In one embodiment, this invention pertains to desalination of seawater by eding methane into seawater at a depth exceeding 100 meters to form methane hydrate which rises to where it is decomposed into methane and water, and recovering water. Methane is recycled.

1. Field of Invention
This invention pertains to desalination of seawater by formation of methane hydrate at appropriate temperature and pressure conditions and subsequent formation of potable water therefrom.
2. Description of Prior Art
Original methods proposed for desalinating seawater involved distillation where seawater is heated to the boiling point and water vapor is then condensed to form fresh water. Distillation includes the use of sunlight to evaporate water and then collecting the condensate to form fresh or potable water.
Desalination by distillation was followed by the use of reverse osmosis which involves diffusion of fresh water from seawater through a semipermeable membrane due to the high pressure applied to the seawater feed tank. Desalination by reverse osmosis is considered more expensive than desalination by distillation primarily due to the cost of the semipermeable membranes and the high pressure pumps required.
Presently, desalination of seawater is effected by freezing. In indirect freezing, freezing is accomplished by circulating a cold refrigerant through a heat exchanger to remove heat from the seawater. Ice is formed on the heat exchanger surface and is removed, washed and melted to produce fresh water. In the category of freeze desalination by direct freezing, where desalination is carried out by the vacuum freezing vapor compression process, heat is removed from seawater by direct contact with a refrigerant. In a secondary refrigerant mode of this process, a refrigerant that has low solubility in water is compressed, cooled to a temperature close to the freezing temperature of salt water and mixed with seawater. As the refrigerant evaporates, heat is absorbed from the mixture and water freezes into ice.
Various alternative proposals for freezing desalination are described in paper entitled "Desalination by Freezing" by Herbert Wiegandt, School of Chemical Engineering, Cornell University, March 1990.
In gas hydrate or clathrate freeze desalination, a gas hydrate spontaneously is formed of an aggregation of water molecules around a hydrocarbon at temperatures higher than the freezing temperature of water. When gas hydrate is melted, fresh water and the hydrocarbon are recovered, thus simultaneously, producing fresh water and the hydrocarbon which can be recirculated. This has the advantage over other direct freezing processes in that the operating temperature is higher, thus reducing power requirements when forming and when melting the gas hydrates.
U.S. Pat. No. 5,553,456 to McCormack, discloses a clathrate freezing desalination system and method in which a clathrate forming agent is injected through a submerged pipeline to a predetermined ocean depth at which the surrounding ocean temperature is less than the clathrate forming temperature. The agent combines with the salt water to form a slurry of clathrate ice crystals and brine. The pipeline is concentric and coaxial with a surrounding outer pipeline in which the slurry is formed. The slurry is pumped back to the surface through the outer pipeline and the ice crystals are washed to remove brine. The washed crystals are then melted and the resultant water is seperated from the clathrate forming agent, which may be discarded or recycled for re-injection through the inner pipeline. The melting of the clathrate ice as well as the cold water and air circulating in the desalination plant can be utilized as a source of air conditioning for local buildings and facilities.
The clathrate forming agents disclosed by the U.S. Pat. No. 5,553,456 include carbon dioxide, halogenated methanes and ethanes, and cyclopropane. A clathrate is a generic term for an inclusion compound composed of water and other molecules of smaller size. Methane hydrate is a specific clathrate.

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


A method for analyzing or processing contrast enhanced medical imaging information includes determining whether one or more candidate voxel sets within a Volume of Interest (VOI) exhibit washout curve behavior. If so, the method may identify a candidate voxel set exhibiting washout behavior as a likely malignancy. Otherwise, a method may determine whether one or more candidate voxel sets within the VOI exhibit plateau curve behavior, in which case the method may identify a candidate voxel set exhibiting plateau behavior as a likely malignancy. Otherwise, the method may identify a candidate voxel set exhibiting persistent enhancement behavior as a likely malignancy. In one embodiment, a candidate voxel set exhibiting a given type of time dependent imaging signal intensity curve or profile may be identified as a likely malignancy based upon a highest percent enhancement value.

Medical imaging technologies can provide detailed information useful for differentiating, diagnosing, or monitoring the condition, structure, and/or extent of various types of tissue within a patient's body. In general, medical imaging technologies detect and record manners in which tissues respond in the presence of applied signals and/or injected or ingested substances, and generate visual representations indicative of such responses.
A variety of medical imaging technologies exist, including Computed Tomography (CT), Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), and Magnetic Resonance Imaging (MRI). Particular imaging techniques, for example, certain MRI techniques, may scan a volume of tissue within a region of anatomical interest. Scan information or data corresponding to an anatomical volume under consideration may be transformed into or reconstructed as a series of planar images or image "slices." For example, data generated during a breast MRI scan may be reconstructed as a set of 40 or more individual image slices. Any given image slice comprises an array of volume elements or voxels, where each voxel corresponds to an imaging signal intensity within an incremental volume that may be defined in accordance with x, y, and z axes. The z axis commonly corresponds to a distance increment between image slices, that is, image slice thickness.
Any given medical imaging technology may be particularly well suited for differentiating between specific types of tissues. A contrast agent administered to the patient may selectively enhance or affect the imaging properties of particular tissue types to facilitate improved tissue differentiation. For example, MRI may excel at distinguishing between various types of soft tissue, such as malignant and/or benign breast tumors or lesions that are contrast enhanced relative to healthy breast tissue in the presence of Gadolinium DPTA or another contrast agent.
Medical imaging techniques may generate or obtain imaging data corresponding to a given anatomical region at different times or sequentially through time to facilitate detection of changes within the anatomical region from one scan to another. Temporally varying or dynamic tissue dependent contrast agent uptake properties may facilitate accurate identification of particular tissue types. For example, in breast tissue, healthy or normal tissue generally exhibits different contrast agent uptake behavior over time than tumorous tissue. Moreover, malignant lesions generally exhibit different contrast agent uptake behavior than benign lesions ("Measurement and visualization of physiological parameters in contrast-enhanced breast magnetic resonance imaging," Paul A. Armitage et al., Medical Imaging Understanding and Analysis, July 2001, University of Birmingham).
In general, at any particular time, the intensity of an imaging signal associated with any particular voxel depends upon the types of tissues within an anatomical region corresponding to the voxel; the presence or absence of a contrast agent in such tissues; and the temporal manners in which such tissues respond following contrast agent administration. In several types of breast MRI situations, normal or healthy tissue exhibits a background signal intensity in the absence of a contrast agent, while abnormal or tumorous tissue exhibits a low or reduced signal intensity relative to the background intensity. Thus, prior to contrast agent administration, abnormal tissue typically appears darker than normal tissue. In the presence of a contrast agent, lesions or certain types of abnormal tissue typically exhibit a time-dependent enhancement of imaging signal intensity relative to the background intensity.
In general, a lesion will exhibit one of three types of time dependent contrast agent uptake behavior. Within imaging data corresponding to a time series of scans, each type of contrast agent uptake behavior manifests as a corresponding type of dynamic imaging signal intensity profile or curve. Each type of dynamic intensity curve probabilistically corresponds to whether the lesion is benign or malignant.
FIG. 1 is a graph 100 that generally illustrates a first, a second, and a third type of dynamic imaging signal intensity or relative enhancement curve 110, 120, 130 that may be obtained for a given region of interest (ROI) (i.e., a set of voxels corresponding to an anatomical region) that encompasses one or more portions of a lesion. In the graph 100, the horizontal axis corresponds to time, while the vertical axis corresponds to imaging signal intensity or the extent to which imaging signal intensity is enhanced relative to an initial or precontrast imaging signal intensity.
Prior to contrast agent administration, a precontrast scan is initiated or performed at a first scan time t0. For any given voxel, the precontrast scan establishes a precontrast imaging signal intensity and/or a reference relative enhancement value that may be represented as a variable S0. Contrast agent administration occurs some time after t0 at a time tc, for example, one minute after t0. Essentially immediately after contrast agent administration, the level of contrast agent within vasculature associated with a lesion increases. Imaging signal intensity or relative imaging signal enhancement associated with the lesion correspondingly increases, typically at a rapid rate during an initial time interval. Depending upon lesion characteristics, tissue dependent contrast agent kinetics may subsequently give rise to in an imaging signal intensity curve that (1) continues to increase or enhance; (2) reaches a peak level of enhancement and then levels off or plateaus in an abrupt or generally abrupt manner; or (3) reaches a peak level of enhancement and subsequently declines to lower or reduced levels of enhancement. Each of the aforementioned curve types is respectively referred to as (1) a continued, steady, or persistent enhancement curve 110; (2) a plateau curve 120; and (3) a washout curve 130.
A first postcontrast scan is performed at a first postcontrast scan time t1, which generally corresponds to a time at or near which a peak in imaging signal intensity and/or relative enhancement S1 would be expected in the context of a plateau or washout curve 120, 130. The first postcontrast scan time t1 may be, for example, one minute after contrast agent administration. For ease of understanding, S1 is shown in FIG. 1 as having an identical value for each curve type 110, 120, 130. More generally, each type of curve 110, 120, 130 may correspond to a unique or distinct S1 value.
A second postcontrast scan is performed at a second postcontrast scan time t2, thereby capturing or acquiring for each voxel another corresponding imaging signal intensity and/or relative enhancement value S2. The interval between t1 and t2 is sufficiently large to improve or maximize a likelihood that imaging signal intensity differences corresponding to times t1 and t2 can facilitate categorization of an imaging signal intensity curve as a persistent enhancement, plateau, or washout curve 110, 120, 130. The time between t1 and t2 may be, for example, approximately 4 minutes.
Dynamic imaging signal intensity or relative enhancement curves are typically numerically characterized in accordance with two parameters, namely, a percent enhancement (PE) value and a signal enhancement ratio (SER). For a given voxel, the PE value is defined as the difference between the first postcontrast imaging signal intensity S1 and the precontrast signal intensity S0, normalized relative to the precontrast signal intensity S0. The SER for any particular voxel may be defined as the difference between the first postcontrast imaging signal intensity S1 and the precontrast signal intensity S0, normalized relative to the difference between the second postcontrast imaging signal intensity S2 and the precontrast signal intensity S0. For persistent enhancement, plateau, and washout curves 110, 120, 130, the SER will have a value that is less than 1.0, equal to 1.0, and greater than 1.0, respectively.
PE values exhibit a correspondence to lesion type. In general, a higher PE value may suggest a higher probability that a lesion is malignant. Some existing systems and/or methods for analyzing dynamic MRI data identify a set of voxels corresponding to a highest PE value or a highest intensity as a malignant lesion. Other existing systems and/or methods may identify (1) a set of voxels corresponding to a PE value above a first reference value as a malignant lesion; (2) a set of voxels corresponding to a PE value below the first reference value and above a second reference value as an indeterminate type of lesion; and (3) a set of voxels corresponding to a PE value below the second reference value as a benign lesion ("Dynamic Breast MR Imaging: Are Signal Intensity Time Course Data Useful for Differential Diagnosis of Enhancing Lesions?", Christiane Kuhl et al., Radiology, April 1999).
Curve type 110, 120, 130 also exhibits a correspondence to lesion type. In particular, a washout curve 130 is strongly indicative of a malignant lesion or weakly indicative of a nonmalignant or benign lesion. A plateau curve 120 may be somewhat more indicative of a malignant lesion than a benign lesion. Finally, a persistent enhancement 110 curve is strongly indicative of a benign lesion or weakly indicative of a malignant lesion. Certain methods for analyzing dynamic MRI data identify a curve shape of washout 130 or plateau 120 as malignant, and a persistent enhancement 110 curve as benign (ibid).
Unfortunately, systems and/or methods that analyze contrast enhanced medical imaging data in manners described above fail to adequately increase or maximize diagnostic sensitivity, specificity, and/or accuracy.

