A clamping mechanism for frictionally securing together two radially adjacent concentric components of a gear drive wherein an annular clamping disc having concentric inner and outer peripheral edges and a substantially conically shaped convex portion between the edges is partially disposed in an annular recess in one of the gear drive components. Force applying means, such as tensioning bolts, cooperate with circumferentially spaced apertures in the convex portion of the clamping disc and threaded bores in the component to urge the peripheral edges of the clamping disc into frictional engagement with wall portions of the annular recess and with a concentric surface of the radially adjacent gear drive component.

A problem frequently recurring in engineering is to releasably interconnect rotationally symmetrical parts. Clamping connections are frequently used for this purpose based on frictional transmission of forces. In such cases, spring forces, fluid pressure devices, or simple screw connections, apply a clamping force which, by acting on friction surfaces, ensures that the two parts are connected so as to rotate with one another. Very high forces are necessary in some cases to maintain the connection and secure the relative position of the two parts. Consequently, ordinary clamping elements are unsuitable or else the requirements that the clamping elements must satisfy are of such high specification that in some cases uneconomical connecting elements have to be used.
In printing engineering it is known, for example, to dispose double gearwheels in the transmission line of sheet-fed rotary presses so that sub-units of the press can be displaced relative to one another. In a double gearwheel of this kind, a gearwheel ring is fitted on a main gearwheel and is clamped fast there by means of clamping elements. The latter must ensure that the relative position between the gearwheel ring and the main gearwheel is maintained even under maximum stress. In some cases the clamping connection is in the form of a simple pressure connection, the friction surfaces between the gearwheel ring and the main gearwheel being used for the force transmission. Typically, the peripheral forces are applied by normal forces of appropriate value. For this purpose, strong springs and a corresponding number of clamping screws are required.
One approach to such an arrangement is described in DE-A1 38 20 026. As shown in this references, the gear ring is coupled to the main gearwheel via a connection in the form of a disc clutch in order to provide a non-positive connection between a fixed gearwheel and a movable gearwheel on a cylinder of a turn-over mechanism in a sheet-fed rotary press. The clutch discs are mounted at the end face of the main gearwheel and clutch discs are also provided concentrically thereof on the gearwheel ring and engage in the spaces between the clutch discs on the main gearwheel. In the region of the overlap, a clamp ring is fitted on the clutch discs and can be clamped relative to the main gearwheel. As a result, the clutch discs are clamped together and the gearwheel ring is frictionally connected to the main gearwheel.
Unfortunately, the entire arrangement of the foregoing reference makes the construction of the double gearwheel relatively complex. Also, there is no safeguard that the frictional forces will be uniformly distributed over the entire periphery. In addition, the construction is expensive due to the large number of parts.
A mechanism for deforming a gearwheel is known from DE-C1 3834429. This reference describes a gearwheel whose hub can be deformed by tensioning elements in order to change the diameter. However, it is not possible to secure the gearwheel with this mechanism.
It is the primary aim of the present invention to provide a clamping mechanism which enables a reliable and secure frictional connection to be achieved between relatively rotatable components of a gear drive.
A related and important object is to provide such a frictional clamping mechanism which achieves a secure connection in a relatively simple manner with greatly reduced forces.
It is also an object of the invention to provide a frictional clamping mechanism that employs only a few parts that may be made relatively economically.
In accordance with the present invention, a clamping mechanism is provided for securing together two radially adjacent concentric components of a gear drive, such components including, for example, a toothed gear ring, a gearwheel, a hub and a shaft. An annular recess is formed in the gear drive component and defines at least one circumferential and one radial wall. A substantially conically shaped convex clamping disc having a plurality of circumferentially spaced apertures is disposed in the annular recess. A plurality of tensioning bolts cooperate with the apertures in the clamping disc and threaded bores in the annular recess to compress the clamping disc and urge its peripheral edges radially into frictional engagement with the concentric gear drive components and axially into frictional engagement with the radial wall of the annular recess.
A particularly advantageous feature of the clamping mechanism of the present invention is that there is not just one friction surface in the axial direction, but also at least one other one directed radially to the gearwheel. Depending on the specific arrangement, two radially directed friction surfaces may be provided, thus enabling the transmissible torques to be additionally increased. Furthermore, the release forces required for tensioning elements of this kind are reduced in comparison with purely screw or spring connections. The conical arrangement of the tensioning element results in differences in clamping forces at the periphery of the gearwheel being substantially uniform. Assembly and removal of the gearwheels or gearwheel rings are also greatly simplified. The mechanism can be used with a direct or indirect action. In addition, the radial tensioning surfaces may optionally be used separately or else the radial and axial tensioning surfaces can be used jointly. Finally, in combination with the tensioning effect, it is also possible to deform the gearwheel ring to correct production errors.
These and other features and advantages of the invention will be more readily apparent upon reading the following description of the preferred embodiments of the invention and upon reference to the accompanying drawings.

Clamping mechanism for frictionally engaging and securing together gear drive components


A measuring instrument includes a detector that outputs a measured value, a digital display unit, an analog display unit having a plurality of display segments, and a display controller. The display controller includes: a tolerance range display unit that lights or blinks display segments corresponding to a preset tolerance range relative to a preset value; a first determiner that obtains a difference between the present value and a present measured value and determines whether the difference is within an analog display range wider than the tolerance range; a difference display unit that lights a display segment corresponding to the last one or the last two digits of the present measured value when the first determiner determines that the difference is within the analog display range; a second determiner that determines whether the difference is within the tolerance range; and an acceptance or rejection display unit that displays a result determined by the second determiner.

1. Field of the Invention
The present invention relates to a measuring instrument that detects a measured value as an electric signal and displays the measured value. More particularly, the present invention relates to a measuring instrument that detects the measured value and determines acceptance or rejection based on whether or not the measured value is within a preset tolerance range. Such a measuring instrument is applicable to a caliper gauge, a dial gauge and the like.
2. Description of Related Art
As such a dial gauge, there has been known an analog dial gauge in which a linear displacement of a spindle is converted into a rotational movement of an indicator through a movement conversion mechanism, an expansion mechanism or the like so as to read a measured value from a scale corresponding to the indicator, and a digital dial gauge in which an encoder is accommodated for detecting a liner displacement of a spindle as an electric signal so as to digitally display a measured value detected by the encoder.
The digital dial gauge is typically used when a high resolution, high accuracy and readability are required, which causes an economic burden, while the analog dial gauge is typically used when the high accuracy is not required. Also, the latter dial gauge is often used when acceptance or rejection is determined based on whether a measured value is within a predetermined range such as a tolerance.
However, in actual measurement, one of the dial gauges cannot be easily selected depending on an object to be measured, a measurement property, user's proficiency level or custom, and the like. Consequently, a dial gauge having both features of the digital dial gauge and the analog dial gauge has been required.
For example, in order to numerically check a deviation of a rejected measured value, the feature of the digital dial gauge needs to be added to the analog dial gauge used for determining acceptance when a measured value is within a tolerance range. Also, the feature of the analog dial gauge needs to be added to the digital dial gauge in order to roughly check a trend in a measured value without reading a digitally displayed value that instantly changes until a final value is determined.
Accordingly, there has been known a measuring instrument called as a digital and analog caliper gauge in which the two dial gauges are combined as disclosed in Document 1 (JP-A-06-288701).
The digital and analog caliper gauge includes a digital display for displaying measured data as a five-digit numerical value at a central position of a display surface of a slider, and an analog display for displaying the last two digits of the numerical value displayed on the digital display, the analog display surrounding the digital display. The analog display includes 100 display segments each having a predetermined width and length arranged at equal intervals on a circumference encircling the digital display, and displays the last two digits by controlling lighting of a single display segment corresponding to the measured value.
In the measuring instrument disclosed in Document 1, the measured value detected by the encoder is digitally displayed as a numerical value on the digital display, and the last two digits of the numerical value are displayed as a point on the analog display. Accordingly, three display segments are lighted at the same time. Namely, a display segment corresponding to the last two digits, a prior display segment thereto, and a subsequent display segment thereto are lighted at the same time.
Since the consecutive three display segments including the display segment corresponding to the last two digits of the measured value are lighted at the same time when the slider remains stationary, the lighted display segments can be visually checked easily.
However, the last two digits of the measured value instantly change when the slider moves. Accordingly, the display segments to be lighted on the analog display are changed at high speed and consequently blinking lights circularly move at high speed. At this time, the last two digits are not easily checked visually and considerable electric power consumption is required.


A mounting apparatus (12) for a personal illumination tool (14) having a removable end cap (84) is provided. The apparatus (12) generally includes a sleeve (16) for receipt and retention of the personal illumination tool (14), more particularly, a ring or ring-like member (26) depends from an interior surface of the sleeve (16) for receipt and retention between portions of the illumination tool (14) in furtherance of forming an interference fit therebetween. The sleeve (16) further includes and end portion (18) adapted for affixation to a mount (34). A combination of the apparatus (12) and illumination tool (14) is likewise provided.

