Disclosed are an apparatus for and a method of performing an inspection and metrology process. The apparatus may include a stage configured to load a substrate thereon, a sensor on the stage, an object lens between the sensor and the stage, a light source generating an illumination light to be transmitted to the substrate through the object lens, a first band filtering part between the light source and the object lens to control a wavelength of the illumination light within a first bandwidth, and a second band filtering part between the light source and the object lens to control a wavelength of the illumination light within a second bandwidth, which is smaller than the first bandwidth.

The present disclosure relates to an apparatus for and a method of performing an inspection and metrology process, and in particular, to an inspection/metrology apparatus, which is used in a process of fabricating a semiconductor device, and a method of inspecting and measuring the semiconductor device using the apparatus.
Semiconductor devices may be a key component of various information and communication instruments. With the rapid advance of information and communication technology, there is an increasing demand for a high-performance and high-density semiconductor devices.
In many cases, the production of semiconductor devices is facilitated by a precisely controlled fabrication process. Such a precisely controlled fabrication process may be used to produce semiconductor devices that include a large number of fine patterns. During this process, an inspection apparatus may be used to inspect the fine patterns, and a measurement apparatus may be used to measure widths or thicknesses of the fine patterns. However, both the inspection apparatus and the measurement apparatus may occupy a significant amount of space in a fabrication line, which may increase the cost, and decrease the efficiency of the fabrication process.

Apparatus for and method of performing inspection and metrology process


Reactive compositions which consist of or comprise (A) at least one polyisocyanate whose isocyanate groups have been partly or fully blocked with propargyl alcohol, (B) at least one constituent which contains on average at least two isocyanate-reactive functional groups in the molecule, and (C) at least one catalyst which catalyzes the addition reaction of the isocyanate-reactive functional groups of (B) with the acetylenically unsaturated triple bond of the propargyl groups, and their use as coating materials, adhesives, and sealing compounds.

