A method for laminating glass, a laminate assembly, and an adhesive-coated plastic material used in a laminate assembly. Specifically an adhesive, once applied to a plastic layer is grooved or textured to allow formerly trapped air to escape from between layers of a laminate assembly during a laminate process. This can allow for the adhesive layer to be thinner, while still providing for a final product that is relatively air bubble-free and optically pleasing or substantially free of optical defects caused by waviness of the plastic layer between two PVB sheets and/or wrinkles of the plastic sheet.

1. Field of the Invention
The present invention is in the field of laminated materials, specifically optically clear rigid materials, and more specifically to glass or plastic laminates utilizing a textured adhesive in their formation.
2. Description of the Related Art
Glass can be laminated with various plastic layers to form laminated safety glass which can be used in windshields for automobiles, windows for buildings and elsewhere. Certain types of plastic and glass can be used to form laminated safety glass that functions as bulletproof (or bullet-resistant) glass. The plastic layer in a glass laminate can have dyes or coatings to impart various optical characteristics to the resulting laminated safety glass. Examples of such optical characteristics include tinting, color, partial reflectivity, infrared reflectivity, infrared absorption, ultraviolet reflectivity, and ultraviolet absorption.
While a variety of different materials can be used as a plastic layer in laminated safety glass, polyethylene terephthalate (PET) is known for use as a plastic layer in laminated glass. Commonly, when PET is used as the plastic layer, the PET layer has an adhesive applied on one or both sides of it; the PET/adhesive layer combination is then sandwiched between two layers of glass in a laminate assembly. The adhesive in such arrangements, applied on at least one side of the PET layer, is often in the form of a preformed poly(vinyl butyral) (PVB) sheet; the PET and PVB layers are stacked on top of each other, with the glass layers then placed external to the PET and PVB layers and the whole stack of PET, PVB and glass layers being laminated.
In order to deal with the issue of air removal in various forms of interlayers, such as those which utilize poly(vinyl butyral) (PVB) sheets as one (or more) adhesive layer(s), the PVB sheets are often embossed with a series of repeating troughs or other patterns, such as, but not limited to, those described in United States Patent Application Publication No. 2008/0268204, or are formed to have various random patterns, such as, but not limited to, those described in United States Patent Application Publication No. 2008/0254302, both of which disclosures are incorporated herein by reference in their entirety.
These adhesive sheets, however, are generally relatively thick, on the order of 1 mm (1000 microns). Thick layers of PVB are generally necessary to allow for sufficient texturing to be applied to the PVB sheet to allow for air flow during de-airing processes and so that the material of the PVB sheet can absorb some of the residual air trapped between layers, further decreasing the size and number of air bubbles in the final glass laminate product.
However, one problem with the use of textured PVB sheets as the adhesive is that, although variations in the thickness of the sheet during the lamination process (i.e., variations associated with the surface roughness of the sheet) may help resolve or address the air bubble issue, such variations can add optical distortion to the laminated safety glass because the variations in the PVB sheet can translate into variations appearing in the resultant glass laminate structure. In effect, if the surface roughness of the PVB sheet does not sufficiently "flow" so that air space is removed and the resultant surface, after lamination, is essentially smooth and flat, the surface roughness (and/or differences in thickness) can be visible as optical distortion. An additional problem associated with a laminate comprising a PET layer between two PVB sheets is the formation of another type of optical distortion referred to as waviness or orange peel. When PET is laminated between two layers of PVB, the PET does not "flow" like the PVB does, so it may look wavy or appear to have a surface that looks like applesauce when laminated, even if there is excellent deairing of the laminate. Another problem associated with a laminate comprising a PET layer between two PVB sheets is the formation of wrinkles, particularly with complex curvature laminates such as windshields.
Therefore, it has generally been considered desirable to use a thinner layer of adhesive in order to decrease optical distortion from variations in the thickness of the adhesive and the use of two thicker layers of adhesive (i.e., two PVB sheets). Further, a thinner layer of adhesive allows a plastic layer to more closely follow the contours of curved glass in certain glass laminates and decrease or eliminate folding or wrinkling of the plastic layer or the adhesive layer during the lamination process, as well as a reduction or elimination of the waviness or applesauce effect of the plastic sheet and reduction or elimination of wrinkles PVB sheets, however, often cannot be made much thinner as they cannot hold surface texturing and may be difficult to work with when they are thinner.
For example, U.S. Pat. No. 6,455,141, the entire disclosure of which is herein incorporated by reference, provides for a smooth thin layer of an adhesive, such as PVB, to be applied to one surface of the plastic sheet. This layer is not provided as a preformed PVB sheet, but is provided as deposited material which is laid down directly on the plastic sheet to form a smooth layer already attached to the plastic layer prior to lamination. Such a thin layer allows for improvements in optical issues associated with curvature and for reduced wrinkling, but is less able to absorb residual air trapped between layers of the glass laminate. In other words, previous efforts have fallen short in simultaneously resolving both the optical distortion issues described above along with the air bubble issue.


A remote visual liquid quantity indicator comprises a flexible cable within a flexible outer sleeve and allows a user to remotely determine the level of a liquid in a container, such as an accumulator without the need for electrical power or a direct line of sight to the container. The flexible cable may be coupled between a reservoir sweeper of the accumulator and an indicator. Changes in the fluid level of the accumulator may provide a linear movement to the flexible cable, which in turn provides a change to the measurement reading of the indicator. The flexible cable/outer sleeve allows for the complex routing scenarios necessary in the congested spaces surrounding aircraft accumulators.

The present invention generally relates to methods and apparatus for determining the fluid level of a container, such as an accumulator, and more specifically, to methods and apparatus for determining the fluid level of a container without the need for either electrical power or a direct line of sight to the container.
Accumulators are frequently used on military and commercial aircraft to accommodate the thermal expansion of coolant and hydraulic fluids. During aircraft servicing, maintenance personnel need to ascertain if the respective liquid loop contains the appropriate fluid level. Often, the accumulator is located in an inconvenient space for visual inspection and there is no aircraft electrical power available to operate a level sensor incorporating a rotary variable differential transformer (RVDT) or a potentiometer.
A measuring device for a tank is disclosed in U.S. Pat. No. 1,170,290. A float is attached to a rigid rod and as the float rises and falls, the rod moves in a linear direction. A vertical tubular member (guide tube) positioned inside the tank guides the movement of the rod. An indicator connected to the rod and positioned outside the tank determines the fluid level inside the tank. The rod and guide tube are positioned in a direct line of sight to the indicator. In an alternate embodiment, a chain is used in place of the rod. This device may not be useful for some applications because indicator placement requires a direct line of sight to the fluid container (tank). This requirement greatly limits the functionality and location of the remote indicator, especially in situations where the fluid container is almost surrounded by other components, beyond which a remote indicator is desired.
A fluid measuring device not requiring a direct line of sight between the fluid container and the indicator is disclosed in U.S. Pat. No. 1,266,743. The described device includes a float attached to a piano wire. The wire raises and lowers as the float raises and lowers. The wire is housed in a copper tube that can be bent to allow misalignment between the indicator and the liquid level. Although this method does not require a direct line of sight to the indicator, it may not be suitable for some applications. For some aircraft applications, for example, installation of the copper tube requires repeatedly bending and unbending the tube to position it around the various components. For some applications requiring complex routing scenarios through congested spaces, installation of the described device may be challenging.
As can be seen, there is a need for improved methods and apparatus for determining the fill level of a container, such as an accumulator, at a location more convenient for maintenance and without the need for electrical power or a direct line of sight to the accumulator.


A deicer comprises a skin heating means immediately subjacent an outer skin overlying an apex of a leading edge, and a skin deflection means immediately subjacent the outer skin chordwise aft of the apex. The skin heating means prevents the formation of ice over the apex and the skin deflection means deflects the outer skin to expulse ice formed chordwise aft of the apex.

In recent years, many aircraft manufacturers have sought improved ice protection systems to enable aircraft to safely fly in atmospheric icing conditions. Ice accumulations on the leading edge surfaces of various aircraft structures can seriously effect the aerodynamic characteristics of an aircraft. Examples of such aircraft structures include wings, engine inlets, and horizontal and vertical stabilizers. A leading edge is that portion of a surface of a structure that functions to meet and break an airstream impinging upon the surface of an aircraft structure. The impinging airstream is induced during flight. Conventional pneumatic deicers, electrothermal deicers and bleed air anti-icers have been used for many years to protect the leading edges of general aviation or commercial aircraft. These ice protection techniques are described in detail by Technical Report ADS-4, Engineering Summary of Airframe Icing Technical Data published by the Federal Aviation Agency, December 1963. In spite of these proven techniques, many aircraft manufacturers and operators have expressed a desire for new systems having better ice removal performance, longer life and decreased weight and energy requirements. In particular, a deicer is desired exhibiting the excellent ice removal performance typical of the devices described above while having increased life, reduced weight, and reduced energy consumption.


A superconductive conductor or cable comprising a core, which comprises at least one string of a ceramic, superconductive material, and where the core is encapsulated by a metal cap. In order to manufacture a conductor or a cable with an encapsulation, and in which it is possible as well during the manufacturing process as under the operation to maintain a controlled atmosphere around the superconductive core, at least one layer of not sintered, ceramic powderous material is provided between the cap and the core, which material has a higher sintering temperature than the superconductive material in the core. The superconductive core may be sintered for formation of the superconductive ceramics by placing in the tubular metal cap a starting material in powderous form, and shaped as a core in the other ceramic powder material and subsequently forgeing the the metal cap with its content, preferably by swaging at an ambient temperature, which is below the sintering temperature of the core.

The present invention relates to a superconductive conductor or cable comprising a core, which comprises at least one string of a ceramic superconductive material, and where the core is encapsulated by a metallic cap. Furthermore the invention relates to a method of manufacturing such a conductor or cable.
Ceramic compounds of the type, which are often designated by, the formula Y-Ba-Cu-O have metals in oxidized form and exhibit electric superconductive characteristics at a substantially higher temperature than that of conventional superconducting materials. Because of the relatively high marginal temperature of the superconductive characteristics, this type of compounds has become more interesting for use in a greater variety of industrial application. The ceramic compounds form a whole group of materials, in which copper and oxygen seem to be the only required materials, as they, in addition to or instead of the metals yttrium and barium, may also comprise e.g. scandium, various lanthanides, calcium or strontium. Superconductors comprising other materials, e.g. bismuth and/or thallium are also known, as such materials may completely or partly replace the abovementioned metals. Furthermore, it is known that the superconductive characteristics may be improved in some cases, if fluorine replaces part of the oxygen.
The use of the superconductive materials is restricted by the fact that the manufacture of these conductors in sufficient lengths and with a sufficiently homogeneous structure for the industrial application of fabricating cables is difficult and costly. An essential problem in this connection is that in the manufacturing process a solid-reaction between suitable compounds, e.g. oxides, carbonates or oxalates must take place; that the reaction must take place under a controlled set of temperature, and that the composition of the surrounding atmosphere may be of considerable importance. In particular, a high partial pressure of oxygen may be necessary. Furthermore there is a considerable risk that the reaction product thus formed may be unstable and liable to split off e.g. oxygen. It may, therefore, be necessary to surround the superconductive core, also under later operation, by a controlled atmosphere.
These problems are discussed in Fujikura Technical Review, No. 17, Feb. (Tokyo JP), H. Osani et al, pages 1-4, in which different materials for the metal cap have been tested, and in Advanced Ceramic Materials--Ceramic Superconductors, Volume 2, No. 38, Special Issue, Jul. 1988, (Westerville, Oh., US), R. W. McCallum et al pages 388-400, in which silver is identified as a preferred material for encapsulation because of its permeability to O.sub.2, and in which addition of silver oxides inside the cap has been suggested as a means for controlling the atmosphere inside the cap during the sintering process of the superconductive material.