Very few tasks can be satisfactorily accomplished by people in darkness. For the most part, it is essential to see what we are doing, and our ability to see is proportional to the amount of available light. To supplement insufficient available light, people often use portable illumination tools or devices. Illumination tools or devices, e.g., flashlights, are readily available and virtually universal in application. While styles of these lights vary widely, with specialized structures for select applications, their capabilities are divisible into definable categories that are well known to those within the illumination tools community, see for example the products of SureFire® LLC, California, USA, "2004 Illumination Tools."
Two categories of lights are personal or hand-carried (i.e., hand), and surface-mounted (i.e., surface). Hand lights generally, do not have, as a functional element, the ability to be attached/secured to anything, save for a pocket, vis-a-vis a clip, as exemplified by U.S. Pat. No. 6,547,415 (Matthews), or a belt, vis-a-vis a holster or scabbard, as exemplified by U.S. Pat. No. 5,593,074 (Matthews). Hand lights have elements and features that make them most functional while being held in the hand, either "in carry" or "in use."
Surface lights, typically characterized by a fixture having an integral lamp, are designed to achieve their functionality (i.e., are optimally functional) when attached to a specific object, the functionality being achieved by means of the provision and arrangement of components to accomplish the specific object attachment. For example, in the context of target illumination devices, a lamp is integrally provided as part of a fixture, e.g., a housing or module, for attachment to a weapon, more particularly, to a weapon rail, see e.g., U.S. Pat. No. 5,685,105 (Teetzel) and U.S. Pat. No. 6,609,810 (Kim), the Bright Light Aiming System Tactical (BLAST) 2 from Laser Devices, Inc., California USA, and/or dedicated forend weaponlights from SureFire. Fixtures for target illumination devices also contemplate vertical foregrips equipped with lamp assemblies, see e.g., those of SureFire.
Heretofore known attempts to secure the aforementioned hybrid functionality for an illumination tool appear limited, known devices suffering a variety of limitations, several among them being a lack of versatility, and a lack of, or at least less than desirable, environmental or use integrity (e.g., device/assembly adjustment, repair and maintenance due to a less than desirable interface between the tool and the surface to which it is attached). For example, U.S. Pat. No. 6,712,485 (Matthews), which is a continuation of Matthews '415 previously noted, discloses a bolt/C-clamp combination wherein the clamp is secured about a tube, a head of the bolt being received in an undercut groove intermediate of a flashlight housing; and, U.S. application Pub. No. US2003/0202345 (Kim) which discloses ring forming elements securable about a switch end of a flashlight, one of the ring forming elements including a clamping element (e.g., Weaver style) for attachment to a rail structure of a firearm.
While it is critical that the interface between the personal illumination tool and the fixture within which it is to be received is secure and unwavering, heretofore known assemblies or fixtures have required tools to accomplish securing or integrating the illumination tool to/with the fixture, see e.g., U.S. Pat. No. 5,560,703 (Capps, III) and U.S. Pat. No. 6,023,875 (Fell et al.). While the use of tools for securing the illumination tool with respect to the fixture is less than desirable, the absence of a secures reliable mechanical interface for the illumination tool, see e.g., U.S. Pat. No. 6,851,214 (Oz), is likewise to be avoided as less than advantageous.
In light of the foregoing, there thus remains a need to provide an apparatus and/or assembly which incorporates or combines the aforementioned functionalities, namely, those of the hand and surface lights. Furthermore, and advantageously, such device and/or assembly should provide for a simple, no-tool mechanical interface. Further yet, such apparatus, and assembly incorporating same, should provide for heretofore unseen versatility, more particularly, a modularity such that an illumination tool, directly or indirectly, might be quickly secured to a variety of select surfaces vis-a-vis a variety of mounting means or fixtures, and still further, such device/assembly should confidently retain the tool in all regards so as to, for example, prevent misalignment of same, and associated misdirection of the light beam so generated, or generally undermine the integrity of either the tool, the device/assembly, or the surface supporting same.

Interface apparatus for mounting a portable illumination tool & related illumination assembly


The present invention provides for antimicrobial compositions, methods of preparing the antimicrobial compositions, methods of using the antimicrobial compositions, and/or kits that include the antimicrobial compositions. The antimicrobial compositions can be in a dry, solid (e.g., powdered) form, or can be in a liquid (e.g., aqueous) form.

A variety of industries are subject to problems occurring with the growth of microorganisms. Such industries include, for example, the sporting equipment industry, the sporting apparel industry, the construction industry, medical healthcare institutions, the medical device industry, the lumber industry, and the textile industry. As such, reduction or elimination of microorganisms on surfaces is important in a broad variety of applications. One approach to interfere with the ability of microorganisms to survive on various materials is to modify the surface of those materials by attachment of antimicrobial agents.
Deciding how best to attach an antimicrobial agent to a material is guided, at least in part, by the planned end-use of the material. One important and useful consideration is that the antimicrobial activity be persistent. This may be achieved by permanently attaching the antimicrobial agent to the surface, so that it is unable to migrate or leach away from the modified material surface when the modified material is exposed to fluids. For example, for applications in which the modified material will come into contact with aqueous fluids, it is important that the antimicrobial agent is not rinsed away when the modified material comes into contact with aqueous fluids. For applications in which the modified material will come into contact with aqueous biological fluids, it is important that the antimicrobial agent is not rinsed away, or otherwise inactivated, when the modified material is exposed to aqueous biological fluids. For applications in which the modified material is to be used repeatedly, it is important that the antimicrobial agent is not washed or rinsed away when the modified material is washed or rinsed in fluids in between repeated uses.
One approach employs methods that attach silane-based quaternary ammonium compounds to particular substrates via a siloxane bond. For example, the AEGIS® product line includes products that utilize 3-(trimethoxysilyl)propyldimethyl octadecyl ammonium chloride. According to product literature, AEM 5700 includes 43% 3-trimethoxysilylpropyloctadecyl ammonium chloride in methanol, which can be used, e.g., to coat the surface of textiles. This is not a polymeric compound, although some interlinking of the applied silane may occur after application to the substrate. The methanol present in the commercial product AEM 5700 can be toxic, hazardous and therefore undesirable for some consumers. Another problem with the AEM liquid is the instability to pH change or temp/pressure changes. The product AEM 5700, upon removal of the methanol, will typically afford an oil or solid that is not readily soluble in water, and can degrade over time when exposed to ambient conditions.
The polymerized version of the AEM 5700 (Biosafe™) is a powder that is difficult to work with and leaves particulates behind upon dissolving in water. The Biosafe™, upon formulation into a sprayable liquid, includes an appreciable amount of undissolved solid particulates that should be removed (e.g., by filtering), or the sprayer can become clogged from the solid particulates. This can lead to costly and time-consuming steps in the production of liquid, sprayable commercial products manufactured from Biosafe™.
Consequently, there exists a need for antimicrobial compositions (e.g., ones that includes 3-(trimethoxysilyl)propyldimethyl octadecyl ammonium chloride), as well as methods of manufacturing the same in a convenient, reliable, and cost-effective manner.


A method for making a crystallized ceramic body containing a two phase composite comprising an alpha prime SiAlON phase that contains ytterbium and a beta prime SiAlON phase, the process includes the steps of: blending together a starting powder mixture that upon densification forms the SiAlON ceramic, the starting powder includes at least about 70 weight percent silicon nitride powder wherein the silicon nitride powder contains beta silicon nitride in an amount less than or equal to about 1.6 weight percent of the silicon nitride powder, and the starting powder further including one or more powders that contribute aluminum, oxygen, and nitrogen to the beta prime SiAlON phase and aluminum, oxygen, nitrogen and ytterbium to the alpha prime SiAlON phase; and densifying the starting powder mixture to form a densified SiAlON ceramic; and heat treating the densified ceramic body so as to form the crystallized ceramic body wherein the alpha prime SiAlON phase comprises at least about 20 weight percent of the two phase composite.

SiAlON materials have a number of uses such as, for example, cutting inserts for various metal cutting application and wear parts for various wear applications (e.g., plunger rods for pumps, plunger ball blanks, down hole pump check valve blanks, bushings, blast nozzles, and other wear and impact applications).
Ceramic materials have also been used in high temperature wear applications in structures like, for example, microturbines. In the microturbine applications, the ceramic materials may comprise the stator (i.e., the stationary blades), the rotor (including the rotor blades), the fuel injector nozzle, and the shroud. These components of the microturbine require adequate high temperature creep resistance and adequate high temperature deformation resistance.
Exemplary patents that disclose SiAlON materials are U.S. Pat. No. 4,563,433 and U.S. Pat. No. 4,711,644. One article that discusses SiAlON materials is Izhevskiy et al., "Progress in SiAlON ceramics, Journal of the European Ceramic Society 20 (2000) pages 2275–2295.
SiAlON materials may contain an alpha prime (or alpha′) phase and a beta prime (or beta′) phase and one or more other phases such as, for example, a glassy phase and/or a crystalline phase. The alpha prime SiAlON phase may be of the formula MxSi12−(m+n)Alm+nOnN16−n where M is Li, Ca, Y or other lanthanides and where the theoretical maximum of x is 2, the value of n ranges between greater than 0 and less than or equal to 2.0, and the value of m ranges between greater than or equal to 0.9 and less than or equal to 3.5. The beta prime SiAlON phase may be of the formula Si6−zAlzOzN8−z where 0<z≦4.2. In the case where M is yttrium, the crystalline phases may include YAG (yttrium aluminum garnet) which is a cubic phase of the formula Y3Al5O12); YAM which is a monoclinic phase of the formula Y4Al2O9; N—YAM which is a monoclinic phase of the formula Y4Si2O7N2; and Y—N-α-Wollastonite which is a monoclinic phase of the formula YSiO2N.
SiAlON materials may comprise an alpha prime SiAlON phase and a beta prime SiAlON phase, as well as further contain silicon carbide particles dispersed throughout the SiAlON matrix. Such a SiAlON material is disclosed in U.S. Pat. No. 4,826,791 to Mehrotra et al.
Other ceramic materials include an alpha prime SiAlON phase, a beta SiAlON phase and an intergranular phase wherein the ceramic optionally contains refractory phases. The ceramic material has an alloyed surface with a higher oxygen and aluminum content. U.S. Pat. No. 4,880,755 to Mehrotra et al. discloses such a ceramic material.
U.S. Pat. No. 5,370,716 to Mehrotra et al. discloses a high Z-SiAlON material comprising beta prime SiAlON phase. The beta prime SiAlON phase has a formula Si6−zAlzOzN8−z where 1<z<3.
U.S. Pat. No. 5,908,798 to Chen et al. discloses a SiAlON material wherein the focus is on the reinforcement of alpha prime SiAlON with elongated grains of alpha prime SiAlON. The examples that include ytterbium produce a material with only alpha prime SiAlON phase that does not contain any beta prime SiAlON phase.
U.S. Pat. No. 6,124,225 to Tien et al. focuses upon the use of gadolinium (Gd) in a SiAlON material to produce an alpha prime SiAlON material that is reinforced by elongated grains of alpha prime SiAlON.
Although current SiAlON cutting inserts exhibit acceptable properties (e.g., hardness, toughness, thermal shock resistance) it would be desirable to provide for an improved SiAlON material that has application as a cutting insert that exhibits improved metal cutting performance properties including hardness, Young's modulus, toughness, thermal conductivity, and thermal shock resistance. The same is true for SiAlON wear parts in that although current SiAlON wear parts have acceptable properties (e.g., hardness, Young's modulus, toughness, thermal conductivity, and thermal shock resistance), it would be desirable to provide an improved SiAlON material that has application as a wear part that exhibits improved properties.

