A split-gate flash memory cell having a three-dimensional source capable of three-dimensional coupling with the floating gate of the cell, as well as a method of forming the same are provided. This is accomplished by first forming an isolation trench, lining it with a conformal oxide, then filling with an isolation oxide and then etching the latter to form a three-dimensional coupling region in the upper portion of the trench. A floating gate is next formed by first filling the three-dimensional region of the trench with polysilicon and etching it. The control gate is formed over the floating gate with an intervening inter-poly oxide. The floating gate forms legs extending into the three-dimensional coupling region of the trench thereby providing a three-dimensional coupling with the source which also assumes a three-dimensional region. The leg or the side-wall of the floating gate forming the third dimension provides the extra area through which coupling between the source and the floating gate is increased. In this manner, a higher coupling ratio is achieved without an increase in the cell size while at the same time alleviating the punchthrough and junction break-down of source region by sharing gate voltage along the side-wall.

(1) Field of the Invention
The present invention relates to the manufacturing of semiconductor memories, and in particular, directed to a split-gate flash memory having an increased coupling ratio of source to floating gate and to a method of forming of the same.
(2) Description of the Related Art
The degree of coupling between a source and floating gate in a split-gate flash memory is determined by the capacity of source implant lateral diffusion under the floating gate. It is desirable to increase the coupling ratio because that results in improved programming speed. However, trying to increase coupling ratio by increasing the source implant lateral diffusion causes the well-known problems of punch-through and junction breakdown. It is disclosed later in the embodiments of this invention a method of increasing the coupling ratio of a split-gate memory cell by extending into the trench isolation region of the cell a three-dimensional source. Because of the additional vertical wall area in the third dimension, the coupling is increased, and the performance of the cell improved.
A conventional split-gate flash memory device is characterized by its split-gate side (between the control gate and the drain) and the stacked-side (between the floating gate and the source) and by a coupling ratio between the floating gate and the source. As is known, the coupling ratio affects the program speed, that is, the larger the coupling ratio, the faster is the programming speed, and is not a fixed value by virtue of the variability of the channel length and hence that of the overlap between the floating gate and the source. Usually, if channel length is increased through greater lateral diffusion in the source region, punchthrough occurs due to excessive current well below the threshold voltage. It is shown in the present invention that the coupling ratio can be increased without increasing the channel length, but by incorporating side-wall coupling of the vertical wall in a three-dimensional source, thus alleviating the punchthrough and junction break-down of source region by sharing gate voltage along the side-wall.
Over the years, numerous improvements in the performance as well as in the size of memory devices have been made by varying the simple, basic one-transistor memory cell, which contains one transistor and one capacitor. The variations consist of different methods of forming capacitors, with single, double or triple layers of polysilicon, and different materials for the word and bit lines. In general, memory devices include electrically erasable and electrically programmable read-only memories (EEPROMs) of flash electrically erasable and electrically programmable read-only memories (flash EEPROMs). Many types of memory cells for EEPROMs or flash EEPROMs may have source and drains regions that are aligned to a floating gate or aligned to spacers. When the source and drain regions are aligned to the floating gate, a gate electrode for a select transistor is separate from the control gate electrode of the floating gate transistor. Separate select and control gates increase the size of the memory cell. If the source and drain regions are aligned to a spacer formed after the floating gate is formed, the floating gate typically does not overlie portions of the source and drain regions. Programming and erasing performance is degraded by the offset between the floating gate and source and drain regions.
Most conventional flash-EEPROM cells use a double-polysilicon (poly) structure of which the well known split-gate cell is shown in FIG. 1. Here, two MOS transistors share a source (25). Each transistor is formed on a semiconductor substrate (10) having a first doped region (20), a second doped region (25), a channel region (23), a gate oxide (30), a floating gate (40), intergate dielectric layer (50) and control gate (60). Substrate (10) and channel region (23) have a first conductivity type, and the first (20) and second (25) doped regions have a second conductivity type that is opposite the first conductivity type.
As seen in FIG. 1, the first doped region, (20), lies within the substrate. The second doped region, (25), also lies within substrate (10) and is spaced apart form the first doped region (20). Channel region (23) lies within substrate (10) and between first (20) and second (25) doped regions. Gate oxide layer (30) overlies substrate (10). Floating gate (40), to which there is no direct electrical connection, and which overlies substrate (10), is separated from substrate (10) by a thin layer of gate oxide (30) while control gate (60), to which there is direct electrical connection, is generally positioned over the floating gate with intergate oxide (50) therebetween.
In the structure shown in FIG. 1, control gate (60) overlaps the channel region, (23 under the floating gate, (40). This structure is needed because when the cell is erased, it leaves a positive charge on the floating gate. As a result, the channel under the floating gate becomes inverted. The series MOS transistor (formed by the control gate over the channel region) is needed in order to prevent current flow from control gate to floating gate. The length of the transistor, that is the overlap of the control gate over the channel region (23) determines the cell performance. Furthermore, edges (41), (43) can affect the programming of the cell by the source size and hot electron injection through the intergate dielectric layer (50) at such edges. Hot electron injection is further affected by, what is called, gate bird's beak (43) that is formed in conventional cells. On the other hand, it will be known to those skilled in the art that corners such as (41) can affect the source coupling ratio also. Any such adverse effects attributable source size can be alleviated as disclosed later in the embodiments of this invention.
To program the transistor shown in FIG. 1, charge is transferred from substrate (10) through gate oxide (30) and is stored on floating gate (40) of the transistor. The amount of charge is set to one of two levels to indicate whether the cell has been programmed "on" of " off." "Reading" of the cell's state is accomplished by applying appropriate voltages to the cell source (25) and drain (20), and to control gate (60), and then sensing the amount of charge on floating gate (40). To erase the contents of the cell, the programming process is reversed, namely, charges are removed from the floating gate by transferring them back to the substrate through the gate oxide.
This programming and erasing of an EEPROM is accomplished electrically and in-circuit by using Fowler-Nordheim tunneling as is well known in prior art. Basically, a sufficiently high voltage is applied to the control gate and drain while the source is grounded to create a flow of electrons in the channel region in the substrate. Some of these electrons gain enough energy to transfer from the substrate to the floating gate through the thin gate oxide layer by means of Fowler-Nordheim tunneling. The tunneling is achieved by raising the voltage level on the control gate to a sufficiently high value of about 12 volts. As the electronic charge builds up on the floating gate, the electric field is reduced, which reduces the electron flow. When, finally, the high voltage is removed, the floating gate remains charged to a value larger than the threshold voltage of a logic high that would turn it on. Thus, even when a logic high is applied to the control gate, the EEPROM remains off. Since tunneling process is reversible, the floating gate can be erased by grounding the control gate and raising the drain voltage, thereby causing the stored charge on the floating gate to flow back to the substrate.
In the conventional memory cell shown in FIG. 1, word lines (not shown) are connected to control gate (60) of the MOS transistor, while the length of the MOS transistor itself is defined by the source (25) drain (20) n+ regions shown in the same Figure. As is well known by those skilled in the art, the transistor channel is defined by masking the n+ regions. However, the channel length of the transistor varies depending upon the alignment of the floating gate (40) with the source and drain regions. This introduces significant variations in cell performance from die to die and from wafer to wafer. Furthermore, the uncertainty in the final position of the n+ regions causes variations in the series resistance of the bit lines connected to those regions, and hence additional variation in the cell performance.
In prior art, different methods for fabricating different split-gate memory cells are taught. In U.S. Pat. No. 5,495,441, Hong discloses a split-gate flash memory cell having a vertical isolation gate and a process for making it. The memory cell has a floating gate transistor formed in a substrate having a channel extending underneath a floating ate, and a vertical isolation transistor formed in the substrate having a channel parallel to a trench holding a portion of a polysilicon control gate and orthogonal to the channel of the floating gate. In another U.S. Pat. No. 5,414,287, Hong teaches a process for high density split-gate memory cell for flash or EPROM. Silicon islands are formed from a silicon substrate implanted with a first conductivity-imparting dopant. A first dielectric layer surround the vertical surfaces of the silicon islands, whereby the first dielectric layer is a get oxide. A first conductive layer is formed over a portion of the vertical surfaces of the first dielectric layer, and acts as a floating gate for the high density split-gate memory cell. A source region is located in the silicon substrate. A drain region is located in the top of the silicon islands. A second dielectric layer is formed over the top and side surfaces of the floating gate, and acts as an interpoly dielectric. A second conductive layer is formed over that remaining portion of the vertical surfaces of the first dielectric layer not covered by the first conductive layer, and surrounds the second dielectric layer, whereby the second conductive layer is a control gate.
A different process for trench-isolated self-aligned split-gate EEPROM transistor and memory array is described by Hazani in U.S. Pat. No. 5,162,247. A still different method of manufacturing an EEPROM with trench-isolated bitlines is taught by Gill, et al., in U.S. Pat. No. 5,173,436. Here, an EEPROM cell is constructed using a floating-gate transistor with or without a split gate. In this cell, the bitlines and source/drain regions are buried beneath relatively thick silicon oxide and the floating ate extends over the thick silicon oxide. Programming and erasing are accomplished by causing electron to tunnel through the oxide in a tunnel window. The tunnel window has a thinner dielectric than the remainder of the oxides under the floating gate to allow Fowler-Nordheim tunneling. Trenches and ditches are used for electrical isolation between individual memory cells, allowing an increase in cell density.
In the present invention, a method to increase the coupling ratio of source to floating gate is disclosed without increasing lateral diffusion under the floating gate. This prevents punch-through and junction breakdown problems. The increase in coupling ratio is accomplished by providing a three-dimensional source extending into trench isolation, whereby the vertical wall in the third dimension provides the extra area through which coupling between the source and the floating gate is also increased. It will be appreciated by those skilled in the art that in this manner a higher coupling ratio is achieved without an increase in the cell size.