System and method for hierarchical analysis of contrast enhanced medical imaging information


The present invention provides N-phosphonomethylglycine guanidine salts. The N-phosphonomethylglycine guanidine salts have improved herbicidal efficacy over glyphosate alone. The present invention also provides guanidine compounds and salts thereof.

The present invention relates to N-phosphonomethylglycine guanidine derivative salts and herbicidal compositions including such salts.
N-phosphonomethylglycine (glyphosate) is well known as a highly effective, widely used and commercially effective herbicide useful for combating the presence of a wide variety of unwanted vegetation. Glyphosate in its strict sense is an acid compound, but the word "glyphosate" is used herein in a less restrictive sense to encompass not only glyphosate acid but also salts, adducts and esters thereof, and compounds of which are converted to glyphosate in plant tissues or which otherwise provide glyphosate ions. Glyphosate has three acid sites, and can therefore form tribasic salts. Monovalent glyphosate anions predominate at around pH 4. Divalent glyphosate anions predominate at about pH 7-8. Preferred aqueous compositions typically have a pH value not greater than about 8. At these pH values the fraction of glyphosate existing as a tribasic salt is negligibly small.
Glyphosate has low water solubility in free acid form, and is often formulated in commercial compositions in the form of a water soluble salt. Salts in commercial use include the ammonium salt, alkylamine salts, including the isopropylamine salts, alkali metal salts and the trimethyl sulfonium salts. Aminoguanidine salts of glyphosate are also common. Exemplary herbicidal salts of glyphosate are disclosed in U.S. Pat. No. 3,799,758 to Franz, U.S. Pat. No. 3,853,530 to Franz, U.S. Pat. No. 4,140,513 to Prill, U.S. Pat. No. 4,315,765 to Large, U.S. Pat. No. 4,405,531 to Franz, U.S. Pat. No. 4,481,026 to Prisbylla and U.S. Pat. No. 4,507,250 to Bakel. In most of these salts, the counterion to the glyphosate anion is a relatively low molecular weight, non amphiphilic cation.
Many commercial formulations of glyphosate salts utilize these low molecular weight, non-amphiphilic salts. Commercial formulations of glyphosate salts containing the isopropylammonium salt include Roundup®, Accord®, and Roundup Ultra® herbicides, all commercially available from Monsanto Company. Commercial formulations of glyphosate containing the ammonium salt include Roundup® Dry and Rival® herbicides, both commercially available from Monsanto Company. Commercial formulations of glyphosate containing the sodium salt include Roundup® Geoforce herbicide of Monsanto Company, and commercial formulations containing the trimethylsulfonium salt include Touchdown® herbicide commercially available from Syngenta.
Salts of glyphosate possessing higher molecular weight, amphiphilic cations have also been disclosed. These amphiphilic cations include those having a hydrophilic moiety such as ammonium, ethanolammonium, polyoxyethylene ammonium, or sulfonium group, and a hydrophobic moiety containing between 1 to 4 hydrocarbyl groups having in total more than 6 carbon atoms. For example, U.S. Pat. No. 4,405,531 discloses primary, secondary, and tertiary ammonium salts of glyphosate possessing an amphiphilic cation having a molecular weight less than 300. U.S. Pat. No. 5,668,085 discloses a salt in which the cations of the glyphosate salt are derived from the surfactant. Specifically, U.S. Pat. No. 5,668,085 discloses ammonium salts of glyphosate with amphiphilic cations derived from polyoxyethylene tertiary C8-22 alkylamine surfactants. U.S. Pat. No. 5,668,085 discloses as an example N-cocoalkyl-N,N-diethanolammonium salt of glyphosate where "cocoalkyl" refers to a mixture of predominantly C12 and C14 alkyl chains, derived from coconut oil.
Glyphosate is usually applied to foliage together with amphiphilic materials, particularly surfactants. Surfactants enhance the biological effect of glyphosate in a number of ways, not all of which are completely understood. When glyphosate is applied to foliage as a dilute aqueous composition by conventional hydraulic spraying, the presence of surfactant in the aqueous composition can generally increase the percentage of smaller spray droplets and decrease the percentage of large spray droplets. Smaller droplets tend to have lower momentum than larger droplets and are more likely to be retained on a foliar surface and less likely to rebound from that surface. Spray retention is also facilitated by adhesion between surfactant molecules in a spray droplet and the foliar surface which is typically waxy and hydrophobic in most plants. This adhesion also aids in preventing the rebounding of droplets from the foliar surface and the run-off of droplets from the foliar surface. Surfactants also tend to increase the area of contact between a spray droplet and the foliar surface and thereby tend to enhance penetration of glyphosate from the droplet into and through the cuticles of leaves to access internal plant tissues.
The basicity possessed by guanidines and guanidine derivatives has contributed to their use in a wide variety of applications, ranging from cleaning products to additives in cosmetics.


A method of manufacturing a fan from a plurality of fan blades (12), comprising the steps of: providing an injection moulding tool (30) which defines a fan hub section (14); assembling a predetermined number of preformed fan blades with the injection moulding so that inner ends (16) of said blades extend into moulding cavities (32) within the tool, injecting synthetic plastics material into the tool, and allowing the injected material to cool or cure to thereby form a moulded hub with the inner ends of the blades bonded therein.

This invention relates to improvements in fans and relates particularly to improvements in axial fans wherein a plurality of fan blades extend radially from a hub.
Fans are commonly formed of synthetic plastics material by injection moulding. An injection moulding tool is made which defines the shape configuration and structural features of the moulded fan. However, the cost of injection moulding tools is extremely high and a different tool is required for fans of different shapes, sizes, blade pitch angles, number of blades, hub structures and shapes and the like.
While it is known to manufacture fans using an assembly process where individual blades are attached to a hub by a fastener or the like, such processes are relatively expensive due to the handling and assembly time.
It is therefore desirable to provide an improved fan structure which obviates at least some of the disadvantages of the existing fans.
It is also desirable to provide an improved method of manufacturing a fan which obviates disadvantages of existing manufacturing methods.
It is also desirable to provide an improved method of manufacturing a fan which facilitates varying the fan characteristics.
It is also desirable to provide an improved fan manufacturing process which is relatively simple and is economical.
It is also desirable to provide an improved fan manufacturing method which produces a single piece fan.
It is also desirable to provide a method of manufacturing fans of different sizes, configurations and with different properties using standard components.


The invention is a thermofusible adhesive composition comprising:. a at least one essentially amorphous poly(alpha-olefin), PA1 b at least one copolymer of ethylene and an alkyl (meth)acrylate, the cloud point being below 170.degree. C.

Thermofusible, or "hot-melt", adhesives are solid at room temperature. It suffices to melt them by heating between 150 and 200.degree. C., setting occurring by cooling.
The main constituents of a thermofusible adhesive are: a base copolymer, a tackifying resin, waxes, stabilizers, and optionally fillers.
Polyolefins, copolymers thereof, polyamides, and so on, may be used as the base copolymer. The base copolymer constitutes the core of the hot melt. It provides and determines its general properties, in particular, cohesion, thermal behavior, and stability.
The tackifying resin imparts better hot adhesive power to the thermofusible adhesive, and thus better adhesion at the application temperatures.
The waxes make it possible to control the viscosity and to modify the rheological curve of the base polymer as a function of the temperature.
The stabilizers are antioxidants or anti-UV agents. They increase the resistance to ageing of the mixture.
The plasticizers modify the cold properties of the hot-melt and in particular the flexibility of the adhesively bonded joint.
U.S. Pat. No. 4,816,306 of the prior art describes thermofusible adhesives composed of:
a. 35 to 45% by weight of the ethylene/n-butyl acrylate copolymer; PA1 b. 35 to 55% of a tackifying resin; PA1 c. 10 to 20% of a wax with a high melting point. PA1 A 100 parts of polymers: PA1 Aa 25 to 75% of an ethylene copolymer, PA1 Ab 75 to 25% of an ethylene/unsaturated carboxylic acid ester copolymer, and PA1 B 25 to 200 parts of a tackifying resin; PA1 a at least one essentially amorphous poly(alpha-olefin), PA1 b at least one copolymer of ethylene and an alkyl (meth)acrylate, PA1 viscosity at 190.degree. C. between 3000 and 50,000 mPa s, PA1 softening temperature (bead and ring, ASTM D 28) between 80 and 160.degree. C., PA1 needle penetration (0.1 mm) of 4 to 21, PA1 density at 23.degree. C. between 0.85 and 0.9 g/cm.sup.3, PA1 viscosity index (J) between 40 and 95 cm.sup.3 /g, PA1 molecular weight MW between 30,000 and 75,000, PA1 intrinsic viscosity (100 ml/g) between 0.4 and 0.9.
Application JP 60 096676 KOKAI published on May 30, 1985 describes thermofusible adhesives consisting of:
at least one of the polymers A being grafted with an unsaturated carboxylic acid or a derivative and the viscosity of these adhesives being, at 180.degree. C., less than 50 Pascal seconds.
The examples show that Aa is chosen from ethylene-propylene or ethylene-butene rubbers and Ab is an ethylene/ethyl acrylate copolymer, at least one being grafted with maleic anhydride.
The quality of the adhesion obtained is measured by the SAFT test according to ASTM D 4498, which measures the cohesion limit temperature at shear, and by the T peeling test according to ASTM 1876-72.


