oxide in the channel between adjacent transistors and an impurity implanted through the same opening in which the field oxide is formed. The gate is deposited over the field oxide and spaced from the supporting epitaxial layer by the field oxide to reduce the gate-to-drain capacitance. The implant impurity blow the field oxide reduce the on-resistance of the device. With these advantages achievable by Tsoi's DMOS device, it is however limited by a difficulty that the size of the transistors can not be further reduced to increase the cell density. The lateral dimension of a transistor cell is limited by a misalignment tolerance between the polysilicon gate and the field oxide. In order to avoid an increase in the device threshold.

Cell density improvement in planar DMOS with farther-spaced body regions and novel gates


A socket (10) for a double-ended lamp has a housing (12); a compression spring (14) within the housing (12); a lamp connector (16) comprising a body (18) with a first portion (20) contained entirely within the housing (12) and a second portion (22) extending beyond the housing (12) and having a given length L, the lamp connector (16) being subjected to an axial movement when a lamp is operatively positioned with the socket (10), the axial movement having a maximum distance AL that is less than the given length L.

Lampholders for some double-ended lamps have comprised a metal housing containing a slidable ceramic body therein. A portion of the ceramic body extends from both ends of the housing and one end of the body is formed to receive, hold, and supply electrical power to an inserted lamp. It was often the case, when inserting a lamp, that the lamp-receiving portion of the body would penetrate the housing to too great an extent and become wedged in the housing. This problem created considerable downtime when changing lamps and resulted in extra costs associated with the lamp replacement.


Recombinant Factor IX characterized by a high percentage of active protein can be obtained in the milk of transgenic animals that incorporate chimeric DNA molecules according to the present invention. Transgenic animals of the present invention are produced by introducing into developing embryos DNA that encodes Factor IX, such that the foreign DNA is stably incorporated in the DNA of germ line cells of the mature animal. Particularly efficient expression was accomplished using a chimeric construct comprising a mammary gland specific promoter, Factor IX cDNA that lacked the complete or any portion of the 5′-untranslated and 3′-untranslated region, which is substituted with a 5-′ and 3′-end of the mouse whey acidic protein gene. In vitro cell cultures of cells explanted from the transgenic mammal of the invention and methods of producing Factor IX from such said culture and methods of treating hemophilia B are also described.