Method of manufacturing a superconductive cable


Compounds of formula (I) ##STR1## wherein A.sub.1 is C or N; E is a five- or six-membered heteroaromatic or six-membered aromatic ring optionally substituted by R.sup.3 or R.sup.4 ; X.sup.1 --X.sup.2 is CHR.sup.1 --CH, CR.sup.1 .dbd.CH, NR.sup.1 --CH, S(O).sub.u --CH or O--CH; X.sup.3 is CR.sup.5 R.sup.5 ', NR.sup.5, S(O).sub.u or O; R.sup.2 is --OR', --NR'R", --NR'SO.sub.2 R'", --NR'OR', --OCR'.sub.2 C(O)OR', --OCR'.sub.2 OC(O)--R', --OCR'.sub.2 C(O)NR'.sub.2, CF.sub.3 or --COCR'.sub.2 R.sup.2 '; R.sup.3, R.sup.4 and R.sup.7 are independently H, halo, --OR.sup.12, --SR.sup.12, --CN, --NR'R.sup.12, --NO.sub.2, --CF.sub.3, CF.sub.3 S(O).sub.r --, --CO.sub.2 R', --CONR'.sub.2, R.sup.14 --C.sub.0-6 alky-, R.sup.14 --C.sub.1-6 oxoalkyl-, R.sup.14 --C.sub.2-6 alkenyl-, R.sup.14 --C.sub.2-6 alkynyl-, R.sup.14 --C.sub.0-6 alkyloxy-, R.sup.14 --C.sub.0-6 alkylamino- or R.sup.14 --C.sub.0-6 alkyl--S(O).sub.r --; R.sup.6 is W--(CR'.sub.2).sub.q --Z--(CR'R.sup.10)--U--(CR'.sub.2).sub.s --V-- or W'--(CR'.sub.2).sub.q --U--(CR'.sub.2).sub.s -- U and V are absent or CO, CR'.sub.2, C(.dbd.CR.sup.15.sub.2), S(O).sub.n, O, NR.sup.15, CR.sup.15 'OR.sup.15, CR'(OR")CR'.sub.2, CR'.sub.2 CR'(OR") C(O)CR'.sub.2, CR.sup.15.sub.2 C(O), CONR.sup.15, NR.sup.15 CO, OC(O), C(O)O, C(S)O, OC(S), C(S)NR.sup.15, NR.sup.15 C(S), SO.sub.2 NR.sup.15, NR.sup.15 SO.sub.2, N.dbd.N, NR.sup.15 NR.sup.15, NR.sup.15 CR.sup.15.sub.2, NR.sup.15 CR.sup.15.sub.2, CR.sup.15.sub.2 O, OCR.sup.15.sub.2, C$(m)ZC, CR.sup.15 .dbd.CR.sup.15, Het, or Ar, provided that U and V are not simultaneously absent, and W and W' are a nitrogen-containing substituent, and integrin receptor antagonists.

Integrins are a family of heterodimeric proteins which generally mediate cell adhesion. Typical of such proteins are the vitronectin receptor (an .alpha..sub.V .beta..sub.3 heterodimer) and the fibrinogen receptor (an .alpha..sub.IIb .beta..sub.3 heterodimer). The natural ligands of these receptors (e.g., vitronectin and fibrinogen) have been found to share a common -Arg-Gly-Asp- amino acid sequence, which appears to be critical for binding. In fact, many of the integrin receptors appear to cross react with ligands which possess such an amino acid sequence. For instance, the .alpha..sub.IIb .beta..sub.3 receptor reacts with fibronectin and vitronectin, thrombospondin and von Willebrand factor, as well as fibrinogen. Functionally fibrinogen, a dimer having two binding sites for .alpha..sub.IIb .beta..sub.3, reacts with activated receptors found on the surface of platelets. The binding of .alpha..sub.IIb .beta..sub.3 receptors on adjacent platelets, by fibrinogen leads to crosslinking and is considered to be a major factor in platelet aggregation. Compounds which inhibit the binding of the .alpha..sub.IIb .beta..sub.3 receptor to fibrinogen have been shown to inhibit the platelet aggregation in vitro, and thrombus formation in vivo. See, for instance, EP-A 0 341 915.
The vitronectin receptor is found on a variety of cell types, such as on osteoclasts and the endothelial cells lining blood vessels. Recent studies have indicated that the attachment of osteoclasts to the bone matrix is mediated through these cell surface adhesion receptors. For instance, Davies, et al., J. Cell Biol., 1989, 109, 1817, disclose that the osteoclast functional antigen, which is implicated in the regulation of bone resorption, is biochemically related to the vitronectin receptor. The vitronectin receptor is known to bind to bone matrix proteins, such as osteopontin, bone sialoprotein and thrombospondin, which contain the tri-peptide Arg-Gly-Asp (or RGD) motif. Thus, Horton, et al., Exp. Cell Res. 1991, 195, 368, disclose that RGD-containing peptides and an anti-vitronectin receptor antibody (23C6) inhibit dentine resorption and cell spreading by osteoclasts. Bertolini et al., J. Bone Min. Res., 6, Sup. 1, S146, 252 have shown that cylco-S,S-N.sup..alpha. -acetyl-cysteinyl-N.sup..alpha. -methyl-argininyl-glycyl-aspartyl-penicillamine amide inhibits osteoclast attachment to bone. In addition, Sato, et al., J. Cell Biol. 1990, 111, 1713 disclose that echistatin, a snake venom peptide which contains the RGD sequence, is a potent inhibitor of bone resorption in tissue culture, and inhibits attachment of osteoclasts to bone. Fisher, et al., Endocrinology 1993, 132, 1411, has further shown that echistatin inhibits bone resorption in vivo in the rat. EP 528 587 and 528 586 report substituted phenyl derivatives which inhibit osteoclast mediated bone resorption.
Bondinell, et aL, in WO 93/00095 (PCT/US92/05463) and WO 94/14776 (PCT/US93/12436) disclose that certain compounds which have a substituted 6-7 bicyclic ring system are useful for inhibiting the fibrinogen (.alpha..sub.IIb .beta..sub.3) receptor. Other 6-7 bicyclic ring systems which inhibit the fibrinogen receptor are disclosed by Blackburn et al. in WO 93/08174 (PCT/US92/08788). Blackburn et al., WO 95/04057 (PCT/US94/07989) also disclose compounds which have a five- or six-membered ring fused to such 6-7 bicyclic ring to form a tricyclic ring system, which are useful as antagonists of the fibrinogen receptor. Other compounds having 6-7 bicyclic ring systems that selectively inhibit the vitronectin receptor are disclosed in WO 96/00730 (PCT/US95/08306) and WO 96/00574 (PCT/US95/08146). It has now been discovered that certain new tricyclic ring systems are useful templates for preparing integrin receptor antagonists. It has also been discovered that such a ring system may be used as a template, which may be suitably substituted to prepare compounds which are selective for either the fibrinogen receptor or the vitronectin receptor.


The present invention relates to reinforced polyamide molding materials with high notch impact strengths, comprising low viscous polyamides and flat glass fibers as a reinforcing medium, characterized in a polyamide matrix, comprising the following components: (A) 0 to 60 wt.-% of at least one aliphatic, partly crystalline polyamide with a solution viscosity, measured in m-cresol (0.5 wt-%), of ηrel less than 1.9, (B) 0 to 60 wt.-% of at least one amorphous or microcrystalline polyamide based on aliphatic, cycloaliphatic or aromatic diamines, dicarboxylic acids, lactams and/or aminocarboxylic acids, preferably with 6 to 36 carbon atoms, or a mixture of such homopolyamides and/or copolyamides, wherein the components (A) and (B) fulfill the condition: (A)+(B)=20 to 60 wt.-% and that, in the case of a mixture of components (A) and (B), at least 50 weight parts aliphatic blocks (A) are present in the mixture, and a filler component, comprising: (C) 40 to 80 wt.-% flat glass fibers with elongated shape, and the glass fibers have a non-circular cross-sectional area and a size ratio of the main cross-sectional axis to the secondary cross-sectional axis of between 2 to 5, particularly between 3 and 4, and (D) 0 to 40 wt.-% particle like or layer like fillers, with the prerequisite that carbon fibers are excluded, wherein the polyamide molding materials optionally comprise up to 5 wt.-% of further usual additives and auxiliary agents (E), and wherein the weight of the components (A) to (E) sums up to 100%.