This patent is subject to a terminal disclaimer.

SiAlON containing ytterbium and method of making


An image forming device which includes a first nozzle group, a second nozzle group, and are arranged by being deviated from the first nozzle group to one side in a predetermined direction, a light irradiation unit which is extended at least in the predetermined direction, a control unit which repeats an ejection operation in which the photo-curable ink is ejected from the nozzle while moving the nozzle group and the light irradiation unit in a direction intersecting the predetermined direction, and a transport operation of the medium in a state where a non-ejection region where the ink is not ejected is provided between the first nozzle group and the second nozzle group in a predetermined direction, and overlappingly forms a main image using the first photo-curable ink, and a background image using the second photo-curable ink.

1. Technical Field
The present invention relates to an image forming device and a method of image forming.
2. Related Art
Among printers as image forming devices, there is a printer in which ink (UV ink) cured when irradiated with UV light is used. Among printers which eject the UV ink while the heads are moving, there is a printer provided with a UV irradiation light source at both end portions in the movement direction of the head (for example, refer to JP-A-2005-254560). Such a printer is able to immediately cure the UV ink which is landed on a medium.
However, there is a concern that the irradiation amount of the UV light which can be radiated to the UV ink on the medium in one movement operation (pass) of the head may be small, and the UV ink on the medium is not sufficiently cured in one pass. For this reason, when the upper image is overlappingly printed on an underlying image in a pass immediately after a pass printing the underlying image in a case where the main image and the background image are overlappingly printed with each other, the upper image is overlapped with the underlying image in a state of not being sufficiently cured.

Image forming device and method of image forming


The present invention provides a method of forming an undoped silicate glass layer on a semiconductor wafer by performing a high density plasma chemical vapor deposition process. The semiconductor wafer being positioned in a deposition chamber. The method comprises forming the undoped silicate glass layer by performing the high density plasma chemical vapor deposition process in the deposition chamber under the following conditions: an argon (Ar) flow rate of 40 to 70 sccm (standard cubic centimeter per minute); an oxygen (O.sub.2) flow rate of 90 to 120 sccm; a silane flow rate of 70 to 100 sccm; a gas pressure of 3 to 10 mtorr; a temperature of 300 to 400.degree. C.; and a low frequency power of 2500 to 3500 watts. Wherein the ratio of Ar to O.sub.2 is 0.53, and O.sub.2 to silane is 1.23.

1. Field of the invention
The present invention relates to a method of forming an undoped silicate glass (USG) layer on a semiconductor wafer, and more particularly, to a method of forming an undoped silicate glass layer on a semiconductor wafer using high-density plasma chemical vapor deposition (HDPCVD).
2. Description of the Prior Art
Prior to metallization, dielectric material must be deposited onto the surface of a semiconductor wafer to isolate the MOS transistors and the metal interconnects subsequently produced. Generally speaking, the deposited dielectric material comprises a thinner undoped silicate glass (USG) layer for protecting and isolating the elements on the semiconductor wafer and a thicker planarization dielectric layer deposited over the USG layer as the main dielectric layer for subsequent metallization. The HDPCVD process is very effective in filling holes and is used to deposit the USG layer. The HDPCVD chamber is connected to the gas transporting system, the plasma generator, and the process control system. The reaction gases and plasma are transported to the deposition chamber then reach the surface of the semiconductor wafer to form solid material on the surface by chemical deposition.
Please refer to FIG. 1 and FIG. 2. FIG. 1 is a schematic diagram of the deposit chamber 10 of HDPCVD according to the prior art. FIG. 2 is a top view of the injector 16 and the semiconductor wafer 14 shown in FIG. 1. The HDPCVD deposition chamber 10 comprises a pedestal 12 for supporting a semiconductor wafer 14 and a plurality of injectors 16 evenly placed on the chamber wall around the periphery of the pedestal 12. Reaction gases are injected in by the injectors 16, then used in processing on the surface of the semiconductor wafer 14.
When USG deposition is performed in the deposition chamber 10, the semiconductor wafer 14 is placed on the pedestal 12 first, then each injector 16 injects a mixed gas of argon, oxygen, and silane. This mixed gas will be ionized by the plasma and then diffuse onto the surface of the semiconductor wafer 14 to form a USG layer. By the nature of HDPCVD, sputtering and etching are simultaneously taken place and it leads to the ion bombardment on the wafer. This is the basic concept behind in-situ deposition and sputtering in HDPCVD process.
Generally, when performing USG deposition in the deposition chamber 10, injectors 16 measuring 4 inches in length are utilized. The opening of each injector 16 is above the area 18 of the surface of the semiconductor wafer 14 as shown in FIG. 2. Because the opening of each injector 16 is above the area 18, most of the mixed gases collect in the area 18 of the surface of the semiconductor wafer 14 during the HDPCVD process. Therefore, the USG layer deposited on the semiconductor wafer 14 will not be uniform with the USG layer within the area 18 being thicker than the USG layer outside the area 18. The USG layer in the center of the semiconductor wafer 14 will be thinnest of all. Usually this non-uniformity of thickness is the biggest drawback of the HDPCVD process causing problems in subsequent processing and greatly affecting the function of the dielectric layer.

Method of forming an undoped silicate glass layer on a semiconductor wafer


A parts-combining method having high quality or yield for a product having a large number of parts. First entering an identification number group of nondefective completed products, a table of a product identification number group and a parts identification number group, a characteristic data group of parts A with respect to identification numbers of the parts A and a characteristic data group of parts B with respect to identification numbers of the parts B, and calculating a nondefective product space. Before a new product is manufactured, entering a characteristic data group of parts A with respect to identification numbers of the parts A and a characteristic data group of parts B with respect to identification numbers of the parts B, and conducting calculations on statistical distances and combinatorial computations between the parts. Finally outputting a combination table having the identification numbers of both the parts A and the parts B.

The present invention relates to a method of manufacturing a product formed with a large number of parts, such as a magnetic storage device, a multi-chip module, liquid-crystal display device, printed circuit board, automobile, or electrical household appliance.
Manufacturing processes for a high-technology hardware product such as a magnetic storage device, multi-chip module, or liquid-crystal display device, generally consist of the parts-forming processes that require thin-flim forming, polishing, and other fine processing, and an assembly process for assembling completed parts. A magnetic storage device, for example, is manufactured by forming its major components, namely, a plurality of magnetic heads and disks in different parts-forming processes and then assembling each magnetic head and disk with a spindle motor, a frame, and other components in an assembly process to complete the device as a product. Also, a multi-chip module is manufactured by forming a plurality of chips on individual wafers in a parts-forming process and then extracting chips from different wafers, mounting the extracted chips mixedly on a wiring substrate or the like, connecting the wiring, and sealing all necessary sections with resin, ceramics, or the like, in an assembly process to complete the device as a product.
During the parts-forming processes and assembly process for manufacturing such a high-technology device, many characteristic values of its components are measured and managed using a technique referred to as SPC (Statistical Process Control). This technique is described in related literature such as "How to Create and Utilize Better Control Charts", a book published by the Japanese Standards Association in 2001, "W. A. Levinson: Statistical Process Control in Microelectronics Manufacturing, Semiconductor International, November, pp. 95-102 (1994)", and "L. S. Nelson: Interpreting Shewhart X-bar Control Charts, Journal of Quality Technology, Vol. 17, No. 2, pp. 114-116 (1985)". SPC is used to analyze changes in chronologically arranged characteristic data and judge whether process abnormalities are occurring, and each characteristic value is independently managed during SPC.
However, it may be difficult to manage each characteristic value independently, and thus, alternative methods to SPC have been proposed. These alternative methods are intended to implement quality control that includes product defect detection, by converting each of process-by-process characteristic data measurements into Mahalanobis distance, a single evaluation measure, or into a statistical distance called Hotelling T2 or the like. The alternative methods are described in Japanese Patent Laid-Open Nos. 2000-114130, 2002-318617, Hei 11-339089, 2004-77188, and 2004-199501, and in related literature such as "Shoh-ichi Tejima and Masahiro Azemoto: Development of a Real-Time Monitoring and Diagnosing System Based on MT System Technology, 11th Quality Engineering Research Papers Presentation Convention, Quality Engineering Society of Japan, pp. 226-229 (2003)", "Technological Development in MT Systems", a book published by the Japanese Standards Association, "R. L. Mason: A Practical Approach for Interpreting Multivariate T2 Control Chart Signals, Journal of Quality Technology, Vol. 29, No. 4, pp. 396-406 (1997)", and "Masashi Nakatsugawa, Masato Yamamoto, and Azuma Oh-uchi: The Mahalanobis Distance in MTS, Quality Engineering, Vol. 8, No. 5, pp. 19-26 (2000)".
The present inventors considered it possible to realize the manufacture of a less expensive product with maintained high quality or high yield by applying any one of the above-mentioned statistical distances to production control. As far as the inventors were able to examine, Japanese Patent Laid-Open No. 2004-145390 was confirmed that describes an example of application of a statistical distance to production control. A method of controlling production by applying a statistical distance to the adjustment of manufacturing process parameters is described in Japanese Patent Laid-Open No. 2004-145390.
In recent years, magnetic storage devices, multi-chip modules, liquid-crystal display devices, printed circuit boards, and other high-technology devices have become more sophisticated in manufacturing process and are facing a situation under which, even if individual components satisfy predefined characteristic data, a completed product does not always become a nondefective product without fail.