The present invention relates to novel reactive compositions. The present invention also relates to the use of the novel reactive compositions as coating materials, adhesives and sealing compounds. The present invention further relates to a novel process for preparing coatings, adhesive layers, and seals, which process can be carried out with no emissions.
Blocked polyisocyanates and processes for their preparation have been known for a long time. Reference is made, for example, to U.S. Pat. No. 4,444,954 A. The blocked polyisocyanates are preferably used as crosslinking agents in externally crosslinking reactive compositions, especially coating materials, adhesives, and sealing compounds.
The use of propargyl alcohol as blocking agents for polyisocyanates is known from German Patent Applications DE 38 09 695 A 1, DE 39 32 816 A 1 or DE 41 42 734 A 1. The polyisocyanates, partially blocked with propargyl alcohol, are incorporated through the reaction of free isocyanate groups into binders, which become self-crosslinking as a result. The polyisocyanates fully blocked with propargyl alcohol serve as crosslinking agents in externally crosslinking reactive compositions.
Externally crosslinking is a term used to refer to those coating materials, adhesives, and sealing compounds in which one variety of the complementary reactive functional groups which bring about crosslinking is present in a binder and the other variety in a hardener, curing agent or crosslinking agent. Self-crosslinking coating materials, adhesives, and sealing compounds are those in which the complementary reactive functional groups are present in one constituent. For further details, reference is made to Rompp Lexikon Lacke und Druckfarben, Georg Thieme Verlag, Stuttgart, New York, 1998, xe2x80x9cCuringxe2x80x9d, pages 274 to 276, especially page 275, bottom.
The crosslinking of the blocked polyisocyanates known from German Patent Application DE 38 09 695 A 1 is catalyzed by catalysts, such as salts or complexes of metals, such as lead, zinc, iron, tin, manganese, and bismuth, for example. Preferred metal catalysts in this context are lead compounds, such as lead carboxylates having from 1 to 10 carbon atoms, or tin compounds, such as dibutyltin diacetate, dibutyltin dilaurate or dibutyltin oxide. As is known, these catalysts accelerate the elimination of blocking agents from the blocked polyisocyanates and the reaction of isocyanate-reactive functional groups in the binders and/or reactive diluents with the formation of urethane, thiourethane and/or urea groups.
The disadvantage of this type of crosslinking is that volatile organic compounds are released which, if they remain in the resultant coats, adhesive films and seals, may adversely affect the profile of performance properties of said coats, adhesive films and seals or, if they depart the resultant coats, adhesive films and seals, constitute unwanted organic emissions.
Furthermore, the coats, adhesive films, and seals which comprise urethane, thiourethane and/or urea groups in their three-dimensional network, as far as pigmentability, leveling, hardness, flexibility, scratch resistance, chemical resistance, weathering stability, adhesion, and gloss are concerned, offer distinct advantages over coats, adhesive films, and seals based on a different crosslinking chemistry.
It would therefore be highly desirable to have available a reactive composition which could be cured without emission to give a three-dimensional network containing urethane, thiourethane and/or urea groups.
It is true that reactive compositions which may be cured without emissions and give three-dimensional networks containing urethane and/or urea groups have been known for a long time. However, these are straight two-component or multicomponent systems in which unblocked polyisocyanates are used as crosslinking agents. These cure even at room temperature. However, until shortly before the application, the high reactivity of the crosslinking agents means that they have to be stored separately from the other constituents of the composition, necessitating a more complex technology and logistics. Furthermore, this makes it very much more difficult, if not impossible, to prepare powder coating materials and powder coating dispersions (powder slurries).
It would therefore be particularly desirable to have available a one-component system which can be cured without emissions and where the crosslinking agents need not be stored separately from the other constituents.
European Patent Application EP 0 852 252 A1 discloses epoxy resins containing propargyl groups and amino groups. The propargyl-containing epoxy resins are used to prepare cathodically depositable electrodeposition coating materials, which are selfcrosslinking via amino groups and propargyl groups or via the acetylenically unsaturated bonds. The cathodically depositable electrodeposition coating material further comprises a constituent such as, for example, tetrabutylammonium bromide which, following its activation by the electrolysis, catalyzes the thermal curing of the deposited electrodeposition coating film. As a result, the electrodeposition coating film may be cured at comparatively low temperatures. If the electrodeposition coating material, however, is not applied electrophoretically but instead, for example, by knife-coating onto a substrate, the resultant coating film does not crosslink below 200xc2x0 C.
It is an object of the present invention to provide new reactive compositions, especially coating materials, adhesives, and sealing compounds, particularly one-component coating materials, adhesives, and sealing compounds, which match if not exceed the technological profile of properties of the known reactive compositions and may be cured, moreover, without emissions. It should be possible to provide the new reactive compositions in the form of finely divided powders, powder slurries, aqueous solutions or dispersions, organic solutions or dispersions, or as essentially water-free and solvent-free liquid systems (100% systems).
It is another object of the present invention to find a new process for the thermal curing of reactive compositions comprising blocked polyisocyanates as crosslinking agents that proceed without emissions.
Furthermore, the new process and the new reactive compositions ought to make it possible to postcrosslink the resultant new coats, adhesive films, and seals with actinic radiation.
It is not least an object of the present invention to provide new coats, adhesive films, and seals which have a profile of performance properties which matches if not exceeds that of the known coats, adhesive films, and seals.
Found accordingly have been the novel reactive compositions which consist of or comprise
(A) at least one polyisocyanate whose isocyanate groups have been partially or fully blocked with propargyl alcohol,
(B) at least one constituent having on average at least two isocyanate-reactive. functional groups in the molecule, and
(C) at least one catalyst which catalyzes the addition reaction of the isocyanate-reactive functional groups of (B) with the acetylenically unsaturated triple bond of the propargyl groups,
and which are referred to below as xe2x80x9ccompositions of the inventionxe2x80x9d.
Also [lacuna] has been the novel process for producing coatings, adhesive films, and seals by
(I) applying coating materials, adhesives, and sealing compounds which consist of or comprise at least one composition of the invention onto and/or into a substrate, and
(II) thermally curing the resultant films and/or compositions,
In the text below, the novel process for producing coats, adhesive films, and seals is referred to as xe2x80x9ccuring process of the inventionxe2x80x9d.
Further subject matter of the invention will emerge from the description.
In the light of the prior art it was surprising and unforeseeable to the skilled worker that the complex of objects on which the present invention was based could be solved through the compositions as claimed in the invention. It was also surprising that specifically the compositions of the invention make it possible to carry out the curing process of the invention without emissions. Surprisingly, the curing process of the invention gave coatings, adhesive films and seals which in the cured state could still be postcrosslinked with actinic radiation.
The compositions of the invention comprise polyisocyanates (A), partly or fully blocked with propargyl alcohol, as crosslinking agents.
The blocked polyisocyanates (A) may be partly blocked. This means that they still contain at least one free isocyanate group. This kind of blocked polyisocyanates is used in particular as intermediates for the controlled introduction of isocyanate groups blocked using propargyl alcohol into compounds comprising isocyanate-reactive functional groups, such as primary amino groups, hydroxyl groups and/or thiol groups, especially hydroxyl groups. This incorporation produces blocked polyisocyanates (A) which are of relatively high functionality and whichxe2x80x94provided excess isocyanate-reactive functional groups are still presentxe2x80x94have selfcrosslinking properties. Examples of suitable compounds of this kind are the reactive diluents and binders (B) described below.
The free isocyanate groups may further be blocked with customary and known blocking agents, so giving mixed-blocked polyisocyanates (A) which are used as crosslinking agents in the compositions of the invention that are one-component systems. This feature is employed in particular in order to realize special technical effects in the context of deblocking and crosslinking.
Moreover, the partly blocked polyisocyanates (A) may be used as crosslinking agents in the compositions of the invention that are two-component or multi-component systems.
Preferably, the blocked polyisocyanates (A) are fully blocked.
For the blocked polyisocyanates (A) it is essential that at least one isocyanate group is blocked with propargyl alcohol. In accordance with the invention it is of particular advantage if all isocyanate groups are blocked with propargyl alcohol.
Polyisocyanates suitable for blocking are virtually all customary and known aromatic, aliphatic and cycloaliphatic diisocyanates and polyisocyanates. Particularly suitable are the diisocyanates and polyisocyanates referred to in the art as paint polyisocyanates.
Examples of suitable aromatic diisocyanates for blocking are tolylene diisocyanate, xylylene diisocyanate, bisphenylene diisocyanate, naphthylene diisocyanate, and diphenylmethane diisocyanate.
Examples of suitable acyclic aliphatic diisocyanates for blocking are trimethylene diisocyanate, tetramethylene diisocyanate, pentamethylene diisocyanate, hexamethylene diisocyanate, ethylethylene diisocyanate, trimethylhexane diisocyanate, heptamethylene diisocyanate, or diisocyanates derived from dimeric fatty acids, as marketed under the commercial designation DDI 1410 by Henkel and described in patents WO 97/49745 and WO 97/49747, especially 2-heptyl-3,4-bis(9-isocyanatononyl)-1-pentylcyclohexane, or 1,2-, 1,4- or 1,3-bis(isocyanatomethyl)cyclohexane, 1,2-, 1,4- or 1,3-bis(2-isocyanatoeth-1-yl)cyclohexane, 1,3-bis(3-isocyanatoprop-1-yl)cyclohexane or 1,2-, 1,4- or 1,3-bis(4-isocyanatobut-1-yl)cyclohexane, especially hexamethylene diisocyanate.
Examples of suitable cycloaliphatic diisocyanates are isophorone diisocyanate (=5-isocyanato-1-isocyanatomethyl-1,3,3-trimethylcyclohexane), 5-isocyanato-1-(2-isocyanatoeth-1-yl)-1,3,3-trimethyl-cyclohexane, 5-isocyanato-1-(3-isocyanatoprop-1-yl)-1,3,3-trimethylcyclohexane, 5-isocyanato-(4-isocyanatobut-1-yl)-1,3,3-trimethylcyclohexane, 1-isocyanato-2-(3-isocyanatoprop-1-yl)cyclohexane, 1-isocyanato-2-(3-isocyanatoeth-1-yl)cyclohexane, 1-isocyanato-2-(4-isocyanatobut-1-yl)cyclohexane, 1,2-diisocyanatocyclobutane, 1,3-diisocyanatocyclobutane, 1,2-diisocyanatocyclopentane, 1,3-diisocyanatocyclopentane, 1,2-diisocyanatocyclohexane, 1,3-diisocyanatocyclohexane, 1,4-diisocyanatocyclohexane, dicyclohexylmethane 2,4xe2x80x2-diisocyanate or dicyclohexylmethane 4,4xe2x80x2-diisocyanate, liquid bis(4-isocyanatocyclohexyl)methane with a trans/trans content of up to 30% by weight, preferably 25% by weight, and in particular 20% by weight, as described in patents DE 44 14 032 A1, GB 1220717 A1, DE 16 18 795 A1 or DE 17 93 785 A1, especially isophorone diisocyanate.
Examples of suitable polyisocyanates for blocking are polyurethane prepolymers which contain isocyanate groups, which may be prepared by reacting polyols with an excess of the above-described aromatic, aliphatic and cycloaliphatic, preferably aliphatic and cycloaliphatic, diisocyanates and which are preferably of low viscosity. In the context of the present invention, the term xe2x80x9ccycloaliphatic diisocyanatexe2x80x9d denotes a diisocyanate in which at least one isocyanate group is attached to a cycloaliphatic radical.
It is also possible to use polyisocyanates containing isocyanurate, biuret, allophanate, iminooxadiazinedione, urethane, urea, carbodiimide and/or uretdione groups, which are prepared in a customary and known manner from the diisocyanates described above. Examples of suitable preparation processes and polyisocyanates are known, for example, from the patents and patent applications CA 2,163,591 A1, U.S. Pat. Nos. 4,419,513 A1, 4,454,317 A1, EP 0 646 608 A1, U.S. Pat. No. 4,801,675 A1, EP 0 183 976 A1, DE 40 15 155 A1, EP 0 303 150 A1, EP 0 496 208 A1, EP 0 524 500 A1, EP 0 566 037 A1, U.S. Pat. Nos. 5,258,482 A1, 5,290,902 A1, EP 0 649 806 A1, DE 42 29 183 A1, and EP 0 531 820 A1.
Also suitable, furthermore, are low molecular mass compounds, oligomeric compounds and polymeric compounds which contain isocyanate groups and groups activated with actinic radiation, especially UV light or electron beams. Examples of suitable compounds of this kind are the urethane (meth)acrylates described in European Patent Application EP 0 928 800 A1, which contain (meth)acrylate groups and free isocyanate groups.
In the context of the present invention, the term oligomers, hereinbelow, refers to resins containing at least 2 up to 15 monomer units in their molecule. In the context of the present invention, polymers are resins which contain at least 10 monomer units in their molecule. For further details of these terms, reference is made to Rxc3x6mpp Lexikon Lacke und Druckfarben, Georg Thieme Verlag, Stuttgart, New York, 1998, xe2x80x9cOligomersxe2x80x9d, page 425.
Particular preference is given to the use of oligomers, preferably trimers, especially the isocyanurate, of hexamethylene diisocyanate.
Examples of suitable customary and known blocking agents are those known from U.S. Pat. No. 4,444,954:
i) phenols such as phenol, cresol, xylenol, nitrophenol, chlorophenol, ethylphenol, t-butyl-phenol, hydroxybenzoic acid, esters of this acid, or 2,5-di-tert-butyl-4-hydroxytoluene;
ii) lactams, such as xcex5-caprolactam, xcex4-valerolactam, xcex3-butyrolactam, or xcex2-propiolactam;
iii) active methylenic compounds, such as diethyl malonate, dimethyl malonate, ethyl or methyl acetoacetate, or acetylacetone;
iv) alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, n-amyl alcohol, t-amyl alcohol, lauryl alcohol, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, propylene glycol monomethyl ether, methoxy-methanol, glycolic acid, glycolic esters, lactic acid, lactic esters, methylolurea, methylolmelamine, diacetone alcohol, ethylenechlorohydrin, ethylenebromohydrin, 1,3-dichloro-2-propanol, 1,4-cyclohexyldimethanol, or acetocyanohydrin;
v) mercaptans such as butyl mercaptan, hexyl mercaptan, t-butyl mercaptan, t-dodecyl mercaptan, 2-mercaptobenzothiazole, thiophenol, methylthiophenol, or ethylthiophenol;
vi) acid amides such as acetoanilide, acetoanisidinamide, acrylamide, methacrylamide, acetamide, stearamide, or benzamide;
vii) imides such as succinimide, phthalimide, or maleimide;
viii)amines such as diphenylamine, phenylnaphthylamine, xylidine, N-phenylxylidine, carbazole, aniline, naphthylamine, butylamine, dibutylamine, or butylphenylamine;
ix) imidazoles such as imidazole or 2-ethylimidazole;
x) ureas such as urea, thiourea, ethyleneurea, ethylenethiourea, or 1,3-diphenylurea;
xi) carbamates such as phenyl N-phenylcarbamate or 2-oxazolidone;
xii) imines such as ethylenimine;
xiii) oximes such as acetone oxime, formaldoxime, acetaldoxime, acetoxime, methyl ethyl ketoxime, diisobutyl ketoxime, diacetyl monoxime, benzophenone oxime, or chlorohexanone oxime;
xiv) salts of sulfurous acid such as sodium bisulfite or potassium bisulfite;
xv) hydroxamic esters such as benzyl methacrylohydroxamate (BMH) or allyl methacrylohydroxamate; or
xvi) substituted pyrazoles such as 3,5- or 3,4-dimethylpyrazole, imidazoles, or triazoles.
These customary and known blocking agents are used, however, only in minor amounts. This means that the essential performance properties of the blocked polyisocyanates (A), such as the baking temperature, for example, are determined primarily by the isocyanate groups blocked with propargyl alcohol.