Reinforced polyamides are playing an increasing role in the field of technical construction materials, since they have high rigidity, high toughness and high heat distortion temperature. Fields of application are, for example, internal and external parts in the automotive sector and in the field of other means of transport, housing material for appliances and equipment for telecommunication, consumer electronics, household appliances, machinery equipment, apparatus in the field of heating and fixing parts for installation. Metal like properties are important for parts, for example, in the automotive sector, but these can only be achieved by highly filled, reinforced molding materials. For thin-walled parts, particularly a high flow length of the molding materials is necessary, which flow length, however cannot or can only very poorly be achieved in molding materials that are reinforced by endless fibers.
There is also a special advantage of reinforced polyamides in the exceptionally good bonding between polymer matrix and reinforcing materials. This is true even at high reinforcement levels, resulting in products with high tensile modulus of elasticity. However, the toughness of the products is not sufficient to fulfil all requirements.
Polymers which are regarded as polyamides in the present invention that have basic building blocks, which are held together by amide bonds (—NH—CO—), and which can be prepared by polycondensation or polymerization of monomers, as for example dicarboxylic acids, dicarboxylic acid halides, dinitriles, diamines, aminocarboxylic acids and/or lactames. They can be homopolyamides or copolyamides. The average molecular weight of the polyamide should be more than 5,000, preferably more than 10,000 but less than 20,000, corresponding to solution viscosities of ηrel lower than 1.9, especially ηrel lower than 1.8, particularly preferred ηrel lower than 1.7.
EP 0 190 011 B1 describes glass fibers with elliptical or rectangular cross-section, as well as their manufacture. The use of these particular glass fibers for the manufacture of composite parts is mentioned. Due to the larger surface of the fibers, higher strength values result in the composites.
EP 0 196 194 B1 describes a strand consisting of a variety of glass monofilaments with a non-circular cross-section, as well as their manufacture. The cross-section of the glass fibers can be oval, elliptical, cocoon shaped or polygonal.
EP 0 199 328 B1 describes a fabric for printed circuit boards, which is essentially made of glass fibers with non-circular cross-section. The individual fibers have oval, elongated or elliptical cross sections. Unsaturated polyester resins, epoxy resins, phenol resins, polyimide resins or PTFE are described as matrices for this fabric.
EP 0 246 620 B1 describes an article made of a glass fiber reinforced thermoplastic resin. The, glass fibers have a rectangular, elliptical or cocoon shaped cross section. It is shown that glass fibers with non-circular cross-section have advantages in terms of strength and toughness, especially at a high degree of reinforcement (≧60%).
EP 0 376 616 B1 describes a thermoplastic polymer composition comprising a thermoplastic resin and 1 to 65% of a fibre like reinforcement with a non-circular cross-section, wherein the cross-sectional area and the ratio of the perpendicular cross-sections of the reinforcing fibers are characterized in more detail. The cross-section of the reinforcing fibers has a semicircular or arcuate contour. The composition is characterized by high dimensional stability and reduced warpage.
EP 0 400 935 B1 describes a flame retardant fiber reinforced polyester composition that includes 1 to 60 wt % glass fibers. According to EP 0 400 935 B1, the used glass fibers have a cross-sectional shape, which is selected from the group of flattened, elliptical, oval, partly circular, curved and rectangular cross-sectional shapes. These flame retardant reinforced polyester composites according to EP 0 400 935 B1 show a decreased deformation without their mechanical properties being adversely influenced by crystalline polyester resins. In this respect, it was found according to EP 0 400 935 B1 that the deformation, i.e. warping of crystalline polyester resins can be reduced without reducing the mechanical properties of the resin, for example, the bending strength and rigidity and the processability.
According to JP 10219026 A2 the thermoplastic matrix is reinforced by a mixture of glass fibers with a circular cross-section and glass fibers with a flat cross section to reduce warpage of thermoplastic parts. Polyamide 66 is used as a polymer matrix in the only example of this document.
JP 2004285487 A1 describes a bundle of glass fibers, consisting of glass filaments with a flat cross-section, which are hold together by a non-volatile sizing, and a thermoplastic composition, consisting of 5 to 75% of glass fiber bundles and a polyolefin matrix.
JP 2006045390 A2 describes a granulate reinforced by long glass fibers, consisting of a thermoplastic matrix and up to 60 wt.-% of glass fibers with a flat cross section. Granulate length and fiber length is identical. Advantageous features of molded parts made from the reinforced composition according to JP 2006045390 A2 are good surface quality and high impact strength.
Polyamide molding materials, which have good mechanical properties and a very small warpage, are described in the still unpublished patent application EP 06014372.4. These properties are obtained by a combination of transparent polyamide with fibrous reinforcing materials and particulate fillers. Regarding the fibrous reinforcement materials there are basically no restrictions. They are preferably selected from the group consisting of glass fibers, carbon fibers, metal fibers, aramide fibers, whiskers and mixtures thereof. The glass fibers can be added as endless fibers or as chopped glass fibers. The glass fibers can have round, oval or rectangular cross section.
The also still unpublished application EP 05025216.2 describes reinforced polyamide molding materials made from a blend of polyamide 66 and a copolyamide 6T/6I. A mixture of glass fibers and carbon fibers is used as a reinforcing material. To further increase the rigidity, a portion of the glass fibers is substituted by carbon fibers, so that a hybrid fiber reinforced compound is used.

Polyamide molding materials reinforced with glass fibers and injection molded parts thereof


A method for connecting a DRAM module to memory portions of a main processor and memory management PCB board assembly (MPMA PBA) included in a main processor hardware (MPH) block and adapted to perform a higher-order control in a full electronic exchange. In accordance with this method, the DRAM, which is of the zigzag-in-line package type, is replaced by that of the module type so that its parity DRAM area is integrated with memory areas included in the DRAM, thereby enabling waste memory portions of the parity DRAM area to be efficiently managed. A common RAS control signal is divided into a plurality of signals respectively adapted to be used as control signals for defining respective memory areas of the DRAM along with other control signals, namely, CAS and WE control signals. A basic address for the DRAM is determined to obtain an easy memory expansion.

1. Field of the Invention
The present invention relates to a method for connecting a DRAM module to a DRAM included in a higher-order control system of a full electronic exchange, and more particularly to a method for connecting a DRAM module to memory portions of a main processor and memory management PCB board assembly (MPMA PBA) included in a main processor hardware (MPH) block and adapted to perform a higher-order control in a full electronic exchange.
2. Description of the Prior Art
Generally, DRAM's used in higher-order control systems of full electronic exchanges have a troublesomeness in expanding their memory capacity because they are fixed to 16 M bytes. This will be described in detail in conjunction with FIG. 1 which shows the relationship between a DRAM included in an MPMA and a central processing unit serving to define memory areas of the DRAM. As shown in FIG. 1, the MPMA includes the central processing unit, which is denoted by the reference numeral 1. The central processing unit 1 serves to control various units of the MPMA. The MPMA further includes an address bus 2 for transmitting address data output from the central processing unit 1 to desired units of the MPMA, and a data bus 3 for transmitting real data output from the central processing unit 1 to desired units of the MPMA. A control signal generating unit 4 is also provided which serves to receive a control signal from the central processing unit 1, thereby outputting control signals selecting respective memory areas of DRAM's 5 and 6 which are also included in the MPMA. The DRAM 5 is stored with practical programs required for the system whereas the DRAM 6 is a 16-bit parity DRAM. To the MPMA, a dependent MPMA is connected, which has the same arrangement as the MPMA. Thus, a double MPMA arrangement is obtained.
The double MPMA arrangement obtained by the dependant MPMA means that it can carry out either a main operation or dependent operation in accordance with the situation. In this arrangement, the main MPMA has a circuit arrangement enabling both reading and writing.
Each DRAM used in the MPMA having the above-mentioned arrangement is a zigzag-in-line package type RAM. This RAM has a total memory area of 4 M.times.36 bits including a data area of 4 m.times.32 bits and a parity area of 4 M.times.4 bits.
The control signal output from the central processing unit 1 is applied to the control signal generating unit 4 which, in turn, converts the signal into control signals for respectively selecting memory areas of the DRAM's 5 and 6.
The inner memory area of the data DRAM 5 is divided into a plurality of sub-areas each having a memory capacity of 4 bytes. Hereinafter, such a sub-area will be referred to as "a bank". The data DRAM 5 includes four banks.
These banks are selected in accordance with associated control signals output from the control signal generating unit 4, respectively. These control signals for selecting the banks of the data DRAM 5 are signals CAS0, CAS1, CAS2 and CAS3, respectively.
All banks of the data DRAM 5 are commonly coupled to a control signal RAS output from the control signal generating unit 4. This RAS signal is used in combination with each CAS signal. Each unit bank is constructed to carry out its 8-, 16- and 32-bit data transmitting operations in accordance with respective signals, WE0, WE1, WE2 and WE3, for writing operations along with an OE signal for reading operations. The reason why each unit bank enables such data transmitting operations is because the zigzag-in-line package type DRAM has a structure including RAS, CAS, WE and OE. All the above-mentioned signals are adapted to operate in a low level (designated "active low" or "/").
The parity DRAM 6 has a memory area having a 16 M-bit size and operates a control signal CASP. This parity DRAM 6 is stored with parity data corresponding to each 8-bit data stored in the data DRAM 5. When data is written on the data DRAM 5, parity data associated with the data being written on the data DRAM 5 is also written on the parity DRAM 6. When the data stored in the data DRAM 5 is read, the data stored in the parity DRAM 6 is also read to determine whether the data read out of the data DRAM 5 is normal or has errors.
In terms of the memory area, the data DRAM 5 and parity DRAM 6 have the relationship that the parity DRAM 6 always requires its entire memory area, namely, a 16 M-bit memory area irrespective of whether the memory area of the data DRAM 5 being used is a 4 M- or 16 M-byte bank.
However, this is a considerable economical loss. Even though the memory capacity of the data DRAM 5 increases using the same circuit as the memory thereof, the parity DRAM 6 still involve the waste of its memory.
Meanwhile, many of full electronic exchanges being presently used require DRAM's for MPMA PBA which have a memory size of larger than 16 M bytes. Furthermore, this requirement is on an increasing trend. For higher-order control systems requiring a memory size of larger than 16 M bytes, a PBA, which is a separate board called "MECA", is used in addition to the data DRAM 5 because the data DRAM 5, which has a divided construction, is fixed to 16 M bytes. This PBA serves to expand the memory size from the 16 M-byte size.
Taking into consideration the double MPMA arrangement, two PBA boards which have the same size as the MPMA PBA are required. In accordance with this method, however, the MPMA PBA can not expand its memory size by itself.

Method for efficient use of DRAM data and parity areas

Hyundai Electronics Industries Co., Ltd.


After ion implantation, thermal ashing is performed using ozone at a pressure of between about 0.01 to about 1000 Torr at below 1000° C. to remove the resist. Since the process includes a substantial amount of ozone, the resist can be completely oxidized, thus leaving no residue or other contaminates to remain on the substrate. Using ozone allows fast resist removal with minimal residue at low temperatures.

1. Field of Invention
This invention generally relates to semiconductor manufacturing methods and, more particularly, to a method for removing organic films and materials used during semiconductor wafer fabrication.
2. Related Art
New processing and manufacturing techniques are continuously being developed to make further advancements in the development of semiconductor devices, especially semiconductor devices of decreased dimensions.
An important aspect of the semiconductor device fabrication process is the removal of the photoresist film. As the size of semiconductor devices continues to decrease, typical photoresist removal methods must be able to increase the rate of residual-free resist removal, and must decrease the amount of damage caused in the substrate layers underlying the resist film.
Typically two types of ashing methods exist—a wet method and a dry method. The wet method is generally preferable to the dry method, since it does not damage the underlying substrate. However, in wet ashing methods the chemical bath that is needed to remove the resist can also contaminate the substrate. In addition, particles that remain in the chemical bath can re-adhere to the substrate. Thus, in the wet ashing method a cleaning step is required before the substrate is ready for the anneal process.
The dry ashing method typically includes exposing the substrate and the photo resist to a plasma. The plasma formation occurs at low pressure. Thus, the amount of reactive gas available to the removal process is low. For example, in an oxygen plasma that is formed at about 1 Torr, the amount of O2 available to react with the photoresist is about 1000 times less than is available in air.
Unfortunately, substrate damage can occur as the substrate is exposed to the plasma due to the ion bombardment. In addition, dry ashing methods usually leave residue on the wafer surface even after the ashing processes are complete. As a result, the photoresist stripped wafer has to be reprocessed by wet cleaning before conducting an ion implant anneal or other process, which adds another level of complexity to the overall substrate processing.
What is needed, therefore, is an ashing method that reduces damage to the substrate, reduces the amount of residue and particle contaminates remaining on the stripped substrate and increases the throughput of the ashing process.