1. Field of the Invention
The present invention relates to the production of natural and modified forms of Factor IX. In particular, the invention relates to a transgenic animal containing, stably incorporated in its genomic DNA, an exogenous Factor IX gene that is expressed specifically in mammary tissue, such that Factor IX is secreted into milk produced by the animal. In particular, the invention relates to the production of human Factor IX in the milk of a transgenic non-human mammal using a DNA molecule that comprises a whey acidic protein promoter gene, 5′ regulatory sequences containing the promoter, human Factor IX cDNA that lacks at least a portion of the complete or any portion of or the complete the 3′-untranslated region of the native human Factor IX gene, but contains the 5′ and 3-untranslated region of the mouse whey acidic protein gene.
2. Background
Human Factor IX, or "Christmas factor," is encoded by a single-copy gene residing on the X-chromosome at q27.1. For a review of Factor IX gene structure and expression, see High et al., "Factor IX," in MOLECULAR BASIS OF THROMBOSIS AND HEMOSTASIS, High (ed.), pages 215-237 (Dekker 1995); Kurachi et al., Thromb. Haemost. 73:333 (1995). The Factor IX gene is at least 34 kilobase (kb) pairs in size, and it is composed of eight exons. The major transcription start site of the Factor IX gene in human liver is located at about nucleotide −176. The human Factor IX mRNA is composed of 205 bases for the 5′ untranslated region, 1383 bases for the prepro Factor IX, a stop codon and 1392 bases for the 3′ untranslated region.
Factor IX is synthesized as a prepropolypetide chain composed of three domains: a signal peptide of 29 amino acids, a propeptide of 17 amino acids, which is required for γ-carboxylation of glutamic acid residues, and a mature Factor IX protein of 415 amino acid residues. The Factor IX zymogen undergoes three types of post-translational modifications before it is secreted into the blood: a vitamin K-dependent conversion of glutamic acid residues to carboxyglutamic acids, addition of hydrocarbon chains, and β-hydroxylation of an aspartic acid. Mature Factor IX protein contains 12 γ-carboxylated glutamic acid (Gla) residues. Due to the requirement of vitamin K by γ-carboxylase, Factor IX is one of several vitamin K-dependent blood coagulation factors.
The activation of Factor IX is achieved by a two-step removal of the activation peptide (Ala146-Arg180) from the molecule. Bajaj et al., "Human factor IX and factor IXa," in METHODS IN ENZYMOLOGY (1993). The first cleavage is made at the Arg145-Ala146site by either Factor XIa or Factor VIIa/tissue factor. The second, and rate limiting cleavage is made at Arg180-Val181. The activation pathways involving Factor XIa and Factor VIIa/tissue factor are both calcium-dependent. However, the Factor VIIa/tissue factor pathway requires tissue factor that is released from damaged endothelial cells. Activated human Factor IX thus exists as a disulfide linked heterodimer of the heavy chain and light chain. For full biological activity, human Factor IX must also have the propeptide removed and must be fully γ-carboxylated. Kurachi et al., Blood Coagulation and Fibrinolysis 4:953 (1993).
Factor IX is the precursor of a serine protease required for blood clotting by the intrinsic clotting pathway. Defects in Factor IX synthesis result in hemophilia B (or Christmas disease), an X-linked disorder that occurs in about one in 30,000 males. Patients with hemophilia B are treated with Factor IX obtained from pooled plasma from normal individuals. Martinowitz et al., Acta Haematol 94(Suppl. 1):35 (1995). Such Factor IX preparations, however, may be pyrogenic and may be contaminated with pathogenic agents or viruses. Accordingly, it would be advantageous to develop a means to prepare purified Factor IX that did not require extraction from human plasma.
In the past, therapeutic proteins have been produced in E. coli. However, limitations in secretion and post-translational modification which occur in all living cells has rendered recombinant protein production a highly species, tissue and cell specific phenomena. In an example of recombinant FIX expression in mammalian cells, the populations of recombinant FIX produced in baby hamster kidney cells are not the same protein products as FIX produced in Chinese hamster ovary cells (Busby et al., Nature 316:684-686 (1985); Kaufman et al., J. Biol. Chem. 261: 9622-9628 (1986)). These proteins have profound differences in γ-carboxylation and propeptide removal and these differences have been established as being very important in determining biological activity. Most importantly, only less than about 40 milliunits/hr/ml of active rFIX were detected in CHO cells even after coexpression of the propeptide cleaving enzyme