Disclosed is a joint guarantee system for vehicle assembly. The disclosed joint guarantee system for vehicle assembly manages a joining history of a joined component joined to a plurality of join points of a joining target, and includes: i) a tool detecting unit installed at a joining tool for joining the joined component to the joining target, and configured to detect movement displacements and angles of the joining tool for the join points based on a zero point of the joining tool; ii) a tool controller configured to receive a joining completion signal of the joining tool for each join point, and transmit a movement displacement value, an angle value, and a joint value for each join point of the joining tool detected by the tool detecting unit; and iii) a main controller configured to determine joining operation patterns for the join points based on the movement displacement value of the joining tool obtained from the tool controller.

1. Field of the Invention
The present invention relates to vehicle assembly system, and more particularly, to a joint guarantee system for vehicle assembly, which is capable of managing a joining history of a component for a vehicle body in an assembly line, in which the component is assembled with the vehicle body, and a control method thereof.
2. Description of Related Art
In general, a vehicle maker assembles tens of thousands of components by a lot of welding and assembly processes within all of the mass production processes until the vehicle is produced.
Particularly, most of the operations performed in an assembly process among production processes for a completed vehicle are a joining process of joining various components to a vehicle body by using a coupling member, such as bolts and nuts.
Since the joining process is directly associated with a quality index of a vehicle, such as durability or silence of a completed vehicle, felt by a consumer, a thorough joining history management of components for the vehicle body is necessary.
However, even though a corresponding business field recognizes significance of the joining history management of the components for the vehicle body, the joining history management having high effectiveness has not been properly performed due to a technical limitation.
The information disclosed in this Background of the Invention section is only for enhancement of understanding of the general background of the invention and should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person skilled in the art.

Joint guarantee system for vehicle assembly and control method of the same


An asynchronous data segmentation/transmission method for synchronous Ethernet and a data structure used therein are disclosed. The asynchronous data segmentation/transmission method can segment and transmit asynchronous data such that the asynchronous data can be transmitted through a transmission frame for each transmission cycle. The method for synchronous Ethernet includes the steps of: a) comparing a size (L2) of asynchronous data to be transmitted with a size (L1) of transmission space vacant in an asynchronous frame part of a transmission frame, b) inserting the asynchronous data to be transmitted into the transmission space if the size (L2) of the asynchronous data is equal to or less than the size (L1) of the transmission space, and c), if the size (L2) of the asynchronous data is larger than the size (L1) of the transmission space, segmenting the asynchronous data to fit the size (L1) of the transmission space to insert the segmented asynchronous data thereto, and inserting remaining asynchronous data (L2-L1) into a next transmission frame. The transmission frame includes a More flag field for indicating asynchronous data segmentation/transmission.

1. Field of the Invention
The present invention relates to synchronous Ethernet, and more particularly to an asynchronous data segmentation/transmission method for synchronous Ethernet and a data structure used therein.
2. Description of the Related Art
Generally, Ethernet is one of the common technologies for communicating data between a variety of terminals through a LAN (Local Area Network). However, the Ethernet technique is not suitable for transmission of moving pictures or voice data that are sensitive to transmission time delay. A technique for synchronously transmitting data such as image and voice has been actively researched and developed based on the conventional Ethernet. This technique is called synchronous Ethernet.
FIG. 1 is a view illustrating a transmission frame structure for general synchronous Ethernet.
As shown in FIG. 1, the transmission frame based on one transmission cycle includes an asynchronous (hereinafter referred to as Asynch) frame part 11 for asynchronous data transmission, a control frame part 12 for control frame transmission, and a synchronous (hereinafter referred to as Sync) frame part 13 for synchronous data transmission. The transmission frame has a transmission cycle of 125 μs.
More specifically, the Synch frame part 13 for synchronous data transmission has the highest priority in the transmission cycle. According to a currently proposed standard (which my be changed in the future), the Synch frame part 13 includes a plurality of 738-byte sub-synchronous frames, basically 10.
Also, the control frame part 12 for control frame transmission includes a TSC (Time Sensitive Control) frame for time control and an MDCP (Media Device Control Protocol) frame for controlling media devices.
Further, the Asynch frame part 11 for asynchronous data transmission includes variable synchronous data based on frame units.
FIG. 2 is a diagram illustrating the structure of general asynchronous data.
As shown in FIG. 2, general asynchronous data, such as Ethernet data, is composed of 7 bytes. The general asynchronous data includes a Preamble field 301 for indicating a start and end of a frame, an SFD (Start-of-Frame Delimiter) field 302, composed of 1 byte, for identifying a byte unit in a frame bit sequence and indicating a start of contents of the frame in a normal state, a Destination Address (DA) field 303, composed of 6 bytes, for indicating a destination MAC (Media Access Control) address to be transmitted to the transmission frame, a Source Address (SA) 304, composed of 6 bytes, field for indicating MAC address of a station transmitting the frame, a length/type (L/T) field 305, composed of 2 bytes, for indicating length information of data in the transmission frame and type information of protocol for the transmission frame, a data field 306 for indicating data of the frame, and a FCS (Frame Check Sequence) field 307, composed of 4 bytes, for detecting errors at respective ends of frames into which information is segmented for transmission.
Frequently, the Preamble field 301 and the SFD field 302 may be represented by a Preamble field including the SFD field 302. In that case, the Preamble field may be composed of, for example, 8 bytes.
FIG. 3 is a diagram describing general asynchronous data transmission in synchronous Ethernet, in which there are two transmission frames based on two transmission cycles.
As shown in FIG. 3, a first transmission frame based on a first transmission cycle includes a Synch frame part 13-1, a control frame part 12-1 and an Asynch frame part 11-1. A second transmission frame based on a second transmission cycle includes a Synch frame part 13-2, a control frame part 12-2 and an Asynch frame part 11-2.
Since the Synch frame parts 13-1 and 13-2 and the control frame parts 12-1 and 12-2 are not related to the subject matter of the present invention, a detailed description thereon will be omitted. Instead the Asynch frame parts 11-1 and 11-2 will be described in detail as below.
The Asynch frame part 11-1 includes Asynch frames 201, 202 and 203, which are variable in length. The Asynch frame part 11-2 also includes Asynch frames 204, 205 and 206, which are variable in length. Accordingly, since the respective Asynch frames are variable in length, their sizes are also different.
In order to perform operations of the transmission frames, if the length of the last Asynch frame 203 within the first transmission cycle 11-1 is L1 and Asynch data 21 to be transmitted has a length of L2, the two lengths are compared before the Asynch data 21 is inserted into the transmission frame for the transmission cycle. If L1 is equal to or greater than L2, the Asynch data 21 to be transmitted is inserted into the Asynch frame 203 and then transmitted to a predetermined destination.
If L1 is less than L2, the Asynch data 21 to be transmitted cannot be inserted into the Asynch frame 203. Therefore, the Asynch frame 203 without data is transmitted to a predetermined destination. Instead the Asynch data 21 is inserted into the first Asynch frame 204 within the second transmission cycle 11-2 and then transmitted to a predetermined destination.
As such, in the prior art transmission method, the Synch frame part and control frame part within a transmission cycle of 125 μm are first transmitted to a predetermined destination and then the Asynch frame part is transmitted based on the comparison of the last Asynch frame length with the length of the Asynch data to be transmitted. However, if the length L2 of the Asynch data 21 is not equal to the length of the last Asynch frame, the Asynch data 21 is not transmitted during the first transmission cycle, and instead must be inserted into the next transmission frame for the next transmission cycle.
Therefore, the prior art transmission method has a disadvantage in that, since a transmission frame including an Asynch frame without Asynch data to be transmitted is transmitted based on a first transmission cycle if the sizes of the Asynch frame and the Asynch data are different from each other, it wastes bandwidth corresponding to the size of the Asynch frame during the first transmission cycle.

Asynchronous data segmentation/transmission method for synchronous Ethernet and data structure used therein

Maetan-Dong, Yeongtong-Gu, Suwon-Si, Gyeonggi-Do


A method and system for automatic object refresh. A target object specification is associated to a source object specification for performing a replacement (refresh) of at least one target object with a corresponding source object. When a target object is accessed for the first time, or released from a last access, one or more source objects may replace (refresh) the locations of one or more corresponding target objects. A comparison of values of an identical attribute may be performed, such as a date/time stamp, or trap count, of corresponding source and target objects. The refresh may be conditional depending on the outcome of the comparison. The conditional refresh is: an automatic replacement of at least one of the objects of the target object specification with a corresponding object of the source object specification, an automatic asynchronous notification that a more current or suitable object exists and option for automatic refresh therefrom, or an automatic replacement of at least one of the objects of the target object specification with a corresponding object of likely better stability. The source object specification and target object specification may be specified with wildcards, map files, or environment variables. The source objects and target objects may be located locally, or remotely, to the data processing system that accesses the objects.