Integrated ashing and implant annealing method using ozone


The present invention relates to new semiconductive polymers, a process for their manufacture and their use in thin film electronic and optical devices, such as organic light emitting diodes (OLED) and photovoltaic devices, e.g. solar cells and photo detectors.

Semiconducting organic materials are attracting a great deal of interest due to their processability and the broad spectrum of optical and electronic properties that may be selected according to the structure of the organic material.
One application of such materials is in switching devices, in particular as organic field effect transistors as described in, for example, Adv. Mater. 1998, 10(5), 365-377. Another application is in opto-electrical devices using a semiconducting organic material for light emission (an organic light emitting device or "OLED") or as the active component of a photocell or photodetector (a "photovoltaic" device). The basic structure of these devices is a semiconducting organic layer sandwiched between a cathode for injecting or accepting negative charge carriers (electrons) and an anode for injecting or accepting positive charge carriers (holes) into the organic layer. In an organic electroluminescent device, electrons and holes are injected into a layer of electroluminescent semiconducting material where they combine to generate excitons that undergo radiative decay. Holes are injected from the anode into the highest occupied molecular orbital (HOMO) of the electroluminescent material; electrons are injected from the cathode into the lowest unoccupied molecular orbital (LUMO) of the electroluminescent material. In WO 90/13148 the organic light-emissive material is a polymer, namely poly(p-phenylenevinylene) ("PPV"). Other light emitting polymers known in the art include polyfluorenes and polyphenylenes. In U.S. Pat. No. 4,539,507 the organic light-emissive material is of the class known as small molecule materials, such as (8-hydroxyquinoline) aluminium ("Alq3"). Light emitting polymers such as polyfluorenes and polyphenylenes are advantageous in that they are solution processable. In particular, solution processable light emitting polymers may be inkjet printed as described in EP 0880303 to produce high information content displays, in particular full colour displays.
An essential requirement for an effective OLED is efficient injection of holes and electrons into the electroluminescent layer of the OLED. Therefore, a focus in the OLED field is the development of hole and/or electron transporting materials to be used in combination with the electroluminescent material. An effective hole transporting material has a HOMO level that lies between the workfunction of the anode and the HOMO level of the electroluminescent material. Furthermore, emission in a typical OLED is usually provided predominantly by the material having the smallest HOMO-LUMO bandgap and so the charge transport material should have a larger HOMO-LUMO bandgap than the electroluminescent material if emission from the charge transport material is undesirable.
Another focus in the OLED field is the development of full colour OLEDs, i.e. OLEDs comprising red, green and blue electroluminescent materials. A drawback of many blue organic electroluminescent materials is that their emission is a relatively pale blue, due to an insufficiently large HOMO-LUMO bandgap, when compared to the standard blue as defined by 1931 CIE co-ordinates.
WO 99/48160 discloses hole transporting co-polymers "TFB" and "PFB":

However, the above identified co-polymers have drawbacks. In particular, the HOMO levels of these materials are not ideally matched to the workfunction of ITO which negatively affects their hole transporting properties.
WO 03/000773 discloses a copolymer of "TFB-PFB" wherein dioctyifluorene units of the above co-polymers are absent.

Polymers of this type wherein a repeat unit such as fluorene is absent can suffer from insolubility, particularly at higher molecular weights. Repeat units such as fluorene could be incorporated Into a polymer containing TFB and PFB units however this breaks up the regularity of directly linked TFB and PFB units.
JP 09-151371 discloses tri- or tetra-amine hole injecting materials of formula (A)
wherein R1-5 is selected from H, methyl, methoxy, phenyl, trifluoromethyl, hydroxy, hydroxymethyl, formyl, NH2, a double bonded group and an epoxy ring; and n is 1 or 2. When used in a device, this material is provided as a hole injecting layer with a separate emissive layer of Alq3.
Similar compounds are disclosed in WO 96/22273 and JP 11-251068. These materials are deposited by evaporation.
Materials of this type are incorporated into a polymer in WO 97/33193 which discloses polyarylpolyamines such as an acrylate polymer of formula (B):

This material is cured to form a hole transporting layer, however the polymer derived from this material is not soluble due to cross-linking of the acrylate groups and as a result the polymer may only be formed by depositing a layer of the above monomer and curing it. Furthermore, use of acrylate groups for polymerisation does not provide any control over regioregularity of the resultant polymer.
It is therefore an object of the invention to provide a solution processable polymer having improved hole transporting properties without adversely affecting the colour of emission of the polymer by narrowing of the HOMO-LUMO bandgap.


Actuators are disposed between a lower wiring substrate and an upper wiring substrate. The actuators, the lower wiring substrate, and the upper wiring substrate are interposed between a lower frame and an upper frame. The end of each actuator is held between pushing parts of the lower frame and upper frame. The free ends of the actuators move projections upward that are displayed in a tactile display.

1. Field of the Invention
The present invention relates to a tactile display device having a tactile display constituted of a plurality of projections and, specifically, relates to a tactile display device that facilitates the wiring for actuators moving the projections.
2. Description of the Related Art
Tactile display devices with a tactile display from which projections selectively protrude are used as Braille cells, which are means for transmitting information for the visually impaired.
Japanese Unexamined Patent Application Publications Nos. 2001-147637 and 2007-71977 describe techniques related to Braille cells. Such a Braille cell has a plurality of holes in an area for contact that comes into contact with the user's finger. Detection pins are placed inside the holes in a retractable manner. Piezoelectric bimorph elements are provided as actuators. The piezoelectric bimorph elements are fixed at the ends, and the other ends are opposed to the bottom of the detection pins. At least one of the actuators is selected, and electricity is supplied thereto. Upon receiving electricity, the actuators bend, causing the corresponding detection pins to protrude due to the bending force of the actuators.
A predetermined number of detection pints, which each correspond to a Braille dot, represents a single Braille letter. Letter information can be obtained by running a finger across the Braille letter.


A method for fabricating a semiconductor device is provided. The method comprises: providing a substrate; forming a gate structure on the substrate, the gate structure including a gate dielectric layer on the substrate and a gate conductive layer on the gate dielectric layer; forming an oxide layer conformally covering the substrate and the gate structure; forming a dielectric layer covering the oxide layer; removing a portion of the dielectric layer to form a spacer on a sidewall of the gate structure, the oxide layer between the spacer and the gate structure as an oxide spacer; performing an oxygen plasma treatment process to form an silicon oxide layer in the substrate below the oxide layer, the silicon oxide layer and the oxide layer being an offset oxide layer; and forming a source/drain region in the substrate at two sides of the gate structure.

1. Field of the Invention
This invention generally relates to a method for fabricating a semiconductor device, and more particularly to a method for fabricating a semiconductor device to enhance the uniformity of the semiconductor device.
2. Description of Related Art
As the line width and the size of the semiconductor device become smaller, it is unavoidable that the polysilicon electrode of the MOSFET and the memory device become smaller. When the integration of the devices increases, the resistance of the source region and the drain region usually increases. However, as the size of the device shrinks and its process margin declines, the uniformity of the semiconductor devices becomes worse.
During the fabrication of the MOSFET, after the gate electrode is formed by forming a gate oxide layer and a polysilicon layer, the spacer made of silicon oxide or silicon nitride will be formed on the two sidewalls of the gate electrode. Later on, the ion implantation is performed to form the source and drain regions at the two sides of the gate electrode and then the salicide process is performed. However, if the silicon oxide spacer is employed, a cleaning step has to be performed to remove the native oxide layer and impurity on the surface of the gate electrode and the substrate before performing the salicide process. A portion of the silicon oxide spacer may be removed during the cleaning step. Hence, the subsequently formed silicide would be very close to the source/drain extension, which is easy to cause the junction leakage problems. On the other hand, if the silicon nitride spacer is employed to avoid the junction leakage problems, because the dielectric constant of silicon nitride is higher than that of silicon oxide, the silicon nitride spacer results in a larger parasitic capacitance between the gate and the source/drain region, thus deteriorating the device performance.
A composite silicon oxide/silicon nitride spacer may also be formed on the sidewalls of the gate after defining the gate electrode. The composite spacer can be formed by forming an offset oxide layer covering the substrate and the gate electrode, forming a silicon nitride layer covering the offset oxide layer and then performing anisotropic etching to remove a portion of silicon nitride layer until the offset oxide layer is exposed. The remaining offset oxide layer can protect the surface of the substrate when performing the ion implantation step to the substrate. However, when the size of the device and the line-width shrink, the thickness of each layer and the process margin in each layer also become smaller. Especially, when the thickness of the offset oxide layer is less than or about 100 Å, the thin offset oxide layer can easily be overetched and the thickness of the remaining offset oxide layer is not uniform in various locations. Since the thickness of the remaining offset oxide layer is varied, the junction depth of the source/drain region becomes non-uniform after the ion implantation step through the non-uniform offset oxide layer. In addition to the non-uniform depth of the source/drain region, the effective channel length of the gate electrode may be changed, which significantly affects the uniformity of the semiconductor devices on the wafer.

Method for fabricating semiconductor device


A washing machine includes a detergent dispenser having at least one fresh-water connection, a free air course disposed downstream of the at least one fresh-water connection, and a detergent chamber. A water guide conduit supplies fresh water to the detergent chamber. A fresh-water diversion line is connected to the water guide conduit downstream of the free air course.

FIELD OF THE INVENTION
The invention relates to a washing machine with a detergent or washing agent dispenser having at least one fresh-water connection, a free air course downstream thereof and a water guide conduit for supplying the fresh water to a detergent chamber, and a fresh-water diversion line.
Such a washing machine is known from German Published, Non-Prosecuted Patent Application DE 38 22 392 A1. There, diverted fresh water is used to fill a pumping-out line, so that a ball valve mounted on the bottom of the tub will be acted upon with sufficient static pressure for reliable closure before detergent is fed into the tub from above through the water guide conduit and the detergent chamber. In one of the exemplary embodiments, the fresh-water diversion line is extended by way of its own free air course. The constrained space in a detergent dispenser and demands in terms of manufacture made of such a dispenser mean that the known proposal does not appear practicable.