Method to increase coupling ratio of source to floating gate in split-gate flash

Taiwan Semiconductor Manufacturing Co., Ltd.


A system and method of verifying the format of a simulated signal produced during the simulation of an electronic circuit is disclosed. One aspect of the present invention includes a method of extracting timing information from a single simulated serial digital audio signal that comprises both data and clock. An embodiment of the present invention may verify operation of the simulated electronic circuit by setting the value of a first simulated signal according to predetermined events that occur in a second simulated signal. The second simulated signal may be parsed using timing information extracted from the second simulated signal, and the format of the second simulated signal may be matched against a predetermined format based upon the results of the parsing. An embodiment of the present invention may, for example, be employed during software simulation to verify the operation of exemplary devices such as application specific circuits (ASICs) used in the generation of signals meeting the Sony/Philips Digital Interconnect Format (SPDIF).

A suite of software verification tools is frequently used as part of a test environment during the development of application specific integrated circuits (ASICs). Prior to committing an ASIC design to silicon, it is common to run a suite of simulations of the ASIC device to verify that the design will function as intended. Often, developers convert portions of this suite of simulation tools from other projects in order to shorten development time.
A problem that sometimes arises in the testing of ASICs designed to generate signals in the Sony/Philips Digital Interconnect Format (SPDIF) involves access to a clock for the data contained within the SPDIF signal. The SPDIF signal is composed of clock and data encoded as a single signal. An engineer involved in the testing of an ASIC generating an SPDIF compliant signal may have software used in testing another SPDIF-related ASIC design. That software may be capable of checking the SPDIF signal generated by the ASIC being simulated. However, due to the fact that the SPDIF signal contains its own clock signal, the software used for testing the simulated SPDIF signal typically requires a clocking signal from within the code simulating the new ASIC device design. The designer may therefore be forced to locate, or in a worst case scenario, synthesize a suitable clocking signal from signals within the ASIC design simulation software for each ASIC design, for use by the simulation software used to verify the SPDIF signal.
A second problem frequently appears once the data carried by the SPDIF signal is recovered. A SPDIF subframe contains a number of types of data, some having no defined timing relationship to others. This complicates testing, in that changes in the ASIC design that result in the generation of a valid SPDIF signal may be misinterpreted by existing design verification tools as representing an error. Currently available verification tools collect the sequence of output transitions and compare them to a "golden" reference file. Each line of output of a present day SPDIF verification tool may contain the following data elements from an SPDIF subframe:                1. subframe preamble        2. audio sample payload        3. channel status bit (C)        4. validity bit (V)        5. user data bit (U)        6. parity bit (P)
Often, in the process of porting a test to a new design, element [2] may be shifted in time relative to elements [1], [3], [4], and [5]. This may cause element [6] to mismatch and made it impossible to find matching lines between the new design output and the "golden" or reference file. This may happen even in cases where each of the individual elements match the reference file contents and the overall design is functioning properly.
Further limitations and disadvantages of conventional and traditional approaches will become apparent to one of ordinary skill in the art through comparison of such systems with the present invention as set forth in the remainder of the present application with reference to the drawings.


A DMA transfer control device includes a setting register group for setting transfer informations, a number-of-transfers register to which the number of transfers to be performed is set, and which updates a value thereof every time one DMA transfer is completed, a transfer control unit, a secondary setting register group for setting other transfer informations different from the transfer informations, and a specified ordinal-number-of-transfer register. Every time one DMA transfer is initiated, either a value of the setting register group or a value of the secondary setting register group is selected for each of the transfer informations in accordance with a result of an arithmetic operation between a value of the number-of-transfers register and a value of the specified ordinal-number-of-transfer register, and inputted to the transfer control unit. As a result, by making settings for one DMA transfer, it is possible to temporarily change the transfer informations.

The present invention relates to a DMA transfer control device for transferring data between devices.
Conventionally, a DMA transfer method for performing a direct data transfer between transfer devices without the intervention of a CPU has been widely known, and used to allow, e.g., a data transfer from one memory to another to be performed directly between the memories.
In a DMA transfer, a transfer operation is executed in such a manner that information necessary for the transfer, such as a data transfer source initiation address, a data transfer destination initiation address, and a data transfer size, is set to a register or the like in a DMA transfer control device, and then a CPU or the like controls the initiation of the transfer. During the transfer, the CPU need not control the transfer. Accordingly, the data transfer can be performed at a higher speed than in the case where the transfer is performed via the CPU, and a load on the CPU can be reduced. When the transfer of data equivalent to the transfer size which is set to the register or the like is completed, a DMA transfer complete interrupt is asserted in accordance with the setting of the DMA transfer control device. On sensing the DMA transfer complete interrupt, the CPU reads information from the register or the like in the DMA transfer control device, and monitors the result of the DMA transfer and the status thereof.
A DMA transfer is mostly used in the case where a plurality of transfer requests are sent, and the same content is transferred or a plurality of DMA transfers are performed from the subsequent addresses. For example, when data is transferred from a peripheral device to a memory, a transfer request is issued after checking the amount of data stored in the FIFO butter of the peripheral device, and a DMA transfer is performed in response to the issued transfer request. This process is performed by the determined total number of transfers.
In the structure described above, when an interrupt is generated in the CPU every time one DMA transfer is completed, transfer informations need to be set every time the interrupt is generated so that transfer efficiency deteriorates. In addition, when data is accumulated in the FIFO buffer before a DMA transfer is performed by re-setting transfer informations to the DMA control device, the FIFO buffer incurs an overflow so that a problem occurs in system.
To counteract such a problem, there has been proposed a conventional DMA transfer control device described in Japanese Laid-Open Patent Publication No. 2002-73527. In the DMA transfer control device, a DMA transfer is repeatedly performed by the number of times set to a number-of-transfers register. Specifically, as shown in FIG. 11, there are provided a CYC register 60 for setting the number of data transfers to be performed in response to one DMA transfer request, a CYC counter 61 for counting the number of data transfers that have been performed, and a TRN counter 52 for updating a value held therein every time the data transfers, the number of which equals the number held in the CYN resister 60, are performed. The data transfers are performed by repeating the operation describe above till the TRN counter 62 reaches a predetermined number.
In the conventional transfer control device, the total amount of data transferred by DMA is given by multiplying the set value (A) in the CYC register 60 by the set value (B) in the TRN counter 62. However, the total amount of data to be transferred by DMA is not necessarily an integral multiple of the set value (A). Accordingly, the total amount of data to be transferred by DMA does not match the product (A)×(B) of the set values (A) and (B), and a fraction may occur occasionally. To implement a transfer at this time, there can be considered the following methods.
1. After data corresponding to the product (A)×(B) is completely transferred, an interrupt is issued to the CPU such that settings are made again for the transfer of data in an amount corresponding to the fraction, and the transfer is executed.
2. The set values are changed so as to reduce the amount of data to be transferred in accordance with the fraction, and provide (A′)×(B′).
3. In addition to the DMA transfer, a dummy transfer is also performed to adjust the total amount of data to be transferred by DMA to the product value (A)×(B).
However, each of the methods mentioned above also has disadvantages. For example, in the method 1 mentioned above, it is necessary to make settings again for the transfer of data corresponding to the fraction after the data other than that corresponding to the fraction is transferred. This involves the additional trouble of setting software. On the other hand, in the method 2 mentioned above, the amount of data which can be transferred by issuing one DMA transfer request is reduced so that the speed of the transfer is also reduced. In addition, there is also a case where, because the transfer speed is less than a required value, data overflows and cannot be retrieved. Further, in the method 3, required data is overwritten by another data as a result of a dummy transfer.
In the prior art technology described above, every time a DMA transfer request is issued, the same setting register is used for a DMA transfer performed in response to the DMA transfer request, and a transfer source initiation address, a transfer destination initiation address, and the like are also fixed or continued from those in the previous DMA transfer. Accordingly, in the case where the amount of data to be transferred is intended to be temporarily changed, or a transfer address is intended to be changed, the settings cannot be flexibly changed.


A ramp restraint apparatus for a vehicle includes an elongate, rigid restraint bar having one end rotatably attached to the ramp and a free end having a notch and a roller at its tip. The restraint bar travels over a bar support on a lock/release assembly mounted to a vehicle bulkhead. The bar support is shaped at one end to receive the notch of the bar and hold the bar in place when the ramp is fully deployed. A release arm has a cam follower that pushes up on and releases the restraint bar when the release arm is rotated, allowing the ramp to close. When the ramp is fully closed, a storage bracket receives and holds the inboard end of the restraint bar.

The U.S. Navy currently uses an amphibious craft called the Landing Craft Air Cushion (LCAC) to transport equipment, cargo, and personnel from a ship at sea to the shore. To do this, the LCAC has a deployable/stowable, i.e. droppable and liftable, ramp which, when deployed, acts as a platform connecting to a cargo deck within the LCAC that provides a pathway for vehicles to exit the craft. However, when lowered in a sea state, the action of waves and other environmental forces can cause the ramp to move in response, which potentially can damage the ramp or adjacent structure. It can also make loading and unloading vehicles onto the ramp difficult, as nothing restrains the ramp against upward buffeting except the weights of the vehicles themselves.

United States of America as represented by the Secretary of the Navy


A device for returning a reciprocating mechanism to a predetermined intermediate position of reciprocating motion, comprises a reciprocating link movable in accordance with a predetermined reciprocating motion, a pair of positioning members provided at both sides of the predetermined intermediate position of reciprocating motion, a pair of movable blocks, and a single resilient member interconnecting the movable blocks. The positioning members is adapted to position the movable blocks by abutting the movable blocks against the respective positioning members via a biasing force created by the single resilient member. The movable blocks is adapted to return the reciprocating link to its predetermined intermediate position by abutment of the reciprocating link on both the movable blocks, for restricting a reciprocating motion of the reciprocating link via the biasing force created by the single resilient member. During the reciprocating motion, one of the movable blocks breaks contact with the associated positioning member and additionally the reciprocating link breaks contact with the other positioning member by pushing the associated one of the movable blocks in a direction of increasing the biasing force created by the single resilient member.