PACE, coexpression of the carboxylase enzyme, and extensive gene amplification with methotrexate in an attempt to increase expression level and activity (Wasley et al. J. Biol. Chem. 268: 8458-8465 (1993); Rehemtulla et al., Proc. Natl. Acad. Sci. (USA), 90: 4611-4615 (1993)). Researchers concluded that multiple limitations in the secretion of active rFIX exist in mammalian cells (Rehemtulla et al., 1993) and that the problem of gene transcription was secondary and indeed trivial with respect to post-translational processing of biologically active rFIX in mammalian cells. Thus, FIX mRNA splicing is a species specific effect occurring in mice and perhaps sheep, but not pigs. Although one might hypothesize that a FIX could be expressed, one could not predict with any certainty whether such product would be a clinically acceptable, practical, recombinant therapeutic FIX product for a given hemophiliac indication.
Production of recombinant Factor IX in mammalian cell culture (HepG2, mouse fibroblast, mouse hepatoma, rat hepatoma, BHK, CHO cells) repeatedly has been shown to be recalcitrant and cell-system specific with respect to intracellular restrictions on secretion and proteolytic processing, post-translational modification, expression levels, biological activity, downstream recovery from production media, and substantiation of circulation half-life (Busby et al., (1985); de la Salle et al. Nature 316: 268-270 (1985); Anson et al., Nature 315: 684-686 (1985); Rehemtulla et al., 1993; Wasley, et al., (1993); Kaufman et al., (1986); Jallat et al., EMBO J. 9: 3295-3301 (1990)). Importantly, the aforementioned works concluded that nontrivial improvements in these combined criteria are needed if a practical prophylactic FIX therapeutic product is to be made available from any recombinant mammalian cell production source. For example, attempts to increase the specific activity of rFIX produced by CHO cells by rectifying problems with under-carboxylation by co-expression of the vitamin K-dependent carboxylase enzyme resulted in no improvement in γ-carboxylation or biological activity (Rehemtulla et al., (1993), implying that multiple rate limitations in this post-translational modification exist.
Similar difficulties in the production of significant amounts of biologicaly active rFIX in the mammary epithelial cells of transgenic animals also has been documented in the literature. Although WO-A-90/05188 and WO-A-91-08216 predict that production of rFIX should be possible in their production systems, no data are presented in WO-A-91-08216, and only very low levels of secreted rFIX (25 ng/ml) with no biological activity were reported in transgenic sheep in WO-A 90/05188 and in related publications, (Clark et al., Bio/Technology 7: 487-4992 (1989)). Higher expression levels have recently been reported in the milk of sheep (5 μg/ml), but again, the product had no biological activity (Colman, IBC Third International Symposium on Exploiting Transgenic Technology for Commercial Development, San Diego, Calif. (1995)). This demonstrates that the polypeptides produced in WO-A-90/05188, Clark et al. (1989), and Colman (1995) were a different species than native human FIX with dissimilar biological activity to human FIX, and could never be used for therapeutic purposes. Work by Clark et al. (1992) stated that problems in synthesis of rFIX in the mammary gland of transgenic mice was the result of aberrant splicing of the rFIX mRNA in the 3′ untranslated region. Correction of the aberrant splicing in transgenic mice has been demonstrated (Yull et al. Proc. Natl. Acad. Sci. USA 92: 10899-10903 (1995); Clark, et al. (1989), WO 95/30000)), resulting in higher expression levels (up to 61 μg/ml) with about 40% biological active material. However, this aberrant splicing phenomenon appears to be species- and tissue-specific in the mouse mammary gland; other reports with the 3′ UTR sequences in CHO cell lines and in the liver of transgenic mice specifically show no evidence of aberrant splicing (Kaufman et al., (1986); Jallat et al., (1990)). In addition, no evidence was reported for aberrant mRNA splicing of FIX transcripts with 3′ UTR sequences in a human hepatoma cell line (de la Salle et al., (1985)), a mouse fibroblast cell line (de la Salle et al., (1985)), a rat hepatoma cell line (Anson et al., 1985)), or a BHK cell line (Busby et al., (1985)). No data are presented to justify the prediction that the altered transgene of WO95/30000 will necessarily improve the secretion and biological activity of rFIX in the milk of transgenic livestock or any other cell line. Therefore the claims presented in WO 95/30000 are purely speculative and are limited to the mammary gland of transgenic mice.