In terms of method, the blocking has no special features, but instead takes place by stoichiometric reaction of the blocking substratesxe2x80x94the diisocyanates and polyisocyanatesxe2x80x94with the propargyl alcohol for use in accordance with the invention, in the melt or in at least one organic solvent that is essentially inert toward isocyanates, preferably under an inert gas atmosphere and in the presence of an appropriate catalyst such as an organotin compound, as described for example in European Patent EP 0 159 117 B1 or in German Patent Application DE 44 41 418 A1 for 3,5-dimethylpyrazole.
On the basis of their particular advantageous performance properties, the blocked polyisocyanates (A) are suitable for all utilities in which blocked diisocyanates and polyisocyanates are commonly used.
Thus they are suitablexe2x80x94as already described abovexe2x80x94as intermediates for the synthesis of mixed-blocked or higher-functional blocked polyisocyanates (A). They may also be used as monomers to prepare oligomers and polymers.
Preferably, they are used as reactive constituents in the compositions of the invention.
The compositions of the invention are reactive. This means that they are stable on storage at room temperature for a greater or lesser period of time, preferably for at least 6 hours in the case of two-component or multicomponent systems or for at least several weeks, in particular for at least one year, in the case of one-component systems, and only when energy, especially thermal energy, is supplied react to give the desired end products.
In principle, the compositions of the invention may be used for all utilities where such behavior is a prerequisite. This is the case, for example, in the production of information carriers such as thermally writable laser-optical disks, resists, and printing plates.
However, the compositions of the invention are used preferably as coating materials, adhesives, and sealing compounds. With particular preference they are used as coating materials of the invention.
The comments made below in relation to the coating materials of the invention apply to the compositions of the invention whatever their application, and, mutatis mutandis, to the adhesives and sealing compounds of the invention.
The amounts of the blocked polyisocyanates (A) in the coating materials of the invention may vary extremely widely. Since the blocked polyisocyanates (A) are able to replace fully the conventional blocked diisocyanates and polyisocyanates in the function of crosslinking agents for thermally curable coating materials, they may be employed in the customary amounts known from the prior art. However, owing to their advantageous performance properties, they may often be used in smaller amounts. On the other hand, owing to their ability to crosslink subsequently on exposure to actinic radiation, they may be used in a quantitative excess over the binders and reactive diluents (B). Preferably, they are used in an amount of from 5 to 70, more preferably from 6 to 67, with particular preference from 7 to 63, with very particular preference from 8 to 60, and in particular from 9 to 57% by weight, based in each case on the solids of the coating material of the invention.
The coating materials of the invention comprise at least one constituent (B) which contains on average at least two isocyanate-reactive functional groups in the molecule. It is preferably at least one binder and/or at least one reactive diluent (B).
The coating materials of the invention comprise customary and known binders (B) as described, for example, in Rxc3x6mpp Lexikon Lacke und Druckfarben, Georg Thieme Verlag, Stuttgart, New York, 1998, under the headword xe2x80x9cBindersxe2x80x9d, pages 73 and 74. Appropriate binders are random, alternating and/or block, linear and/or branched and/or comb, oligomeric or polymeric addition (co)polymers of ethylenically unsaturated monomers, or polyaddition resins and/or polycondensation resins, as described in Rxc3x6mpp Lexikon Lacke und Druckfarben, Georg Thieme Verlag, Stuttgart, New York, 1998, page 457: xe2x80x9cPolyadditionxe2x80x9d and xe2x80x9cPolyaddition resins (polyadducts)xe2x80x9d, pages 463 and 464: xe2x80x9cPolycondensatesxe2x80x9d, xe2x80x9cPolycondensationxe2x80x9d and xe2x80x9cPolycondensation resinsxe2x80x9d. The binders comprise the above-described isocyanate-reactive functional groups. They may additionally comprise further reactive functional groups which are able to enter into thermally initiated crosslinking reactions with the complementary reactive functional groups of the customary and known crosslinking agents that may be present, as described below. In addition, they may comprise groups activatable with actinic radiation, such as acrylate groups.
In addition to the above-described oligomeric or polymeric binders (B), or instead of these, the coating material of the invention comprises at least one low molecular mass compound and/or a comparatively low molecular mass oligomer. These compounds and oligomers are also referred to as reactive diluents (B).
Examples of suitable reactive diluents (B) are the polyhydroxy- and/or polythiol-functionalized cyclic and/or acyclic alkanes having 9 to 16 carbon atoms in the molecule, such as the positionally isomeric diethyloctanediols, as described in German Patent Application DE 198 09 643 A1, the hyperbranched compounds having a tetrafunctional central group, as described in German Patent Application DE 198 40 605 A1, or the hydroformylated and hydrogenated oligomers, obtainable by metathesis of acyclic monoolefins and cyclic monoolefins, hydroformylation of the resultant oligomers, and subsequent hydrogenation, as described in German Patent Application DE 198 05 421 A1.
This variant of the coating material of the invention is employed in particular when its solid content is to be particularly high, for example, up to 100% by weight in the case of the liquid 100% systems.
The amount of these binders and/or reactive diluents (B) in the coating compositions of the invention may likewise vary extremely widely and is guided in particular by the functionality of the binders and/or reactive diluents, on the one hand, and of the blocked polyisocyanates (A), on the other. The amount is preferably from 30 to 95, more preferably from 33 to 94, with particular preference from 37 to 93, with very particular preference from 40 to 92, and in particular from 43 to 91% by weight, based in each case on the solids of the coating material of the invention.
Furthermore, the coating material of the invention comprises at least one catalyst (C) for the thermal crosslinking.
The catalyst (C) for inventive use controls the crosslinking reaction in such a way that in the course of the thermal cure it does not proceed xe2x80x9cconventionallyxe2x80x9d with elimination of the propargyl alcohol from the blocked polyisocyanates of the invention and reaction of the deblocked isocyanate groups with the isocyanate-reactive groups in the binders and/or reactive diluents (B), with the formation of urethane, thiourethane and/or urea groups, especially urethane groups.
Instead, in the curing process of the invention, the catalysts (C) control the crosslinking reaction such that in the context of the thermal cure it proceeds predominantly or completely in the sense of the addition reaction of the isocyanate-reactive groups of the binders and/or reactive diluents (B) with the propargyl groups of the blocked polyisocyanates (A) with the formation of vinyl ethers, vinyl thioethers and/or enamines, especially vinyl ether groups.
The resultant coatings of the invention are further distinguished by the fact that, owing to the vinyl groups they contain, they can be postcrosslinked with actinic light. By actinic light is meant electromagnetic radiation such as near infrared, visible light or UV light, especially UV light, and corpuscular radiation such as electron beams.
Examples of suitable catalysts (C) are
catalytically active organometallic chelates such as zinc acetylacetonate;
alkali metal hydroxides such as NaOH or KOH;
alkali metal alkoxides such as sodium or potassium ethoxide, isopropoxide or tert-butoxide;
onium salts such as ammonium, phosphonium or sulfonium salts, preferably the fully alkylated and/or arylated ammonium, phosphonium or sulfonium salts, especially the N,N,N,N-tetramethyl-, tetraethyl-, -tetrapropyl- or -tetrabutylammonium salts or N,N,N-trimethyl-N-cetylammonium salts, triethylphenylphosphonium salts or tributylsulfonium salts with hydroxide ions and/or halide ions, especially chloride ions or bromide ions, as counterions;
quaternary ammonium salts prepared from epoxides or epoxy resins and tertiary amines, or
ternary sulfonium salts prepared from epoxides or epoxy resins and secondary sulfides.
Very particular preference is given to the use of N,N,N-trimethyl-N-cetylammonium bromide.
The catalysts (C) are preferably present in the coating materials of the invention in an amount of from 0.01 to 5, more preferably from 0.05 to 4.5, with particular preference from 0.1 to 4, with very particular preference from 0.5 to 4, and in particular from 0.7 to 3.5% by weight, based in each case on the solids of the coating material of the.invention.
Furthermore, the coating materials of the invention may comprise minor amounts of customary and known crosslinking agents, which means that the blocked polyisocyanates (A) continue to determine primarily the curing properties of the coating materials.
Examples of suitable additional crosslinking agents are amino resins, as described for example in Rxc3x6mpp Lexikon Lacke und Druckfarben, Georg Thieme Verlag, 1998, page 29, xe2x80x9cAmino resinsxe2x80x9d, in the text book xe2x80x9cLackadditivexe2x80x9d [Coatings additives] by Johan Bieleman, Wiley-VCH, Weinheim, N.Y., 1998, pages 242 ff., in the book xe2x80x9cPaints, coatings and solventsxe2x80x9d, second, completely revised edition, edited by D. Stoye and W. Freitag, Wiley-VCH, Weinheim, N.Y., 1998, pages 80 ff., in the patents U.S. Pat. No. 4,710,542 A1 or EP-B-0 245 700 A1, and in the article by B. Singh and coworkers, xe2x80x9cCarbamylmethylated melamines, novel crosslinkers for the coatings industryxe2x80x9d in Advanced Organic Coatings Science and Technology Series, 1991, Volume 13, pages 193 to 207; carboxyl-containing compounds or resins, as described for example in the patent DE 196 52 813 A1; compounds and resins containing epoxide groups, as described for example in the patents EP 0 299 420 A1, DE 22 14 650 B1, DE 27 49 576 B1, U.S. Pat. Nos. 4,091,048 A1 or 3,781,379 A1; blocked polyisocyanates, as described for example in the patents U.S. Pat. No. 4,444,954 A1, DE 196 17 086 A1, DE 196 31 269 A1, EP 0 004 571 A1 or EP 0 582 051 A1; tris(alkoxycarbonylamino)triazines, as described in the U.S. Pat. Nos. 4,939,213 A1, 5,084,541 A1, 5,288,865 A1 or EP 0 604 922 A1; and/or the higher-functional polyisocyanates described above.
The coating compositions of the invention may further comprise at least one additive.
Examples of suitable additives are organic and inorganic color and/or effect pigments, organic and inorganic fillers, reactive diluents curable with actinic radiation (cf. Rxc3x6mpp Lexikon Lacke und Druckfarben, Stuttgart, N.Y., 1998, page 491), low-boiling organic solvents and/or high-boiling organic solvents (xe2x80x9clong solventsxe2x80x9d), binders curable with actinic radiation, UV absorbers, light stabilizers, free-radical scavengers, thermally unstable free-radical initiators, photoinitiators, crosslinking catalysts, devolatilizers, slip additives, poly-merization merization inhibitors, defoamers, emulsifiers, wetting agents, adhesion promoters, leveling agents, film-forming auxiliaries, rheology control additives, and flame retardants. Further examples of suitable coating additives are described in the text book xe2x80x9cLackadditivexe2x80x9d by Johan Bieleman, Wiley-VCH, Weinheim, N.Y., 1998.
As already remarked above, the coating materials of the invention may be one-component systems or two-component or multicomponent systems. They are preferably one-component systems.
Furthermore, the coating materials of the invention may be essentially free of water and/or organic solvents and may be in powder form or liquid (100% systems). In the context of the present invention, xe2x80x9cessentially freexe2x80x9d means that the amount of water and/or organic solvents is less than 5.0, preferably less than 3.0, more preferably less than 2.0, with particular preference less than 1.0, and with very particular preference less than 0.5% by weight, and in particular below the gas-chromatographic detection limit. In this form they may be used, for example, as powder surfacers, powder basecoats, powder clearcoats or liquid clearcoats.
Alternatively, the coating material in question may be a water-based coating material, especially an electrodeposition coating material, an aqueous surfacer, an aqueous basecoat, an aqueous clearcoat, or an aqueous powder coating dispersion (unpigmented powder slurry clearcoat or pigmented powder slurry basecoat).
Not least, the coating material of the invention may also comprise a conventionalxe2x80x94in this context, i.e., organic-solventbornexe2x80x94coating material, such as a conventional surfacer, basecoat or clearcoat.
The preparation of the coating materials of the invention has no particular features but instead takes place in a customary and known manner by mixing of the above-described constituents in appropriate mixing equipment, such as stirred vessels, dissolvers, stirred mills, static mixers, toothed-wheel dispersers or extruders, by the techniques suitable for preparing the respective coating materials.
The coating materials of the invention may be applied by all customary methods of application, such as electrodeposition coating, spraying, knifecoating, brushing, flow coating, dipping, impregnating, trickling, or roller coating, for example. The substrate to be coated may be itself at rest, with the application device or unit being moved. Alternatively, the substrate to be coated, in particular a coil, may be moved, with the application unit being at rest relative to the substrate or being moved in an appropriate way.
The thermal curing of the applied coating materials of the invention likewise has no special features as to its method but instead takes place in a customary and known manner by heating with infrared or near-infrared radiation or with hot air blowers, with or without the assistance of exposure to actinic radiation, if the coating materials of the invention include appropriate constituents.
In this case, the particular advantage of the coating materials of the invention is manifested to a particular extent, namely that the thermal crosslinking takes place completely even at temperatures below 160, preferably 150, and in particular 140xc2x0 C., thereby permitting the coating of comparatively heat-sensitive substrates.
The basecoats and/or clearcoats of the invention are outstandingly suitable for producing multicoat color and/or effect coating systems of the invention by the wet-on-wet technique, where a basecoat film is applied, dried and overcoated with a clearcoat film, after which basecoat film and clearcoat film are cured together. As is known, this technique is employed with advantage in the OEM finishing and refinishing of motor vehicles.
The pigmented powder slurries of the invention are outstandingly suitable for producing combination effect coats. These are coatings which in a color and/or effect coating system fulfil at least two functions. Functions of this kind are, in particular, corrosion protection, adhesion promotion, the absorption of mechanical energy, and the provision of color and/or effect. In accordance with the invention, the combination effect coat serves above all to absorb mechanical energy and to provide color and/or effect at the same time; it therefore fulfils the functions of a surfacer coat or antistonechip primer and of a basecoat. Preferably, furthermore, the combination effect coat also possesses corrosion protection and/or adhesion promotion activity.
Furthermore, however, owing to their particularly advantageous properties, the coating materials of the invention are also appropriate for the coating of interior and exterior constructions, for the coating of furniture, windows or doors, and for industrial coating, including coil coating, container coating, and the impregnation or coating of electrical components. In the context of industrial coating, they are suitable for coating virtually all parts for domestic or industrial use, such as radiators, domestic appliances, small metal parts such as nuts and bolts, wheel caps, rims, packaging, or electrical components such as motor windings or transformer windings.
The adhesives and sealing compounds of the invention are outstandingly suitable for the production of adhesive films and seals of especially high, long-term bond strength and sealing capacity even under extreme and/or rapidly changing climatic conditions.
Accordingly, the primed or unprimed substrates commonly employed in the abovementioned technological fields, comprising metal, glass, plastic, textile, wood, paper, cardboard or mineral materials of construction, or composites of these materials, that are coated with at least one coat of the invention, bonded with at least one adhesive film of the invention, and/or sealed with at least one seal of the invention, combine a particularly advantageous profile of performance properties with a particularly long service life, which makes them particularly attractive from an economic standpoint.