A software product typically goes through many iterations of development releases, usually in parallel with problem fixes, functionality upgrades, performance improvements, etc. In a dynamic environment where it is important to take advantage of application functions as they become available, for example, for test or use purposes, a user is burdened with figuring out when to refresh executable code for the most current release. A user seeks status for when a later revision of executable code is available. Then the later version may be installed, or the files of importance from the development build must be copied to the correct location. There are many manual steps in this refresh process. A method is needed for automatically performing object code refreshes as soon as is appropriate, without user intervention, to assure the latest greatest level of software at all times.
A user may experience difficulty with later revisions of developed software. It becomes advantageous to backout the system to the previous and more stable level of software. Upon determining that the current product build warrants refreshing object code with a previous version, there are manual processes involved with performing the backout. Different users may also have different tolerances of when to backout. In such situations, an automated method is needed for consistently determining when backout is required, and then backing out a software refresh to a more stable level.

Method and system for automatic object refresh


An oscillating shuttle, including a shuttle race having a substantially annular guide groove including two end portions opposed to each other in a circumferential direction thereof, a shuttle body which includes a part-annular guided portion and a hook portion and which is oscillatory while the guided portion is guided by the guide groove, a driver which rotates the shuttle body about an axis line, wherein when the hook portion hooks a thread loop, the shuttle body is rotated by the driver in one of opposite directions such that the tail portion passes through one of the two end portions of the guide groove and enters an upper opening of the shuttle race and, when the shuttle body is rotated back in the other direction, a tail portion of the guided portion enters the one end portion of the guide groove, and at least one of the one end portion of the guide groove which has, in a direction parallel to the axis line, a width greater than a width of a remaining portion of the guide groove, and the tail portion of the guided portion which has, in a direction parallel to the axis line, a width smaller than a width of a remaining portion of the guided portion.

1. Field of the Invention
The present invention generally relates to an oscillating shuttle of a sewing machine and relates particularly to the art of preventing a needle-thread loop from being bitten by the oscillating shuttle.
2. Related Art Statement
There is known a lock-stitch sewing machine which employs, as a thread-loop catcher including a hook portion for hooking or catching a loop of a needle thread conveyed by the eye of a sewing needle, and locking the needle-thread loop with a bobbin thread, a rotary hook which is fully rotatable at a high speed. There is also known a twin-needle sewing machine which employs, for performing bar-tack stitching on thick work sheets, two oscillating shuttles each of which has a driver which drives a shuttle body and includes a needle guard for preventing a corresponding sewing needle from being excessively moved toward the shuttle during its sewing operation. Since, in an oscillating shuttle, a loop of a needle thread is released from a hook portion at an early timing, the needle thread is easily drawn up and the needle-thread loop is well tightened. An oscillating shuttle includes a first shuttle race member which is attached to a bed of a sewing machine such that the first race member takes a horizontal attitude; a second shuttle race member which is detachably attached to the first race member to provide a shuttle race; a shuttle body which is accommodated in an inner space of the shuttle race; and a driver which drives or half-rotates the shuttle body in opposite directions.
FIG. 10 shows a known oscillating shuttle 100 which includes a first shuttle race member 102; a second shuttle race member 103 which is detachably attached to the first race member 102 to provide a shuttle race having a substantially annular guide groove 107 at an interface where the second race member 103 is attached to the first race member 102; a shuttle body 104 which has a generally semi-circular shape as viewed from its front side and which includes a generally semi-annular guided portion 104b which is provided over a substantially entire outer surface thereof and which has a generally rectangular cross section; and a driver (not shown) which half-rotates the shuttle body 104 in opposite directions in synchronism with upward and downward movements of a sewing needle 111, while the guided portion 104b is slideably guided by the guide groove 107.
The known oscillating shuttle 100 is operated such that, when the sewing needle 111 is moved up by a small distance from its lowest position, the needle thread 112 conveyed by the eye of the needle 111 is hooked or caught by a hook portion 104a of the shuttle body 104 being rotated in a forward direction and, when the shuttle body 104 is generally half rotated in the forward direction, a widened loop 112a slips from the hook portion 104a. Then, as the shuttle body 104 is rotated in a backward direction opposite to the forward direction, and as a needle-thread take-up is substantially simultaneously moved up, the needle-thread loop 112a is tightened up while being locked with a bobbin thread supplied from a bobbin (not shown) accommodated in a bobbin case (not shown) supported by the shuttle body 104. The needle-thread loop 112a is passed between the driver and a rear end portion of the shuttle body 104 opposite to the hook portion 104a, and is drawn up through a throat plate 110, so that a lock stitch is formed on thick work sheets W1, W2.
In the case where the known oscillating shuttle 100 is used for sewing, using a thick needle thread, the plurality of thick work sheets W1, W2 (e.g., denim sheets) superposed on each other, the shuttle body 104 starts its reverse rotation at a timing at which the needle-thread loop 112a widened by the hook portion 104a slips from the same 14a. Substantially simultaneously, the needle-thread take-up starts its upward movement and accordingly the needle-thread loop is tightened. However, since the superposed thick work sheets W1, W2 exert a great resistance to the needle thread 112 being moved therethrough, the needle-thread take-up may fail to draw up a sufficient length of the needle thread 112. That is, as shown in FIG. 10, a lower end portion of the needle-thread loop 112a may be caught by a tail portion of the shuttle body 104 because the tightening of the loop 112 delays when the tail portion of the shuttle body 104 is moved back through an upper opening formed in respective upper end portions of the first and second race members 102, 103.
Thus, the lower end portion of the needle-thread loop 112a is forced to enter the spaces defined by opposite surfaces of the guided portion 104b of the shuttle body 104 and opposed surfaces of the first and second race members 102, 103 which cooperate with each other to define the guide groove 107. Since those spaces are very narrow, the loop 112a is bitten fast, and breaks.


A flow volume measurement device or a flow velocity measurement device include a measurement cell including a main pipe, an incident tube that is connected to the main pipe, an emission tube that is connected to the main pipe, and a first purge-fluid supply tube that is connected to the incident tube, a purge-fluid supply unit that supplies purge fluid into the first purge-fluid supply tube of the measurement cell, a light emitting unit that emits a laser beam to the measurement cell, a light receiving unit that receives the laser beam emitted from the light emitting unit and having passed through the measurement cell, and outputs a received amount of light as a light reception signal, a calculation unit that calculates a flow volume or a flow velocity of exhaust fluid flowing in the measurement cell, based on a light reception signal output from the light receiving unit.

As a method of measuring a flow volume of gas flowing in a flow channel, various methods have been proposed. For example, Patent Literature 1 describes a differential pressure flowmeter in which an orifice plate is arranged in a pipe, and a flow volume of fluid flowing in the pipe is measured by a pressure difference in the pipe at the front and back of the orifice plate.
Furthermore, Patent Literature 2 describes a flow volume measurement device in which a transmission element and a reception element of an ultrasonic wave are installed relative to each other with a certain angle in a flow direction of fluid, thereby measuring a flow volume of the fluid based on an ultrasonic propagation time. This flow volume measurement device includes means for oscillating an ultrasonic wave of a sinusoidal signal having frequency components of a first frequency and a second frequency that are different from each other, means for obtaining a phase difference between the first and second frequency components of the ultrasonic wave having propagated in the fluid, and means for computing an ultrasonic propagation time from the obtained phase difference. The flow volume measurement device calculates a flow velocity of the fluid from the ultrasonic propagation time to obtain the flow volume.

Flow volume measurement device and flow velocity measurement device


A method and system for exercising areas of the body such as the neck, the wrist, the ankle, and the torso which require a wide range of motion and effective resistance over this range. A first member can rotate in relation to a frame and a user interface (second member) is moveable in relation to the first member. As a user pushes on the user interface in any of an X-Y direction the user interface travels in a controlled arcuate three-dimensional motion. The user interface is attached to a lead (rope or cable) which holds the user interface at a rest position and also provides a force on the user interface in the opposite direction of the users force. The lead is attached to an adjustable resistive system and/or a damping system that resists the movement of the sliding assembly. The lead spools in and out of from a central location through a fairlead. Many mechanical configurations can be utilized to allow the user interface to travel in an arcuate path in the direction which it is pushed.

Exercise has become an important part of life in the civilized world. It has been proven that exercise can increase longevity, can rehabilitate injuries, can prevent injuries, can improve athletic performance, and can improve the way of life for many. Current exercise methods and apparatuses provide less-than-perfect performance for exercising certain body parts. More particularly, body parts that have a full range of motion have portions of the motion (directions of movement) that cannot be properly or safely loaded by a force during exercise. For example, current exercise apparatuses do not provide an effective multidirectional loaded movement for exercising the neck, wrist, lower back, shoulder, etc. Many joints such as the wrist and ankle bend, pronate and rotate. It is difficult if not impossible to exercise these parts of the body under load throughout their entire range of motion because these portions of the body move in almost all directions about a bone/socket arrangement or a vertebra-ligament-disk configuration. For example, the wrist can partially exercised by holding a barbell with the fingers and rotating the wrist but the current art lacks a controlled and uniform motion and load which allows a wrist to move under load in a 360-degree rotation during pronation or other complex movement about the wrist joint. An additional shortcoming with modern exercise equipment is that uncontrolled force in awkward positions or uncontrolled joint movements can cause injury. Although humans can move most joints 360 degrees, certain areas or ranges of movement are weak and too much load at a particular location and in a particular direction can tear connective tissue such as muscles ligaments and tendons. For example, during exercise with free weights, if the weight is too heavy or if the weight pulls the user into an awkward position, an exercise apparatus can easily tear muscles, tendons or ligaments causing injury. Thus, controlling the motion of the exercise, the direction of movement, the velocity of movement and amount and direction of the force during the exercise can prevent injuries, yet exercise regions that are currently dangerous to exercise and thus underserved. The present invention also allows the user to move to a rest position (position with no net force) after an exercise is over which is in the normal range of motion after exercise is complete, eliminating the need to "drop the weights". There are also shortcomings in evaluating athletic performance during these non-traditional motions and positions.