Method for manufacturing product formed with a plurality of parts and method for combining parts


A signal indicator lamp includes an LED mounting substrate 2, and is made up of a plurality of consecutively provided lens units 3 with cylindrical light guiding radiation portions 20 provided so as to enclose the LED mounting substrate 2. An LED 14 is mounted at a position biased to the side of an end portion 2D from a central position 2C in a short-side direction S of the LED mounting substrate 2. In the light guiding radiation portion 20, a slit portion 23 is defined which is cut away in an axial direction X such that the LED 14 is arranged therein when the lens unit 3 encloses the LED mounting substrate 2. Light made incident into the lens unit 3 from incident surfaces 24 being a pair of opposite end faces of the slit portion 23 is guided by the light guiding radiation portion 20, and is radiated outward in the entire circumferential region thereof.

A common signal indicator lamp is a cylindrical body, and can radiate light across the entire region in its circumferential direction.
In a light indicator device proposed in the following Patent Literature 1 as an example of the signal indicator lamp, a light-emitting diode substrate and a case that stores the substrate are included. On the substrate, a plurality of light source portions made up of LEDs are disposed. The case includes a base portion in a circular cylindrical shape with a bottom and three covers having translucency and showing circular cylindrical shapes. These covers are connected in three stages stacked with respect to the base portion. Each cover has a ring-shaped top wall at the inner peripheral side, and the top wall has a pair of bulging portions facing each other. At mutually opposite distal end portions in the pair of bulging portions, slits are defined. The substrate stored in the case is, inside of each cover, fitted in the respective slits of the pair of bulging portions. Light emitted from each light source portion of the substrate passes through the cover around the light source portion to be sent out to the outside.


A thermal fuse includes a first electrical contact extending through and engaged in electrical contact with a second contact. A spring is compressed between the first and second contacts. A thermally deformable pin retains the second contact against the compressed spring. The pin is responsive to a high temperature condition such that the pin deforms, thereby allowing the spring to disengage the first and second contacts.

Electrical appliances often include mechanisms that terminate operation of the motor in response to thermal overload conditions that could result in permanent damage to the motor or associated equipment. A thermal overload, such as an excessively high winding or rotor temperature, may occur as a result of a locked rotor, a high mechanical load, a supply overvoltage, a high ambient temperature, or some combination of these conditions.
Conventional thermal cut-outs (TCOs) are based on a thermally responsive element that fuses in response to a thermal overload condition, and which thereby interrupts the flow of electrical power to the protected apparatus, One typical approach uses a spring loaded contact pin or lead that is held in electrical connection with an opposing contact by a fusible material such as solder. Another typical approach uses one or more springs, which are independent from the electrical contacts, that drive the contacts apart into a displaceable fusible stop material. These known approaches have several significant drawbacks. In the first approach, the electrical power flows directly through the fusible material. Thus, self-heating in the fusible material itself, particularly in high power applications, can seriously impair the ability of the TCO to be responsive only to the temperature of the protected apparatus. In both described approaches, the TCO typically comprises a complex arrangement of springs and contact elements that are mounted in a housing. Thus, these approaches are costly, and do not allow for the direct inspection of the TCO because the fusible material and contact conditions are not usually visible through the housing.


A cylindrical shell for a motor/generator may be formed by cutting a rectangular blank, offsetting an edge, rolling the blank into a cylinder with the offset edge overlapping its opposite edge, punching through the overlapping edges to interlock them and form the cylinder, and then joining a base to the cylinder through a similar interlocking, punching process. In a variation, the base may be simultaneously joined to the cylinder as the edges are punched. Holes, or holes with locating nibs, may be used to align the blank in a cylindrical shape to reliably control the shell I.D. during fabrication.

Cylindrical shells are typically used for encasing motors, generators, and other rotating dynamoelectric devices, such as fractional horsepower motors. In the prior art, these cylindrical shells have been formed by a process which involves first cutting a flat rectangular piece of sheet steel, rolling it into a cylinder with the edges abutting, and resistance welding the edges together. The resistance weld may be cleaned up by grinding or the like to finish the shell cylinder The diameter and length of the shell is then checked and adjusted to size. Next, a rigid base for mounting of the motor is attached to the shell by another welding process at what may be six locations in the cradle of the base. This process is widely used throughout the motor industry for forming cylindrical shells and attaching bases to those shells to encase motors
In order to improve this process by reducing steps and costs, the inventor herein has succeeded in designing and developing a process for forming a cylindrical motor shell, as well as attaching a base thereto, which eliminates welding, grinding, and permits production line processes to be used. With this invention, a process is implemented which includes the steps of forming a blank of a flat rectangular piece of sheet steel, as before. Next, an edge of the blank is offset so that as the blank is rolled into a cylinder, the offset edge conveniently overlaps with its opposite edge. The overlapping edges are then joined with a single press stroke which interlocks the edges. The tooling and interlocking method is commercially available under the trade name Tog-L-Loc.RTM. from BTM Corporation in Marysville, Mich. With the interlock formed by the Tog-L-Loc.RTM. process, not only are the overlapping edges joined to withstand significant shear loads, but may also withstand "peel" loads which might otherwise tend to separate the shell as the motor is used under load. This is especially important as the Tog-L-Loc.RTM. method is also used to attach the base to the cylindrical shell either simultaneously with joining the overlapping edges, or in a separate step after the cylinder has been formed. As can be appreciated, with a side load of any appreciable amount, a force is created which has a tendency to "peel" the motor and shell from the base. With the Tog-L-Loc.RTM. interlock, sufficient strength is provided to prevent this "peeling" and hence is sufficient for this application.
As is well known, there are many punching, staking, and other prior art methods for joining two pieces of metal which, to the inventor's knowledge, have never been successfully used for this application. All of these prior art methods are directed to providing shear strength and are generally considered by those of ordinary skill in the art to adequately join two pieces of metal to resist shear forces. However, the same is not true for peel forces and it is believed that this low peel strength has prevented the adoption and use of these prior art punching, staking methods for being utilized for this particular application. Also, for smaller motor shells as would be used in fractional horsepower motors, those of ordinary skill in the art would typically consider that prior art tooling would seem to be too expensive, or very difficult, to create.
Perhaps another reason why those of ordinary skill in the art have been unsuccessful in adapting any kind of punching or staking operation to this application is that the typical motor/generator design incorporates a full round lamination. Therefore, if the inner surface of the cylindrical shell is interrupted, then a full round lamination will not conveniently fit therewithin. However, there are other motor/generator designs which do not utilize the full round lamination and hence would be particularly adapted for use with the present invention.
In addition to the method and apparatus for forming and joining the cylindrical shell to its base with an interlocking process, the inventor herein has also succeeded in developing a method useful in this process for holding the cylindrical shell I.D. as the interlocks are formed without the need to "size" or expand the shell to proper dimension after forming, as is presently done with the prior art processes.
While the principal advantages and features of the present invention have been described above, a more complete and thorough understanding of the invention may be attained by referring to the drawings and description of the preferred embodiment which follow.

Method for joining a motor shell and base


A local game-area network includes a plurality of gaming devices and local game-area servers. Each local game-area server is associated with a corresponding gaming device. Each local game-area server in the local game-area network is operatively associated with every other local game-area server in the local game-area network. Additionally, one of the local game-area servers is a host local game-area server while the remaining gaming devices and associated local game-area servers are clients. Furthermore, the host status of the host local game-area server moves dynamically to an available local game-area server in the local game-area network in response to the host local game-area server becoming non-operational.