The stability of the rFIX product in the milk of transgenic livestock during upstream and downstream processing is a critical issue for the production of a practical therapeutic. Data presented in Clark et al. (1989) showed that Clark's method of downstream recovery of what little rFIX was in the milk of their transgenic sheep was not reproducible: in one of the preparations, a significant amount of rFIX was proteolytically activated. The infusion of activated FIX (FIXa) into a patient is fatal (Kingdon et al., Thrombosis, Diathes. Haemorrh. (Stuttg.) 33: 617 (1975)). FIX can be activated by FXI and/or FVIIa/Tissue factor complex in the presence of calcium and phospholipids (Kurachi et al., Blood Coagulation and Fibrinolysis 4: 953-974 (1993)). Milk is a medium containing calcium and phospholipid surfaces. In addition, there is extensively conserved homology between mammalian blood coagulation factors, especially between porcine FXI and human FXI (Mashiko and Takahashi, Biol. Chem. Hoppe-Seyler 375: 481-484 (1994)). Detectable levels of porcine FVII(a) and FXI(a) in the milk of nontransgenic pigs, and elevated levels of FVII(a) and FXI(a) in the milk of a pig with mastitic milk have been measured. Thus, one could predict that the recovery of a useful unactivated rFIX produced in the milk of transgenic livestock will be very sensitive to the health of the mammary gland (i.e., no subclinical or clinical mastitis), to the milking procedure (i.e., no tissue damage), to pretreatment of the milk immediately after collection, to storage of the milk before processing, and to the purification and formulation process itself. One would also predict that the undesirable in vivo activation of rFIX also can be minimized by the coexpression of inhibitors to FVIIa/TF such as the Tissue Factor Pathway Inhibitor (TFPI) protein, also called LACI, or the hybrid protein FX-LACI which is also a known inhibitor to FVIIa/TF. Although specific inhibitors of FXIa have not been identified, a similar approach can be made for neutralizing FXIa activation by coexpression of analogues of polypeptide substrates of FXIa similar to those that are commercially available for amidolytic assays. Yet another strategy may be to overexpress rFIX at very high levels (>1 g/l milk) such that the FIX activating enzyme is extremely limiting. Otherwise, steps must be taken immediately after milk collection to minimize activation. These include, but are not limited to, chelation of calcium (e.g., addition of EDTA), phospholipid removal, adjustment of pH, storage in ultra-low freezers, controlled thawing procedures, addition of protease inhibitors, and purification procedures that maintain minimal activation conduciveness. If activated rFIX still persists in the purified product, removal can be facilitated by lectin chromatography(N-linked carbohydrate moieties exist only in the activation peptide), immunoaffinity chromatography using a Mab directed to the activation peptide, or by metal ion induced precipitation techniques that can select for the differences in molecular stability of unactivated vs. activated FIX. Because of these inherent difficulties in production of active FIX at sufficiently high levels in mammalian cells and transgenic livestock, gene therapy has been cited as perhaps a more practical way of achieving a prophylactic therapeutic rather than recombinant technology (Kurachi et al., (1993); Kay et al., Proc. Natl. Acad. Sci. USA 91: 2353-2357 (1994)); Fallaux et al., Thromb-Haemost. 74: 266-73 (1995)). This is certainly a profound reality because it specifically teaches a product suitable for FIX prophylaxis has not yet been found using recombinant production in mammalian cells, even those that have been shown to express active FIX, albeit at low levels. The best recombinant FIX cell production system made from CHO cells is produced at low secretion levels (Rehemtulla et al., (1993)) and is in fact not suitable for prophylaxis. Furthermore, the data have shown that the homologous plasma proteins. FIX and protein C all have very different, cell-specific restrictions on post-translational processing, proteolytic processing, and secretion which preclude on a protein-specific basis the predictability of high expression levels, biological activity, downstream recovery from production media, and predictable circulation half-life (Grinnell et al., "Native and Modified recombinant human protein C: function, secretion, and postranslational modifications," In Protein C and Related Anticoagulants, eds. D. F. Bruley and Drohan 29-63, Gulf Publishing Co., Houston, Tex. (1990); Yan et al., Trends in Biochem. Sci. (1989); Busby et al., (1985)).
Therefore, a need still exists for a means to obtain significant amounts of purified Factor IX from a source other than human plasma. A need also exists for a practical means for producing in mammalian cells rFIX, which is suitable as a treatment for hemophilia B.