Exercise apparatus having a user interface which can move arcuately in three dimensions


A biotissue excising instrument includes a tubular sheath inserted into a body, manipulator inserted into the sheath through leading end of the manipulator and having a loop portion that can be unfolded and contracted to accommodate biotissue to be excised. A slit is formed leading end the sheath to project and sink loop portion of the treatment portion so that manipulator is advanced or retreated to laterally project or sink the loop portion out of or into the or contract the loop portion, the sheath, and a treatment portion provided at thus excising the biotissue loop portion.

The present invention relates to a biotissue excising instrument used to excise biotissue using, for example, a high-frequency current.
A high-frequency snare has hitherto been known as biotissue excising instrument used to excise biotissue using a high-frequency current. The high-frequency snare is, for example, composed of a sheath 100 inserted endoscopically into a coelom through, for example, a treatment instrument insertion channel in an endoscope, a manipulation portion 102 provided at a proximal end of the sheath 100, a manipulation wire 104 inserted into the sheath 100 from the manipulation portion 102, and a slider 106 provided in the manipulation portion 102 to manipulate the manipulation wire 104 so as to advance and retreat freely, as shown in FIG. 26.
The manipulation wire 104 has a snare wire 110 at its leading end portion as a treatment portion that freely projects out of and sinks into an opening 100a in the leading end of the sheath 100. The snare wire 110 is shaped like a loop. It unfolds owing to its own recovery force when projected out of the opening 100a in the leading end of the sheath 100 when the slider 106 slides forward as shown in FIG. 26. Further, the snare wire 110 is compressed to reduce its own diameter when the slider 106 is slid toward an operator to pull part of the snare wire 110 into the sheath 100 via the manipulation wire 104 as shown in FIG. 27.
Accordingly, to excise biotissue, for example, a polyp using a high-frequency snare configured as described above, the snare wire 110 projected out of the opening 100a in the leading end of the sheath 100 and then unfolded is first caught on the polyp A as shown in FIG. 28A. Subsequently, in this caught state, the manipulation wire 104 is pulled toward the operator (the slider 106 is slid toward the operator) to reduce the diameter of the snare wire 110 as shown in FIG. 28B. Thus, the polyp A is bound tightly. In this tightly bound state, a high-frequency current is passed through the snare wire 110 to excise the polyp A.
All conventional high-frequency snares are of a frontward projecting type in which the snare wire 110 projects out of the opening 100a in the leading end of the sheath 100. Thus, when biotissue is excised using only this forward-projecting type of high-frequency snare, several problems may occur as described below.
That is, with the forward projecting type high-frequency snare, the snare wire 110 is continuously contracted by the inner surface of the sheath 100 until the snare wire 110 projects out of the opening 100a in the leading end of the sheath 100. Thus, the snare wire 100 is not opened until it is projected out of the opening 100a in the leading end of the sheath 100 by a certain distance by sliding the slider 106 of the manipulation portion 102 forward by a predetermined stroke. That is, with the forward projecting type high-frequency snare, the stroke of the slider 106 of the manipulation portion 102 cannot be used efficiently for the operation of increasing the diameter of the snare wire 110. Thus, the snare wire 110 cannot be linearly unfolded according to the stroke of the slider 106.
Further, with the forward projecting type high-frequency snare, the snare wire 100 must be unfolded with the leading end of the sheath 100 located in front of the polyp A and then allowed to approach the polyp A from above it so that the loop portion of the snare wire 100 is caught on the polyp A as shown in FIGS. 29A and 29B. However, the polyp A formed in the body does not always accommodate such an approach. It may be difficult to excise the polyp using the forward projecting type high-frequency snare depending on the manner of formation of the polyp.
Furthermore, with the forward projecting type high-frequency snare, rotation of the sheath 100 only causes the snare wire 100 to rotate around the axis of the sheath 100. Thus, in spite a change in the direction in which the loop is opened, the position of the snare wire 110 is not changed. Consequently, if the polyp A is located, for example, at the side of the snare wire 110 and it is difficult to allow the snare wire to approach the polyp A (direct the opening 100a in the leading end of the sheath 100 toward the polyp A), then the snare wire 110 cannot be caught on the polyp A. Therefore, it may be virtually impossible to carry out excision using the snare wire 110.


A light for a vehicle has a reflector, a light source, a light-permeable disk covering a light outlet opening, the reflector having a central region which surrounds the light source and a lateral region, the central region of the reflector having a lateral opening through which a light emitted by the light source can reach the lateral reflector region, the lateral reflector region having at least in one zone a plurality of stepped reflection profiles, the lateral reflector region having an upper edge and a lower edge, at least one reflection segment arranged near one of the edges so that a light emitted from the light source impinges on the reflection segment through the opening of the central reflection region, the reflection segment having a greater extension than the reflection profile at least in a horizontal direction.

The present invention relates to a light for vehicles.
One of such lights is disclosed for example in the German patent document DE 32 39 754 C2. This light has a reflector, a light source and a light-permeable disk which covers the light outlet opening. The reflector has a central region which surrounds the light source and a lateral region. The central region of the reflector has a lateral recess, through which the light emitted by the light source can reach the lateral region of the reflector. The central region of the reflector is formed by two parts in form of parabeloid portions, through which the light emitted by the light source is reflected substantially parallel to the optical axis. The lateral region of the reflector is provided with a plurality of step wedge-shape reflection profiles, by which the light emitted from the light source is reflected. Thereby the light eliminates over its whole width, but the illumination of the lateral region of the reflector and thereby of the light is weaker than in the central region, since the light reflected only from the surfaces of the reflection profile which face the light source, while the surfaces of the reflection profile which away the light source does not receive any light and they are seen as dark. Moreover, a clear weakening of the illumination at the transition between the central and the lateral region of the reflector is visible.

Light for vehicles with stepped lateral reflector region


A transfer device which transfers a clamped load, by sliding the load, between a rack and an elevating table that are adjacent to each other, includes a contact body which comes into contact with the load; an arm which generates, through the contact body, a force in a clamping direction that is a horizontal direction with respect to the load; and a joint which connects the contact body and the arm movably in a vertical direction, without moving the contact body in the clamping direction with respect to the arm.

1. Field of the Invention
The present invention relates to a transfer device which transfers a load, by sliding the load, from a first storage space to a second storage space, and preferably may be used for a stacker crane, a station for automated transfer system, and other applications.
2. Description of the Related Art
A load transfer device is mounted on a stacker crane in order to transfer a load between a rack for holding the load and the stacker crane for loading and unloading the load to and from the rack. Such a load transfer device is also used for a station at which a load is loaded to or unloaded from a transfer vehicle for automatically transferring a load. Examples of a method for transferring a load between the first storage space and the second storage space include: a fork lifting method which includes lifting a load with forks; a suction pick-up method which includes picking up a load by applying suction thereto; a pick-up belt method which includes moving a load by a pick-up belt conveyor, and a pull-up method which includes pulling up a load using a claw placed on the back side of the load.
These methods for transferring have various disadvantages. For instance, in the fork lifting method, the load needs to be moved up and down at the time of transfer, and thus a relatively large space is required in upward and downward directions of the load. As a result, such a space becomes a dead space for a rack for storing the load. In the suction pick-up method, the load is held by a suction cup, and thus a surface condition of the load is limited. In the pick-up belt method, there are many restrictions such as a load having to overhang from a rack. In the pull-up method, a difference in level between a transfer origin and a transfer destination causes damage to a load which results from being scraped at the edge of the transfer destination or collapse of a corner of the load which results from being dropped onto the transfer destination.
Examples of a method for transferring which has relatively fewer disadvantages include a clamping method (see Japanese Unexamined Patent Application Publication No. 2002-167008). The clamping method includes: inserting arms 101 into a space available at the sides or the like of a load 200 in a direction (indicated by an arrow B) opposite to a transfer direction (indicated by an arrow A), as shown in FIGS. 8A and 8B; clamping the load with the arms 101, as shown in FIG. 8C; and sliding and transferring the load by moving the arms 101 holding the load 200 in the transfer direction.
The clamping method has, for example, an advantage of completing transfer in a short time in the case where shapes of loads to be transferred are standardized.
In the clamping method, however, the level of the transfer destination is often set slightly lower than that of the transfer origin so that a load is smoothly transferred. In such a situation, it is not possible to receive, from a surface of the transfer destination, a force for supporting the load from below at the time of transferring the load from the transfer origin to the transfer destination. When a portion in contact with the load cannot support the weight of the load, a frictional force is generated between the portion in contact with the load and the load, which may result in frictional wear of or damage to the portion in contact with the load. In particular, when an elastic body such as rubber is used for the portion in contact with the load, a problem such as necessity of frequently replacing the elastic body occurs. In contrast, when a transfer device continues to support the load, it is necessary to clamp the load excessively, thereby stressing the load. Moreover, releasing the clamped load causes the entire load to fall freely, thereby damaging the load or generating a kinetic friction force on the portion in contact with the load.


A method and apparatus for producing schedules for a wafer in a multichamber semiconductor wafer processing tool comprising the steps of providing a trace defining a series of chambers that are visited by a wafer as the wafer is processed by the tool; initializing a sequence generator with a value of a variable defining initial wafer positioning within the tool; generating all successor variables for the initial variable value to produce a series of values of the variable that represent a partial schedule; backtracking through the series of variables to produce further partial schedules; and stopping the backtracking when all possible variable combinations are produced that represent all possible valid schedules for the trace. All the possible schedules are analyzed to determine a schedule that produces the highest throughput of all the schedules.