Gaming industry cabinets are fairly standardized as to general configuration. This is partly due to the needs of the casinos, who want to fit the maximum number of gaming devices into a given amount of floor space. It is also due to the physical needs of players, who need a certain minimum amount of cabinet area in front of them to play the game while not crowding their fellow players on the next gaming machine. It is also due to the requirements of the game components, encompassing both regulated and non-regulated aspects. Game components include a video monitor or reels, input and output devices (buttons, network interface, voucher or ticket printers, and magnetic strip card readers are typical) together with a main processor board. The main processor board has interfaces to the various input and output devices, and has at least a processor and memory which enables gaming software to be installed and run on the processor board. In most gaming machines the processor board, power supply and other related mechanical and electrical elements are typically co-located near the base of the gaming machine. Disposed thereabove at approximately chest level of the player is the gaming display, such as the rotatable reel displays in a slot machine or a video monitor for video-based games.
FIG. 1 illustrates a common prior art gaming machine. The gaming machine 100 has a top candle 108, a video screen or reel area 102, player input area 104 (generally having buttons, coin-in and/or bill-in, card reader, and in newer machines a printer), and pull handle 106. Gaming machine 100 has, in its interior, a processor board whose location is generally indicated as 110 (the actual processor board and mounting hardware are on the inside of the cabinet).
The processor board, in addition to have physical mounts such as guides, rails, standoff mounts, board slots, board slides, or board tray, will further have cabinet electronic interfaces, typically at the back of the board (towards the front of the cabinet, from a player's perspective). Processor boards will typically have a set of multi-pin plugs or bus connectors that slide into mating plugs or bus connectors when the processor board is correctly seated in its mounts.
FIG. 2 shows a picture of a prior art processor board 200, in this case a processor board from an 1GT® Game King® gaming machine. Shown is the top of the board, with the front of the board facing the bottom of the figure. As is typical, the sides of the board slide into the game cabinet using guide rails in the cabinet, with the cabinet bus or connector interfaces 202 mating to specially positioned and configured plugs in the cabinet.
If the board needs work, the entire processor board is replaced. In addition to a replacement board from the manufacturer (in this case IGT®), there are commercially available replacement boards having the same or nearly the same features, speed, memory capacity, etc., from after market manufacturers. No matter where the board originates from, they follow the same configuration, that is, they consist of a single board that replaces the processor board supplied with the game having similar functionality and the same form. In addition to their physical similarity, they employ a monolithic software architecture; that is, the game cabinet-specific operating system and specific game software are not a modular, layered design using modem software engineering practices. An example of an aftermarket replacement processor board for the IGT® Game King® gaming cabinet is, or was sold by, Happ Controls™, 106 Garlisch Drive, Elk Grove, Ill. 60007. It has the same basic physical, electronic, and software architecture as the original.
Upgrade processor boards are also available for some games. The reason for considering upgrade boards is that it may be possible to run newer games in a cabinet already owned by a casino if improvements are made to processor speed, memory, graphic support chips, and other components. Game upgrades interface to some degree with the internal busses of the game cabinet, but require cabinet modifications. Currently available upgraded boards do not fit in the slot used by the original processor board; rather, they must be mounted elsewhere in the cabinet. In addition to requiring the accompanying mechanical fabrication and electrical work, the upgrade boards are a fixed upgrade. That is, if the configuration of the upgraded game itself needs to be upgraded a few years later, you have to purchase and install a completely new upgrade kit which requires going through the same installation problems that were encountered with the original upgrade. This is a significant deterrent to upgrading activity.
In addition, each proprietary processor board as well as upgraded game boards typically uses its own interface to the game software, requiring game rewrites each time a hardware upgrade occurs. This makes gradual or incremental game enhancement prohibitively expensive.
Thus, it would be desirable to provide a game processor that is usable in upgrades in existing cabinets, as well as usable for new game cabinets, that is more cost effective, is easier to install, provides for incremental upgrades itself, and provides more standard interfaces to the game development community.
Furthermore, most gaming systems today are embedded systems. Existing gaming systems typically contain limited resources such as processing power, memory, and program storage. Because of these limitations gaming platform programs have generally been implemented as one monolithic program, where all of the code is compiled into one executable program. Monolithic programs which drive the gaming system typically use interrupts to handle all real-time background activities. These interrupts are driven by the hardware components. The interrupts typically process time critical data and place this data or status information into memory variables which are shared by the main line code. Monolithic programs usually have a series of tasks that need to be performed in the main line code. These tasks might include acting on status information from interrupts, and processing player input and other events that drive the gaming application.
The problem with monolithic programs is that the program must be stored in one media device such as an EPROM, series of EPROMs acting as one media device, flash memory devices, or hard drive. Any modification to the monolithic program requires an update to the program storage device. This means that if a bug is found in a particular core feature, such as paying coins from the hopper, then all game programs must be rebuilt and re-released to the regulatory agencies for approval. A core feature modification such as this can require a gaming manufacturer to re-release hundreds of programs. Each program must be retested and approved by the regulatory agencies causing considerable delays and increased costs to the gaming manufacturer.
Another method that gaming manufacturers have performed in the past, is to separate the media that contains the game paytables from the media that contains the monolithic program. The game paytable is typically a table of pay rates that control how the gaming machine program plays and pays out wins. The benefit to this method is that regulatory agencies do not need to retest a paytable if it does not change. By making a modification to the monolithic program, the paytable media stays the same, allowing the regulators to assume the paytable will work as it did before.
While there are some benefits to this method, there are some very constraining drawbacks. First, the paytable media only contains data tables that drive the execution of the game program. The paytable media does not contain executable code. This means the monolithic game program must contain the core gaming system code along with the game code. The program must support all game code and game variations that can be driven by the paytable data media. It is not feasible for a game program to support hundreds of different game variations due to the limited resources of the embedded system. The paytable media can only be changed to effect changes in the game features or payouts that are already in the game program. It is also very difficult to continually maintain the core gaming modules along with all of the hundreds of game modules in the manufacturers library.


In one embodiment, a quality of one or more links of a particular node in a communication network may be determined, and then whether the quality of the one or more links is below a threshold may also be determined. In response to determining that the quality of at least one of the one or more links is above the threshold, a select one of the at least one of the one or more links with quality above the threshold may be utilized for communication with the particular node. Conversely, in response to determining that the quality of each of the one or more links is below the threshold, multi-path forwarding over a plurality of links of the particular node may be utilized for communication with the particular node.

Low power and Lossy Networks (LLNs), e.g., sensor networks, have a myriad of applications, such as Smart Grid and Smart Cities. Various challenges are presented with LLNs, such as lossy links, low bandwidth, battery operation, low memory and/or processing capability, etc. One example routing solution to LLN challenges is a protocol called Routing Protocol for LLNs or "RPL," which is a distance vector routing protocol that builds a Destination Oriented Directed Acyclic Graph (DODAG, or simply DAG) in addition to a set of features to bound the control traffic, support local (and slow) repair, etc. The RPL architecture provides a flexible method by which each node performs DODAG discovery, construction, and maintenance.
One of the main challenges in LLNs is not only the limited bandwidth offered by links such as Low Power WiFi, IEEE 802.15.4, or PLC (IEEE P1901.2), but also the very high loss rates experienced on those links and the frequency at which such links may "flap" (be available or not, intermittently). Note that it is not uncommon to lose connectivity for seconds or even minutes, and to see a packet delivery ratio as low as 40% to 50%.
Most existing approaches detect transmission failures using explicit acknowledgments at the Media Access Control (MAC) layer or at higher layers (e.g., transport or application layers). Failure to receive an acknowledgment after attempting a transmission indicates that the intended receiver may not have received the packet. As a result, the transmitter will attempt to retransmit the packet at a later time. In LLNs, dynamic link qualities can easily lead to several retransmissions of a single packet before successfully receiving an acknowledgment. Such an approach can significantly increase communication delay, channel utilization, energy costs associated with transmissions, and other associated transmission costs.

Dynamic multi-path forwarding for shared-media communication networks


Systems and methods for deriving content information about a work of multimedia content and embedding the derived content information in a multimedia bitstream to form a hybrid multimedia bitstream are disclosed. The embedded derived content information may be extracted from the multimedia bitstream by an executable module to assist in compressing the performance duration of the multimedia bitstream.

The need to analyze, edit, and process digital multimedia content, for example, digital audio or digital video, has become a necessity for those who manipulate multimedia content. Processing and editing multimedia content, at one time, was thought of as a task only performed by professional studios. However, advances in computing hardware and the technology used for editing audio and video has opened the door to non-professionals as well.
For example, a home movie may be recorded using a personal camcorder and transferred to a personal computer for processing, editing, or long-term storage. Digital camcorders, for example, record audio, video, and other information related to the home movie in digital form, such as on tape, computer memory, or a mass storage medium. The home movie may then be transferred to a personal computer using any number of interfaces, and then stored as a digital stream such as multimedia file in a number of common formats such as MPEG-1, MPEG-2, or DV, for example.
Due to algorithm complexity and the relatively large amounts of multimedia data that is typically edited and/or processed, the task of analyzing, processing, and editing multimedia content can take a considerable amount of time, even on powerful computers.
One example of processing of multimedia that may be performed is the conversion of a work of multimedia content from one format to another format. Typically, converting a work from one format to another involves a lot of analysis of the content included in the work.
This analysis is typically completed in a vacuum, without the consideration of prior processing or analysis that may have been performed on the multimedia bitstream. Thus, in a subsequent analysis of the multimedia bitstream, the multimedia bitstream is completely re-analyzed without consideration of the prior analysis. Additionally, if the multimedia bitstream is analyzed for other purposes, such as in preparation for temporally modifying the multimedia bitstream, the analysis is performed without regard to the prior analysis. This may be true even though the same type of analysis (e.g. motion detection, etc.) was performed previously when determining the commercial positions.
Additionally, if the multimedia bitstream is passed to another user or analyzed using different software, as is common, the information from any prior analysis is lost. Thus, any analysis of the multimedia bitstream already performed is repeated. This repeated reanalysis of the multimedia bitstream can be very time consuming and wasteful of computing and personnel resources.

Apparatus and method for embedding content information in a video bit stream


A vehicle body frame structure includes a side frame, a sub-frame, a cabin side support member, an under-floor frame, and a link stay. The sub-frame includes a separate side fastening portion, an adjacent side fastening portion, and a central bending point. In the link stay, a first end portion side is fastened to a lower surface of the cabin side support member together with the adjacent side fastening portion so as to be extractable, and a second end portion side is fastened to the under-floor frame. A nut for fastening the second end portion side of the link stay is held by a lateral wall on a side separating from the floor tunnel portion of the link stay, and the support bolt is fitted into the nut from a lower side of a floor tunnel portion in a vehicle width direction serving as an axis.

A technology is known in which in a case of vehicle front collision, a certain vehicle among automobiles ensures a crash stroke of a vehicle body front part by bending down a lower member located behind a front cross member, and by causing a suspension component such as a stabilizer supported by the lower member to be displaced downward (refer to Patent Document 1).
In addition, as a technology for ensuring the crash stroke in the case of vehicle front collision, a technology is known in which a sub-frame for supporting the suspension component is disposed on a lower side of the vehicle body front part, and which is configured to forcibly disconnect a vehicle body fixing portion in a rear portion side of the sub-frame in the case of a vehicle front collision (refer to Patent Document 2).
In a vehicle body frame structure disclosed in Patent Document 2, a rear end portion of the sub-frame is fastened and fixed to a cabin side frame by a bolt and a nut, and a rotary lever arm for loosening the nut by using a thrust force of an explosive in the case of vehicle front collision is disposed. When this vehicle body frame structure is employed, if the rotary lever arm loosens the nut by using the thrust force of the explosive in the case of vehicle front collision, the rear end portion of the sub-frame falls down together with the bolt, thereby causing the mounted suspension component to be displaced downward.
In addition, a technology is known in which the sub-frame for supporting a suspension member is provided in a lower portion of the vehicle body front part, in which the nut is loosened from the bolt for fixing the rear end portion of the sub-frame by exploding the explosive, regarding the front collision as a trigger, and the rotary lever arm for extracting the bolt disposed in the rear end of the sub-frame is rotated. In this manner, the crash stroke of the vehicle body front part is ensured by extracting the bolt and causing the suspension member to be displaced downward (refer to Patent Document 2).