Treatment of hemophilia with human Factor IX produced in mammary tissue of transgenic mammals

Virginia Tech Intellectual Properties, Inc.


A throttle control apparatus which is adapted to be disposed near the accelerator pedal of a vehicle includes an electric motor, and an operational member which is operatively connected to the output shaft of the electric motor for abutting against the accelerator pedal in order to swing the accelerator pedal during operation of the motor. The motor is positioned within a housing and is operatively connected to the operational member by way of interengaging gears located in the housing and a rotation shaft extending through the housing. To facilitate the mounting of the housing on the vehicle dashboard, a two-piece bracket can be employed.

A conventional throttle control apparatus is disclosed in "Leone New Car Features July, 1984" issued by Fuji Heavy Industries Ltd. The throttle control apparatus disclosed in this publication includes a vacuum pump installed in the engine compartment and a vacuum actuator disposed in the passenger compartment of the vehicle.
The vacuum actuator of the throttle control apparatus is driven by negative air pressure supplied from the vacuum pump in order to move the accelerator pedal connected to the vacuum actuator. The accelerator pedal controls the throttle opening of the engine.
In accordance with this known throttle control apparatus, the vacuum actuator does not have to be connected to the accelerator pedal with a cable because the vacuum actuator is not disposed in the engine compartment. Therefore, undesirable sliding resistance is not generated when the vacuum actuator is operated. Further, the throttle control apparatus can be manufactured at a relatively low cost because the throttle control apparatus does not require a complex link mechanism.
However, the throttle control apparatus does require a vacuum tube that connects the vacuum pump and the vacuum actuator. This vacuum tube must pass or extend through the dashboard that separates the engine compartment from the passenger compartment. For this reason, an opening is provided in the dashboard through which the vacuum tube extends. Thus, a seal member must be fitted in the opening in the dashboard to prevent rain water from entering the passenger compartment. Further, the vacuum tube must be located in the engine compartment. This construction increases the cost associated with outfitting the vehicle with such a throttle control apparatus.
In light of the foregoing, a need exists for a throttle control apparatus which is relatively less expensive to implement in a vehicle.


A cigarette pack holder with an adjacent built-in ashtray section. The ashtray chamber is latterly adjacent the compartment for the cigarettes and extends downwardly and under the cigarette compartment. The ashtray section has a hinged cap that when in the closed position acts as a boss to engage a notch on the cover to secure the cover in place. The bottom of the device has a slider opening for removal of ashes. Spaced up from the bottom is a shelf to retain the cigarette or cigar pack. The ashtray is separated from the cigarette pack storage compartment by a heat resistant vertical wall. Other walls of the device should also be made of heat resistant material.

In today's society less and less people smoke, due to the recognition of the health hazard. Today's society is also requiring that cigarette smokers look after their cigarette ashes and butts, just as society is requiring dog lovers to clean up their dog's messes. In this new age of "take responsibility for yourself" there is indeed a market for a combination cigarette pack holder and ashtray. The invention of this application fills that need safely and easily and at a low price.
The invention accordingly comprises the device possessing the features, properties, and the selection of components which are exemplified in the following detailed disclosure, and the scope of the application of which will be indicated in the appended claims.
For a fuller understanding of the nature and objects of the invention, reference should be made to the following detailed description, taken in conjunction with the accompanying drawings.

Combined cigarette pack holder and ashtray


A system for the automatic adjustment of resources devoted to query optimization according to estimated query execution time. The disclosed system permits the query optimizer to automatically trade off the time spent estimating the execution cost of alternate query execution plans against the potential savings in execution time that one of those alternate plans may yield. The number of alternate plans considered is adjusted by selecting compile-time parameters and heuristic criteria for limiting the primitive database operators used in the alternate plans, thereby establishing a new search space. The parameters and criteria are adjusted according to the estimate of execution cost for the optimal plan from a first search space. The first search space may be relatively small and quickly evaluated. Evaluation of larger subsequent search spaces is optional according to an automatic thresholding process of the disclosed system.