1. Field of the Invention
The present invention relates to a device for returning or holding a reciprocating mechanism, such as a valve opening-and-closing mechanism reciprocating as along a straight line or along a curved line, a swinging mechanism oscillating across its neutral position in a straight line or in a curved line or the like, to or at a predetermined position, and specifically to a return-to-neutral device which is applicable to a throttle-returnmechanism of an electronically-operated throttle valve.
2. Description of the Prior Art
In recent years, there have been proposed and developed various return-to-neutral devices suitable for a throttle-return mechanism for automotive engines. One such return-to-neutral device has been disclosed in an international application No. PCT/DE87/00404, filed Sep. 4, 1987 (PCT publication No. WO 88/02064, published Mar. 24, 1988), corresponding to Japanese patent publication No. 2-500677, published Mar. 8, 1990. Referring now to FIG. 3, there is shown a throttle-return device for an electronically-controlled throttle valve 2, as disclosed in the international application No. PCT/DE87/00404. As seen in FIG. 3, the throttle valve 2, interleaved in the intake-air passage 1, is driven by means of a throttle-valve actuator 3 such as an electric motor often called a "throttle motor". The throttle-valve actuator 3 is controlled in response to a control signal (or a drive signal) from an electronic control unit (ECU) or an electronic engine control module (ECM), irrespective of depression of the driver. The conventional throttle-return device includes a first resilient member 5 such as a helical torsion spring and a second resilient member 6 such as a helical torsion spring. The first resilient member 5 is connected to one end of the throttle-valve shaft 4 for biasing the throttle-valve shaft in a direction of wide-open throttle (clockwise, viewing FIG. 3), whereas the second resilient member 6 is connected to the other end of the throttle-valve shaft 4 for biasing the throttle-valve shaft in a direction of closed throttle. For example, when the ECU or the throttle-valve actuator (the throttle motor)does not operate owing to breakage in harness connector to the ECU, faulty throttle motor, loose or poor connector contact, or the like, the throttle-return device disclosed in the international application No. PCT/DE87/00404 functions to return or hold the electronically-controlled throttle valve 2 to a predetermined substantially neutral throttle-opening position or a predetermined intermediate angular position by virtue of proper balance between the clockwise biasing force caused by the first resilient member 5 and the counter-clockwise biasing force caused by the second resilient member 6. In the electronically-controlled throttle valve, for example due to a faulty throttle control section of the ECM or a faulty throttle motor, the electronically-controlled throttle valve 2 remains in a closed position, there is a tendency that the engine fails to start. In this case, the use of the throttle-return device for the electronically-controlled throttle valve 2 is effective to prevent the engine from failing to start. In automotive vehicles with an electronically-controlled throttle valve as described above, in order to compensate for load on/off modes at idle, the opening of the throttle valve 2 is controllable depending on engine load changes resulting from an increased load of a power steering, an air conditioner turned on or off, or changes in the other electrical loads. Thus, on vehicles employing such an electronically-controlled throttle valve, a so-called auxiliary-air control valve (generally abbreviated to "ACC valve"), or an idle speed control valve (generally abbreviated to "ISC"), or a fast idle control device (generally abbreviated to "FICD") can be eliminated. However, without the auxiliary-air control valve, there is no air-supply bypassing the throttle valve when starting the engine. Thus, if the electronically-controlled throttle valve 2 is placed into the closed position when the engine is stopped, intake air cannot be delivered into the engine cylinder with the throttle valve closed. In this case, the accelerator pedal must be depressed for starting the engine. To avoid this, automotive vehicles with an electronically-controlled throttle valve generally employ the previously-noted throttle-return device. The conventional throttle-return device disclosed in the international application No. PCT/DE87/00404 utilizes a proper balance of biasing-force between the two resilient members 5 and 6 in order to return the throttle valve to the predetermined intermediate angular position. The previously-noted conventional throttle-return device comprising at least the first and second resilient members, namely two different torsion springs 5 and 6, suffers from the drawback that it is difficult to set pre-loads of the first and second springs 5 and 6 in such a manner as to conform a first spring rate, measured when beginning to open the throttle valve 2 from the predetermined intermediate angular position to a second spring rate, measured when beginning to close the throttle valve 2 from the predetermined intermediate angular position. This lowers the controllability of the throttle valve in both directions, namely a direction of the opening-throttle mode and a direction of the closing-throttle mode. A slight manufacturing error of spring rate of the first resilient member 5 and a slight manufacturing error of spring rate of the second resilient member 6 may cause an increased deviation of a spring-loaded position of the throttle valve 2 from the predetermined intermediate angular position. As a result of the use of two resilient members 5 and 6, the structure of the conventional throttle-return device is complicated, thus increasing the time required for assembling, and total production cost of the throttle-return device. The complicated structure of the device composed of the two different resilient members 5 and 6 requires an increased mounting space. The two springs 5 and 6 must be installed on the respective different positions. This is troublesome. As set forth above, a conventional reciprocating-mechanism return device such as a throttle-return device composed of at least two resilient members is insufficient from the view point of a controllability of a reciprocating member (for example a throttle valve) in both directions of reciprocating motion, an increased degree of freedom in designing, a simple structure and reduction in installation efficiency and production costs.

Device for returning reciprocating mechanism to predetermined position


Probes for use in a scanning probe microscope and methods of manufacturing such probes. Each probe includes a probe tip having a substantially vertical sidewall formed by an anisotropic etching process and a flared post underlying the probe tip that is formed by an etching process that is not anisotropic. A source gas comprising a bromine-containing gas and an oxygen-containing gas is used to etch the probe tip and flared post of the probe in a batch process. The probe tips may be qualified using any suitable criterion for use by a customer in an atomic force microscope without individual inspection.

Atomic force microscopes (AFM's) were developed, among other reasons, to meet a demand in the semiconductor industry for accurately measuring critical dimensions (CDs) during integrated circuit (IC) fabrication. Critical dimensions constitute the width of a line or space on a substrate identified as crucial for proper operation of the device being fabricated. Critical dimensions are measured on some or all of a batch of substrates following any photolithography or etching process in which the dimensions are critical. A critical dimension may be the width of a patterned line, the distance between two lines or devices, or the size of a contact.
Due to their inherently high spatial resolution, AFM's are well suited for measuring critical dimensions nondestructively during process stages of IC fabrication. Generally, AFM's are equipped to sense atoms on or in sample surfaces, thereby providing atomic level surface imaging for measuring critical dimensions at a significantly higher resolution than comparable measurements taken from cross-sectional scanning electron micrographs acquired before and after an IC fabrication stage. AFM images are reconstructed from digital data acquired during grid scanning of a probe tip across the sample surface. Probe tips for measuring critical dimensions must be capable of resolving nanometer size structures.
Conventional processes for fabricating probe tips capable of measuring critical dimensions suffer from several disadvantages that limit not only process yield, but the quality of the probe tips as well. In particular, CD probe tips exhibit a limited cantilever-to-tip height, which negatively affects AFM performance due, for example, to low quality factors and high squeeze film dampening. In addition, conventional fabrication processes for CD probe tips may rely on a wet etching process, which restricts control over tip shape and makes batch processing difficult. Another conventional fabrication process for CD probe tips relies on dry etching with a plasma formed from a source gas composed primarily of a fluorine-based gas, such as sulfur hexafluoride (SF6). However, such conventional dry etching processes produce extraneous projections at locations other than the intended locations for the probe tips. The presence of these extraneous projections lowers process yields, which is a significant hindrance to batch fabrication of probe tips. As a result, conventional probe tips are manufactured individually with multiple tedious inspections made using scanning electron microscopy at various stages of the manufacturing process to verify tip quality and to adjust, if necessary, the dry etching process recipe.
What is needed, therefore, are probes and probe tips suitable for use in an atomic force microscope to measure critical dimensions and methods of accurately manufacturing such probes and probe tips that overcome these and other deficiencies of conventional probes and probe tips and conventional manufacturing methods.

Probes for use in scanning probe microscopes and methods of fabricating such probes


A golf club having multiple interchangeable striking face plate inserts and a movable weight element positioned therewithin. A number of different angularly inclined striker face plates are keyed to a club head body allowing the club to function as a multiple club configuration. Adjustable weight inserts are provided which impart their kinetic energy during the club swing to increase striking power of the club with the target ball during use.