Vehicle body frame structure for automobile


A one or two-dimensional capacitive micro-machined ultrasonic transducer (CMUT) array with supporting frame is provided. The CMUT array has at least three array elements deposited on a conductive substrate. The invention also has at least one CMUT cell in the array element, a conductive top layer deposited to a top side of the element, and a conductive via disposed within the elements. The via is isolated from the conductive top layer and conducts with the substrate. There are at least two isolation trenches in the conductive substrate, and the trenches are disposed between adjacent vias to conductively isolating the vias. A substrate region between the trenches forms a mechanical support frame. At least one conductive electrode is deposited to a bottom surface of the conductive substrate, where the electrode conducts with the via. The support frame eliminates the need for a carrier wafer in the process steps.

In large, fully populated 1D and 2D transducer arrays, providing connection to each array element is a challenge. In the case of 2D CMUT arrays, researchers have reported on interconnect techniques both based on through-wafer vias and through wafer trench isolation. In the through-wafer via implementation, a conductive material, usually doped polysilicon, is used to fill the vias and serves as the conductor between the front and back sides of the array elements. It was found that after the deposition of the polysilicon, performing wafer-to-wafer fusion bonding is difficult. Therefore, the through-wafer via approach is limited to only surface micromachining CMUT processes.
It has further been reported that in the trench isolation process, a carrier wafer is required during the deep reactive ion etching (DRIE) and the flip-chip bonding steps to provide the mechanical support for the membranes. This particular requirement presents certain drawbacks in processing. Good adhesion between the carrier wafer and the membrane surface is required for adequate mechanical support for the membranes. However, it is difficult to separate the carrier wafer and the membrane after the flip-chip bonding. The adhesive material may also swell in the solvent, creating stress that can break the CMUT membranes. It is highly desirable to eliminate the need of the carrier wafer for the trench isolation process.

Trench isolated capacitive micromachined ultrasonic transducer arrays with a supporting frame

The Board of Trustees of the Leland Stanford Junior University


In the manufacture of a seat belt retractor, it is usual to join together a pre-stressed spring cassette with a part which includes the seat belt reel. A spring cassette is provided which includes a pin (20) for locking the spring core (16) and spring cover (10) to prevent them from rotating once the spring (14) has been pre-stressed to exert a desired torque. The spring cassette can then be conveniently handled when assembling the seat belt retractor, and then the pin (20) can be slid within the spring cassette to unlock the spring core (16) and spring cover (10) to allow the seat belt retractor to function as usual.

It is well known to provide seat belts in motor vehicles for the safety of the occupants. When worn, a seat belt restrains an occupant of a seat, in particular in a motor accident. A seat belt is typically provided with a retractor which serves two purposes; when the belt is not in use it is wound onto a reel which keeps the belt out of the way and secondly the retractor maintains the belt in tension across the body of an occupant of the seat when in use. Thus there is no slack in the belt and the occupant is effectively restrained by an inertia locking mechanism on the belt reel when the vehicle is subject to a sudden change in speed such as in an accident. However the retractor does still allow gradual movement for the comfort of the occupant when in normal use.
A conventional seat belt retractor has a reel around which the belt is wound inside a casing and has a spring cassette. The spring cassette includes a spring cover, a spring core and a spring. When assembled the spring cover is fixed to the retractor case and the spring core is connected to the reel on which the belt is wound. The spring provides a torque which tends to rotate the spring core and belt reel with respect to the case. This torque keeps the belt taut and also rotates the reel to wind in the belt when not in use. When assembling the seat belt retractor it is necessary that the spring is pre-stressed so that it provides a predetermined tension in the belt even when fully retracted. This is achieved by assembling the components of the spring cassette and then rotating the spring core relative to the spring cover until the spring is exerting the required torque. However, it is difficult to maintain this torque while the spring cassette and belt reel are being coupled together.


A device includes an anoscope including an elongated hollow member with a longitudinal slot configured to receive tissue in an interior of the hollow member. The device also includes a clip applicator. The clip applicator includes a body slidably received in the slot and jaws at a distal end of the body configured to hold a ligation clip. The clip applicator further includes a plunger slidably coupled to the body configured to actuate the jaws. When the clip applicator is inserted into the slot and the plunger is moved relative to the body, the jaws close and deform the ligation clip from an open position into a closed position around tissue received in the slot.

Hemorrhoids are swollen and inflamed veins around the anus or in the lower rectum. Hemorrhoids may be external, forming under the skin around the anus, or internal, forming in the lining of the anus and the lower rectum. Ligation is a common method for treating hemorrhoids. A band or clip is placed at the base of the hemorrhoid strangulating blood flow thereto, reducing inflammation and eventually eliminating the hemorrhoid. The clips may be metal and deformable such that closing the clip about the base of the hemorrhoid will deform the clip into a closed, crimped shape.

Devices and methods for treatment of hemorrhoids


A glassmelting furnace is heated by combustion of fuel having an atomic ratio of hydrogen to carbon of 0.9 or less.

In the manufacture of glass, glassmaking materials are provided into a glassmelting furnace and melted into molten glass which is then poured into molds to produce products such as, for example, glass bottles. The glassmaking materials for soda-lime-silicate glass include sand, soda ash, lime, and batch oxidizers such as salt cake (calcium sulfate, CaSO4) and/or niter (sodium nitrate, NaNO3, and/or potassium nitrate, KNO3) in order to control the redox state of the glass.
The glassmaking materials are melted in the furnace by heat provided by the combustion of fuel and oxidant. Water vapor resulting from the combustion reacts with alkali oxides in the molten glass to form alkali hydroxides which vaporize out from the molten glass. These alkali hydroxides, such as sodium hydroxide, NaOH, react with furnace refractory walls and cause refractory corrosion, and also react in flue passage(s) from the furnace with sulfur dioxide, SO2, and oxygen to form sodium sulfate, Na2SO4, and other sulfate and sulfite compounds which form particulates and often require expensive electrostatic precipitators or baghouses to ensure that they are not emitted to the atmosphere.
Accelerated corrosion is experienced in silica refractory bricks in the crown of glassmelting furnaces that are converted to oxy-fuel firing (i.e. combustion in which the oxidant has a higher, often much higher, oxygen content than that of air). In particular, severe loss of silica crown is observed in some glassmelting furnaces such as in glass melting for TV panels. It is generally believed that the main cause of the accelerated corrosion is the higher concentrations associated with oxy-fuel firing.
In oxy-fuel firing nitrogen contained in the combustion air is largely absent, so the volume of the combustion products is typically reduced to ⅓ to ¼ of that of the combustion products of conventional air firing. Thus the concentrations of alkali species would increase three to four times, if the same amount of volatile alkali species are generated in conventional air firing.
Accelerated corrosion shortens the furnace life and results in costly furnace repairs. In addition, corrosion increases glass defects in some glass tanks due to dripping of slag into the glass bath. Corrosion resistant refractory bricks such as alumina and alumina-zirconia-slica (AZS) bricks have been used to alleviate this corrosion. For example, AZS is often used for the side walls and flue port walls of glass furnaces, to control the corrosion problems. Silica bricks are the most widely used refractory material for the crown of furnaces because they are lighter, less heat-conductive, and substantially less expensive than alumina and AZS bricks. Also, there is concern that increased glass defects caused by zirconia "refractory stones" might occur when AZS is used for the crown. When silica is used as the material that makes up the crown of the furnace, corrosion, which causes dripping of slag into the glass bath, does not necessarily result in glass defects. This is because silica is the main composition of glass.
It would be very desirable to provide a glassmelting method wherein silica bricks can be used to line the crown of the furnace under oxy-fuel firing and wherein volatilization of alkali species is reduced to minimize corrosion of the crown and emissions of particulates.

Reducing corrosion and particulate emission in glassmelting furnaces


In vitro methods are disclosed that rely on a novel phenomenon of secondary sprouting by cultured endothelial precursor cells, after angiogenic-like tube formation and collapse have occurred on a basement membrane matrix. Particularly disclosed is an in vitro method of isolating and expanding, from a mixed population of mammalian cells originating from a tissue sample, a cellular population enriched for endothelial sprout cells, including cells having one or more physiological and/or immunological features of endothelial precursor cells. Also disclosed is an in vitro method for a screening a substance for potential proangiogenic or antiangiogenic activity.