1. Field of the Invention
This invention relates to automatic query optimization methods in database systems and, more specifically, to a system for adjusting the resources devoted to query optimization responsive to estimated query execution time.
2. Description of the Related Art
Query optimizers operate in relational database management systems to translate queries posed in a non-procedural language such as SQL into an efficiently executable plan. Reference is made to C. J. Date, An Introduction to Database Systems, Vol. 1, Fourth Edition, "Chapter 16: Query Optimization", p. 335, Addison-Wesley Publishing Co., Reading, Mass. (1986), for an overview of the optimization process. According to Date, the overall optimization process can be viewed as four broad stages. These are (1) casting the user query into some internal representation, (2) converting to canonical form, (3) choosing prospective implementation procedures, and (4) generating executable plans and choosing the cheapest of such plans.
The desired query execution plan consists of an ordered series of primitive database operators and is typically developed by choosing the plan having the least estimated execution cost from among several alternative plans making up a "search space". A search space embraces a number of query execution plans that are limited according to the type and sequence of the primitive database operators allowed in the plans. Since only two-way join operators are usually provided as primitives, an optimizer is normally obliged to select the "best" sequence of two-way joins to achieve the N-way join of data tables requested by a non-procedural user query.
Thus, the computational complexity of the optimization process and the execution efficiency of the plan chosen by that process are dominated by the number of such possible primitive operator sequences that must be evaluated by the optimizer. That is, they are dominated by the size of the "search space" spanned by the query optimizer. An exhaustive enumeration is clearly exponential in the number of tables and hence is impractical for all but trivial queries. Thus, some scheme for limiting the search space must be provided to any query optimizer.
The typical query optimizer, for efficiency during optimization, limits the query space of join sequences to be evaluated by (1) using a form of dynamic programming to eliminate sub-plans whose estimated cost is greater than other sub-plans producing equivalent results, (2) restricting the "inner" operand of each join to be a single table, and (3) requiring each join to have at least one equi-join predicate of the form (column1=column2), where (column1) must be in one operand of the join and (column2) is in the other join operand. The restrictive form of this third limitation implies that predicates involving inequality, arithmetic or type conversion or more than two tables do not satisfy the criteria for a "feasible" join sequence and are excluded from the limited search space.
It is easily proven that dynamic programming never eliminates a potentially better plan but the second and third limitations mentioned above are heuristics that may exclude a superior plan without notice under some circumstances. Each query plan is built by combining a set of candidate implementation procedures, one such procedure for each of the primitive database operations in the query. There are normally many feasible plans for any given query and it is often not reasonable to generate all possible plans because of the expense of doing so. The process of establishing primitive database operator selection criteria to reduce the number of query execution plans to be evaluated can viewed as "reducing the search space". Accordingly, a "search space" herein denotes a set of executable query plans that are selected on the basis of some formal or heuristic criteria related to primitive database operators.
When a given query is to be executed repeatedly, additional optimization efforts such as considering more join sequences over a larger search space can be justified by the resulting improvement in execution costs leveraged over multiple query executions. On the other hand, response time for interactive ad hoc queries includes both optimization and execution costs. Thus, heuristics that severely limit the optimizer's search space are usually beneficial for interactive systems. Also, certain knowledge peculiar to an application may generate special heuristics for excluding plans that are dominated in that application but not in others. Thus, there is a clearly felt need for greater flexibility in selecting feasible join sequences over the fixed join selection criteria in query optimizers known in the art.
Practitioners in the art have responded to this need by proposing new methods for improving query optimizer efficiency. Reference is made to K. Ono et al, "Extensible Enumeration of Feasible Joins for Relational Query Optimization", IBM Research Report, RJ 6625 (63936) Dec. 28, 1988, IBM Almaden Research Center, San Jose, Calif., for disclosure of a query optimizer that allows simple adjustment of the number of alternative join sequences that are automatically generated, including a new criterion that requires an explicit or implied join predicate for any join, where such join predicate can be any predicate relating more than one table.
Essentially, Ono et al teach a method for quickly and effectively adjusting the size of the search space by changing the primitive database operator selection criteria. Their extensible join enumeration algorithm enumerates a wider variety of feasible two-way joins than other methods previously known in the art because it exploits predicates that (a) reference more than two tables, (b) involve arithmetic or conversion operators, or (c) are implied by other predicates. Also, the Ono et al method can parametrically adjust the space of join sequences evaluated by the optimizer to allow or disallow (1) composite tables as the inner operand of a join or (2) joins between two tables having no join predicate linking them, such as Cartesian products. Both Cartesian products and composite tables that are themselves a result of a join are usually excluded by query optimizer systems to limit the search space size. The blanket exclusion of these two database operations functions as an inflexible limit on query optimizer flexibility and efficiency.
Reference is also made to Ono et al, "Measuring the Complexity of Join Enumeration in Query Optimization", Proceedings of the 16th VLDB Conference, Brusbane, Australia (1990), pp. 314-325. Ono et al conclude that enumeration of the join sequences for a query is the dominant factor in both the query optimization costs and the quality of the resulting execution plans. Their join enumeration procedure generates better execution plans by enlarging the set of feasible plans to include composite inners and Cartesian products at any place in the join sequences. This allows the search space to be adjusted by making incremental changes to the join sequence selection criteria. However, Ono et al do not consider the problem of automatically varying the search space and do not teach how to ensure global query optimization.