Reactive mixtures of substances on the basis of propargyl-alcohol blocked polyisocyanates, method for preparing the same and the use thereof


The present invention discloses a fault diagnosis and life testing machine for a flexible precision thin-wall bearing (16), including a rack, and an axial loading device, a main driving device, a bearing mounting device, a clamping tooling, a data acquisition device, a hydraulic and a pneumatic auxiliary device which are provided on the rack. The main driving device is connected to a rear side of the axial loading device, and the clamping tooling is arranged at a front side of the axial loading device, for clamping the thin-wall bearing (16) onto the bearing mounting device. The data acquisition device is arranged in the axial loading device and at a side of the rack, the hydraulic and pneumatic auxiliary device is arranged at a side of the rack, and the axial loading device and the main driving device are connected by a pipeline. This testing machine can apply dynamic and static loads to the precision flexible thin-wall bearing (16), can realize measurement of a bearing vibration, a bearing temperature, a bearing rotation progress and a rotation speed, and has advantages such as clever structure, perfect test function and relatively high test accuracy, safe and reliable detection process, and highly feedback results.

Harmonic reducer makes a flexible wheel generate controllable elastic deformation by a wave generator, and uses a controllable elastic deformation of a flexible bearing to transmit motion and power. As a reducer with high reduction ratio, small mass, light weight and high transmission precision, the harmonic reducer is recognized as the "best" transmission gear for robots, and is widely applied to various fields of transmission systems, such as spacecraft, spaceship, robot, radar equipment and medical equipment.
At present, China is vigorously developing high-end intelligent equipment industry represented by robots. Since 2013, China has become the largest market for industrial robots in the world for three consecutive years. China is gradually entering the stage of development of industrialization for the industrial robots. In the process of industrialization for the industrial robots, however, there are many puzzles that hinder the development. Among them, the status quo that core components represented by precision reducers cannot be self-sufficient is particularly prominent.
Precision flexible thin-wall bearing is a core component of the harmonic reducer and plays a vital role in an overall performance of the harmonic reducer. Under working condition, the precision flexible thin-wall bearing is not only subjected to elastic deformation under extrude-bulge of an inner ring of the thin-wall bearing precisely matching with an elliptical axis, but also subjected to an alternating stress generated by its own operation, and in the case of unsatisfactory working conditions, the precision flexible thin-wall bearing is also subjected to different static or dynamic loads from the outside world. Therefore, in the research and development process of the flexible thin-wall bearing used for the harmonic reducer, stability, rotation precision and life of the precision flexible thin-wall bearing should be tested. Only after all the performances meet requirements can the industrial production be put into operation, thereby solving a bottleneck problem of the core component of the industrial robots in China, providing support for the industrialization and wide application of the industrial robots in China. However, there are very few reports on the flexible thin-wall bearing, a life testing machine thereof and a flexible thin wall fault diagnosis method at home and abroad.
As a key component of the harmonic reducer, the rotation precision and stability of the precision flexible thin-wall bearing under different working conditions plays a very important role in the overall performance of the harmonic reducer. A geometric cross-sectional shape of the precision flexible thin-wall bearing is circular, and becomes elliptical when loaded in the harmonic reducer. Thus, the development of the fault diagnosis and life testing machine for the precision flexible thin-wall bearing used for the harmonic reducer should simulate the life testing of the flexible thin-wall bearing under actual working conditions as much as possible.