1. Field of the Invention
This invention relates to the medical arts. In particular, it relates to an in vitro method of isolating and expanding a cellular population enriched for cells having one or more physiological and/or immunological features of endothelial precursor cells (EPCs) and uses for those EPCs.
2. Discussion of the Related Art
Angiogenesis is a highly regulated biological process of sprouting new blood vessels from preexisting blood vessels, which supports growth and maturation. Angiogenesis begins in the mammalian embryo when primitive blood vessels are formed from endothelial cell precursors (EPCs; also known as endothelial progenitor cells or endothelial stem cells). Increasingly complex networks of vessels are formed from these primitive precursors.
Endothelial cell precursors progress through various stages before becoming mature cells. The earlier precursor cells are able to give rise to more cell types if given the right signals and environment. Cells derived from older and more mature precursors have a more limited repertoire.
Generally, molecular markers are used to keep track of the different developmental steps taken of endthelial cells, as certain molecules are present only during certain periods. Cells that can give rise to endothelial cells as well as other cell types are called hematopoietic stem/progenitor cells (HSPC) and/or hemangioblasts. The most primitive are usually derived from umbilical cord blood, peripheral blood or bone marrow and are generally positive for CD34 while being negative for CD38 and HLA-DR. CD34+ cells can be further subdivided according to their expression of CD45RA and CD71. Cells which are CD34+ CD45RA− and CD71− give rise to multipotent progenitor cells, including those which will produce endothelial cell precursors (angioblasts); those that are CD34+ CD45RA+ and CD71−, give rise to granulocyte and monocye progenitors whereas those which are CD34+ CD45RA− and CD71+ give rise to erythrocyte progenitors. (Mayani H and Lansdorp P M, Biology of Human Umbilical Cord Blood-Derived Hematopoietic Stem/Progenitor Cells. Stem Cells. 1998; 16:153–165).
CD34+ cells can be manipulated by the right culture conditions to produce mature endothelial cells expressing von Willebrand factor, CD31, CD54 and CD62. (Mayani H and Lansdorp P M, Biology of Human Umbilical Cord Blood-Derived Hematopoietic Stem/Progenitor Cells. Stem Cells. 1998; 16:153–165). Considerable controversy exists regarding the specific pathway(s), as well as the number of intermediates in the transition between hemangioblasts and differentiated endothelial cells. However, "presumptive hemangioblasts" express CD34, FLK-1, SCL, LMO2 and GATA-2. (Orkin S H and Zon L I. Hematopoiesis and stem cells: plasticity versus developmental heterogeneity. Nature Immunology. 2002. 3(4):323–328).
Even though there is strong support for the expression of CD34 in hematopoietic stem cells, many groups have reported it to be "reversible", "changing", or "absent". (Ishikawa F. Reversible expression of CD34 by hematopoietic stem cells. Ronsho Ketsueki. 2002. 43(1):1–4; Ogawa M. Changing phenotypes of hematopoietic stem cells. Exp Hematol. 2002. 30(1):3–6; Huss R. Perspectives on the morphology and biology of CD34-negative stem cells. J Hematother Stem Cell Res. 2000. 9:783–793). These controversies may be due to the different origins of these stem cells (organs vs. blood or bone marrow) or to the analysis of a vast number of potential intermediates in the differentiation pathway.
There is a specific set of markers present only in EPCs, but not in differentiated endothelial cells. These include AC133, CD166, and AML-1. (Asahara T., et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997. 275:964–967; Matsumoto K., et al. In vitro proliferation potential of AC133 positive cells in peripheral blood. Stem Cells. 2000. 18:196–203; Ohneda O., et al. ALCAM (CD166): its role in hematopoietic and endothelial development. Blood. 2001. 98(7): 2134–2142; Okuda T., et al. RUNX1/AML-1: a central player in hematopoiesis. Int. J. Hematol. 2001. 74:252–257).
In contrast, some markers are expressed only on "mature endothelial cells", and not the EPCs, such as CD31, CD36 and CD62, V-Cadherin. (Reyes M., et al. Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest. 2002. 109(3):337–346).
When precursor cells divide, they can either produce daughter cells more mature than themselves (proliferation) or produce more precursor cells like themselves (expansion). The cellular environment, including cytokines and growth factors, controls these processes. (Mayani H and Lansdorp P M, Biology of Human Umbilical Cord Blood-Derived Hematopoietic Stem/Progenitor Cells. Stem Cells. 1998; 16:153–165).
In adults, nonpathogenic angiogenesis is restricted and transient, for example, as part of the wound healing process and during the female reproductive cycle in the endometrium and ovarian follicle.
Because of the role angiogenesis is thought to play in human diseases, pathogenic angiogenesis has been intensively studied. The highly regulated process of angiogenesis is considered a physiological response to the balance between the actions of proangiogenic and antiangiogenic factors, synthesized by endothelial cells, stromal cells, blood, the extracellular matrix, and tumor cells (Carmeliet, P. and Jain, R. K., Angiogenesis in cancer and other diseases, Nature (2000) 407:249–257 [2000]). When proangiogenic factors are synthesized, stimulated by metabolic stress, mechanical stress, inflammation, or genetic mutations, new blood vessels are created from preexisting ones and pathogenic states result (Carmeliet, P. and Jain, R. K. [2000]). Proangiogenic factors create new blood vessels in six distinct steps: vascular destabilization caused by pericyte detachment, extracellular matrix degradation by endothelial proteases, endothelial cell migration, endothelial cell proliferation, tube formation by endothelial cells, and recruitment of pericytes to stabilize vasculature. (Sato, Y., Molecular mechanism of angiogenesis. Transcription factors and their therapeutic relevance, Pharm & Ther 87:51–60 [2000]).
All of these steps are mediated by proangiogenic factors acting in concert with one another. For example, vascular endothelial growth factor (VEGF) and related molecules stimulate vessel leakage, matrix metalloproteases (MMPs) remodel extracellular matrix and release and activate growth factors, platelet-derived growth factor BB (PDGF-BB) and receptors recruit smooth muscle cells, vascular endothelial growth factor receptor (VEGFR) and NRP-1 integrate angiogenic and survival signals, plasminogen activator inhibitor-1 (PAI-1) stabilizes nascent vessels, and angiopoietin 1 (Ang1) and its receptor precursor (Tie2) in turn stabilize vessels (Carmeliet, P. and Jain, R. K. [2000]) 407:249–257).
For many years, tube formation on a reconstituted basement membrane matrix (MATRIGEL™ biological cell culture substrate) has been the assay of choice for the assessment of angiogenesis in vitro (Baatout S., Endothelial differentiation using Matrigel (review), Anticancer Res. 17: 451–6 [1997]; Benelli, R. and Albini, A., In vitro models of angiogenesis: the use of Matrigel, Int. J. Biol. Markers. 14, 243–6 [1999]). MATRIGEL™ biological cell culture substrate is derived from the extracellular matrix deposited by a mouse EHS tumor. MATRIGEL™ biological cell culture substrate is a complex mixture of basement membrane proteins (laminin, type IV collagen, entactin/nidogen, and heparan sulfate proteoglycans) and it also contains certain growth factors. (Kleinman, H. K. et al., Isolation and characterization of type IV procollagen, laminin, and heparan sulfate proteoglycan from the EHS sarcoma, Biochemistry. 21: 6188–93 [1982]; Vukicevic, S. et al., Identification of multiple active growth factors in basement membrane Matrigel suggests caution in interpretation of cellular activity related to extracellular matrix components, Exp Cell Res. 202: 1–8 [1992]). Unlike the commonly used type I collagen gels (Schor, A. M. et al., Collagen gel assay for angiogenesis. In: Methods in molecular medicine, angiogenesis protocols [Murray J. C., ed.], Humana Press, Totowa, N.J., pp. 145–62 [2001]), the reconstituted basement membrane matrix contains natural substrates that endothelial cells encounter under physiological conditions, i.e., basement membrane components. It has previously been thought that endothelial cells plated on a reconstituted basement membrane matrix 1) stop proliferating, 2) migrate and form capillary-like tubes by 24–36 hr, 3) do not invade the matrix, 4) collapse into clumps, and 5) die. (E.g., Pollman et al., Endothelial cell apoptosis in capillary network remodeling., J. Cell Physiol. 178, 359–70 [1999]; Benelli and Albini [1999]). Because this was thought to be the endpoint of the assay, no previous experiments have extended beyond this point.
The survival of tumors is now considered to be dependent upon tumor angiogenesis. For this reason, cancer chemotherapy is beginning to exploit angiogenesis inhibition as a mechanism to limit tumor metastases and angiogenesis is increasingly being used as a diagnostic/prognostic marker. For example, tumor vascularity in solid tumors may inversely correlate with prognosis, and both basic fibroblast growth factor (bFGF; or FGF-2) and VEGF expression have been reported to predict prognosis. (Takahashi, Y. et al., Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer, Cancer Res 55:3964–68 [1995]). Breast cancer prognosis can also be based on the extent of angiogenesis. (Weidner, N. et al., Tumor angiogenesis: a new significant and independent prognostic factor in early-stage breast carcinoma, J. Natl. Cancer Inst. 84:1875–1887 [1992]; Horak, E. R. et al., Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metasteses and survival in breast cancer, Lancet 340:1120–1124 [1992]). Not only are tumor growth, progression, and metastasis dependent on access to vasculature, but it is also apparent that an "angiogenic switch" is activated during the transition from mid to late dysplasia, causing a change in tissue angiogenic phenotype preceding the histological tissue transition. (Hanahan, D. and Folkman, J., Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 86:353–64 [1996]).