1. Field of the Invention
The present invention relates to a multiple chamber wafer processing tool and, more particularly, to a method and apparatus for automatically generating a schedule(s) for a semiconductor wafer within a multiple chamber semiconductor wafer processing tool.
2. Description of the Background Art
Semiconductor wafers are processed to produce integrated circuits using a plurality of sequential process steps. These steps are performed using a plurality of process chambers. An assemblage of process chambers served by a wafer transport robot is known as a multiple chamber semiconductor wafer processing tool or cluster tool. FIG. 1 depicts, in part, a schematic diagram of an illustrative cluster tool known as the Endura(copyright) System manufactured by Applied Materials, Inc. of Santa Clara, Calif.
The cluster tool 100 contains, for example, four process chambers 104, 106, 108, 110, a transfer chamber 112, a preclean chamber 114, a buffer chamber 116, a wafer orienter/degas chamber 118, a cooldown chamber 102, and a pair of loadlock chambers 120 and 122. Each chamber represents a different stage or phase of semiconductor wafer processing. The buffer chamber 116 is centrally located with respect to the loadlock chambers 120 and 122, the wafer orienter/degas chamber 118, the preclean chamber 114 and the cooldown chamber 102. To effectuate wafer transfer amongst these chambers, the buffer chamber 116 contains a first robotic transfer mechanism 124. The wafers 128 are typically carried from storage to the system in a plastic transport cassette 126 that is placed within one of the loadlock chambers 120 or 122. The robotic transport mechanism 124 transports the wafers 128, one at a time, from the cassette 126 to any of the three chambers 118, 102, or 114. Typically, a given wafer is first placed in the wafer orienter/degas chamber 118, then moved to the preclean chamber 114. The cooldown chamber 102 is generally not used until after the wafer is processed within the process chambers 104, 106, 108, 110. Individual wafers are carried upon a wafer transport blade 130 that is located at the distal end of the first robotic mechanism 124. The transport operation is controlled by a sequencer 136.
The transfer chamber 112 is surrounded by and has access to the four process chambers 104, 106, 108 and 110 as well as the preclean chamber 114 and the cooldown chamber 102. To effectuate transport of a wafer amongst the chambers, the transfer chamber 112 contains a second robotic transport mechanism 132. The mechanism 132 has a wafer transport blade 134 attached to its distal end for carrying the individual wafers. In operation, the wafer transport blade 134 of the second transport mechanism 132 retrieves a wafer from the preclean chamber 114 and carries that wafer to the first stage of processing, for example, a physical vapor deposition (PVD) stage within chamber 104. Once the wafer is processed and the PVD stage deposits material upon the wafer, the wafer can then be moved to a second stage of processing and so on.
Once processing is complete within the process chambers, the transport mechanism 132 moves the wafer from the process chamber and transports the wafer to the cooldown chamber 102. The wafer is then removed from the cooldown chamber using the first transport mechanism 124 within the buffer chamber 116. Lastly, the wafer is placed in the transport cassette 126 within the loadlock chamber 122.
More generally, a cluster tool contains n chambers, denoted by C1, C2, . . . , Cn, one or more transfer chambers (robots) 112 and 116, and one or more loadlocks 120 and 122. The exact arrangement of chambers, robots and loadlocks is referred to as the xe2x80x9cconfigurationxe2x80x9d of the tool. A wafer Wa to be processed is taken from a loadlock, placed successively into various chambers as each chamber performs a particular process upon the wafer.
A wafer""s trace is the trajectory of a particular wafer through the cluster tool; that is, a trace is the order in which chambers are visited by a wafer (not necessarily Ci+1 after Ci). This should be distinguished from the term xe2x80x9cprocessing sequencexe2x80x9d which is the order of applying processes (recipes) to a wafer. If more than one chamber performs the same process (parallel chambers), a given processing sequence may be satisfied by several different traces.
A wafer which completes its processing sequence and is returned to the loadlock is said to be processed by the tool. Roughly speaking, a tool""s throughput is the number of wafers processed by the tool per unit of time. That is, if the tool needs t seconds to process nt wafers, then                               S          t                :=                              n            t                    t                                    (        3        )
is the tool""s throughput measured in the interval [0,t].
There are many ways to improve the tool""s throughput for a given processing sequence. However, one important improvement is to use efficient scheduling routines for a given processing sequence.
The optimization of scheduling involves the choice of criteria used in deciding when to transfer a wafer from one chamber into the next (and which wafers should be moved, if any, prior to that move). A routine which schedules the movement of wafers through the cluster tool (based on a given processing sequence) is referred to as a xe2x80x9cscheduling routine.xe2x80x9d
The steady-state throughput of a tool under scheduling routine A is denoted by S(A). If n greater than 1 then, depending on a given processing sequence, one may consider a number of scheduling routines that fulfill the processing sequence. The routine which maximizes the value of throughput is deemed the xe2x80x9coptimumxe2x80x9d routine and the maximum attainable value of throughput is known as the tool""s xe2x80x9ccapacity.xe2x80x9d That is, if A is the set of all possible scheduling routines for a given processing sequence, then A* is optimum if
S(A*)=max{S(A)|A∈A}xe2x80x83xe2x80x83(4)
Clearly, the tool""s capacity S(A*) depends on a given processing sequence as well as on chamber and robot parameters within the processing sequence. The problem of finding efficient scheduling routines for a given processing sequence (especially, finding optimum routines, where possible) is of considerable practical importance.
Presently there is not an automatic method of determining the best schedule, given a particular trace, that provides the highest throughput for that trace. Typically, a trial and error method is used until a schedule is determined that provides a sufficient throughput. However, the sufficient throughput may not be the best throughput that is possible for a given trace.
Therefore, a need exists in the art for a method and apparatus that determines all possible schedules given a particular trace and, using a throughput modeling program determines the throughput for each of the possible schedules and selects a schedule for use within a cluster tool that provides the maximum throughput for the given trace.
The disadvantages heretofore associated with the prior art are overcome by an invention of a method and apparatus for determining all possible schedules that accomplish a given trace, applying a throughput model to each of the schedules, and determining the schedule or schedules that result in the highest throughput.
More specifically, the invention uses a set of deterministic rules to compute the various schedules. First, a schedule is defined as a series of xe2x80x9clettersxe2x80x9d that form a xe2x80x9cwordxe2x80x9d. Each letter in the word defines a possible positioning of wafers within a cluster tool. Of course, the positioning of the wafers within the tool must fulfill the trace, i.e., each letter must follow from a predecessor letter in accordance with a particular set of rules that define the trace.
Given a letter (input letter) representing present wafer positions, the invention computes all possible successor wafer positions, i.e., all possible valid successor letters, as well as the total number of successors for the input letter. The invention provides individual xe2x80x9cmodulesxe2x80x9d for successor computation for serial traces, parallel traces, and mixed traces. Using a backtracking technique to repeatedly compute, from any letter, all possible successor letters, and then compute all possible successor letters of the successor letters, a schedule tree is derived. The schedule tree contains all possible schedules that will fulfill a given trace. Each and every schedule can then be modeled to determine the expected throughput of each schedule. By comparing the throughput associated with each schedule, an optimal schedule or schedules is identified.

Method and apparatus for automatically generating schedules for wafer processing within a multichamber semiconductor wafer processing tool


Long-afterglow adhesive tape consisting of. a) a first layer of aliphatic polyurethane acrylate or polyester acrylate in which a long-afterglow pigment is incorporated in a proportion of from 40% by weight to 80% by weight, preferably 75% by weight, PA1 b) a second layer containing a white pigment, PA1 c) a third layer comprising an ageing-resistant self-adhesive composition or a heat-activatable adhesive film, and PA1 d) if desired, a fourth layer comprising a release material with an antiadhesive coating.

For workplace safety marking in buildings and on ships, there is a wide range available of marking materials with long-afterglow surfaces. The requirements regarding these materials are described in Germany in the standards series DIN 67510, Part 1 -4. For use on ships in particular, there is an additional requirement of low surface flammability in accordance with Resolution A.653(16) of the IMO (International Maritime Organization).
The adhesive tapes currently employed have, as described in DIN 67510, the following structure: a highly transparent, smooth, printable top layer for UV protection and scratchproofing, an interlayer of softened, transparent plastic with embedded long-afterglow pigments, and a bottom layer of softened, white plastic, treated with an ageing-resistant self-adhesive composition and covered with a silicone-release paper.
These currently employed adhesive tapes meet the requirement of DIN 67510 but have two decisive disadvantages. Firstly, the very thick and tear-resistant structure makes it possible without any great problem to pull the adhesive tapes off from the substrate again after they have been applied, as a result of which the unauthorized removal of these safety systems is easy. Secondly, these adhesive tapes do not withstand the fire test of IMO Resolution A.653(16).
The object of the invention, then, is to provide a long-afterglow adhesive tape which does not have the disadvantages of the prior art, or at least not to the same extent, and whose usefulness is not restricted like that of the known products.


The present invention relates to apoptosis specific eucaryotic initiation factor 5A (eIF-5A), referred to as apoptosis factor 5A1 or simply factor 5A1, apoptosis factor 5A1 nucleic acids and polypeptides and methods for inhibiting or suppressing apoptosis in cells using antisense nucleotides or siRNAs to inhibit expression of factor 5A1. The invention also relates to suppressing or inhibiting expression of pro-inflammatory cytokines by inhibiting expression of apoptosis factor 5A.