1. Technical Field
This invention relates directly to golf clubs, specifically golf club heads which have enhanced structural performance characteristic and play features.
2. Description of Prior Art
Golf clubs have, in recent years, undergone a variety of technical improvements to enhance the performance characteristic of the golfer's play. Many significant improvements have been made concerning the material used in the golf heads as well as redistribution of weight or mass within the club itself. It has been found by providing additional weight or weight that is active, such clubs have improved performance, specifically in the length of the drive which is important and critical in the game of golf.
Other technical improvements include the reduction of weight in the golf club head to increase club head speed and presumably accuracy in relation to the sweet spot of the club to impart optimal projectory and distance of the ball.
Prior art devices of this type can be seen, for example, in U.S. Pat. Nos. 4,461,481, 5,366,222, 6,514,154, 6,641,490, 6,551,199, 6,872,148, 6,743,117 and U.S. Patent Publication 2002/013576 A1 and 2007/0087860 A1.
In U.S. Pat. No. 4,461,481 a golf club device is disclosed and directed towards having a cylindrical weight slidably positioned within the club head for improved ball striking capabilities.
U.S. Pat. No. 5,366,222 discloses a golf club head having a head cavity with a movable weight positioned within.
U.S. Pat. No. 6,514,154 claims a golf club having an adjustable weight rotatably mounted within a threaded bore.
U.S. Pat. No. 6,641,490 shows a golf club head with a U-shaped hollow passageway in which a flowable solid is captured.
U.S. Pat. No. 6,551,199 an inertia capsule for a golf club is described having an elongated capsule filled with mercury that is flowably disposed during use, transferring mass appropriately therewithin.
A golf club in U.S. Pat. No. 6,872,148 has a movable member with an explosive charge in the head which activates during club head movement.
U.S. Pat. No. 6,743,117 claims a golf head with a multiple face insert that can be replaceably inserted on the club head.
U.S. Patent Publication 2002/2013576 A1 discloses a golf club head with an adjustable weight having a pair of tubular weight receiving chambers within.
Finally, U.S. Patent Publication 2007/0087860 A1 illustrates a golf club head having an enlarged striking power by use of multiple spring loaded weight elements with corresponding guide bores.

Golf club head having interchangeable and weight displacement system


There is disclosed a backlight assembly for maximizing a light incidence efficiency by changing a construction of a light guide plate and a liquid crystal display device having the same. A light incidence surface of the light guide plate receiving a light from a lamp is inclined to make an obtuse angle with a light-emitting surface through which the light is transferred to the display unit. An open surface of a lamp cover that is disposed to face towards the light incidence surface is formed to have the same inclined angle as the light incidence surface of the light guide plate. In addition, a light reflecting plate and an optical sheet are respectively disposed on the top and bottom surfaces of the light guide plate, on which light absorbing layers, for absorbing light that leaks from the light guide plate, are formed at both ends thereof. Accordingly, there are advantages in that the light incidence efficiency of the light is improved even though a thickness of the light guide plate is not increased, and that it is possible to remove the light concentrated at an edge of the light incidence surface of the light guide plate.

1. Field of the Invention
The present invention relates to a liquid crystal display device, and more particularly, to a back light assembly for maximizing a light incident efficiency by changing a structure of a light guide plate for guiding lights from a lamp to a display unit for displaying images and a liquid display device having the same.
2. Description of the Related Art
At the present time, information processing devices are rapidly developing with trends towards various architectures, functions and faster information processing speed. Information processed in these information processing devices has an electrical signal format. In order to visually confirm information processed in an information processing device, a display should be provided as an interface device. An example of such a display device is the liquid crystal display (LCD).
LCDs offer numerous advantages as display devices such as light weight, small size, high resolution, and low power consumption. They are also environmentally friendly and they offer a display of full colors compared with the traditional cathode ray tube (CRT). Such advantages allow the LCDs to replace the CRTs and to be recognized as a next generation display.
LCDs apply electric power to liquid crystal having a specific molecular configuration so as to vary the molecular arrangement of the liquid crystal. The variation in the molecular configuration of the liquid crystal causes a variation in optical properties such as birefringence, optical rotary power, dichroism and light scattering. The LCDs utilize such variations in optical properties to display an image.
In the LCD device, functions of a backlight assembly bring attention to a more important problem. The reason is that the backlight assembly affects both the mechanical and optical characteristics of the LCD device such that the size and the light efficiency of the LCD device undergo a change. This is discussed, along with a description of prior art systems, in conjunction with FIGS. 1–3 below.
FIG. 1 is an exploded perspective view schematically showing the LCD device according to the conventional art schematically. FIG. 2 is a sectional view schematically showing the constructions of a lamp unit and a light guide unit in the backlight assembly as shown in FIG. 1. FIG. 3 is a view showing a pathway of the light in the light guide plate shown in FIG. 2.
Referring first to FIG. 1, the LCD device 900 has a LCD module 700 for displaying images when image signals are applied thereto and a case (not shown) for receiving the LCD module 700. The LCD module 700 includes a display unit 710 having a LCD panel for showing the images.
The display unit 710 includes the LCD panel 712, a data-side printed circuit board (PCB) 714, a gate-side PCB 717, a data-side tape carrier package 716 and a gate-side tape carrier package 718.
The LCD panel 712 includes a thin film transistor substrate 712a, a color filter substrate 712b and liquid crystal (not shown) between the thin film transistor substrate 712a and the color filter substrate 712b.
The thin film transistor substrate 712a is a transparent glass on which the thin film transistors are formed in a matrix form. Data lines are respectively connected with source terminals of the thin film transistors and gate lines are connected with gate terminals of the thin film transistors. Furthermore, pixel electrodes are respectively formed at drain terminals of the thin film transistors, which are made of a transparent conductive material such as Indium Tin Oxide (ITO).
The color filter substrate 712b is provided to face the thin film transistor substrate 712a. RGB pixels are formed on the color filter substrate 712b by means of a thin film process, which presents a predetermined color while the light passes through the color filter substrate 712b. Common electrodes made of the ITO are coated on the front surface of the color filter substrate 712b.
When the thin film transistors of the thin film transistor substrate 712a are turned on, an electric field is created between the pixel electrodes of the thin film transistor substrate 712a and the common electrodes of the color filter substrate 712b. The electric field causes the liquid crystal to change the array angle, which results in the permeability of the light being changed. As a result, the desired pixels are obtained.
A driving signal and a timing signal are applied to the gate lines and data lines of the thin film transistor in order to control the array angle of the liquid crystal and the time of arraying the liquid crystal in the LCD panel 712. A source part for providing the data driving signal to the LCD panel 712 is formed on the data-side PCB 714, and a gate part for providing the gate driving signal to the gate lines is formed on the gate-side PCB 717. In other words, the PCBs 714 and 717 generate and apply the gate driving signal and the data signal for driving the LCD device as well as a plurality of timing signals for applying the gate driving signal and the data signal to the gate lines and the data lines of the LCD panel 712.
Continuing with FIG. 1, the backlight assembly 720 is provided under the display unit 710 so as to uniformly supply the light to the display unit 710. The backlight assembly 720 includes a lamp 721 for generating the light. The lamp 721 is protected by means of a lamp cover 722.
The light guide plate 724 has a size corresponding to that of the liquid crystal panel 712 of the display unit 710, which is disposed under the liquid crystal panel 712 to guide the light emitted by the lamp 721 toward the display unit 710 by changing a pathway of the light.
A plurality of optical sheets is provided on the light guide plate 724 so as to uniformly adjust the brightness of the light that transmitted from the light guide plate 724 to the LCD panel 712. In addition, a light reflecting plate 728 is provided under the light guide plate 724 to reflect the light, which is leaked from the light guide plate 724, towards the light guide plate 728 so as to improve the efficiency of the light.
The display unit 710 and the backlight assembly 720 are supported by means of a mold frame 820 used as a receptacle. The mold frame 820 is provided with a chassis 740 for preventing the display unit 710 from departing from the mold frame 820 while the data-side PCB 714 and the gate-side PCB 717 are bent towards the outside of the mold frame 820 and are fixed to the bottom surface of the mold frame 820.
Referring now to FIG. 2, the light guide plate 724 is of an edge-type having a uniform thickness, and a lamp 721 for supplying the light is provided at an end of the light guide plate 724. Typically, the light emitted from the lamp 721 of the edge-type light guide plate 724 is transmitted through a pathway as shown in FIG. 3.
As shown in FIG. 3, the light emitted from the lamp 721 is transmitted to the top and bottom surfaces 724a and 724b of the light guide plate 724 according to the incidence angle thereof. A part of the light transmitted to the top surface 724a of the light guide plate 724 is provided to the display unit 710 after passing through the top surface 724a of the light guide plate 724, while the remainder of the light is reflected at the bottom surface 724b of the light guide plate 724 and then transmitted toward the top surface 724a of the light guide plate 724.
Meanwhile, the light transmitted to the bottom surface 724b of the light guide plate 724 is reflected by means of printed patterns (not shown) that are formed on the bottom surface 724b of the light guide plate 724, and then the light passes through the top surface 724a of the light guide plate 724. Ultimately, the light is provided to the display unit 710. At this time, a part of the light transmitted to the bottom surface 724b of the light guide plate 724 passes through the bottom surface 724b and leaks out of the light guide plate 724. However, the leaked light is reflected to the display unit 710 by means of the light is reflecting plate 728 that is disposed between the light guide plate 724 and the mold frame 820 (see FIG. 1).
With relation to the light guide plate 724, the brightness of the light that is supplied to the display unit 710 increases in proportion to the thickness of the light guide plate 724. Accordingly, a method of increasing the thickness of the light guide plate 724 can be adopted to maximize the incidence efficiency of the light. When the thickness of the light guide plate 724 increases, however, there is a problem in that the LCD device becomes heavier and has an increased thickness.

Backlight assembly and liquid crystal display device having the same


A safety system is provided for an automobile, which includes a plurality of sensors for monitoring a plurality of parameters. The safety system also includes a processor to ascertain an imminent accident. The system further includes one or more parasols that cover one or more day light openings (DLOs) of the automobile when the imminent accident is ascertained.