Other practitioners have applied global optimization strategies to the problem of optimization of large join queries. The global optimization problem can generally be considered to be a problem of locating the global optimum in a large space having many local optima. The usual solution is to search through the space while indexing across several of the local optima until such time as the search "should" be terminated according to some criteria. Reference is made to, for instance, Boender, et al, "Bayesien Stopping Rules for Multi-Start Global Optimization Methods", Mathematical Programming, Vol. 37, pp. 59-80, (1987), for a discussion of the art of solving the unconstrained global optimization problem. Reference is also made to A. Swami, et al, "Optimization of Large Join Queries", Proceedings of ACM-SIGMOD International Conference on Management of Data, pp 8-17, June 1988, for a discussion of their application of global optimization techniques to the query optimizer problem Swami et al express the query optimizer problem as an optimal join order problem by using several commonly known heuristics for limiting search space size. They first severely limit the size of their search space and then perform global optimization according to simple iterative improvement and simulated annealing methods. They neither teach nor suggest means for dynamically varying the search space in response to estimated query cost and their method does not guarantee that the universally optimum query plan even exists in their limited search space.
A similar approach is suggested by Xerox Advanced Information Technology researchers in an unpublished memorandum. This Pilot Pass approach uses an initial "pilot" phase of optimization over a limited search space to determine an estimated execution time. The set of alternatives is limited in this first pass by setting an upper bound on the longest constituent operation time in any evaluated plan rather than excluding entire classes of plans to limit the search space. If this longest constituent operation time exceeds the estimated execution time for the optimum plan, then no plan that is excluded by the pilot phase can possibly run in less that the estimated execution time so the plan found in the pilot phase is clearly optimal. Otherwise, a second phase of optimization then considers the entire set of alternative plans by setting the longest constituent operation time threshold to infinity and then pruning any plan whose execution time estimate exceeds the initial pilot pass estimate of query execution time. This Pilot Pass approach does not consider adjusting the size of the search space but rather defines a filter that summarily eliminates a plan from consideration as soon as one of its constituent operations is found to exceed an arbitrary execution time threshold. This approach neither considers nor suggests a method for trading off optimization time automatically in response to prospects for improved execution time because the second "unlimited" search space evaluation is always executed if the longest constituent plan operation time is less than the pilot pass estimate of execution time, even if the estimate for execution time is smaller than the time required to evaluate the "unlimited" search space.
In U.S. Pat. No. 4,769,772, P. A. Dwyer discloses an automated query optimization method using both global and local optimization for distributed databases. Dwyer chooses to optimize locally if such is more efficient than optimizing over the distributed system. She neither suggests nor considers adjusting the size of the search space and uses a fixed set of criteria to establish the local and distributed search spaces without providing any estimation of optimization costs.
In U.S. Pat. No. 4,531,186, J. M. Knapman discloses a user-friendly database access method for writing user queries for a special type of database system. Knapman does not consider the problem of query optimization for large databases, generally limiting his teachings to evaluation and selection of database access paths by constructing a data directory and accordingly choosing application programs and program communication blocks.
In U.S. Pat. No. 4,829,427, N. L. Green discloses a database query code generation and optimization technique responsive to the cost of alternative access methods. Green also does not consider the problem of optimizing query execution plans but limits her teachings to methods for choosing data access paths after a query execution plan is already established. Green neither considers nor suggests methods for adjusting query execution plan efficiency according to the interaction between query plan and data access path.
Reference is made M. S. Lakshmi, et al, "Access Path Selection in Relational Database Systems", IBM Technical Disclosure Bulletin, Vol. 30, No. 9, February 1988, pp. 420-421, for another discussion of data access path optimization limited in application to single variable relational queries in database management systems. Again, Lakshmi et al do not consider the problem of query execution plan optimization but teach instead one of many useful methods for quickly defining an elementary search space.
Reference is made to D. Cornell, et al, "Relational Assignments for Distributed Database Systems", IBM Technical Disclosure Bulletin, Vol. 31, No. 1, June 1988, pp. 219-225, for discussion of a technique for parsing distributed database queries into communication and relational steps for optimization with respect to inter-node communication requirements. Cornell et al propose procedures for decomposing queries into simple relational steps expanded with potential message steps to equalize the work load across multiple systems and are primarily concerned with load sharing rather than query optimization.
Reference is made to S. Brady, et al, "Extended Disjunctive Normal Form for Efficient Processing of Recursive Logic Queries", IBM Technical Disclosure Bulletin, Vol. 30, No. 1, June 1987, pp. 360-366, for a discussion of a procedure that eliminates unnecessary temporary tables during optimization of the type of formal query procedure used in expert system. The Brady et al technique is useful for optimizing queries within a single search space but nether suggests nor considers methods for adjusting the search space responsive to query execution time.
Increasing the set of feasible plans to form a larger search space may improve the chance of locating the universal optimum but does not guarantee it. Unfortunately, increasing a search space size does guarantee an increase in the query evaluation and optimization costs. A major challenge in the design of query optimizer to ensure that the space of feasible plans contains efficient plans without making it too big to be generated practically. The techniques in the art for query optimization do not provide means for automatically adjusting the search space in response to query execution time and do not suggest practical means for guaranteeing inclusion of the universal optimum.
These unresolved problems and deficiencies are clearly felt in the art and are solved by this invention in the manner described below.