Fault diagnosis and life testing machine for flexible precision thin-wall bearing


Methods to synthesize fuels and chemicals from natural gas liquids are described. Higher alcohols are synthesized starting from natural gas liquid compounds by converting an alkane from a NGL to an olefin, dimerizing said olefin, and, hydrating said olefin product to form a higher alcohol. Higher alcohols are synthesized starting from natural gas liquid compounds by converting an alkane from a NGL to an olefin, oxidizing the olefin to form a ketone or aldehyde and, hydrogenating the aldehyde or ketone product to form a higher alcohol. Thus, NGL component butane may be dehydrogenated to form butane, butylene is oxidized in the presence of a catalyst to form methylethyl ketone and methylethyl ketone hydrogenated to form butanol.

Petroleum is a vital source of fuels for transportation, industrial chemicals that produce polymers, plastics, pharmaceuticals, paints and other important chemicals. Recently, technologies have emerged that indicate vast new resources of hydrocarbons that are being recovered by hydraulic fracturing. Currently liquid-rich raw natural gas is being flared in large quantities at numerous locations by oil producers. This activity entails massive loss of income. Furthermore, the large-scale flaring of natural gas has raised environmental issues that could cause state and/or federal regulators to take action to close such operations down.
There is therefore an important need for a solution to address the problems mentioned above. The present invention addresses these issues and is a novel method to synthesize fuels and chemicals from lower hydrocarbons.


A system for eliminating the need to reposition a tracked/wheeled radial stacker during stacking operations is provided, the stacker having a linear conveyor having front and rear portions, the front and rear portions being displaceable between raised and lowered positions, a bogie having a pair of continuous tracks that are selectively elevated off the ground, a pair of wheels mounted to the bogie that are displaced upwardly and downwardly, the wheels defining axes that may be shifted to position the wheels in either a substantially radial or substantially longitudinal direction, and a hydraulic cylinder system mounted to the wheels for displacing the wheels upwardly to lower the tracks to the ground or downwardly to elevate the tracks off the ground. A pair of hydraulically driven, telescoping frame members may extend rearwardly from the bogie to a mounting system that mounts the frame members to the conveyor, the mounting system defining a longitudinally extending slot with a trolley slidably mounted to the slot, the telescoping frame members being mounted to the trolley at spaced mounting points so that by extending and retracting the frame members, the rear portion of the conveyor can be raised and lowered, thereby changing inclination of the conveyor, wherein the trolley moving longitudinally in the slot takes up longitudinal movement of the conveyor as the inclination of the conveyor is changed.

Portable radial stackers have been used for many years to stack bulk materials such as aggregate for road construction, grain and coal. Radial stackers, which swing around in a radius to stack material in an arc, permit substantially more material to be stacked than is possible using a conventional stationary stacker that permits only a single conical stack.
Radial stackers typically include a wheeled axle disposed between a hopper and the top of the stacker from which the material is discharged. The wheels permit the stacker to be swung in an arc, with the hopper including a pivot plate on which the stacker pivots.
In recent years, tracked drives have been used in quarries, agricultural and mining operations to enable equipment to be moved over harsh terrain for ideal positioning for stacking operations. While tracked vehicles have proven to be of great benefit for such purposes, the use of tracks instead of wheels makes it more difficult to shift a stacker radially to facilitate the stacking of material in an arc instead of a cone. Also, because tracked vehicles are not typically permitted to be driven on road surfaces, they are normally loaded onto flatbed trucks for transit from one work site to another. These two drawbacks with the use of tracks has to a certain extent limited the use of tracked vehicles.
McCloskey International has developed a line of stackers with both tracks and wheels in which the wheels can pivot by so the stacker can either be operated in a radial fashion at a job site or can be operated in a longitudinal disposition to permit the stacker to be hauled down a road. Such systems are disclosed in the following U. S. patents, all of which are incorporated by reference: U.S. Pat. Nos. 10,011,443; 10,414,598; 10,414,599; 10,450,153; 10,556,752; and 10,683,177. Another more primitive design in that it does not include pivotable wheels is disclosed in EP 2883819.
While these prior systems exhibit many advantages over the prior art, one feature that is common to most of them is that as the angle of inclination of the conveyor is changed, the rear end where the hopper is disposed is longitudinally shifting its position as the conveyor arcs upwardly and downwardly. In smaller units or units where the position of the feeder can be easily adjusted, this may not be much of a drawback. However, in large stackers with conveyors that might extend 150 feet or more, this shifting may be quite dramatic. Or, where the feeder to the hopper cannot be moved, the entire stacker may need to be moved rearwardly or forwardly, which may not be a straightforward operation when the stacker is supported on radially-extending wheels.
Slider/trolleys have sometimes been incorporated into wheeled stackers to reduce the tendency of the rear of the stacker to shift longitudinally with changes in the inclination of the conveyor. However, such systems have not generally been incorporated into modern stackers having both wheels and tracks and in any event are limited in the manner in which they can change the inclination of the conveyor while utilizing a slider/trolley.


The present invention relates to a mobile terminal and a control method therefor and, more specifically, provides a mobile terminal comprising a camera, a sensing unit, a display unit, and a control unit, wherein the control unit outputs, on the display unit, a preview image captured through the camera in a state in which camera content is executed, the preview image includes at least one object, a control icon scrollable within a preset region is outputted on the display unit, the length of the control icon is a first length, and when the camera is focused on a first object included in the outputted preview image, at least one condition among size, outputted location, and speed of the first object is detected, and the length of the control icon is changed on the basis of the detected condition.

Terminals may be generally classified as mobile/portable terminals or stationary terminals according to their mobility. Mobile terminals may also be classified as handheld terminals or vehicle mounted terminals according to whether or not a user can directly carry the terminal.
A mobile terminal is a device which may be configured to perform various functions. Examples of such functions include data and voice communications, capturing images and video via a camera, recording audio, playing music files and outputting music via a speaker system, and displaying images and video on a display. Some terminals include additional functionality which supports game playing, while other terminals are also configured as multimedia players. More recently, mobile terminals have been configured to receive broadcast and multicast signals which permit viewing of contents, such as videos and television programs.
As functions of the terminal are getting diversified, the terminal tends to be implemented as a multimedia player provided with complex functions such as photographing of photos or videos, playback of music or video files, game play, broadcast reception and the like for example.
Efforts are ongoing to support and increase the functionality of mobile terminals. Such efforts include software and hardware improvements, as well as changes and improvements in the structural components.
Furthermore, in recent years, taking pictures and moving pictures using the mobile terminal is not only universal, but also users want to use more specialized camera functions using the mobile terminal.
In this regard, a technique is needed that can control camera content of the mobile terminal using a control icon.

Mobile terminal and corresponding control method for changing the length of a control icon based on a size, position and/or a moving speed of a first object in a preview image


A system, configured to facilitate processing and detection of nucleic acids, the system comprising a process fluid container and a cartridge comprising: a top layer, a set of sample port-reagent port pairs, a shared fluid port, a vent region, a heating region, and a set of detection chambers; an intermediate substrate, coupled to the top layer comprising a waste chamber; an elastomeric layer, partially situated on the intermediate substrate; and a set of fluidic pathways, each formed by at least a portion of the top layer and a portion of the elastomeric layer, wherein each fluidic pathway is fluidically coupled to a sample port-reagent port pair, the shared fluid port, and a detection chamber, comprises a portion passing through the heating region, and is configured to be occluded upon deformation of the elastomeric layer, to transfer a waste fluid to the waste chamber, and to pass through the vent region.

Molecular diagnostics is a laboratory discipline that has developed rapidly during the last 25 years. It originated from basic biochemistry and molecular biology research procedures, but now has become an independent discipline focused on routine analysis of nucleic acids (NA), including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) for diagnostic use in healthcare and other fields requiring nucleic acid analysis. Molecular diagnostic analysis of biological samples can include the detection and/or monitoring of one or more nucleic acid materials present in the specimen. The particular analysis performed may be either qualitative and/or quantitative. Methods of analysis may involve isolation, purification, and amplification of nucleic acid materials, and polymerase chain reaction (PCR) is a common technique used to amplify nucleic acids. Often, a nucleic acid sample to be analyzed is obtained in insufficient quantity, quality, and/or purity, hindering a robust implementation of a diagnostic technique. Current sample processing methods and molecular diagnostic techniques are also labor/time intensive, low throughput, and expensive, and systems of analysis are insufficient. Furthermore, methods of isolation, processing, and amplification are often specific to certain nucleic acid types and not applicable across multiple acid types. Due to these and other deficiencies of current molecular diagnostic systems and methods, there is thus a need for improved devices for processing and amplifying nucleic acids. Thus, there is a need in the molecular diagnostics field to create an improved microfluidic cartridge to facilitate processing and detecting of nucleic acids. This invention provides such a microfluidic cartridge.