Various studies on road accidents provide conclusive evidence that the ejection of an occupant out of an automobile and the protrusion of the occupant's body parts out of the automobile are the major causes of injuries and casualties in road accidents. Generally, in an accident such as a rollover or a collision, the window glasses and windshields of the automobile are shattered. In such a case, there are no barriers that restrain the occupant from being thrown out of the automobile. Further, due to the absence of any barriers, foreign material such as debris may enter the automobile, causing injury to the occupant. In the worst cases, the occupant can be ejected out the automobile due to the impact of the accident, resulting in serious injury and even death.
Various systems exist to prevent the above-mentioned situations. One such system includes a shield that covers the windows of an automobile when the automobile decelerates rapidly. Another system includes a curtain with an inflatable and an uninflatable portion. The inflatable portion covers a significant region of the windows of the automobile during an accident. The uninflatable portion covers the area of the window that is not covered by the inflatable portion. Yet another system includes inflatable airbags at the windows of an automobile. During an accident, the airbags are inflated with gas and cover the windows.
In the light of the foregoing discussion, there is a need for a system for preventing the ejection of an occupant and the protrusion of the occupant's body parts from an automobile during an accident. The system should provide a barrier that protects the occupant from the shattered glass pieces and other debris from outside. It should also prevent the airbags from getting damaged by the shattered glass pieces and other debris. Further, it should provide a safe exit route to the occupant after the accident.


A system including at least three robots. Each robot including a proximity sensor unit and an imaging device. At least one robot including a processor to perform a method of estimating a pose of a human, the method including obtaining a first pose estimate for the human, the first pose estimate based on proximity sensor information, obtaining a second pose estimate for the human, the second pose estimate based on imaging device information, and generating a refined pose estimate for the human by fusing the first pose estimate with the second pose estimate, where the first pose information provides predictive values and the second pose estimate provides correction values. The method including applying a deep neural network (DNN) human model, and applying a DNN human pose model. A method to generate a refined pose estimation for a human and a non-transitory computer readable medium are also disclosed.

Human-robot teaming and/or collaboration is applicable to military, industrial, services and other domains. During the collaboration process, robots need to estimate the position/orientation of human peers in the environment, either globally or locally. Based on the positional estimation results, robots can plan the collaborative actions according to the intention recognition and situation identification results. Advances in locating a human in an indoor environment considerable. Conventional approaches and solutions use stationery sensors placed within the environ, and a sensor located on the human team member(s). Proximity sensory signals are analyzed, and frequently triangulated, to determine the pose of a human.
In a dynamic outdoor environment, the conventional approach of advance installation of stationery sensors is impractical and unrealizable. Sensors mounted on robot team member can be in motion and positionally unknown at any instant of time, which increases the challenge for conventional approaches.
FIG. 1 illustrates a conventional approach to locating the position of human (H) using sensors S1, S2, S3, S4, S5. Conventional approaches require that human (H) be within a perimeter (P) defined by the sensors' positions. If the human(s) is not within this perimeter, conventional approaches cannot locate the person(s).

Systems and methods for locating humans using dynamic field robotic-sensor network of human robot team


A compound of the formula (I) or a pharmaceutically acceptable salt, enantiomer, racemate, diastereomers or mixtures thereof, or a solvate thereof, formulations and methods of use thereof, as opioid receptor antagonists are disclosed wherein the variables are as described herein.

Three types of opioid receptors, mu, kappa, and delta opioid receptors are generally reported. Recent evidence points to the interactions between receptor dimer combinations of mu, kappa and/or delta receptors (called heterodimers) as also contributing to opioid activity. Opioid receptors and their normal regulation or lack thereof, has been implicated in disease states including irritable bowel syndrome, nausea, vomiting, pruritic dermatoses, depression, smoking and alcohol addiction, sexual dysfunction, stroke and trauma in animals. Therefore it is not surprising that the ability to antagonistically bind opioid receptors has been shown to produce ameliorative, preventative and/or treatment effects in animals including humans afflicted with one or more of these disease states.
More recently, antagonists of the opioid receptors have been found to increase metabolic energy consumption, and reduction of weight in obese rats while maintaining muscle mass. These findings indicate that an effective opioid antagonist may be useful in preventing, treating and or ameliorating the effect of obesity. Considering the percentage of the population that is obese in Western societies and the indirect costs associated with treating the effects and symptoms of obesity and Related Diseases, the impact of these findings cannot be overstated.
Though many opioid antagonists have been disclosed, the search continues for alternative and/or improved or more effective antagonists having an overall benefit to the patient with little or no major side effects. U.S. Pat. No. 4,891,379 discloses phenylpiperidine opioid antagonists useful for the treatment of diabetes and obesity. Clinical development of a compound claimed in U.S. Pat. No. 4,191,771 was discontinued due to poor oral bioavailability characteristics. Bicyclic analogs of phenyl piperidine have been prepared and reported as opioid antagonists by Wentland, et al., Biorganic and Medicinal Chemistry Letters 11 (2001) 623-626; see also Wentland, et al., Biorganic and Medicinal Chemistry Letters 11 (2001) 1717-1721. Finally, European Patent application number EP 1 072592A2 filed May 18, 2000, discloses phenylpiperidine compounds of formula I

wherein A, D, R1, R2, R3X, and n have meanings given in the description, which are useful in the prophylaxis and in the treatment of diseases mediated by opioid receptors such as pruritus.
In spite of these and other disclosures of compounds useful as opioid receptor antagonists, there remains an unmet medical need for safe, effective and/or alternate treatment or prophylaxis of diseases associated with opioid receptors, particularly obesity and Related Diseases.

6-substituted nicotinamide derivatives as opioid receptor antagonists


An improved vacuum crane game and method. Multiple prizes are provided on a rotating turntable. A player may control horizontal movement of a vacuum pick-up device positioned above the prize area. The pick up device includes a vacuum head that may be raised and lowered relative to the turntable in a z-direction. The vacuum head is used to pick up one of the prizes using a suction force that is provided by a vacuum pump coupled to the vacuum head by a hose and located away from the vacuum head. In one embodiment, a vacuum sensor in the vacuum head may sense whether a prize is picked up. The pick-up device is moved to a dispenser area and the suction force is removed to allow the prize to fall to a conveyor device, which moves the prize to a dispenser where it is delivered to the player.

1. Field of the Invention
This invention relates to arcade games, and more particularly to crane-type arcade games in which a player controls a mechanical apparatus to pick up and dispense offered prizes.
2. Background of the Related Art
Crane-type or "claw machine" arcade games are popular amusement devices often provided in game arcades, stores, or other public places. In these types of games, prize objects are provided within a closed housing and are viewable by a player through transparent glass or the like. Upon the insertion of a coin or other monetary input into the game, the player controls a mechanical claw or other grasping implement with controls such as a joystick, buttons, or toggle switch. Typically, the claw is provided above the prize objects and the player can change the position of the claw over the prizes. The claw is lowered towards the prizes upon activation by either a controller such as a computer or the player, depending on the particular embodiment. The claw is either automatically opened when it reaches the level of the prizes or is opened under the player's control. After a predetermined amount of time, the claw is automatically elevated. The claw may or may not be able to grasp a prize and hold onto the prize as the claw is raised. The controller then moves the claw over to a dispensing container and opens the claw, allowing the prize (if any is held) to drop into the dispensing chute and to be guided through the dispenser to an opening accessible to the player. In a common implementation, a sensor within the dispenser detects whether a prize has been won by the player. After the claw is opened over the dispenser, the controller moves the claw to its original starting position and waits for another insertion of the coin (unless the player is provided with multiple tries).
The prizes that the operator of a claw-type crane game can provide in the game are usually limited in selection. Since the claw must surround an object to be able to pick it up, most prizes in claw-type crane games have been limited to large stuffed dolls or other soft, rough-surfaced merchandise that can be surrounded and grabbed by the claw fingers and raised from the supporting surface. Usually, flat, smooth or thin objects are not able to be picked up and held by the claw. However, a large number of flat, smooth, and thin objects are desirable to used as prizes in a crane-type game, such as smooth-surfaced spheres or eggshell containers, boxes, gumballs, cups, bulbs, Christmas ornaments, trading cards, jewelry, etc. Players desire to win these types of items and operators desire to provide them; however, the standard claw type mechanism cannot be used to pick them up.
One solution to the inability of claw-type cranes to pick up these objects is to provide a different type of pick-up device. One type of device that is used is a vacuum device that uses air suction to grab and hold an object. In U.S. Pat. No. 5,513,772 of Glaser, a vacuum embodiment of a crane pick-up game is disclosed in which a vacuum motor is suspended from a string and concealed by a facade or enclosure. The player may move the motor and lower the motor towards a field of prizes similarly to the claw in claw-type crane games. A spinning fan within the motor creates a suction force which is used to pick up and hold prizes. An orifice with a screen is used to prevent items from being sucked into the orifice. Prizes captured and held by the suction are dispensed to the player through a dispenser.
The Glaser vacuum device can pick up some objects which cannot be picked up and held by prior claw-type crane games. However, the Glaser device has many drawbacks. The vacuum motor used by Glaser is a large, bulky device. Since this motor must be concealed to add to the aesthetic appeal of the game, a large cover or enclosure is placed over the motor, which obscures the orifice on the device where prizes are captured by the air suction. This prevents the player from positioning the suction orifice with any great accuracy to pick up a prize, thus, decreasing the skill element of the game.
In addition, the vacuum motor used by Glaser is a high powered, heavy, noisy, and inefficient device. Since the vacuum motor creates large centrifugal forces when it is powered, the motor tends to rotate as it is suspended on the string. To prevent this, a telescoping rod is attached to a side of the device to prevent the spinning. The rod adds further complexity and expense to the unit. Also, the large weight of the motor and enclosure can be difficult to lift and adds to the weight carried and moved by the positioning motors, thus requiring that prizes of smaller weight be provided to decrease the total carried weight. Furthermore, the screen suction orifice of Glaser is inefficient at creating suction, thus requiring the high suction force to grab any objects.
Also, the Glaser device only detects prizes that have been dispensed through the dispensing chute to the player. Thus, the game does not detect whether a prize has been picked up until the crane motor is moved over to the dispenser opening and the suction turned off so that the prize can drop into the opening. If no prize is then detected in the dispenser, the player must control the motor to move back over to the field of prizes to continue the process of picking up a prize, which causes inefficient waste of time and power.