Washing machine with a detergent dispenser


An apparatus and method of selecting a routing path through a mesh network that includes a mobile access node is disclosed. The method includes each access node of the mesh network capable of receiving routing beacons from at least one upstream access node. The routing beacons including information of all upstream access nodes along a path to a gateway access node. The mobile access node selecting a route through an upstream access node based upon a quality of beacons received from at least one upstream access node, and whether the at least one upstream access node is a fixed access node or another mobile access node.

Packet networking is a form of data communication in which data packets are routed from a source device to a destination device. Packets can be networked directly between a source node and a destination node, or the packets can be relayed through a number of intermediate nodes.
A wireless network can include a wireless device being connected to a network through a base station that is wired to the network. The wireless device can transmit data packets that are received by the base station and then routed through the network. The wireless network can include many base stations that are each wired to the network.
FIG. 1 shows a prior art mesh network that includes a gateway 110 connecting a client device 140 to a network (internet) 100 through fixed access nodes 120, 130. The connections between the gateway 110 and the access nodes 120, 130 can be wireless. Additionally, the connection between the access nodes 120, 130 and the client 140 can be wireless. Wireless connections typically are subject to conditions that can make the connections unreliable. Such conditions include fading, multi-path and signal interference. Additionally, the client 140 can roam. Therefore, the optimal routing conditions between the client 140 and the gateway 110 can vary, requiring the routing to be updated over time. Roaming of the client 140 typically requires the client 140 to include specialized software or hardware.
Some mesh networks can additionally include mobile access nodes. Mobile access nodes add another layer of complexity because optimal routes continually change for access nodes that are mobile.
It is desirable to have a wireless mesh network that includes fixed and mobile access nodes, that continually analyzes the quality of routing paths through the wireless mesh network, and selects an optimal path from among all available routing paths. It is additionally desirable that clients be able to roam between access nodes without being required to include specialized hardware and/or software.

Mesh network that includes fixed and mobile access nodes


A thin electronic input device has a film layer, a conducting layer, a covering layer, character display layer, an IC control unit and a connecting unit. The film layer is made of a flexible material. The conducting layer is mounted on the film layer for sensing a human pulse wave. The covering layer is mounted on the conducting layer. The character display layer is mounted on the covering layer; furthermore, the character display layer also has a plurality of keyboard characters printed thereon. The IC control unit is electrically connected to the conducting layer. The connecting unit is electrically connected to the conducting layer. When a user touches the character display layer to provide a human pulse wave, the conducting layer receives a touch signal for inputting information.

(1). Field of the Invention
The present invention relates to a thin electronic input device, and more particularly to a thin electronic input device mounted on a PDA (mobile phone or tablet PC) for inputting a lot of information.
(2). Description of the Related Art
Personal digital assistants, or PDA's, are handheld devices that are capable of performing various functions of personal computers and cellular phones depending upon the model or style of PDA.
A PDA may be used for wireless communication, like a cellular phone, to send and receive electronic mail. A PDA may also be used to store and display calendars, addresses and telephone numbers, to-do lists, and other electronic information. Commonly, a PDA will include control buttons or a touch screen that may be activated by a separate handheld stylus to activate certain functions. The stylus can be used to input information for the purposes of sending electronic mail or entering data related to the stored and displayed information.
A PDA (Personal Digital Assistant) is thus a very popular electronic product. A PDA has a volume smaller than a notebook easy portability. A lot of information often used by people can be stored in the PDA. Now people can immediately find information for greater convenience.
Reference is made to FIG. 1, which illustrates a conventional electronic device 100 such as a PDA (mobile phone or tablet PC) having a touch screen 101 and a stylus 102. An area of the touch screen 101 is too small so that the touch screen 101 is not easily operated. Besides, a recognition rate of the touch screen 101 is suboptimal, so input of large quantities of information is inconvenient. A keyboard can be combined with a PDA for inputting a lot of information, but the keyboard is big and the PDA is then not easily carried.
Therefore, according to above descriptions, the conventional electronic device 100 such as a PDA (mobile phone or tablet PC) still has some issues of inconvenience, which need to be improved.


A dual type vehicle air conditioning system has a rear air conditioning system for rear seats and a front air conditioning system for front seats. The rear conditioning system has a rear conditioner unit defining a main air passage for directing inside air through an evaporator and a condenser in sequence. The rear conditioner unit further has a bypass air passage for introducing the inside air to the condenser, bypassing the evaporator, and an exhaust air passage for directing the inside air from the evaporator to the outside of the vehicle.

The present invention relates to a dual type vehicle air conditioner comprising separated air conditioning systems.
Recently, dual type vehicle air conditioning systems are mounted on part of luxury cars, wagons and minivans (or one-box cars).
A vehicle air conditioning system of this type includes a first air conditioning system for air-conditioning inside air and directing conditioned air toward rear seats, and a second air conditioning system for air-conditioning inside and outside air selectively and supplying conditioned air to front seats. Each of the first and second air conditioning systems includes a heater core using hot water (engine cooling water) supplied from an engine as a heat source for warming air.
The heater core, however, tends to become insufficient in heating ability when the outside temperature is low in winter. Specifically, a lean-burn engine generates less heat and the heat quantity of engine cooling water tends to be too small.


This invention provides a process to convert alkanes to primary alcohols of the same carbon number. Carbon numbers of particular interest are C8 to C18. The process comprises the steps of: a) halogenating a linear or branched (or mixture of linear and branched) alkane to produce a mixture of primary mono-haloalkanes, internal mono-haloalkanes, unreacted alkanes, hydrogen halide, and possibly multi-haloalkanes in the presence of a catalyst and/or by heating the reaction mixture; b) separating the hydrogen halide from the mixture and optionally neutralizing it with a metal oxide to produce a partially halogenated metal oxide and/or metal halide which may be regenerated; c) separating the primary mono-haloalkanes from the mixture; d) reacting the separated primary mono-haloalkanes in a reactor with a metal oxide or combination of metal oxides and water to convert the aforesaid primary mono-haloalkane to a mixture of products that contains primary alcohols, unconverted primary mono-haloalkanes, and possibly other reaction products, and a partially halogenated metal oxide and/or metal halide which may be regenerated; e) regenerating the partially halogenated metal oxide and/or metal halide to halogen (such as Cl2) and/or acid and a metal oxide for recycle by reaction with air or oxygen; and f) removing the unreacted primary mono-haloalkane from the reaction mixture and then purifying the primary alcohol.

Primary alcohols are readily derivatized and used in a number of major end use markets. For example, they could be reacted with phthalic anhydride and used as plasticizers for polyvinyl chloride (PVC), or ethoxylated, sulfated, or sulfonated and used in detergent applications. In general, primary alcohols are much preferred over internal (eg. secondary) alcohols because of the relative ease of the derivatization reactions. This invention may be used to produce primary alcohols from relatively inexpensive C6–C18 alkanes, linear or branched, for example from gas-to-liquids (GTL) plants. Prior art such as that described in U.S. Pat. No. 5,849,960 teaches the conversion of either alpha or internal olefins to primary alcohols. In addition, recent prior art suggests that the conversion of paraffins to alkyl-halides followed by reaction with a metal oxide may produce predominantly internal alcohols. Examples of such prior art include U.S. Pat. Nos. 6,462,243, 6,465,699, 6,472,572, 6,486,368, and 6,465,696, all of which are herein incorporated by reference.

Process to convert alkanes into primary alcohols


Anti-human B7-H4 antibody “6H3”, antigen-binding fragments, derivatives, and humanized variants thereof that are capable of immunospecifically binding to B7-H4, and the uses of such molecules in the diagnosis and the treatment of cancer and other diseases are disclosed. In preferred embodiments, the molecules are used to retard or prevent tumor growth, inhibit tumor-mediated suppression, eliminate tumors and/or deplete or block the activity of tumor-associated macrophages (“TAMs”) so as to alter their activity and/or decrease TAM-mediated immune suppression.