This patent is subject to a terminal disclaimer.

Microfluidic cartridge for processing and detecting nucleic acids


A mild surfactant composition suitable for use on periocular surface tissues includes an anionic surfactant, a nonionic surfactant and an amine oxide. The pH of the composition is substantially at neutrality.

The present invention relates generally to surfactant compositions. More particularly, it relates to a surfactant composition which is composed of a combination of surfactants that make it an effective cleansing agent, but with non-irritating properties such that it is especially effective for use on periocular and ocular surface tissues.
For some time a desirable surfactant product has been sought in which the advantageous foaming properties of an anionic surfactant can be maintained while avoiding the irritation to the skin that such surfactants normally cause. The characteristic of irritating sensitive human skin and membranes is particularly evident when the surfactant is to be utilized in the vicinity of the human eye. Such surfactants or shampoos have previously been utilized to help in the control of oily debris, cosmetics and encrusted material that may form on the scalp and face. Yet there is definite need for a surfactant composition for use in conditions requiring good eyelid and eyelash cleansing.
An example of one such condition is acute and chronic blepharitis. Blepharitis is an inflammation of the eyelids that arises in the glands found at the base of the eyelashes (glands of Zeis and Moll) and just behind the eyelashes (meibomian glands). These glands secrete an oily lipid material (meibom), which is essential for maintenance of the normal tear film on the ocular surface as well as the natural lubrication of the eyelids. When these glands become inflamed or clogged by thickened secretions, cosmetics, infection, or other causes not yet identified, the surrounding tissues become inflamed. The resulting inflammation of the eyelids and ocular surface is called blepharitis and can produce a variety of symptoms of ocular dysfunction. These symptoms may include but not be limited to any or all of the following: irritation, itching, burning, dryness, tearing, redness of the eyelids and conjunctiva, filmy vision, chalazion or hordeolum formation, and loss of eyelashes. Severe cases can even produce corneal opacification and decreased vision.
The mainstay of present therapy for blepharitis is the combined use of warm compresses and daily lid hygiene to clean the oily secretions, crusting and other forms of debris which accumulate on the eyelids and eyelashes, thereby exacerbating the inflammatory problem. Certain oral and topical medications are then added to this primary therapy as needed in each individual case. However, at present there is no cleansing surfactant product specifically designed for use by the patient to clean the eyelids and eyelashes. Therefore eye care professionals currently recommend the use of mineral oil or mild hair shampoos. These shampoos must be diluted by the patient with water to reduce the irritancy of the cleansing component in the shampoo. Despite using dilute hair shampoos, many patients develop a secondary ocular irritation from the cleansing agents, themselves. These shampoos have the additional disadvantage of containing dyes and/or perfumes which do not enhance the cleansing potential but may act as ocular irritants.
Consequently, a desirable surfactant product combines the advantages of foaming and cleansing properties of anionic surfactants with other surfactants and pharmaceutical agents such that the resulting composition is nonirritating to skin, periocular tissues and ocular surface tissue. It is, therefore, a primary object of the present invention to provide such a surfactant composition which maintains the foaming and cleansing characteristics of an anionic surfactant, while at the same time significantly ameliorating the irritating characteristics of such anionics. This surfactant composition is suitable for use in those conditions requiring daily lid hygiene such as blepharitis. This surfactant composition has further utility as a nonirritating cleanser of cosmetics. It is a further object to provide such a surfactant composition that can be used to effectively clean skin, mucous membrane and ocular surface tissue prior to invasive and noninvasive treatments while avoiding the introduction of concomitant irritation. Finally, it is a further object to provide such a surfactant composition which can be used to cleanse nonbiological surfaces, which are then placed on or near the eye.
These and other objects of the present invention will become more apparent to one of skill in this art from the summary and detailed description of the invention provided hereinafter.


Image reproduction devices and a management device each hold moving image data. The management device goes into a reproduction standby state in which the moving image data can be reproduced and instructs the image reproduction devices to go into the reproduction standby state, by cascade communication. The management device starts reproduction of the moving image data and instructs the image reproduction devices to start reproduction of the moving image data, by broadcast communication. The management device periodically broadcasts synchronization information. The image reproduction devices use the synchronization information to specify a frame number of a frame displayed on the management device. Frames corresponding to the specified frame number are displayed on the display parts.

In retail stores such as supermarkets, convenience stores, and the like, generally, display racks are placed in the stores and commercial goods are displayed on the display racks. Further, for the purpose of sales promotion of the goods displayed on the display racks, a technique called "electronic POP (Point Of Purchase)" has been conventionally used.
[Patent Document 1] Japanese Patent Application Laid Open Gazette No. 2001-100683
[Patent Document 2] Japanese Patent Application Laid Open Gazette No. 2007-289636
Patent Document 1 discloses an electronic POP apparatus using a thin display panel such as a liquid crystal display panel or the like. In the electronic POP apparatus disclosed in Patent Document 1, an advertising video image is displayed on the liquid crystal display panel or the like by reproducing moving image data or the like stored in a storage medium. For using the electronic POP apparatus of Patent Document 1, however, another space for setting the electronic POP apparatus is needed separately from the space for displaying the commercial goods.
Patent Document 2 discloses a display rack on which a video image for electronic POP can be displayed. A projector is set inside the display rack and a transmission screen is attached to a front surface of a shelf board on which the commercial goods are placed. An advertising video image is displayed entirely on the display rack by displaying the advertising video image projected from the projector on the screen. The display rack of Patent Document 2 allows display of the advertising video image thereon, not requiring any space for setting an electronic POP apparatus, and it is thereby possible to efficiently use the salesrooms in the retail stores.
Electronic POP systems in each of which one video image is displayed on a plurality of display devices have been also used. In order to synchronize video images displayed on the display devices, such an electronic POP system needs a content reproduction device for generating frames to be displayed on the display devices, respectively, from moving image data and distributing the frames to the display devices. Therefore, the electronic POP system using a plurality of display devices disadvantageously has a complicated configuration, and this arises a problem that it is difficult to lower the price thereof.

Display system and image reproduction device


A liquid crystal display (LCD) device, comprising, a display panel having pixels arranged in a matrix configuration, a main supporter supporting a rear edge and a side of the display panel, a top case coupled to a side of the main supporter and pressing an upper edge of the display panel, and a lower cover supporting a backlight assembly coupled to the side of the main supporter and having at least one guide supporting the side of the main supporter.

1. Field of the Invention
The present invention relates to a liquid crystal display (LCD) device, and more particularly, to an LCD device having a coupling structure.
2. Description of the Related Art
In general, an LCD device displays a desired image by individually providing a data signal to pixels arranged in a matrix configuration according to image information, thereby controlling light transmittance of the pixels. Accordingly, the LCD device includes a display panel where pixels are arranged in the matrix configuration and a driving unit for driving the pixels.
The display panel includes a thin film transistor array substrate and a color filter substrate bonded to each other by a uniform cell-gap, and a liquid crystal layer formed at an isolation interval between the color filter substrate and the thin film transistor array substrate. The display panel is provided with a common electrode and a pixel electrode to apply an electric field to the liquid crystal layer. Accordingly, if a voltage of a data signal applied to the pixel electrode is controlled in a state that a voltage has been applied to the common electrode, liquid crystals of the liquid crystal layer are rotated according to the electric field generated between the common electrode and the pixel electrode by dielectric anisotropy, thereby transmitting or cutting off light pixel by pixel to display text or an image.
In addition, the LCD device cannot emit light by itself, but can display an image by controlling transmittance of light. For this reason, the LCD device requires a backlight assembly for emitting light to the display panel. The backlight assembly is divided into perpendicular-type and edge type devices. In the perpendicular-type device, a lamp is disposed at a rear surface of the display panel and light is directly transmitted to a front surface of the display panel. In the edge-type device, a lamp is disposed at at least one side of the display panel, and light is reflected, diffused, and collected through a light guide plate, a reflection plate, and sheets to be transmitted to the front surface of the display panel.
As mentioned above, the LCD device includes the display panel and the backlight assembly. In order to support and couple the display panel and the backlight assembly, various elements have been utilized, which will now be described in detail with reference to accompanying drawings.
FIG. 1 is a schematic cross-sectional view of an exemplary LCD device according to the related art. Referring to FIG. 1, the related art LCD device includes a display panel 10 where pixels are arranged in a matrix configuration, a main supporter 20 for supporting a rear edge and a side of the display panel 10, a top case 30 coupled to a side of the main supporter 20 by pressing an upper edge of the display panel 10, and a lower cover 50 coupled to a side of the main supporter 20 by a screw 51 and supporting a backlight assembly 40.
The backlight assembly 40 includes a reflection plate 41 provided at an upper surface of the lower cover 50, a light source part 43 having a plurality lamps 42 disposed on the reflection plate 41 to make light incident onto an entire rear surface of the display panel 10, a diffusion plate 44 corresponding to the entire rear surface of the display panel 10 to cover the light source part 43 and having a rear edge supported by the lower cover 50, and an optical sheet 45 disposed at an upper surface of the diffusion plate 44. The display panel 10 and the optical sheet 45 have a predetermined gap therebetween by a protrusion of the main supporter 20.
In a case where an edge area on which no image is displayed (i.e., a bezel) is formed in a minimum size, the LCD device is fabricated with the upper edge of the display panel 10, covered with the top case 30 and the main supporter 20 that are formed in a minimum size in effort to make a light and small LCD device in the same sized model. However, the related art LCD device has following problems.
When the LCD device is fabricated to have the upper edge of the display panel, covered with the top case 30 and the main supporter 20 that are made in the minimum size, the square frame-shaped main supporter 20 for supporting a lower edge of the display panel 10 and its side is vulnerable to surface tension parallel to the ground. Thus, the display panel 10 and the optical sheet 45 of the backlight assembly 40 supported by the main supporter 20 become detached from the main supporter 20 and are damaged by the protrusion of the main supporter 20.
Therefore, the related art LCD device utilizes the screw 51 to couple the side of the main supporter 20 and the lower cover 50, or a double sided tape to adhere them to each other, whereby the square frame shaped main supporter bar 20 is not affected by the surface tension parallel to the ground. However, it becomes complex and difficult to assemble the LCD device because of an additional operation for coupling the side of the main supporter 20 and the lower cover 50 by the screw 51, or adhering them by the double sided tape to ensure that the square frame shaped main supporter 20 is not affected by the surface tension parallel to the ground. Also, this additional operation causes deterioration in productivity of the LCD device. Moreover, fabrication costs are increased due to usage of subsidiary materials such as the screw 51, the double sided tape, or the like.