Crane game including vacuum and rotary table


An electromechanical power steering unit for a motor vehicle includes an integral component having a torque sensor unit, which detects the rotation of the upper steering shaft relative to the lower steering shaft. The torque sensor unit includes a ring magnet rotationally fixed to the upper steering shaft and a magnetic flux guide connected to the lower steering shaft. A magnet sensor detects the rotation of the shaft connected to the ring magnet with respect to the lower shaft connected to the magnetic flux guide and the ring magnet is carried by a ring magnet sleeve, which sits on the upper steering shaft and is made from a thermoplastic material and is molded by way of ultrasound forming in the upper steering shaft in one region for mounting on the upper steering shaft.

Electromechanical motor vehicle power steering comprises servo-units which can be arranged as a power assist mechanism on a pinion or a rack of the steering transmission. Usually the steering shafts in motor vehicles are divided into an upper steering shaft, which is connected to a control wheel or steering wheel, and a lower steering shaft, which is connected to the steering transmission for swiveling the wheels. The upper and lower steering shaft are joined together in rotationally elastic manner by a torsion bar. The rotation of the upper steering shaft relative to the lower steering shaft is used to measure the torque applied by a driver to the steering system, which is required in order to determine the steering assist.
The detecting of a relative moment between the upper steering shaft and the lower steering shaft is done by means of a torque sensor.
From the patent application DE 10 2011 101 482 A1 there is known a sensor assembly comprising an encoder fastened on a rotatable shaft and having an encoder element, where the encoder element is provided with a readable encoding for an associated sensor element and it is carried by a support sleeve. The support sleeve is made of a thermoplastic material, which is molded into a recess of the shaft by means of ultrasound forming. However, the ultrasound welding process has drawbacks in terms of the strength of the welded seams, especially because only slight pressing forces are presentable during the welding process.
A torque sensor is known for example from the document DE 10 2007 043 502 A1. The torque sensor mechanism is arranged on two opposite shaft pieces in the axial direction or the upper steering shaft and the lower steering shaft of the steering shaft, which are joined together by a torsion bar. On the upper steering shaft there is arranged a magnet—such as a ring magnet—while on the lower steering shaft there is arranged a holder with a magnetic stator, which is located opposite the permanent magnet by a small air gap in the radial direction. The magnetic flux of the magnet is conducted across the stator—which usually consists of two separate stator pieces—to a first and a second flux guide, which then relinquish the magnetic flux to a magnet sensor—such as a Hall sensor. The magnet sensor is located between the two flux guides.
Traditionally, the magnet is fastened at a mounting seat on the upper steering shaft by pressing into a sleeve integrated in a magnet holder by injection molding. However, the press fitting and the serration involved in this process are a problem, since the required low tolerances of the serration are hard to achieve in the injection molding process and furthermore the design is prone to cracks. Moreover, the production of the sleeve and the press fitting involve high costs.
Thus a need exists for a technical solution for a connection of a ring magnet or stator holder of a torque sensor to a shaft, which simplifies the manufacture and can prevent high stresses or cracks on the components.

Method for mounting of an integral structural unit in an electromechanical motor vehicle steering system having a torque sensor unit and a steering angle sensor unit by means of ultrasonic welding


Disclosed are substantially pure AGE-1 polypeptides and purified DNAs, vectors, and cells encoding those polypeptides. Also disclosed are methods for determining longevity and isolating antagonists using the AGE-1 sequence.

This invention relates to polypeptides and nucleic acid sequences involved in aging, as well as methods for their use.
As the average age of the population of the United States and other countries increases, there is a growing interest in efforts to delay the aging process. It has long been accepted that environmental factors which trigger DNA damage or are otherwise toxic to cells might negatively influence longevity. Increasingly, the role of genetics in this process has become accepted as well, and has resulted in a search for genes which participate in and control aging or senescence. These genes are valuable because they may encode therapeutic products which retard senescence or death. Alternatively, these proteins may be used as targets for the design or isolation of antagonist-type drugs which themselves prolong life-span or delay the onset of age-related conditions.

AGE-1 polypeptides and related molecules and methods


Methods and compositions comprising isolated nucleic acid molecules specific to Neisseria meningitidis, Candida glabrata and Aspergillus fumigatus heat shock proteins (Hsps), as well as vector constructs and isolated polypeptides specific to the same are provided. Such compositions and methods are useful for the diagnosis of infections by these organisms and for generating an immune response to the organisms.