A. Cell Mediated Immune Responses
The immune system of humans and other mammals is responsible for providing protection against infection and disease. Such protection is provided both by a humoral immune response and by a cell-mediated immune response. The humoral response results in the production of antibodies and other biomolecules that are capable of recognizing and neutralizing foreign targets (antigens). In contrast, the cell-mediated immune response involves the activation of macrophages, natural killer cells (NK), and antigen-specific cytotoxic T-lymphocytes by T cells, and the release of various cytokines in response to the recognition of an antigen (Dong, C. et al. (2003) "Immune Regulation by Novel Costimulatory Molecules," Immunolog. Res. 28(1):39-48).
The ability of T cells to optimally mediate an immune response against an antigen requires two distinct signaling interactions (Viglietta, V. et al. (2007) "Modulating Co-Stimulation," Neurotherapeutics 4:666-675; Korman, A. J. et al. (2007) "Checkpoint Blockade in Cancer Immunotherapy," Adv. Immunol. 90:297-339). First, antigen that has been arrayed on the surface of antigen-presenting cells (APC) must be presented to an antigen-specific naive CD4+ T cell. Such presentation delivers a signal via the T cell receptor (TCR) that directs the T cell to initiate an immune response that will be specific to the presented antigen. Second, a series of co-stimulatory signals, mediated through interactions between the APC and distinct T cell surface molecules, triggers first the activation and proliferation of the T cells and ultimately their inhibition. Thus, the first signal confers specificity to the immune response whereas the second signal serves to determine the nature, magnitude and duration of the response.
The immune system is tightly controlled by co-stimulatory ligands and receptors. These molecules provide the second signal for T cell activation and provide a balanced network of positive and negative signals to maximize immune responses against infection while limiting immunity to self (Wang, L. et al. (Mar. 7, 2011) "VISTA, A Novel Mouse Ig Superfamily Ligand That Negatively Regulates T Cell Responses," J. Exp. Med. 10.1084/jem.20100619:1-16; Lepenies, B. et al. (2008) "The Role Of Negative Costimulators During Parasitic Infections," Endocrine, Metabolic & Immune Disorders—Drug Targets 8:279-288). Of particular importance is binding between the B7.1 (CD80) and B7.2 (CD86) ligands of the APC and the CD28 and CTLA-4 receptors of T-lymphocytes (Sharpe, A. H. et al. (2002) "The B7-CD28 Superfamily," Nature Rev. Immunol. 2:116-126; Dong, C. et al. (2003) "Immune Regulation by Novel Costimulatory Molecules," Immunolog. Res. 28(1):39-48; Lindley, P. S. et al. (2009) "The Clinical Utility Of Inhibiting CD28-Mediated Costimulation," Immunol Rev. 229:307-321). Binding of B7.1 or of B7.2 to CD28 stimulates T cell activation; binding of B7.1 or B7.2 to CTLA4 inhibits such activation (Dong, C. et al. (2003) "Immune Regulation by Novel Costimulatory Molecules," Immunolog. Res. 28(1):39-48; Lindley, P. S. et al. (2009) "The Clinical Utility Of Inhibiting CD28-Mediated Costimulation," Immunol. Rev. 229:307-321; Greenwald, R. J. et al. (2005) "The B7 Family Revisited," Ann. Rev. Immunol. 23:515-548). CD28 is constitutively expressed on the surface of T cells (Gross, J., et al. (1992) "Identification And Distribution Of The Costimulatory Receptor CD28 In The Mouse," J. Immunol. 149:380-388), whereas CTLA4 expression is rapidly up-regulated following T-cell activation (Linsley, P. et al. (1996) "Intracellular Trafficking Of CTLA4 And Focal Localization Towards Sites Of TCR Engagement," Immunity 4:535-543). Since CTLA4 is the higher affinity receptor (Sharpe, A. H. et al. (2002) "The B7-CD28 Superfamily," Nature Rev. Immunol. 2:116-126), binding first initiates T cell proliferation (via CD28) and then inhibits it (via nascent expression of CTLA4), thereby dampening the effect when proliferation is no longer needed.
Further investigations into the ligands of the CD28 receptor have led to the identification and characterization of a set of related B7 molecules (the "B7 Superfamily") (Coyle, A. J. et al. (2001) "The Expanding B7 Superfamily: Increasing Complexity In Costimulatory Signals Regulating T Cell Function," Nature Immunol. 2(3):203-209; Sharpe, A. H. et al. (2002) "The B7-CD28 Superfamily," Nature Rev. Immunol. 2:116-126; Greenwald, R. J. et al. (2005) "The B7 Family Revisited," Ann. Rev. Immunol. 23:515-548; Collins, M. et al. (2005) "The B7 Family Of Immune-Regulatory Ligands," Genome Biol. 6:223.1-223.7; Loke, P. et al. (2004) "Emerging Mechanisms Of Immune Regulation: The Extended B7 Family And Regulatory T Cells." Arthritis Res. Ther. 6:208-214; Korman, A. J. et al. (2007) "Checkpoint Blockade in Cancer Immunotherapy," Adv. Immunol. 90:297-339; Flies, D. B. et al. (2007) "The New B7s: Playing a Pivotal Role in Tumor Immunity," J. Immunother. 30(3):251-260; Agarwal, A. et al. (2008) "The Role Of Positive Costimulatory Molecules In Transplantation And Tolerance," Curr. Opin. Organ Transplant. 13:366-372; Lenschow, D. J. et al. (1996) "CD28/B7 System of T Cell Costimulation," Ann. Rev. Immunol. 14:233-258; Wang, S. et al. (2004) "Co-Signaling Molecules Of The B7-CD28 Family In Positive And Negative Regulation Of T Lymphocyte Responses," Microbes Infect. 6:759-766). There are at least eight members of the family: B7.1 (CD80), B7.2 (CD86), the inducible co-stimulator ligand (ICOS-L; B7-H2), the programmed cell death-1 ligand 1 (PD-L1; B7-H1), the programmed cell death-1 ligand 2 (PD-L2; B7-DC), B7-H3 (B7-RP2), B7-H4 (also referred to as B7x and B7S1; Sica, G. L. et al. (2003) "B7-H4, A Molecule Of The B7 Family, Negatively Regulates T Cell Immunity," Immunity 18:849-861; Zang, X. et al. (2003) B7x: A Widely Expressed B7 Family Member That Inhibits T Cell Activation," Proc. Natl. Acad. Sci. (USA) 100:10388-10392; Prasad, D. V. et al. (2003) B7S1, A Novel B7 Family Member That Negatively Regulates T Cell Activation," Immunity 18:863-873) and B7-H6 (Brandt, C. S. et al. (2009) "The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans", J Exp Med. 206(7):1495-503).
Soluble forms of B7-CD28 family molecules are also implicated in the progression of rheumatoid diseases. Studies have shown that soluble PD-1 could be detected in rheumatoid arthritis (RA) patients and that the levels of soluble PD-1 correlated with TNF-α concentration in synovial fluid. Soluble B7-H4 (sH4) has been detected in ovarian cancer patients as a potential biomarker, and results from a study of 68 patients with RA and 24 healthy volunteers indicated that soluble B7-H4 was present in blood of 65% of patients with RA, compared with only 13% of healthy people (Simon, I. et al. (2006) "B7-H4 Is A Novel Membrane-Bound Protein And A Candidate Serum And Tissue Biomarker For Ovarian Cancer," Cancer Res. 66(3):1570-1575, Azuma, T. et al. (2009) "Potential Role Of Decoy B7-H4 In The Pathogenesis Of Rheumatoid Arthritis: A Mouse Model Informed By Clinical Data," PLoS Med., 6(10):e1000166). The levels of soluble B7-H4 were significantly higher in RA patients (96.1 ng/ml) relative to healthy people (<5 ng/ml).
In vivo studies in a murine model indicate that both overexpression of sH4 and deletion of B7-H4 caused inflammation (Azuma, T. et al. (2009) "Potential Role Of Decoy B7-H4 In The Pathogenesis Of Rheumatoid Arthritis: A Mouse Model Informed By Clinical Data," PLoS Med. 6(10):e1000166). Symptoms in the mice appeared earlier and were more severe than controls, and inflammatory effects of soluble B7-H4 were shown to be dependent on neutrophils. Using a protein that mimics the normal signaling by B7-H4, disease development was prevented in the mice.
B. B7-H4
cDNA encoding the human B7-H4 protein was identified and cloned from placental cDNA (Sica, G. L. et al. (2003) "B7-H4, A Molecule Of The B7 Family, Negatively Regulates T Cell Immunity," Immunity 18:849-861; Zang, X. et al. (2003) B7x: A Widely Expressed B7 Family Member That Inhibits T Cell Activation," Proc. Natl. Acad. Sci. (USA) 100:10388-10392). B7-H4 is discussed in U.S. Pat. Nos. 7,931,896; 7,875,702; 7,847,081; 7,622,565; in United States Patent Publications No. 2011/0085970; 2011/0020325; 2010/0256000; 2010/0240585; 2010/0227343; 2010/0227335; 2010/0158936; 2010/0092524; 2010/0028450; 2009/0275633; 2009/0215084; 2009/0176317; 2009/0142342; 2009/0118175; 2009/0087416; 2009/0048122; 2009/0022747; 2009/0018315; 2008/0206235; 2008/0160036; 2008/0177039; 2008/0050370; 2007/0218032; 2007/0184473; 2007/0172504; 2007/0160578; 2007/0122378; 2007/0036783; 2006/0003452; in European Patent Publications Nos. EP 2124998 and EP 2109455; and in PCT Patent Publications WO 2011/026132A2; WO 2011/026122A2; WO 2011/005566A2; WO 2010/144295A1; WO 2010/102177A1; WO 2010/102167A1; WO 2009/111315A2; WO 2009/073533A2; WO 2008/092153A2; WO 2008/083239A2; WO 2008/083228A2; WO 2007/124361A2; WO 2007/122369A2; WO 2007/109254A2; WO 2007/087341A2; WO 2007/082154A2; WO 2007/067682A2; WO 2007/067681A2; WO 2007/041694A2; WO 2006/138670A2; WO 2006/133396A2; WO 2006/121991A2; WO 2006/066229A2; and WO 2006/007539A1.
Anti-B7-H4 antibodies are disclosed in U.S. Pat. Nos. 7,888,477; 7,737,255; 7,619,068; 6,962,980, and in United States Patent Publication No. 20080199461. WO/2013/025779 is of particular relevance.
Human B7-H4 protein possesses 282 amino acid residues, which have been categorized as including an amino terminal extracellular domain, a large hydrophobic transmembrane domain and a very short intracellular domain (consisting of only 2 amino acid residues). Like other B7 family members, B7-H4 possesses a pair of Ig-like regions in its extracellular domain. The B7-H4 protein has an overall structure of a type I transmembrane protein. The protein has minimal (about 25%) homology with other B7 family members (Zang, X. et al. (2003) B7x: A Widely Expressed B7 Family Member That Inhibits T Cell Activation," Proc. Natl. Acad. Sci. (USA) 100:10388-10392).
The human B7-H4 cDNA sequence has been used to identify a murine B7-H4 homolog. The level of identity between the murine and human orthologs (approximately 87%) suggests that B7-H4 is highly conserved evolutionarily (Sica, G. L. et al. (2003) "B7-H4, A Molecule Of The B7 Family, Negatively Regulates T Cell Immunity," Immunity 18:849-861; Zang, X. et al. (2003) B7x: A Widely Expressed B7 Family Member That Inhibits T Cell Activation," Proc. Natl. Acad. Sci. (USA) 100:10388-10392). The extensive homology increases to 91% for the IgV domains of the proteins, which are believed to be involved in binding the B7-H4 receptor (Stamper, C. C. et al. (2001) "Crystal Structure Of The B7-1/CTLA-4 Complex That Inhibits Human Immune Responses," Nature 410: 608-611; Schwartz, J. C. et al. (2001) "Structural Basis For Co-Stimulation By The Human CTLA-4/B7-2 Complex," Nature 410:604-608).
In contrast to other B7 members, B7-H4 mRNA is widely expressed. Its expression has been found in the brain, heart, kidney, liver, lung, ovary, pancreas, placenta, prostate, skeletal muscle, skin, small intestine, spleen, stomach, testis, thymus, thymus, and uterus (Sica, G. L. et al. (2003) "B7-H4, A Molecule Of The B7 Family, Negatively Regulates T Cell Immunity," Immunity 18:849-861; Zang, X. et al. (2003) B7x: A Widely Expressed B7 Family Member That Inhibits T Cell Activation," Proc. Natl. Acad. Sci. (USA) 100:10388-10392; Prasad, D. V. et al. (2003) B7S1, A Novel B7 Family Member That Negatively Regulates T Cell Activation," Immunity 18:863-873; Prasad, D. V. et al. (2003) B7S1, A Novel B7 Family Member That Negatively Regulates T Cell Activation," Immunity 18:863-873).