During tumor-associated angiogenesis, sustained production of angiogenic factors by cancer cells, or indirect macrophage stimulation, causes dysregulated immature vessel growth. (Folkman, J. and Shing, Y., Angiogenesis, J Biol. Chem. 267:10931–10934[1992]). Several cytokines and growth factors are highly associated with intratumoral angiogenesis, including bFGF and VEGF which modulate angiogenesis in vivo with a paracrine mode of action. (Bikfalvi, A. et al., Biological roles of fibroblast growth factor-2, Endocr. Rev. 18:26–45 [1997]; Ferrara, N. and Davis-Smyth, T., The biology of vascular endothelial growth factor, Endocr Rev 18:4–25 [1997]; Relf, M et al., Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis, Cancer Res. 57(5):963–69 [1997]; Linderholm, B. et al., Vascular endothelial growth factor is of high prognostic value in node-negative breast carcinoma, J. Clin. Oncol. 16:3121–28 [1998]). bFGF and VEGF may synergistically influence angiogenesis, with bFGF modulating endothelial expression of VEGF through both autocrine and paracrine actions. (Seghezzi, G. et al., Fibroblast growth factor-2 (FGF-2) induces vascular endothelial growth factor (VEGF) expression in the endothelial cells of forming capillaries: An autocrine mechanism contributing to angiogenesis, J. Cell. Biol. 141(7):1659–73 [1998]).
For these reasons, drugs acting through an antiangiogenic mechanism are contemplated to prevent neoplastic growth. As an example, Hunter et al. described a method of treating a tumor excision site with a composition including paclitaxel or a paclitaxel analog with a polymer to prevent residual blood vessel formation. (U.S. Pat. No. 5,886,026).
In addition to cancer, other pathological states require angiogenesis including diabetes mellitus, Alzheimer's disease, asthma, and hypertension. The pathological progression in endometriosis is also thought to involve angiogensis. (E.g., Taylor, R N et al., Angiogenic factors in endometriosis, Ann N Y Acad Sci 955:89–100 [2002]; Shawki, O et al., Apoptosis and angiogenesis in endometriosis: relationship to development and progression, Fertil Steril. 77 Suppl 1:S44 [2002]; Gazvani, R et al., Peritoneal environment, cytokines and angiogenesis in the pathophysiology of endometriosis, Reproduction 123(2):217–26 [2002]; Taylor, R N et al., Endocrine and paracrine regulation of endometrial angiogenesis, Ann N Y Acad. Sci. 943:109–21 [2001]; Gazvani, R et al., New considerations for the pathogenesis of endometriosis, Int J Gynaecol Obstet. 2002 Feb.;76(2):117–26 [2002]; Fujimoto, J et al., Angiogenesis in endometriosis and angiogenic factors, Gynecol Obstet Invest. 48 Suppl 1:14–20 [1999]; Healy, D L et al., Angiogenesis: a new theory for endometriosis, Hum. Reprod. Update. 1998 Sep.–Oct.;4(5):736–40 [1998]; Matsuzaki, S et al., Angiogenesis in endometriosis, Gynecol. Obstet. Invest. 46(2):111–15 [1998]).
Inflammatory disorders can involve excessive angiogenesis in various organs. Blood cells including platelets, mast cells, monocytes, and macrophages release angiogenic factors, such as VEGF, ANG1, bFGF, TGF-β1, PDGF, TNF-α, hepatocyte growth factor (HGF), and insulin-like growth factor (IGF-I). Additionally, blood cells contain proteases that degrade barriers for migrating vasculature and activate growth factors from extracellular matrix. Wound repair is an example of how the inflammatory response influences angiogenesis in a non-pathogenic way. Angiogenesis in wound repair can be described in the following steps: 1) endothelial cells are released from the basement membrane degraded by metalloproteinases and other proteases, and 2) the endothelial cells migrate to connective tissue and differentiate into tubes where they resynthesize the basement membrane, all in response to the proangiogenic factors being secreted at the wound site. (Kleinman, H. K. and Malinda K. M., Role of angiogenesis in wound healing, in Angiogenesis Inhibitors and Stimulators: Potential Therapeutic Implications, Ed. Mousa, S. A., pp. 102–109 [2000]).
The primary cause of pathological angiogenesis in non-neoplastic disease states is hypoxia. Hypoxia-induced transcription factors (HIFs) induce the expression of angiogenic factors including VEGF, nitric oxide synthase, PDGF, Ang2, and others (Carmeliet, P. and Jain, R. K. [2000]). As a result, hypoxia-induced angiogenesis leads to blindness in premature newborns, diabetics, and hemorrhagic rupture of atherosclerotic plaques. Additionally, vascular remodeling caused by hypoxia induces chronic obstructive lung disease, characterized by the thickening of vascular muscular coat and pulmonary hypertension. Although hypoxia-induced angiogenesis can be pathological, it also salvages ischemic myocardium and promotes survival after stroke. For these reasons, the use of proangiogenic factors has been proposed as therapy for ischemic diseases, such as arteriosclerotic occlusion of the lower limb or angina pectoris/myocardial infarction.
Diabetic retinopathy, the most severe ocular complication of diabetes mellitus, may be defined as a disease of retinal microvasculature. Diabetic retinopathy is the leading cause of new blindness in persons 25 to 74 years of age in the United States, accounting for about 8,000 new blindness cases each year. (Aiello L P et al., Diabetic retinopathy, Diabetes Care 21:143–156 [1998]; Lim J I et al., Review of diabetic retinopathy, Curr. Opin. Ophthalmol. 2:315–323 [1991]). Two types of diabetic retinopathy are recognized clinically: (1) nonproliferative diabetic retinopathy (NPDR), associated with retinal ischemia, pericyte loss, capillary closure, retinal infarctions/cotton wool spots, retinal hemorrhages, microaneurisms, intraretinal microvascular abnormalities, and macular edema; and (2) proliferative diabetic retinopathy (PDR), associated with intravitreal hemorrhages, optic disc or peripheral neovascularization, preretinal fibrovascular membranes, and vitreoretinal traction with retinal detachments (Aiello L P et al. [1998]; Lim J I et al. [1991]). Sadly, 43% of juvenile-onset and 60% of adult-onset diabetics lose vision within 5 years of the onset of PDR.
Supporting the conclusion that diabetic retinopathy is a disease of retinal microvasculature, abnormally high concentrations of angiogenic growth factors have been detected in the vitreous of diabetic retinopathy and PDR patients. (Aiello L P, and Hata Y., Molecular mechanisms of growth factor action in diabetic retinopathy, Curr. Opin. Endocrinol. Diabetes 6:146–156 [1999]; Boulton, M. et al., Intravitreal growth factors in proliferative diabetic retinopathy: correlation with neovascular activity and glycaemic management, Br. J. Ophthalmol. 81:228–233 [1997]; Freyberger, H. et al., Increased levels of platelet-derived growth factor in vitreous fluid of patients with proliferative diabetic retinopathy, Exp. Clin. Endocrinol. Diabetes 108:106–109 [2000]). Additionally, VEGF induced by hypoxia and hyperglycemia has been implicated in causing PDR neovascularization and vascular hyperpermeability. (Aiello L P, and Hata Y., Molecular mechanisms of growth factor action in diabetic retinopathy, Curr. Opin. Endocrinol. Diabetes 6:146–156 [1999]; Aiello, L P and Wong, J S, Role of vascular endothelial growth factor in diabetic vascular complications, Kidney Int. 58 (Suppl. 77):113–119 [2000]).
Retinas in proliferative diabetic retinopathy (PDR) have increased expression of VEGF, PlGF, and tenascin, a vascular basement membrane protein. (E.g., Ljubimov A V et al., Basement membrane abnormalities in human eyes with diabetic retinopathy, J. Histochem. Cytochem. 1996;44:1469–1479 [1996]; Spirin K S et al., Basement membrane and growth factor gene expression in normal and diabetic human retinas, Curr. Eye Res. 18:490–499 [1999]). Hypoxia-inducible VEGF is considered as the main growth factor that mediates PDR neovascularization (Smith L E et al., Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor, Nat. Med. 5:1390–1395 [1999]).
However, VEGF inhibitors only partially prevent ocular neovascularization and vessel hyperpermeability. (Campochiaro, P A, Retinal and choroidal neovascularization, J. Cell Physiol. 184:301–310 [2000]; Aiello L P, Vascular endothelial growth factor. 20th-century mechanisms, 21st-century therapies. Invest. Ophthalmol. Vis. Sci. 38:1647–1652 [1997]; Ozaki H et al., Blockade of vascular endothelial cell growth factor receptor signaling is sufficient to completely prevent retinal neovascularization, Am. J. Pathol. 156:697–707 [2000]; Aiello L P, Vascular endothelial growth factor and the eye: Biochemical mechanisms of action and implications for novel therapies, Ophthalmic Res. 1997;29:354–362; Aiello L P et al., Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective β-isoform-selective inhibitor, Diabetes 46:1473–1480 [1997]; Campochiaro P A, Retinal and choroidal neovascularization, J. Cell Physiol. 184:301–310 [2000]; Penn J S, Bullard L E, VEGF signal transduction proteins ERK-1 and ERK-2 are targets for the inhibition of retinal angiogenesis, Exp. Eye Res. (ICER Abstracts) 71(Suppl. 1):S.5 [2000]).
This implies that other factors may be involved in this process. (See, Castellon, R. et al., Effects of Angiogenic Growth Factor Combinations on Retinal Endothelial Cells, Exp. Eye Res. 74:523–35 [2002]). Growth factor synergies have been reported in other tissues. (Goto F et al., Synergistic effects of vascular endothelial growth factor and basic fibroblast growth factor on the proliferation and cord formation of bovine capillary endothelial cells within collagen gels, Lab. Invest. 69:508–517 [1993]; Stavri G T et al., Hypoxia and platelet-derived growth factor-BB synergistically upregulate the expression of vascular endothelial growth factor in vascular smooth muscle cells, FEBS Lett. 358:311–315 [1995a]; Stavri G T et al., Basic fibroblast growth factor upregulates the expression of vascular endothelial growth factor in vascular smooth muscle cells. Synergistic interaction with hypoxia, Circulation 92:11–14 [1995b]; Hata Y et al., Basic fibroblast growth factor induces expression of VEGF receptor KDR through a protein kinase C and p44/p42 mitogen-activated protein kinase-dependent pathway, Diabetes 48:1145–1155 [1999]; Miele C et al., Insulin and insulin-like growth factor-I induce vascular endothelial growth factor mRNA expression via different signaling pathways, J. Biol. Chem. 275:21695–21702 [2000]).
There remains a need for an in vitro method of isolating and expanding a cellular population enriched for endothelial precursor cells that can be used to further the study of biochemical mechanisms of angiogenesis and antiangiogenesis, and can be employed to screen substances for potential new proangiogenic and antiangiogenic agents that could be useful for therapeutic purposes. These and other benefits are provided by the present invention as described herein.

Secondary sprouting for isolation and expansion of endothelial sprout cells and endothelial precursor cells from a mixed population and for screening substances