This invention relates to heat shock proteins of the Hsp60 family from Candida glabrata and Aspergillus fumigatus and a heat shock protein of the Hsp70 family from Neisseria meningitidis, including fragments thereof, and uses of such proteins and nucleic acid molecules encoding these proteins.
Meningitis is an infection of the fluid of the spinal cord and the fluid that surrounds the brain. The disease is caused either by a viral or a bacterial infection. Viral meningitis is typically less severe than bacterial meningitis and resolves without specific treatment. In contrast, bacterial meningitis can be rather severe and can cause brain damage, hearing loss or learning disability. Symptoms of meningitis are high fever, headache and stiff neck. These symptoms may develop over a span of several hours, or may take 1-2 days. Other symptoms may be nausea, vomiting, discomfort looking into bright light, confusion or sleepiness. In young children, the classical symptoms may be absent or may not be easily detected, and the child may appear to be slow, inactive, irritable, vomiting or feeding poorly. As the disease progresses, seizures may occur.
Bacterial meningitis may be caused by Haemophilus influenzae, Streptococcus pneumoniae or Neisseria meningitidis. Because all children (in the U.S.) are now given a vaccine against Haemophilus influenzae in the course of their routine immunizations, meningitis due to this organism is now relatively uncommon. Thus, the major bacterial disease-causing agents are now Streptococcus pneumoniae and Neisseria meningitidis.
Early diagnosis and treatment are critically important. It must be determined whether symptoms are due to a viral or bacterial agents, and, if they are caused by a bacterial agent, which bacterium is involved. Present methods of diagnosis are relatively slow. They involve obtaining spinal fluid by performing a spinal tap. Bacteria are identified by cultivation of spinal fluid.
Bacterially-caused meningitis can be treated by antibiotics. However, it is critically important that treatment commence early in the course of the disease. Obviously, antibiotic therapy may be jeopardized by the development of antibiotic-resistant strains of disease-causing bacteria. Because of this concern, and also because of cost-benefit considerations, vaccination against the bacteria causing the disease would be preferable, at least in regions, in which the disease is endemic. As discussed before, U.S. children are routinely vaccinated against Haemophilus influenzae, but not against Neisseria meningitidis and Streptococcus pneumoniae. One such vaccine protects against four strains of Neisseria meningitidis. However, the vaccine appears not to be effective in children under 18 months of age. Similarly, a vaccine containing polysaccharide antigens for 14 of the 83 capsular types of Streptococcus pneumoniae was developed. The vaccine was found to be 57% effective in two large studies. As with the Neisseria vaccine, children under the age of two years do not appear to be protected by the vaccine. Thus, there is a need for improved vaccine against the latter two species of bacteria. The information provided here was obtained from publications by the Division of Bacterial and Mycotic Diseases of the National Center for Infectious Diseases, and the Centers for Disease Control and prevention, by Lonks and Medeiros, Antimicrobial Therapy 1 79:523-535, 1995, by Butler et al., JAMA 270:1826, 1993, and by Gotschlich et al., Antibodies in Human Diagnosis and Therapy 391-402 (Haber and Krause eds., 1977).
Aspergillosis is an opportunistic infection occurring in compromised individuals and is caused by molds of the genus Aspergillus, of which Aspergillus fumigatus is an important species. Aspergillus is ubiquitous and is distributed worldwide. Infection generally involves inhalation of fungal elements. Aspergillosis has several clinical manifestations, including colonization of the ear or the lungs, allergic pulmonary involvement, and invasive pulmonary and disseminated infections. The pulmonary invasive and disseminated forms of infections have a grave prognosis, including a high rate of mortality. Susceptible hosts include cancer patients, patients treated with immunosuppressive or cytotoxic drugs, and those otherwise debilitated such as AIDS patients, neutropenic cancer patients, or patients receiving adrenal corticosteroid drugs. Segal, Vaccines against Fungal Infections, CRC Crit. Rev. Microbiology 14:229, 1987. Rolston and Bodey, Infections in patients with cancer, Cancer Medicine (Holland et al. eds), 1997. The true incidence of aspergillosis is not known in the HIV/AIDS population, in part because the condition is frequently not diagnosed. However, it is clear that the incidence is increasing. Ampel has reported that more than 75 cases have been documented in the literature. Ampel, Emerging disease issues and fungal pathogens associated with HIV infection, Emerging Infectious Diseases 2:109-116, 1996. Aspergillosis has been reported to occur in 20-50% of patients with acute leukemia. It is noted that many cases of Aspergillus infection in cancer patients are not diagnosed until an autopsy is performed after death. Clearly, aspergillosis is becoming increasingly common among neutropenic patients and in cancer patients receiving corticosteroid drugs. Rolston and Bodey, supra. An article in 1992 by Bodey et al. reports on the incidence of fungal infections based on an international autopsy survey. Bodey et al., Fungal Infections In Cancer Patients, An International Autopsy Survey, Eur. J. Clin. Microbiol. Infect. Dis. 11:99-109, 1992. Countries included are Austria, Belgium, Canada, Germany, Italy, Japan, Netherlands and the UK. It was concluded that 25% of leukemia patients had fungal infections. Of these infected patients, 66% had candidiasis, and 34% aspergillosis. Estimates of rates of fungal infections in organ transplant patients as high as about 40% were published. Paya, Clin. Infect. Dis. 16:677-688, 1993. More than 80% of these infections were due to Candida and Aspergillus. As alluded to before, diagnosis of aspergillosis is not infrequently missed, and there is therefore a need for improved methods of diagnosis.
Candidiasis is a fungal infection caused by yeasts of the genus Candida. Among the more than 80 known species, only seven species appear to be pathogenic. The major disease-causing species is Candida albicans. Among the pathogenic species s also found Candida glabrata, formerly known as Torulopsis glabrata. Clinical manifestations of Candida infection range from superficial cutaneous infections to disseminated disease. Infections range from acute to chronic. They can involve skin and nails, the mucosal membranes of the mouth and vagina, and various internal organs such as the lungs, gastrointestinal tract, and circulatory and central nervous systems. Manifestations can be oral thrush, vaginitis, balanitis, diaper rash, chronic mucocutaneous conditions, bronchitis or pneumonia, meningitis, endocarditis, and septicemia. While the superficial forms of candidiasis have been well known since antiquity, the incidence of the disseminated forms has increased recently, presumably because of the extensive use of antibiotics, corticosteroids, cytotoxic drugs, organ transplantation and other complex surgical procedures. It is important to note that today the majority of systemic or invasive fungal infections are due to Candida species. Segal, supra. Stringer, Mass. High Tech. 14:3, 1997.
Mortality from systemic candidiasis remains high, in the order of 38-59%. The mainstay for treatment is amphotericin B, and an alternative is fluconazole. In a multicenter trial, amphotericin B was 79% effective, and fluconazole 70%. Note that Candida glabrata is resistant to fluconazole. Because mortality remains high, an effective vaccine against candidiasis to be used in high-risk populations would be desirable.
Since Candida albicans is the major cause of candidiasis, essentially all work relating to both diagnosis and vaccination concerned this particular species. Thus, it is not clear to what extent diagnostic procedures developed and vaccination approaches taken would also detect or protect against other species such as Candida glabrata.
Therefore, there is a need in the art to identify and isolate novel stress proteins and nucleic acids encoding the same from Neisseria meningitidis, Candida glabrata and Aspergillus fumigatus, which are useful in the detection, diagnosis and treatment of infections caused by these organisms.
The present invention provides methods and compositions comprising isolated nucleic acid molecules specific to Neisseria meningitidis, Candida glabrata and Aspergillus fumigatus, as well as vector constructs and isolated polypeptides specific to Neisseria meningitidis, Candida glabrata and Aspergillus fumigatus. Such compositions and methods are useful for the diagnosis of infection and for generating an immune response to the respective organisms.
Thus, in one aspect the present invention provides an isolated nucleic acid molecule encoding a Neisseria meningitidis Hsp70. In some embodiments, the isolated nucleotide molecule is selected from the group consisting of: (a) an isolated nucleic acid molecule comprising the sequence of SEQ ID NO:1 (FIG. 4); (b) an isolated nucleic acid molecule comprising the sequence of SEQ ID NO:1 from nucleotides 358-2286; (c) an isolated nucleic acid molecule comprising the sequence of SEQ ID NO:2 (FIG. 6) from nucleotides 4-1932; (d) an isolated nucleic acid molecule comprising the sequence of SEQ ID NO:3 (FIG. 8); (e) an isolated nucleic acid molecule comprising the sequence of SEQ ID NO:4 (FIG. 9); (f) an isolated nucleic acid molecule complementary to any one of the nucleotides of SEQ ID NOS: 1 to 4 set forth in (a) through (e), respectively.
In another aspect, the present invention provides an isolated nucleic acid molecule which is a variant of, or is substantially similar to, the Neisseria Hsp70 nucleotide molecules described above. In further aspects the present invention provides an isolated nucleic acid molecule comprising a nucleotide sequence that is identical to a segment of contiguous nucleotide bases comprising at least 25% of SEQ ID NOS: 1 to 4 or a complement thereof or an isolated nucleic acid molecule encoding Hsp70 comprising a nucleic acid sequence that encodes a polypeptide comprising any one of SEQ ID NOS: 2, 3, or 4 or a variant Hsp70 that is at least 95% homologous to a polypeptide according to any one of SEQ ID NOS: 2, 3, or 4.
In one embodiment, the present invention provides an isolated nucleic acid molecule as described above, the molecule encoding a polypeptide that is able to be selectively bound by an antibody specific for a Neisseria meningitidis Hsp70.
In still another aspect, the present invention provides an isolated nucleic acid molecule encoding at least 8 contiguous amino acids of a Neisseria meningitis Hsp70 polypeptide selected from amino acid residues of FIG. 6, wherein the encoded Neisseria meningitidis Hsp70 polypeptide is able to bind to a major histocompatibility complex.
In still further aspects the present invention provides an isolated Neisseria meningitidis Hsp70 polypeptide.
In some embodiments, the isolated Hsp70 polypeptide comprises the amino acid sequence of FIG. 6, or variants thereof, preferably wherein the polypeptide is able to be selectively bound by an antibody specific for a Neisseria meningitidis Hsp70. In further embodiments, the isolated Hsp70 polypeptide is fused to an additional polypeptide to create a fusion protein.
In still yet further aspects the present invention provides an isolated Hsp70 polypeptide comprising at least 8 contiguous amino acids selected from amino acid residues of FIG. 6, wherein the Hsp70 polypeptide is capable of binding to a major histocompatibility complex and eliciting or enhancing an immune response to Neisseria meningitidis in a human being.
In certain embodiments, the isolated Hsp70 polypeptide is derived by proteolytic cleavage or chemical synthesis, or is an expression product of a transformed host cell containing a nucleic acid molecule encoding the Hsp70 or portion thereof. In further certain embodiments, the isolated Hsp70 polypeptide comprises greater than 95% homology to the Hsp70 polypeptide of FIG. 6, and the isolated Hsp70 polypeptide is able to be selectively bound by an antibody specific for a Neisseria meningitidis Hsp70.
In still yet another aspect the present invention provides an isolated polypeptide wherein the polypeptide is an expression product of a transformed host cell containing one of the aforementioned nucleic acid molecules derived from Neisseria.
In still yet further aspects the present invention provides vectors comprising at least one of the aforementioned nucleic acid molecules derived from Neisseria. In certain embodiments, the vector is an expression vector comprising a promoter in operative linkage with the isolated nucleic acid molecule encoding the Hsp70 or portion thereof, preferably further comprising a selectable or identifiable marker and/or wherein the promoter is a constitutive or an inducible promoter. The present invention also provides host cells containing such vectors. In certain embodiments, the host cell is selected from the group consisting of a bacterial cell, a mammalian cell, a yeast cell, a plant cell and an insect cell.
In still yet other aspects the present invention provides compositions comprising a Neisseria Hsp70 polypeptide in combination with a pharmaceutically acceptable carrier or diluent. In certain embodiments, the composition is suitable for systemic administration, oral administration, intranasal administration or parenteral administration.