Despite the widespread expression of B7-H4 mRNA, the presence of B7-H4 protein on the surface of normal cells seems to be limited (Sica, G. L. et al. (2003) "B7-H4, A Molecule Of The B7 Family, Negatively Regulates T Cell Immunity," Immunity 18:849-861; Choi, I. H. et al. (2003) "Genomic Organization And Expression Analysis Of B7-H4, An Immune Inhibitory Molecule Of The B7 Family," J. Immunol. 171:4650-4654). Although freshly isolated human T cells, B cells, monocytes, and dendritic cells do not express B7-H4 on their cell surfaces (as determined via FACS analysis), its expression can be induced on such cells after in vitro stimulation lipopolysaccharides (LPS), phytohemagglutinin (PHA), gamma interferon (IFN-γ), phorbol 12-myristate 13-acetate (PMA), or ionomycin (Sica, G. L. et al. (2003) "B7-H4, A Molecule Of The B7 Family, Negatively Regulates T Cell Immunity," Immunity 18:849-861). The finding of such a wide distribution of B7-H4 expression indicates that the function of B7-H4 is quite distinct from that of other inhibitory B7 molecules (see, Zang, X. et al. (2003) B7x: A Widely Expressed B7 Family Member That Inhibits T Cell Activation," Proc. Natl. Acad. Sci. (USA) 100:10388-10392).
Consistent with this finding and the observation that the extracellular domain of B7-H4 has only about 25% amino acid homology with other B7 family members, B7-H4 does not bind to known B7 family receptors (i.e., CTLA-4, ICOS, PD-1 or CD28). Efforts to identify a B7-H4-specific receptor have revealed that such a receptor is expressed on activated T cells (Sica, G. L. et al. (2003) "B7-H4, A Molecule Of The B7 Family, Negatively Regulates T Cell Immunity," Immunity 18:849-861). Binding of B7-H4 fusion protein to its putative receptor on T cells was found to significantly inhibit T cell proliferation and cytokine (IL-2 and IL-10) production and such inhibition was found to be non-reversible by CD28 costimulation (Zang, X. et al. (2003) B7x: A Widely Expressed B7 Family Member That Inhibits T Cell Activation," Proc. Natl. Acad. Sci. (USA) 100:10388-10392; Prasad, D. V. et al. (2003) B7S1, A Novel B7 Family Member That Negatively Regulates T Cell Activation," Immunity 18:863-873). B7-H4 has been found to arrest cell cycle progression of T cells in G0/G1 phase (Sica, G. L. et al. (2003) "B7-H4, A Molecule Of The B7 Family, Negatively Regulates T Cell Immunity," Immunity 18:849-861) indicating that the protein mediates its inhibitory effects by arresting the cell cycle rather than by inducing apoptosis.
Anti-B7-H4 antibodies have been found to greatly increase the levels of IL-2 production by spleen cells in vitro, and to lead to a stronger immune response in vivo (Prasad, D. V. et al. (2003) B7S1, A Novel B7 Family Member That Negatively Regulates T Cell Activation," Immunity 18:863-873; Zang, X. et al. (2003) B7x: A Widely Expressed B7 Family Member That Inhibits T Cell Activation," Proc. Natl. Acad. Sci. (USA) 100:10388-10392; Prasad, D. V. et al. (2003) B7S1, A Novel B7 Family Member That Negatively Regulates T Cell Activation," Immunity 18:863-873).
An absence of B7-H4 has been demonstrated to lead to resistance to Listeria monocytogenes infection through the direct regulation of the growth of neutrophil progenitors (Zhu, G. et al. (2009) "B7-H4 Deficient Mice Display Augmented Neutrophil-Mediated Innate Immunity," Blood 113:1759-1769; Wei, J. et al. (2011) "Tissue-Specific Expression Of B7x Protects From CD4 T Cell-Mediated Autoimmunity," J. Exper. Med. 208(8):1683-1694). As such B7-H4 has been proposed to play a role in immunity, especially autoimmunity and resistance to infection. Thus agonist anti-B7-H4 antibodies and soluble protein agonists of B7-H4 have been proposed for the treatment of inflammatory disorders (U.S. Pat. No. 7,931,896; United States Patent Publications Nos. 2007/0122378; 2008/0160036; 2009/0142342; and 2011/0020325; European Patent Publication No. EP 2124998; PCT Patent Publications Nos. WO 2006/133396; WO 2007/041694; WO 2008/083228; WO 2009/111315; WO 2010/144295; WO 2011/005566; WO 2011/026122; and WO 2011/026132).
The in vivo significance of B7-H4 is additionally demonstrated by the high levels of B7-H4 expression found in numerous tumor tissues, for example, human ovarian cancers (Choi, I. H. et al. (2003) "Genomic Organization And Expression Analysis Of B7-H4, An Immune Inhibitory Molecule Of The B7 Family," J. Immunol. 171:4650-4654; Kryczek, I. et al. (2006) "B7-H4 Expression Identifies A Novel Suppressive Macrophage Population In Human Ovarian Carcinoma," J. Exp. Med. 203(4):871-881; Bignotti, E. et al. (2006) "Differential Gene Expression Profiles Between Tumor Biopsies And Short Term Primary Cultures Of Ovarian Serous Carcinomas: Identification Of Novel Molecular Biomarkers For Early Diagnosis And Therapy," Gynecol. Oncol. 103:405-416; Tringler, B. et al. (2006) "B7-H4 Overexpression In Ovarian Tumors," Gynecol. Oncol. 100:44-52; Simon, I. et al. (2006) "B7-h4 Is A Novel Membrane-Bound Protein And A Candidate Serum And Tissue Biomarker For Ovarian Cancer," Cancer Res. 66:1570-1575; Salceda, S. et al. (2005) "The Immunomodulatory Protein B7-H4 Is Overexpressed In Breast And Ovarian Cancers And Promotes Epithelial Cell Transformation," Exp. Cell Res. 306:128-141), non-small-cell lung cancer (Sun, Y. et al. (2006) "B7-H3 And B7-H4 Expression In Non-Small-Cell Lung Cancer," Lung Cancer 53:143-151), ductal and lobular breast cancer (Salceda, S. et al. (2005) "The Immunomodulatory Protein B7-H4 Is Overexpressed In Breast And Ovarian Cancers And Promotes Epithelial Cell Transformation," Exp. Cell Res. 306:128-141; Tringler, B. et al. (2005) "B7-H4 Is Highly Expressed In Ductal And Lobular Breast Cancer," Clin. Cancer Res. 11:1842-1848), and renal cell carcinoma (Krambeck, A. E. et al. (2006) "B7-H4 Expression In Renal Cell Carcinoma And Tumor Vasculature: Associations With Cancer Progression And Survival," Proc. Natl. Acad. Sci. (USA) 103:10391-10396). The expression of B7-H4 on tumor cells has been found to correlate with adverse clinical and pathologic features, including tumor aggressiveness (Krambeck, A. E. et al. (2006) "B7-H4 Expression In Renal Cell Carcinoma And Tumor Vasculature: Associations With Cancer Progression And Survival," Proc. Natl. Acad. Sci. (U.S.A.) 103(2): 10391-10396).
C. Tumor-Associated Macrophages (TAMs)
The association between inflammation and cancer dates back more than a century to observations noting infiltration of large numbers of white blood cells into tumor sites (Balkwill, F. et al. (2001) "Inflammation And Cancer: Back To Virchow?," Lancet 357:539-545; Coussens, L. M. et al. (2002) "Inflammation and Cancer," Nature 420:860-867). Several studies have now identified two main pathways linking inflammation and cancer: an intrinsic and an extrinsic pathway (Allavena, P. et al. (2008) "Pathways Connecting Inflammation and Cancer," Curr. Opin. Genet. Devel. 18:3-10; Colotta, F. (2009) "Cancer-Related Inflammation, The Seventh Hallmark of Cancer: Links to Genetic Instability," Carcinogenesis 30(7): 1073-1081; Porta, C. et al. (2009) "Cellular and Molecular Pathways Linking Inflammation and Cancer," Immunobiology 214:761-777). The intrinsic pathway includes genetic alterations that lead to inflammation and carcinogenesis, whereas the extrinsic pathway is characterized by microbial/viral infections or autoimmune diseases that trigger chronic inflammation in tissues associated with cancer development. Both pathways activate pivotal transcription factors of inflammatory mediators (e.g., NF-κB, STAT3, and HIF-1) and result in the recruitment of leukocytes that play a key role in inflammation (Solinas, G. et al. (2009) "Tumor-Associated Macrophages (TAM) As Major Players Of The Cancer-Related Inflammation," J. Leukoc. Biol. 86(5):1065-1073).
TAMs provide a link between inflammation and cancer. Macrophages are immune system cells derived from activated blood monocytes. They are primarily recognized as participating in inflammatory responses induced by pathogens or tissue damage by acting to remove (i.e., phagocytose) pathogens, dead cells, cellular debris, and various components of the extra-cellular matrix (ECM). Macrophages have been found to constitute an important constituent in the tumor microenvironment and to represent up to 50% of the tumor mass.
In addition to mediating phagocytosis, macrophages secrete pro-angiogenic growth factors and matrix-remodeling proteases, and thus play a role in the development of the vascular infrastructure (i.e., angiogenesis) needed for tumor development and growth (Pollard, J. W. (2009) "Trophic Macrophages In Development And Disease," Nat. Rev. Immunol. 9:259-270). As such, the presence of macrophages within a tumor appears to assist the growth of the tumor. A number of studies provide evidence that the presence of tumor-associated macrophages within the tumor is a negative prognostic factor of survival (Farinha, P. et al. (2005) "Analysis Of Multiple Biomarkers Shows That Lymphoma-Associated Macrophage (LAM) Content Is An Independent Predictor Of Survival In Follicular Lymphoma (FL)," Blood 106:2169-2174; Dave, S. S. et al. (2004) "Prediction Of Survival In Follicular Lymphoma Based On Molecular Features Of Tumor-Infiltrating Immune Cells," N. Engl. J. Med. 351:2159-2169; Solinas, G. et al. (2009) "Tumor-Associated Macrophages (TAM) As Major Players Of The Cancer-Related Inflammation," J. Leukoc. Biol. 86(5):1065-1073).
Incipient tumors need to generate their own vasculature to enable oxygen and nourishment delivery to the expanding tumor cells. Thus, the progression of tumors requires coordinated signaling between tumor cells and non-malignant cells in the tumor microenvironment (Kaler, P. et al. (2010) "Tumor Associated Macrophages Protect Colon Cancer Cells from TRAIL-Induced Apoptosis through IL-1β-Dependent Stabilization of Snail in Tumor Cells," PLos ONE 5(7):e11700 1-13). It is now well established that TAMs, as well as neutrophils, fibroblasts and other cells cooperate with tumor cells to facilitate angiogenesis in tumors (Nucera, S. et al. (2011) "The Interplay Between Macrophages And Angiogenesis In Development, Tissue Injury And Regeneration," Int. J. Dev. Biol. doi: 10.1387/ijdb.103227sn; Zamarron, B. F. et al. (2011) "Dual Roles Of Immune Cells And Their Factors In Cancer Development And Progression," Int. J. Biol. Sci. 7(5):651-658; Liu, J. et al. (2011) "Tumor-Associated Macrophages Recruit CCR6+ Regulatory T Cells And Promote The Development Of Colorectal Cancer Via Enhancing CCL20 Production In Mice," PLoS One. 6(4):e19495; Rigo, A. et al. (2010) "Macrophages May Promote Cancer Growth Via A GM-CSF/HB-EGF Paracrine Loop That Is Enhanced By CXCL12," Molec. Cancer 9(273):1-13; Lin, J. Y. et al. (2011) "Clinical Significance Of Tumor-Associated Macrophage Infiltration In Supraglottic Laryngeal Carcinoma," Chin. J. Cancer 30(4):280-286; Vergati, M. (2011) "The Consequence Of Immune Suppressive Cells In The Use Of Therapeutic Cancer Vaccines And Their Importance In Immune Monitoring," J. Biomed. Biotechnol. 2011:182413).
B7-H4 has been shown to be over-expressed in TAMs including those present in ovarian tumors (Kryczek, I. et al. (2006) "B7-H4 Expression Identifies A Novel Suppressive Macrophage Population In Human Ovarian Carcinoma," J. Exp. Med. 203(4):871-881; Kryczek, I. et al. (2007) "Relationship Between B7-H4, Regulatory T Cells, And Patient Outcome In Human Ovarian Carcinoma," Cancer Res. 67(18):8900-8905).
Despite all prior advances in the treatment of inflammation and cancer, a need remains for improved compositions capable of providing enhanced immunotherapy for the treatment of cancer. Therefore, compositions and their use to treat cancer and other diseases and conditions are provided.
It is an object of the invention to provide compositions and methods for inducing surface B7-H4 internalization to suppress B7-H4 mediated immune evasion for a treatment of cancer, or bacteria or viral infections.
It is another object of the invention to provide compositions and methods for B7-H4 mAb-payload drug-conjugate to target B7-H4 positive tumors for a treatment of cancer.