The disclosure provides a bidet nozzle assembly, which includes a nozzle housing; a nozzle, the nozzle having a distal end and a proximal end, the nozzle including a channel through to the distal end and to the proximal end, the channel having a first channel opening at the distal end and a second channel opening at the proximal end; a nozzle insert, the nozzle insert located at the first channel opening of the distal end of the nozzle, the nozzle insert having at least one nozzle hole; and a nozzle cap.

A bidet apparatus for washing and cleaning body parts (e.g., genital and/or anal) using water spray was initially developed in the form of a bidet that provided a single spray of water and was permanently built into a toilet bowl. These bidets were expensive to build and a new generation of bidets were developed that reversibly attached to the seat or bowl of a toilet, and which included a plurality of nozzles for multiple water sprays for washing body parts as well as the bidet itself.
Existing bidets fail to address all concerns relating to the design and function in the general field of bidets. For example, pollution of the outer surface of the nozzles is a common problem and causes aesthetic and hygienic issues. This is particularly important in bidets used, for example, by infirm or sick people who have to be especially cautious about maintaining hygiene and preventing infections.
Mobile cleaning and bidet systems have been developed, which operate according to various techniques in order to overcome these problems, for example, bidets disclosed in U.S. Patent Application Nos. 2014/0101838 and 2015/0305577, the disclosures of each of which are hereby incorporated by reference in their entireties. Such bidets include a mechanical system that retracts the nozzles within a cylindrical covering to prevent pollution during use. When activated by a mechanical signal, the nozzles move forward within the body of the cylinder. The mechanical signal acts by the force of the washing water that pushes the nozzle out of its outer covering and thus, washing water is sprayed on the person sitting on the toilet. When the washing water supply is stopped, the nozzle is retracted. Therefore, when a user uses the lavatory, the user's excrement is not splattered directly on the nozzles since the nozzles are accommodated within the outer covering.
The nozzles of a bidet may still become dirty when the user is being washed by the washing water sprayed from the nozzle. Some bidets overcome this by allowing the user to pull out the nozzle manually and clean the nozzle after use. This is both cumbersome and unpleasant. Some other bidets have a cleaning nozzle to wash the washing nozzles after usage. This is also undesirable because of nozzle positions and dripping of the nozzle washing water. Therefore, there remains a need in the art for a bidet apparatus that includes interchangeable and replaceable bidet nozzles.


Overlaying images in automated insurance policy form generation includes electronically converting a first form in a first format to a second format to and in response to receiving a Web page request, electronically communicating the second form to be displayed within the Web browser instead of electronically communicating the first form in the first format to be displayed within the Web browser. In the case where the first format is Adobe® portable document format (PDF) and the second format is Joint Picture Expert Group (JPEG) format, this enables the user of the browser to overlay images on the forms within the Web page interface of the browser, while it appears to the user they are overlaying images on the original PDF versions of the forms. The final integrated PDF form is then generated from the data indicating the location of the overlay image on the underlying JPEG form. This process may also apply to insurance policy forms wherein the overlay image is a state specific stamp to be placed on the underlying form.

1. Technical Field
This disclosure generally relates to data services, and to automated form generation and completion.
2. Description of the Related Art
Insurance agents (e.g., general agents) often compile a repository of insurance endorsement forms, organize that collection and maintain the format and version of the forms over time separately for various different insurance carriers. These processes consume a high number of hours of working time and, due to the fact that many of the forms have similar appearances and file names, such processes can be prone to user error. The insurance carrier delegates which forms belong on a policy and applies rules for determining when those forms are mandatory or optional.
Some existing insurance policy issuance utilities require that the general agent maintain insurance policy document templates (either in electronic or paper form) to which the user (e.g., general agent) must attach the proper policy jackets and include the proper state specific insurance policy stamps. Typically, a policy is provided in the form of a policy jacket including one or more paper documents. The time spent on this insurance policy form maintenance and generation in the process of issuing insurance policies can add up to hundreds of hours wasted each year, reducing the number of policies an individual insurance agent can process.


A method for establishing a geostress field distribution of slopes in canyon areas includes: obtaining a persistence ratio of a fracture surface based on a structural plane trace length and a rock bridge length of the fracture surface, and then obtaining a fracture stage of a crack according to progressive failure characteristics of rock mass, combining a character of the fracture surface to obtain magnitude and direction of a maximum principal stress, and establishing the geostress field distribution. The method is simple to operate, does not need to carry out geostress testing, does not need a large amount of manpower and material resources, does not need redundant fund investment, and can simply and effectively obtain geostress field data. Moreover, combining with the geostress field inversion technology, a large-scale geostress field distribution condition can be obtained, which can provide a basis for engineering site selection and engineering rock mass stability determination.

Geostress is one of important occurrence environments for geological bodies. Phenomena such as landslides, tunnel slope deformation and damage, and fault activities are mechanical behaviors of geological bodies with certain deformation strength characteristics under the action of geostress. In the engineering geological fieldwork, it is very important to determine a magnitude of the geostress in the geological body, and the stability of rock-soil mass under natural conditions or after engineering disturbance can be estimated according to the geostress.
At present, the geostress is mainly obtained by geostress testing methods such as a stress relief method, a stress recovery method and a hydraulic fracturing method, but these methods require specialized equipment and are time-consuming and laborious. Therefore, there is a need of a method that can quickly estimate the geostress in engineering geological investigations.

Method for establishing geostress field distribution of slopes in a canyon area

INSTITUTE OF GEOLOGY AND GEOPHYSICS, CHINESE ACADEMY OF SCIENCES


A buttonhole sewing machine for producing buttonhole seams with seam end sections of various shapes in a work piece comprises an input equipment for feeding buttonhole parameters; and a computer for calculating, from the buttonhole parameters, sewing data that determine the respective buttonhole geometry. It further comprises a memory for storing the computed sewing data and a key to be shifted into two key statuses, by means of which to trigger conversion of a buttonhole seam from a position to the left to a position to the right or vice versa, and storage thereof.