In yet other aspects the present invention provides methods for eliciting or enhancing an immune response in a mammal against Neisseria, comprising administering to the mammal in an amount effective to elicit or enhance the response, a Neisseria Hsp70 polypeptide in combination with a pharmaceutically acceptable carrier or diluent; methods for eliciting or enhancing an immune response in a mammal to a polypeptide comprising administering to the mammal a fusion protein containing sequences of the polypeptide fused to the Neisseria Hsp70 polypeptide in combination with a pharmaceutically acceptable carrier or diluent; and methods for eliciting or enhancing an immune response in a mammal against a target antigen comprising administering to the mammal the target antigen joined to a Neisseria Hsp70 polypeptide in combination with a pharmaceutically acceptable carrier or diluent.
In still another aspect, this invention provides PCR primers and probes for detecting DNA encoding a Neisseria meningitidis. Hsp70 that includes at least about 15 contiguous bases from any one of SEQ. ID NOS: 1-4, or to compliment thereof. In a related aspect, the invention provides a method for diagnosing the presence of a Neisseria meningitidis in a subject sample that includes the steps of obtaining a DNA fraction from the subject sample; and performing a PCR amplification of the DNA fraction using at least one PCR primer that includes at least about 15 contiguous bases from any one of SEQ. ID NOS: 1-4, or a compliment thereof.
The present invention also provides an isolated nucleic acid molecule encoding a Aspergillus fumigatus Hsp60. In some embodiments, the isolated nucleotide molecule is selected from the group consisting of: (a) an isolated nucleic acid molecule comprising the sequence of SEQ ID NO:5 (FIG. 14); (b) an isolated nucleic acid molecule comprising the sequence of SEQ ID NO:5 from nucleotides 300-2234; (c) an isolated nucleic acid molecule comprising the sequence of SEQ ID NO:5 from nucleotides 300-410, nucleotides 514-655 and nucleotides 724-2234; (d) an isolated nucleic acid molecule comprising the sequence of SEQ ID NO:6 (FIG. 16); (e) an isolated nucleic acid molecule comprising the sequence of SEQ ID NO:7 (FIG. 18); (f) an isolated nucleic acid molecule complementary to any one of the nucleotides of SEQ ID NOS: 5 to 7 set forth in (a) through (e), respectively.
In another aspect, the present invention provides an isolated nucleic acid molecule that is a variant of, or is substantially similar to, the Aspergillus Hsp60 nucleotide molecules described above. In further aspects, the present invention provides an isolated nucleic acid molecule comprising a nucleotide sequence that is identical to a segment of contiguous nucleotide bases comprising at least 25% of SEQ ID NOS: 5 to 7, or a complement thereof, or an isolated nucleic acid molecule encoding Hsp60 and comprising a nucleic acid sequence of any one of SEQ ID NOS: 5, 6 or 7 or a variant Hsp60 that is at least 95% homologous to a nucleic acid sequence comprising any one of SEQ ID NOS: 5, 6, or 7.
In one embodiment, the present invention provides an isolated nucleic acid molecule according as described above, the molecule encoding a polypeptide that is able to be selectively bound by an antibody specific for a Aspergillus fumigatus Hsp60.
In still another aspect in one aspect the present invention provides an isolated nucleic acid molecule encoding at least 8 contiguous amino acids of a Aspergillus fumigatus Hsp60 polypeptide selected from amino acid residues according to FIG. 14, wherein the encoded Aspergillus fumigatus Hsp60 polypeptide is able to bind to a major histocompatibility complex.
In still further aspects the present invention provides an isolated Aspergillus fumigatus Hsp60 polypeptide.
In some embodiments, the isolated Hsp60 polypeptide comprises the amino acid sequence of FIG. 14, or variants thereof, preferably wherein the polypeptide is able to be selectively bound by an antibody specific for a Aspergillus fumigatus Hsp60. In further embodiments, the isolated Hsp60 polypeptide is fused to an additional polypeptide to create a fusion protein.
In still yet further aspects the present invention provides an isolated Hsp60 polypeptide comprising at least 8 contiguous amino acids selected from amino acid residues according to FIG. 14, wherein the Hsp60 polypeptide is capable of binding to a major histocompatibility complex and eliciting or enhancing an immune response to Aspergillus fumigatus in a human being.
In certain embodiments, the isolated Hsp60 polypeptide is derived from proteolytic cleavage or chemical synthesis, or is an expression product of a transformed host cell containing a nucleic acid molecule encoding the Hsp60 or portion thereof. In certain further embodiments, the isolated Hsp60 polypeptide comprises greater than 95% homology to the Hsp60 polypeptide of FIG. 14, and the isolated Hsp60 polypeptide is able to be selectively bound by an antibody specific for a Aspergillus fumigatus Hsp60.
In still yet another aspect the present invention provides an isolated polypeptide wherein the polypeptide is an expression product of a transformed host cell containing at least one of the nucleic acid molecules derived from the aforementioned Aspergillus molecules.
In still yet further aspects the present invention provides vectors comprising at least one of the aforementioned nucleic acid molecules derived from Aspergillus. In certain embodiments, the vector is an expression vector comprising a promoter in operative linkage with the isolated nucleic acid molecule encoding the Hsp60 or portion thereof, preferably further comprising a selectable or identifiable marker and/or wherein the promoter is a constitutive or an inducible promoter. The present invention also provides host cells containing such vectors. In certain embodiments, the host cell is selected from the group consisting of a bacterial cell, a mammalian cell, a yeast cell, a plant cell and an insect cell.
In still yet other aspects the present invention provides compositions comprising an Aspergillus Hsp60 polypeptide in combination with a pharmaceutically acceptable carrier or diluent. In certain embodiments, the composition is suitable for systemic administration, oral administration, intranasal administration or parenteral administration.
In yet other aspects the present invention provides methods for eliciting or enhancing an immune response in a mammal against Aspergillus, comprising administering to the mammal in an amount effective to elicit or enhance the response, an Aspergilllus Hsp60 polypeptide in combination with a pharmaceutically acceptable carrier or diluent; methods for eliciting or enhancing an immune response in a mammal to a polypeptide comprising administering to the mammal a fusion protein containing sequences of the polypeptide fused to the Hsp60 polypeptide in combination with a pharmaceutically acceptable carrier or diluent; and methods for eliciting or enhancing an immune response in a mammal against a target antigen comprising administering to the mammal the target antigen joined to an Aspergillus Hsp60 polypeptide in combination with a pharmaceutically acceptable carrier or diluent.
In still another aspect, this invention provides PCR primers and probes for detecting DNA encoding a Aspergillus fumigatus Hsp60 that includes at least about 15 contiguous bases from any one of SEQ. ID NOS: 5-7, or to compliment thereof. In a related aspect, the invention provides a method for diagnosing the presence of a Aspergillus fumigatus in a subject sample that includes the steps of obtaining a DNA fraction from the subject sample; and performing a PCR amplification of the DNA fraction using at least one PCR primer that includes at least about 15 contiguous bases from any one of SEQ. ID NOS: 5-7, or a compliment thereof.
The present invention further provides an isolated nucleic acid molecule encoding a Candida glabrata Hsp60. In some embodiments, the isolated nucleotide molecule is selected from the group consisting of: (a) an isolated nucleic acid molecule comprising the sequence of SEQ ID NO:8 (FIG. 21); (b) an isolated nucleic acid molecule comprising the sequence of SEQ ID NO:8 from nucleotides 258-1964; (c) an isolated nucleic acid molecule comprising the sequence of SEQ ID NO:9 (FIG. 23); (d) an isolated nucleic acid molecule comprising the sequence of SEQ ID NO:10 (FIG. 25); (e) an isolated nucleic acid molecule complementary to any one of the nucleotides of SEQ ID NOS: 8 to 10 set forth in (a) through (d), respectively.
In another aspect, the present invention provides an isolated nucleic acid molecule which is a variant of, or is substantially similar to, the Candida Hsp60 nucleotide molecules described above. In further aspects the present invention provides an isolated nucleic acid molecule comprising a nucleotide sequence that is identical to a segment of contiguous nucleotide bases comprising at least 25% of SEQ ID NOS: 8 to 10 or a complement thereof or an isolated nucleic acid molecule encoding Hsp60 comprising a nucleic acid sequence that encodes a polypeptide comprising any one of the polypeptides according to FIG. 21, 23 or 25, or a variant Hsp60 that is at least 95% homologous to a polypeptide according to any one of FIG. 21, 23 or 25.
In one embodiment, the present invention provides an isolated nucleic acid molecule according as described above, the molecule encoding a polypeptide that is able to be selectively bound by an antibody specific for a Candida glabrata Hsp60.
In still another aspect in one aspect the present invention provides an isolated nucleic acid molecule encoding at least 8 contiguous amino acids of a Candida glabrata Hsp60 polypeptide selected from amino acid residues according to FIG. 21, wherein the encoded Candida glabrata Hsp60 polypeptide is able to bind to a major histocompatibility complex.
In still further aspects the present invention provides an isolated Candida glabrata Hsp60 polypeptide.
In some embodiments, the isolated Hsp60 polypeptide comprises the amino acid sequence of FIG. 21, or variants thereof, preferably wherein the polypeptide is able to be selectively bound by an antibody specific for a Candida glabrata Hsp60. In further embodiments, the isolated Hsp60 polypeptide is fused to an additional polypeptide to create a fusion protein.
In still yet further aspects the present invention provides an isolated Hsp60 polypeptide comprising at least 8 contiguous amino acids selected from amino acid residues according to FIG. 21, wherein the Hsp60 polypeptide is capable of binding to a major histocompatibility complex and eliciting or enhancing an immune response to Candida glabrata in a human being.
In certain embodiments, the isolated Hsp60 polypeptide is derived from proteolytic cleavage or chemical synthesis, or is an expression product of a transformed host cell containing a nucleic acid molecule encoding the Hsp60 or portion thereof. In further certain embodiments, the isolated Hsp60 polypeptide comprises greater than 95% homology to the Hsp60 polypeptide of FIG. 21, and the isolated Hsp60 polypeptide is able to be selectively bound by an antibody specific for a Candida glabrata Hsp60.
In still yet another aspect the present invention provides an isolated polypeptide wherein the polypeptide is an expression product of a transformed host cell containing at least one of the aforementioned nucleic acid molecules derived from Candida.
In still yet further aspects the present invention provides vectors comprising at least one of the aforementioned nucleic acid molecules derived from Candida. In certain embodiments, the vector is an expression vector comprising a promoter in operative linkage with the isolated nucleic acid molecule encoding the Hsp60 or portion thereof, preferably further comprising a selectable or identifiable marker and/or wherein the promoter is a constitutive or an inducible promoter. The present invention also provides host cells containing such vectors. In certain embodiments, the host cell is selected from the group consisting of a bacterial cell, a mammalian cell, a yeast cell, a plant cell and an insect cell.
In still yet other aspects the present invention provides compositions comprising a Candida Hsp60 polypeptide in combination with a pharmaceutically acceptable carrier or diluent. In certain embodiments, the composition is suitable for systemic administration, oral administration, intranasal administration or parenteral administration.
In yet other aspects the present invention provides methods for eliciting or enhancing an immune response in a mammal against Candida, comprising administering to the mammal in an amount effective to elicit or enhance the response, a Candida Hsp60 polypeptide in combination with a pharmaceutically acceptable carrier or diluent; methods for eliciting or enhancing an immune response in a mammal to a polypeptide comprising administering to the mammal a fusion protein containing sequences of the polypeptide fused to the Candida Hsp60 polypeptide in combination with a pharmaceutically acceptable carrier or diluent; and methods for eliciting or enhancing an immune response in a mammal against a target antigen comprising administering to the mammal the target antigen joined to a Candida Hsp60 polypeptide in combination with a pharmaceutically acceptable carrier or diluent.
In still another aspect, this invention provides PCR primers and probes for detecting DNA encoding a Candida glabrata Hsp60 that includes at least about 15 contiguous bases from any one of SEQ. ID NOS: 8-10, or to compliment thereof. In a related aspect, the invention provides a method for diagnosing the presence of Candida glabrata in a subject sample that includes the steps of obtaining a DNA fraction from the subject sample; and performing a PCR amplification of the DNA fraction using at least one PCR primer that includes at least about 15 contiguous bases from any one of SEQ. ID NOS: 8-10, or a compliment thereof.
These and other aspects of the present invention will become evident upon reference to the present specification and the attached drawings. In addition, various references are set forth herein that describe in more detail certain procedures or compositions (e.g., plasmids, etc.); all such references are incorporated herein in their entirety by reference.

Heat shock genes and proteins from Neisseria meningitidis, Candida glabrata and Aspergillus fumigatus