Anti-human B7-H4 antibodies and their uses


A recording of a first selectable process signal of a system is indexed by a second process signal that is different from the timing signal of the system. First process signals acquired in this way are stored in a memory as a function of the index-forming second process signal, wherein a measurement value represented by a first process signal is distributed over adjacent memory locations of the memory if the first acquired process signal has a non-integer index.

The present invention relates to a method for recording a selectable process signal of a system, and more particularly to a method for recording process signals as a function of system variables other that the timing signal of the system.
Certain functions, sometimes also referred to as trace functions, are employed in drive controllers and other types of controllers which store selectable process signals indexed by a clock signal, typically having equidistant time intervals. Either temporal functions or, after a transformation, frequency functions are recorded.
Functions to be recorded that do not depend on the time, but from other process variables, still have to be stored with a time index as independent variable. Due to the limited number of memory locations, measurements can only be recorded over a limited time, which may prevent significant mutual dependencies of the process signals to be inferred. It is then also not possible to directly average the process signal to be recorded with respect to the index-forming signal in the trace memory.
For this reason, external auxiliary devices with special functionality are frequently employed to process the measurement values.
It would therefore be desirable and advantageous to provide a trace function which allows indexed measurement values to be stored independent of a time index. It would also be desirable and advantageous to directly average a process signal to be recorded with respect to an index-forming signal.

Averaging trace function with indexing by a process signal


An automatic transmission includes a parallel-axis gear pair including a first gear having a shaft portion and a gear portion, and a second gear which meshes with the first gear; a case that has a supporting wall which is adjacent to the gear portion of the first gear and rotatably supports the shaft portion of the first gear; and a frictional engagement apparatus that includes friction members, a piston that presses on, so as to apply, the friction members, and a hydraulic chamber that holds hydraulic fluid which moves the piston in the direction of the friction members. As a result, both the shaft to shaft dimension as well as the axial dimension of the automatic transmission can be reduced.

1. Field of the Invention
The invention relates to an automatic transmission, and more particularly, an automatic transmission provided with a parallel-axis gear pair.
2. Description of the Related Art
An automatic transmission provided with a parallel-axis gear pair has been known. For example, there is an automatic transmission provided with a plurality of planetary gear sets, which has a countershaft provided parallel with an input shaft, and a parallel-axis gear pair for transmitting the rotation of the input shaft to the countershaft. One example of this kind of automatic transmission is disclosed in a non-patent reference, "Manual for the New Model Harrier", published by Toyota Motor Corporation on Dec. 25, 1997. FIG. 4 shows a cross-section of a portion of the automatic transmission described on pages 2-2 to 2-8 of that reference.
As shown in FIG. 4, a counter drive gear 100 is able to rotate around a second input shaft 104 that rotates together with a first input shaft 102 that is coupled to a torque converter, not shown. A counter driven gear 106 is able to rotate around a countershaft 108.
The counter drive gear 100 includes a shaft portion 110 and a gear portion 112, which is perpendicular to the shaft portion 110 and provided on one end of the shaft portion 110. The shaft portion 110 is supported by a supporting wall 118 of a case 116 via a bearing 114.
Also, an outside peripheral portion 112a of the gear portion 112 of the counter drive gear 100 is wider than an inner peripheral portion 112b of the gear portion 112. Further, the center of the outer peripheral portion 112a in the axial direction is closer to the supporting wall 118 side than is the center of the inner peripheral portion 112b in the axial direction, such that the outer peripheral portion 112a protrudes farther toward the supporting wall 118 than does the inner peripheral portion 112b. A concave portion 120 that accommodates the outer peripheral portion 112a of the counter drive gear 100 is formed in the supporting wall 118.
Further, a clutch 130 is provided on the side of the counter drive gear 100 opposite the supporting wall 118. The clutch 130 includes a plurality of friction plates 122, a piston 124 that presses on the plurality of friction plates 122, a spring 126 that urges the piston 124 away from the friction plates 122, and a hydraulic chamber 128 and the like. When the plurality of friction plates 122 are forced together, an intermediate shaft 132 which encompasses the second input shaft 104 and is coupled to a sun gear of a planetary gear set, not shown, becomes coupled to the first input shaft 102.
Accordingly, by forming the concave portion 120 in the supporting wall 118 and accommodating the outer peripheral portion 112a of the gear portion 112 of the counter drive gear 100 in this concave portion 120, the automatic transmission shown in FIG. 4 can be made shorter in the axial direction.
Not only is it necessary to make the dimensions of the automatic transmission shorter in the axial direction, but there is also a need to reduce the shaft to shaft dimension of the automatic transmission, i.e., the dimension of the automatic transmission in the direction perpendicular to the axis. In order to decrease the shaft to shaft dimension of the automatic transmission shown in FIG. 4, it is conceivable to reduce the diameter of the gear portion 112 of the counter drive gear 100. With this structure, however, the concave portion 120 of the supporting wall 118 is prevented from being moved much to the inside in the radial direction by the bearing 114, so unless position of the concave portion 120 is changed, the diameter of the gear 112 of the counter drive gear 100 can not be reduced. While the diameter of the gear portion 112 could be reduced if the counter drive gear 100 were moved toward the first input shaft 102 side, doing so would simply increase the length of the automatic transmission in the axial direction.


Provided is a mechanism capable of allowing signals transmitted by use of different communication methods classified as V2X communication to appropriately coexist in a resource pool. A terminal apparatus for performing communication using any of communication methods classified as vehicle to X (V2X) communication, the terminal apparatus including: an acquisition unit that acquires allocation information regarding allocation of a first resource pool and setting information regarding priority use of the first resource pool, the first resource pool being available to a plurality of terminal apparatuses using the different communication methods classified as V2X communication; and a transmission processing unit that performs a process of packet transmission using the first resource pool on the basis of the communication method of the terminal apparatus itself, the allocation information, and the setting information regarding priority use.

Direct communication between a mobile object, such as a vehicle, and various objects is implemented by use of a communication apparatus mounted on the mobile object. Communication between a communication apparatus mounted on a mobile object and various other communication apparatuses is referred to as vehicle to X (V2X) communication. With regard to V2X communication, communication systems using dedicated short range communication (DSRC) have been discussed thus far. Meanwhile, in recent years, communication systems using cellular communication standards such as Long Term Evolution (LTE) are under discussion.
For example, Non-Patent Documents 1 and 2 below disclose techniques related to resource pools that can be shared by terminals that perform V2X communication using the cellular communication standards. According to such techniques, a resource pool can be shared by, for example, a vehicular UE and a pedestrian UE.

Terminal apparatus, base station, method, and recording medium


In a scroll type compressor wherein a fixed scroll (8) has an end plate (8b) and an involute vane (8a) fixed to the end plate and is coupled to a movable scroll (5) so as to define a pair of working spaces therebetween, the end plate of the fixed scroll are formed a pair of cylinders each of which communicates with the working spaces via bypass holes (15a) and (15b) formed in the end plate of the fixed scroll. In each of the cylinders, a cylindrical piston valve member (10) is slidably received for opening and closing the bypass holes. Opening or closing of each bypass hole is determined depending on a position of an axial end of the piston valve member relative to the corresponding bypass hole.

The present invention relates to a variable displacement scroll type compressor to be used, for example, as a refrigerant compressor for an automobile air conditioner and, in particular, to a variable displacement mechanism of a scroll type compressor.
Variable displacement mechanisms of scroll type compressors are disclosed in, for example, Japanese First (unexamined) Utility Model Publication No. 1-162094 and Japanese First (unexamined) Patent Publication No. 5-280476.
In the former publication, a pair of cylinders each communicating with bypass holes are provided in an end plate of a fixed scroll, and a hollow valve member is slidably-received in each of the cylinders for opening and closing the bypass holes. Opening of the innermost bypass hole is achieved by moving the valve member to a position where a hole formed at an intermediate portion of the valve member coincides with the innermost bypass hole. When the innermost bypass hole is opened, refrigerant gas is relieved to the suction side through the innermost bypass hole, the valve member hole and the hollow inside of the valve member.
On the other hand, in the latter publication, one cylinder communicating with bypass holes is provided in an end plate of a fixed scroll, and a valve member is slidably received in the cylinder for opening and closing the bypass holes. Opening of the innermost bypass hole is achieved by moving the valve member to an innermost position in the cylinder so as to pass the innermost bypass hole.
In the former publication, a diameter of the cylinder is required to be the sum of a diameter of the hollow inside of the valve member and thicknesses of the walls of the valve member. Further, it is possible that the valve member rotates in the cylinder so that the coincidence of the innermost bypass hole and the valve member hole is not guaranteed. Considering the rotation of the valve member, an annular groove communicating with the valve member hole may be necessary on the outer circumference of the valve member. Provision of the annular groove increases thicknesses of the walls of the valve member and thus a diameter of the valve member to thereby increase a diameter of the cylinder. Accordingly, the thickness of the end plate of the fixed scroll is increased to further increase the axial length and the weight of the compressor.
On the other hand, in the latter publication, only one cylinder is provided for relieving the refrigerant gas via the bypass holes while a pair of crescent-shaped sealed working spaces are formed as pressure chambers. Thus, the flow rate of the refrigerant gas through the cylinder is large to cause a large pressure loss. For lowering the required power during the reduced displacement operation of the compressor, it is necessary to reduce the pressure loss at the cylinder and thus design the cylinder with a larger bore. Accordingly, like the former publication, the thickness of the end plate of the fixed scroll is increased to further increase the axial length and the weight of the compressor.

Scroll type compressor with improved variable displacement mechanism