System for adapting query optimization effort to expected execution time

International Business Machines Corporation


A vehicle occupant restraint system comprises an airbag module (12) which includes an airbag (16) as well as an inflator (18) which upon activation supplies filling gas for the airbag (16). The airbag (16) is folded prior to activation into an airbag package (14) so that a main package (48) which contains a restraint part (52) of the airbag (16) constituting a major part of the airbag volume as well as a connecting portion (50) is formed which comprises a neck (54) of the airbag (16) connecting the restraint part (52) to the inflator (18), wherein the restraint part (52) is folded differently from the neck (54).

The invention relates to a vehicle occupant restraint system comprising an airbag module.
For protecting the vehicle occupants, very successfully airbags have been employed. They develop the best protective effect when the vehicle occupant to be absorbed is located in a defined position relative to the inflated airbag. With large-volume airbags of complex shape care has to be taken that they deploy in the vehicle interior in a precise and reproducible manner.

Vehicle passenger restraint system comprising an airbag module


An integrated circuit includes a clock source tier and at least two clock distribution tiers disposed in a vertical stack with the clock source tier. The clock source tier includes a clock circuit. Each of the at least two clock distribution tiers includes a clock distribution circuit. Each clock distribution circuit includes at least one pair of cross-coupled inverters.

The disclosed circuits and methods relate to integrated circuits. More particularly, the disclosed circuits and methods relate to clock distribution networks in three-dimensional integrated circuits.
Microprocessors and other integrated circuits include clock distribution networks for routing a clock signal to the circuitry of the microprocessor or other integrated circuits. These clock network are typically formed in a two-dimensional layout and have stringent timing and power requirements. Skew and jitter of the clock network cause clock uncertainty and decrease the timing margins.

3D clock distribution circuits and methods

Taiwan Semiconductor Manufacturing Co., Ltd.


A stay-in-place concrete formwork system allows stucco to be applied directly to the formwork, avoiding the need to provide a further surface treatment of the wall prior to applying stucco. Apertures are provided on an exterior facing wall of the formwork panel to receive and embed stucco therein. The panel may also be formed with outward stucco-engaging projections. Other features include using rigid insulation to brace the stucco and keep concrete from the apertures, a sealing joint element, extendible panels for use in curved formwork, rainscreen features and an alligator connector panel for adjustable lengths of formwork faces.

It is known to provide concrete formwork comprising modular inter-connectable panels that stay in place after the concrete has set. Canadian Patent No. 2,226,497 exemplifies such a modular inter-connectable formwork system.
Stucco can be applied to such structures by then securing a mesh to the outside of the wall, with the stucco being applied to the mesh in the conventional manner. Any insulation is typically placed on the inside surface of the concrete wall after the concrete has set.

Stay-in-place ready-to-stucco formwork system