Apoptosis is a genetically programmed cellular event that is characterized by well-defined morphological features, such as cell shrinkage, chromatin condensation, nuclear fragmentation, and membrane blebbing. Kerr et al. (1972) Br. J. Cancer, 26, 239-257; Wyllie et al. (1980) Int. Rev. Cytol., 68, 251-306. It plays an important role in normal tissue development and homeostasis, and defects in the apoptotic program are thought to contribute to a wide range of human disorders ranging from neurodegenerative and autoimmunity disorders to neoplasms. Thompson (1995) Science, 267, 1456-1462; Mullauer et al. (2001) Mutat. Res, 488, 211-231. Although the morphological characteristics of apoptotic cells are well characterized, the molecular pathways that regulate this process have only begun to be elucidated.
One group of proteins that is thought to play a key role in apoptosis is a family of cysteine proteases, termed caspases, which appear to be required for most pathways of apoptosis. Creagh & Martin (2001) Biochem. Soc. Trans, 29, 696-701; Dales et al. (2001) Leuk. Lymphoma, 41, 247-253. Caspases trigger apoptosis in response to apoptotic stimuli by cleaving various cellular proteins, which results in classic manifestations of apoptosis, including cell shrinkage, membrane blebbing and DNA fragmentation. Chang & Yang (2000) Microbiol. Mol. Biol. Rev., 64, 821-846.
Pro-apoptotic proteins, such as Bax or Bak, also play a key role in the apoptotic pathway by releasing caspase-activating molecules, such as mitochondrial cytochrome c, thereby promoting cell death through apoptosis. Martinou & Green (2001) Nat. Rev. Mol. Cell. Biol., 2, 63-67; Zou et al. (1997) Cell, 90, 405-413. Anti-apoptotic proteins, such as Bcl-2, promote cell survival by antagonizing the activity of the pro-apoptotic proteins, Bax and Bak. Tsujimoto (1998) Genes Cells, 3, 697-707; Kroemer (1997) Nature Med., 3, 614-620. The ratio of Bax:Bcl-2 is thought to be one way in which cell fate is determined; an excess of Bax promotes apoptosis and an excess of Bcl-2 promotes cell survival. Salomons et al. (1997) Int. J. Cancer, 71, 959-965; Wallace-Brodeur & Lowe (1999) Cell Mol. Life Sci., 55, 64-75.
Another key protein involved in apoptosis is that encoded by the tumor suppressor gene p53. This protein is a transcription factor that regulates cell growth and induces apoptosis in cells that are damaged and genetically unstable, presumably through up-regulation of Bax. Bold et al. (1997) Surgical Oncology, 6, 133-142; Ronen et al., 1996; Schuler & Green (2001) Biochem. Soc. Trans., 29, 684-688; Ryan et al. (2001) Curr. Opin. Cell Biol., 13, 332-337; Zörnig et al. (2001) Biochem. Biophys. Acta, 1551, F1-F37.
The distinct morphological features that characterize cells undergoing apoptosis have given rise to a number of methods for assessing the onset and progress of apoptosis. One such feature of apoptotic cells that can be exploited for their detection is activation of a flippase, which results in externalization of phosphatidylserine, a phospholipid normally localized to the inner leaflet of the plasma membrane. Fadok et al. (1992) J. Immunol., 149, 4029-4035. Apoptotic cells bearing externalized phosphatidylserine can be detected by staining with a phosphatidylserine-binding protein, Annexin V, conjugated to a fluorescent dye. The characteristic DNA fragmentation that occurs during the apoptotic process can be detected by labeling the exposed 3′-OH ends of the DNA fragments with fluorescein-labeled deoxynucleotides. Fluorescent dyes that bind nucleic acids, such as Hoescht 33258, can be used to detect chromatin condensation and nuclear fragmentation in apoptotic cells. The degree of apoptosis in a cell population can also be inferred from the extent of caspase proteolytic activity present in cellular extracts.
As a genetically defined process, apoptosis, like any other developmental program, can be disrupted by mutation. Alterations in the apoptotic pathways are believed to play a key role in a number of disease processes, including cancer. Wyllie et al. (1980) Int. Rev. Cytol., 68, 251-306; Thompson (1995) Science, 267, 1456-1462; Sen & D'Incalci (1992) FEBS Letters, 307, 122-127; McDonnell et al. (1995) Seminars in Cancer and Biology, 6, 53-60. Investigations into cancer development and progression have traditionally been focused on cellular proliferation. However, the important role that apoptosis plays in tumorigenesis has recently become apparent. In fact, much of what is now known about apoptosis has been learned using tumor models, since the control of apoptosis is invariably altered in some way in tumor cells. Bold et al. (1997) Surgical Oncology, 6, 133-142.
Apoptosis can be triggered during tumor development by a variety of signals. Extracellular signals include growth or survival factor depletion, hypoxia and ionizing radiation. Internal signals that can trigger apoptosis include DNA damage, shortening telomeres, and oncogenic mutations that produce inappropriate proliferative signals. Lowe & Lin (2000) Carcinogenesis, 21, 485-495. Ionizing radiation and nearly all cytotoxic chemotherapy agents used to treat malignancies are thought to act by triggering endogenous apoptotic mechanisms to induce cell death. Rowan & Fisher (1997) Leukemia, 11, 457-465; Kerr et al. (1994) Cancer, 73, 2013-2026; Martin & Schwartz (1997) Oncology Research, 9,1-5.
Evidence would suggest that early in the progression of cancer, tumor cells are sensitive to agents (such as ionizing radiation or chemotherapeutic drugs) that induce apoptosis. However, as the tumor progresses, the cells develop resistance to apoptotic stimuli. Naik et al. (1996) Genes and Development, 10, 2105-2116. This may explain why early cancers respond better to treatment than more advanced lesions. The ability of late-stage cancers to develop resistance to chemotherapy and radiation therapy appears to be linked to alterations in the apoptotic pathway that limit the ability of tumor cells to respond to apoptotic stimuli. Reed et al. (1996) Journal of Cellular Biology, 60, 23-32; Meyn et al. (1996) Cancer Metastasis Reviews, 15, 119-131; Hannun (1997) Blood, 89, 1845-1853; Reed (1995) Toxicology Letters, 82-83, 155-158; Hickman (1996) European Journal of Cancer, 32A, 921-926. Resistance to chemotherapy has been correlated to overexpression of the anti-apoptotic gene bcl-2 and deletion or mutation of the pro-apoptotic bax gene in chronic lymphocytic leukemia and colon cancer, respectively.
The ability of tumor cells to successfully establish disseminated metastases also appears to involve alterations in the apoptotic pathway. Bold et al. (1997) Surgical Oncology, 6, 133-142. For example, mutations in the tumor suppressor gene p53 are thought to occur in 70% of tumors. Evan et al. (1995) Curr. Opin. Cell Biol., 7, 825-834. Mutations that inactivate p53 limit the ability of cells to induce apoptosis in response to DNA damage, leaving the cell vulnerable to further mutations. Ko & Prives (1996) Genes and Development, 10, 1054-1072.
Therefore, apoptosis is intimately involved in the development and progression of neoplastic transformation and metastases, and a better understanding of the apoptotic pathways involved may lead to new potential targets for the treatment of cancer by the modulation of apoptotic pathways through gene therapy approaches. Bold et al. (1997) Surgical Oncology, 6, 133-142.
The present invention relates to cloning of an eIF-5A cDNA that is up regulated immediately before the induction of apoptosis. This apoptosis-specific eIF-5A is likely to be a suitable target for intervention in apoptosis-causing disease states since it appears to act at the level of post-transcriptional regulation of downstream effectors and transcription factors involved in the apoptotic pathway. Specifically, the apoptosis-specific eIF-5A appears to selectively facilitate the translocation of mRNAs encoding downstream effectors and transcription factors of apoptosis from the nucleus to the cytoplasm, where they are subsequently translated. The ultimate decision to initiate apoptosis appears to stem from a complex interaction between internal and external pro- and anti-apoptotic signals. Lowe & Lin (2000) Carcinogenesis, 21, 485-495. Through its ability to facilitate the translation of downstream apoptosis effectors and transcription factors, the apoptosis-related eIF-5A appears to tip the balance between these signals in favor of apoptosis.
As described previously, it is well established that anticancer agents induce apoptosis and that alterations in the apoptotic pathways can attenuate drug-induced cell death. Schmitt & Lowe (1999) J. Pathol., 187, 127-137. For example, many anticancer drugs upregulate p53, and tumor cells that have lost p53 develop resistance to these drugs. However, nearly all chemotherapy agents can induce apoptosis independently of p53 if the dose is sufficient, indicating that even in drug-resistant tumors, the pathways to apoptosis are not completely blocked. Wallace-Brodeur & Lowe (1999) Cell Mol. Life Sci., 55, 64-75. This suggests that induction of apoptosis eIF-5A, even though it may not correct the mutated gene, may be able to circumvent the p53-dependent pathway and induce apoptosis by promoting alternative pathways.
Induction of apoptosis-related eIF-5A has the potential to selectively target cancer cells while having little or no effect on normal neighboring cells. This arises because mitogenic oncogenes expressed in tumor cells provide an apoptotic signal in the form of specific species of mRNA that are not present in normal cells. Lowe et al. (1993) Cell, 74, 954-967; Lowe & Lin (2000) Carcinogenesis, 21, 485-495. For example, restoration of wild-type p53 in p53-mutant tumor cells can directly induce apoptosis as well as increase drug sensitivity in tumor cell lines and xenographs. (Spitz et al., 1996; Badie et al. 1998).
The selectivity of apoptosis-eIF-5A arises from the fact that it selectively facilitates translation of mRNAs for downstream apoptosis effectors and transcription factors by mediating their translocation from the nucleus into the cytoplasm. Thus, for apoptosis eIF-5A to have an effect, mRNAs for these effectors and transcription factors have to be transcribed. Inasmuch as these mRNAs would be transcribed in cancer cells, but not in neighboring normal cells, it is to be expected that apoptosis eIF-5A would promote apoptosis in cancer cells but have minimal, if any, effect on normal cells. Thus, restoration of apoptotic potential in tumor cells with apoptosis-related eIF-5A may decrease the toxicity and side effects experienced by cancer patients due to selective targeting of tumor cells. Induction of apoptotic eIF-5A also has the potential to potentiate the response of tumor cells to anti-cancer drugs and thereby improve the effectiveness of these agents against drug-resistant tumors. This in turn could result in lower doses of anti-cancer drugs for efficacy and reduced toxicity to the patient.
Alternations in the apoptotic pathways are also believed to play a role in degeneration of retinal ganglion cells causing blindness due to glaucoma. Glaucoma describes a group of eye conditions in which increased intra-ocular pressure (IOP) leads to damage of the optic nerve and progressive blindness. Although glaucoma is currently managed by drugs or surgery to control IOP to reduce damage to the optic nerve or the use of neuro-protectors, there remains a need to protect retinal ganglion cells from degeneration by apoptosis in the glaucomatous eye.
Cytokines have also been implicated in the apoptotic pathway. Biological systems require cellular interactions for their regulation, and cross-talk between cells generally involves a large variety of cytokines. Cytokines are mediators that are produced in response to a wide variety of stimuli by many different cell types. Cytokines are pleiotropic molecules that can exert many different effects on many different cell types, but are especially important in regulation of the immune response and hematopoietic cell proliferation and differentiation. The actions of cytokines on target cells can promote cell survival, proliferation, activation, differentiation, or apoptosis depending on the particular cytokine, relative concentration, and presence of other mediators.
The use of anti-cytokines to treat autoimmune disorders (psoriasis, rheumatoid arthritis, Crohn's disease) is gaining popularity. The pro-inflammatory cytokines IL-1 and TNF play a large role in the pathology of these chronic disorders and anti-cytokine therapies that reduce the biological activities of these two cytokines can provide therapeutic benefits (Dinarello and Abraham, 2002).
Interleukin 1 (IL-1) is an important cytokine that mediates local and systemic inflammatory reactions and which can synergize with TNF in the pathogenesis of many disorders, including vasculitis, osteoporosis, neurodegenerative disorders, diabetes, lupus nephritis, and autoimmune disorders such as rheumatoid arthritis. The importance of IL-1β in tumour angiogenesis and invasiveness was also recently demonstrated by the resistance of IL-1β knockout mice to metastases and angiogenesis when injected with melanoma cells (Voronov et al., 2003).
Interleukin 18 (IL-18) is a recently discovered member of the IL-1 family and is related by structure, receptors, and function to IL-1. IL-18 is a central cytokine involved in inflammatory and autoimmune disorders as a result of its ability to induce interferon-gamma (IFN-λ), TNF-α, and IL-1. IL-1β and IL-18 are both capable of inducing production of TNF-α, a cytokine known to contribute to cardiac dysfunction during myocardial ischemia (Maekawa et al., 2002). Inhibition of IL-18 by neutralization with an IL-18 binding protein was found to reduce ischemia-induced myocardial dysfunction in an ischemia/reperfusion model of suprafused human atrial myocardium (Dinarello, 2001). Neutralization of IL-18 using a mouse IL-18 binding protein was also able to decrease IFN-λ, TNF-α, and IL-1β transcript levels and reduce joint damage in a collagen-induced arthritis mouse model (Banda et al., 2003). A reduction of IL-18 production or availability may also prove beneficial to control metastatic cancer as injection of IL-18 binding protein in a mouse melanoma model successfully inhibited metastases (Carrascal et al., 2003). As a further indication of its importance as a pro-inflammatory cytokine, plasma levels of IL-18 were elevated in patients with chronic liver disease and increased levels were correlated with the severity of the disease (Ludwiczek et al., 2002). Similarly, IL-18 and TNF-α were elevated in the serum of diabetes mellitus patients with nephropathy (Moriwaki et al., 2003). Neuroinflammation following traumatic brain injury is also mediated by pro-inflammatory cytokines and inhibition of IL-18 by the IL-18 binding protein improved neurological recovery in mice following brain trauma (Yatsiv et al., 2002).
TNF-α, a member of the TNF family of cytokines, is a pro-inflammatory cytokine with pleiotropic effects ranging from co-mitogenic effects on hematopoietic cells, induction of inflammatory responses, and induction of cell death in many cell types. TNF-α is normally induced by bacterial lipopolysaccharides, parasites, viruses, malignant cells and cytokines and usually acts beneficially to protect cells from infection and cancer. However, inappropriate induction of TNF-α is a major contributor to disorders resulting from acute and chronic inflammation such as autoimmune disorders and can also contribute to cancer, AIDS, heart disease, and sepsis (reviewed by Aggarwal and Natarajan, 1996; Sharma and Anker, 2002). Experimental animal models of disease (i.e. septic shock and rheumatoid arthritis) as well as human disorders (i.e. inflammatory bowel diseases and acute graft-versus-host disease) have demonstrated the beneficial effects of blocking TNF-α (Wallach et al., 1999). Inhibition of TNF-α has also been effective in providing relief to patients suffering autoimmune disorders such as Crohn's disease (van Deventer, 1999) and rheumatoid arthritis (Richard-Miceli and Dougados, 2001). The ability of TNF-α to promote the survival and growth of B lymphocytes is also thought to play a role in the pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) and the levels of TNF-α being expressed by T cells in B-CLL was positively correlated with tumour mass and stage of the disease (Bojarska-Junak et al., 2002). Interleukin-1β (IL-1β) is a cytokine known to induce TNF-α production.
Deoxyhypusine synthase (DHS) and hypusine-containing eucaryotic translation initiation Factor-5A (eIF-5A) are known to play important roles in many cellular processes including cell growth and differentiation. Hypusine, a unique amino acid, is found in all examined eucaryotes and archaebacteria, but not in eubacteria, and eIF-5A is the only known hypusine-containing protein. Park (1988) J. Biol. Chem., 263, 7447-7449; Schümann & Klink (1989) System. Appl. Microbiol., 11, 103-107; Bartig et al. (1990) System. Appl. Microbiol., 13, 112-116; Gordon et al. (1987a) J. Biol. Chem., 262, 16585-16589. Active eIF-5A is formed in two post-translational steps: the first step is the formation of a deoxyhypusine residue by the transfer of the 4-aminobutyl moiety of spermidine to the α-amino group of a specific lysine of the precursor eIF-5A catalyzed by deoxyhypusine synthase; the second step involves the hydroxylation of this 4-aminobutyl moiety by deoxyhypusine hydroxylase to form hypusine.
The amino acid sequence of eIF-5A is well conserved between species, and there is strict conservation of the amino acid sequence surrounding the hypusine residue in eIF-5A, which suggests that this modification may be important for survival. Park et al. (1993) Biofactors, 4, 95-104. This assumption is further supported by the observation that inactivation of both isoforms of eIF-5A found to date in yeast, or inactivation of the DHS gene, which catalyzes the first step in their activation, blocks cell division. Schnier et al. (1991) Mol. Cell. Biol., 11, 3105-3114; Sasaki et al. (1996) FEBS Lett., 384, 151-154; Park et al. (1998) J. Biol. Chem., 273, 1677-1683. However, depletion of eIF-5A protein in yeast resulted in only a small decrease in total protein synthesis suggesting that eIF-5A may be required for the translation of specific subsets of mRNA's rather than for protein global synthesis. Kang et al. (1993), "Effect of initiation factor eIF-5A depletion on cell proliferation and protein synthesis," in Tuite, M. (ed.), Protein Synthesis and Targeting in Yeast, NATO Series H. The recent finding that ligands that bind eIF-5A share highly conserved motifs also supports the importance of eIF-5A. Xu & Chen (2001) J. Biol. Chem., 276, 2555-2561. In addition, the hypusine residue of modified eIF-5A was found to be essential for sequence-specific binding to RNA, and binding did not provide protection from ribonucleases.
In addition, intracellular depletion of eIF-5A results in a significant accumulation of specific mRNAs in the nucleus, indicating that eIF-5A may be responsible for shuttling specific classes of mRNAs from the nucleus to the cytoplasm. Liu & Tartakoff (1997) Supplement to Molecular Biology of the Cell, 8, 426a. Abstract No. 2476, 37th American Society for Cell Biology Annual Meeting. The accumulation of eIF-5A at nuclear pore-associated intranuclear filaments and its interaction with a general nuclear export receptor further suggest that eIF-5A is a nucleocytoplasmic shuttle protein, rather than a component of polysomes. Rosorius et al. (1999) J. Cell Science, 112, 2369-2380.
The first cDNA for eIF-5A was cloned from human in 1989 by Smit-McBride et al., and since then cDNAs or genes for eIF-5A have been cloned from various eukaryotes including yeast, rat, chick embryo, alfalfa, and tomato. Smit-McBride et al. (1989a) J. Biol. Chem., 264, 1578-1583; Schnier et al. (1991) (yeast); Sano, A. (1995) in Imahori, M. et al. (eds), Polyamines, Basic and Clinical Aspects, VNU Science Press, The Netherlands, 81-88 (rat); Rinaudo & Park (1992) FASEB J., 6, A453 (chick embryo); Pay et al. (1991) Plant Mol. Biol., 17, 927-929 (alfalfa); Wang et al. (2001) J. Biol. Chem., 276, 17541-17549 (tomato).
Expression of eIF-5A mRNA has been explored in various human tissues and mammalian cell lines. For example, changes in eIF-5A expression have been observed in human fibroblast cells after addition of serum following serum deprivation. Pang & Chen (1994) J. Cell Physiol., 160, 531-538. Age-related decreases in deoxyhypusine synthase activity and abundance of precursor eIF-5A have also been observed in senescing fibroblast cells, although the possibility that this reflects averaging of differential changes in isoforms was not determined. Chen & Chen (1997b) J. Cell Physiol., 170, 248-254.
Studies have shown that eIF-5A may be the cellular target of viral proteins such as the human immunodeficiency virus type 1 Rev protein and human T cell leukemia virus type 1 Rex protein. Ruhl et al. (1993) J. Cell Biol.,123, 1309-1320; Katahira et al. (1995) J. Virol., 69, 3125-3133. Preliminary studies indicate that eIF-5A may target RNA by interacting with other RNA-binding proteins such as Rev, suggesting that these viral proteins may recruit eIF-5A for viral RNA processing. Liu et al. (1997) Biol. Signals, 6, 166-174.
Thus, although eIF-5A and DHS are known, there remains a need in understanding how these proteins are involved in apoptotic pathways as well as cytokine stimulation to be able to modulate apoptosis and cytokine expression. The present invention fulfills this need.

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Use of antisense oligonucleotides or siRNA to suppress expression of eIF-5A1