1. Field of the Invention
The invention relates to a buttonhole sewing machine for producing in a work piece buttonhole seams with seam end sections of various shapes.
2. Background Art
In clothes such as coats, jackets, shirts etc. which are closed at the front by buttons and buttonholes, the menswear buttonholes are disposed in mirror-image arrangement as compared to ladies"" wear buttonholes. In these buttonholes, the thread supplied by the needle to the sewing machine extends approximately in the form of a line on the externally visible side where the button comes to rest after buttoning.
In some clothes, for example in knitwear, the buttonholes run lengthwise in parallel to the edge of the work piece. The buttonholes are disposed one after the other in the longitudinal direction. They have seam end sections of varying shape i.e., stay stitching of various shapes such as round stays, wedge-shaped stays, zigzag stays or eye-type stays.
For buttonhole seams of this type to be sewn, U.S. Pat. No. 3,216,381 describes a buttonhole sewing machine of the generic type, comprising a base plate, a top arm and a standard that unites the base plate and the arm, and a needle bar which is lodged in the arm and provided with a needle and which reciprocates up and down, drivable substantially in a z direction by means of a main driving motor. Furthermore, this sewing machine comprises a work piece clamp which is displaceable in the y direction i.e., in the longitudinal direction of the machine, clamping the work piece. The standard stands back from a y-z plane that passes through the needle. This design enables a work piece to be placed with its buttonhole edge in parallel to the longitudinal direction of the arm i.e., in the longitudinal direction of the sewing machine, without being obstructed by the standard. Producing the buttonhole seams, mentioned at the outset, of mirror-image design depending on whether they are intended for ladies"" wear or menswear will require a specific sewing machine in each case.
It is an object of the invention to embody a buttonhole sewing machine of the generic type in such a way that it can easily be reconverted, enabling mirror-inverted production of buttonholes of varying end sections.
According to the invention, this object is attained in a buttonhole sewing machine for producing buttonhole seams with seam end sections of various shapes in a work piece, comprising a base plate, a top arm and a standard that unites the base plate and the arm; a needle bar, which is housed in the arm and provided with a needle and which reciprocates up and down, drivable by a main driving motor substantially in a z direction; a table which is displaceable by a y driving motor in a y direction; a work piece clamp, which is disposed on the table, clamping the work piece on the table; a driving motor for producing a motion, in an x direction, of the needle relative to the work piece; a control system for controlling the driving motors, which an input equipment for buttonhole-parameter input is allocated to, which comprises a computer for computation, from the buttonhole parameters, of sewing data that determine a respective buttonhole geometry, which comprises a memory for storage of the computed sewing data, and which comprises a key to be shifted into two key statuses and by which to trigger conversion of the sewing data of a buttonhole seam from a position to the left into a position to the right or vice versa, and storage thereof. The buttonhole sewing machine according to the invention is embodied such that mirror-imaged or mirror-inverted buttonholes can be produced without any complicated program-input requirements. Placing the work piece in one direction or the other, as for example lapels to the left or to the right, enables the sewing data i.e., stitching coordinates, to be converted rather flexibly at the touch of a button as it were, The control system causes the driving motors and control units to be correspondingly triggered. Based on the measures according to the invention, the parameters that have been stored for a buttonhole can be used for a mirror-inverted buttonhole. Online calculation of the stitching coordinates takes place for the desired buttonhole. An available memory can be used for varying programs. Program conversion takes place rapidly and easily. Machine standstill is reduced. Simplicity of operation facilitates work. High operational reliability is accomplished because errors due to maloperation and faulty programming are strongly reduced.
Details of the invention will become apparent from the ensuing description of an exemplary embodiment, taken in conjunction with the drawing.


A medical image display apparatus which displays, in a display screen, a display image having undergone gray level transform of changing number of gray levels of a medical image, obtains a representative value of pixel values concerning a region of a block, in the medical image, which corresponds to each partial region in a region designated in the display image. The medical image display apparatus sets a specific region in the display screen so as to include the designated region, and superimposes/displays and arranges obtained representative values on the specific region in correspondence with the arrangement of the partial regions.

With recent advances in the digitization of medical data, various types of medical images are archived as digital images, and doctors have increasing chances of performing image diagnosis upon displaying digital images on displays. In general, medical images are stored in formats complying with DICOM (Digital Imaging and Communications in Medicine) international standards. Medical images include CT (Computed Tomography) images and MRI (Magnetic Resonance Imaging) images. Each type of image includes a large amount of three-dimensional image data constituted by many tomographic images. A medical image display apparatus is used to efficiently and meticulously observe such a large amount of image data.
A conventional medical image display apparatus has, as display functions for tomographic images, a function of moving a tomographic position, a function of enlarging/reducing an overall image, a function of translating a display position, a gray level transform function, and the like. In this case, the gray level transform function is a function of transforming each pixel value of a gray scale according to a predetermined rule. In general, a CT image is expressed by a 12-bit gray level (4,096 gray levels) HU (Hounsfield Unit) value per pixel, which is stored as a pixel value. When a doctor observes a CT image, a medical image display apparatus displays the CT image upon transforming the HU values into the number of gray levels suitable for display. In this transform, 12-bit gray level pixel values are transformed into 8-bit gray levels by using, for example, two gray level transform parameters, that is, WC (Window Center) and WW (Window Width), defined by DICOM standards. That is, the image (display image) having simultaneously undergone a change in the number of gray levels and a change in gray level distribution is displayed on a display. This makes it easy to see the difference in HU value (gray level difference) between a specific organ and a tissue. For an image other than a CT image (for example, an MRI image, PET image, or ultrasound image), gray level transform similar to that described above is performed to make it easy to see the differences between pixel values (gray level differences).
Although the above gray level transform function makes it easy to see image gray level differences, this rather makes it difficult to see original pixel values (HU values of a CT image) (before changes in the number of gray levels and gray level distribution). For this reason, some computer software has a function of displaying the original pixel value of each pixel in numerical string. For example, as shown in FIG. 6, when the user designates a target region by drawing a rectangle (graphic 52), the software obtains an image in the target region, enlarges and displays the image in another window 62 at a high magnification, and displays the original pixel value (HU value) of each pixel on the enlarged image.
Computer software used in general has an enlarged display function called loupe function for a frame in a rectangular region, as shown in FIG. 7. With the loupe function, when the user moves the cursor, the software generates a frame by enlarging a frame in a rectangular region with a predetermined size centered on the cursor position at a predetermined magnification, and displays the frame (graphic 63). In this case, the software displays the enlarged frame such that its center coincides with the cursor position (http://www.mathworks.co.jp/jp/help/images/ref/impixelregion.html).
When using a medical image display apparatus like that described above, there are demands to see a display image before enlargement, that is, an overall image, and simultaneously see an enlarged image in a target region and each pixel value in the target region. However, in the above pixel value display, since a display image and each pixel value are respectively displayed in windows at different positions, it is difficult for the user to simultaneously see them. On the other hand, when using the loupe function, although an enlarged frame is displayed at the cursor position, the frame before enlargement is hidden in the region where the enlarged frame is displayed. Even if, therefore, the pixel value display function is combined with the loupe function, the above problem cannot be solved.

Medical image display apparatus and control method therefor


The present invention is intended to suppress a short circuit between a heat generation element and a case in an electrically heated catalyst. An electrically heated catalyst (1) according to the present invention is provided with a heat generation element (3), a case (4), an insulating support member (5) arranged between said heat generation element (3) and said case (4), an inner pipe (6) inserted into said insulating support member (5) with its ends protruding into an exhaust gas from end faces of said insulating support member (5), and a catalyst (10) having an oxidation function that covers at least outer peripheral surfaces of protrusion portions (6a, 6b) of said inner pipe (6) protruding into the exhaust gas from the end faces of said insulating support member (5), except for predetermined ranges which are in contact with the end faces of said insulating support member (5).

In the past, as an exhaust gas purification catalyst arranged in an exhaust passage of an internal combustion engine, there has been developed an electrically heated catalyst (Electric Heating Catalyst: hereinafter referred to as an EHC) in which a catalyst is heated by means of a heat generation element which generates heat by electrical energization thereof.
In the EHC, an insulating support member which serves to support the heat generation element and to insulate electricity is arranged between the heat generation element which generates heat by electrical energization thereof, and a case in which the heat generation element is received. For example, in Patent Document 1, there is disclosed a technique in which in an EHC, a mat of an insulating material is arranged between a carrier which is electrically energized to generate heat and a case in which the carrier is received.


A process chamber 27 is provided with several successive cathode arrangements 7, 8 which have targets to be sputtered, wherein diaphragms 39, 40 are held between the respective targets 3, 4 and the path of the workpieces 1, 2. In addition to their center openings 66, 67 for the passage of the flow of coating material, further window-like apertures 68, 69 in the area of the material flow, respectively, which are disposed offset to one another and transversely to the conveying direction F of the substrates and thus produce test strips 70, 71 on the workpieces or special test substrates which are passed by the cathode arrangements 7, 8. The test strips each correspond to one single layer of a layer package 72, produced on the substrate, whereby thickness of each layer may be measured by acquiring data on the transmission, reflection, or resistance properties, or by mechanically measuring each layer.

The invention relates to an arrangement for measuring the thickness of thin layers which can be applied on workpieces or substrates during the coating of the latter while being conveyed through the process chamber. The thickness measuring is carried out by detecting transmission, reflection or resistance properties or by mechanically measuring the thin layer.
A test glass support for the optic measurement of layer properties is known (German patent No. 29 32 483) having several indentations for test glasses which are equidistantly arranged in a circle on a plate. A drive shaft serves to move the glasses, one at a time, in a transfer movement into the flow of coating material and into the beam of a measuring light; each of the test glasses is associated with a certain coating material so as to always provide the same coating material to be intermittently deposited on the same test glass. This test glass support is used for vacuum coating systems having a carousel which can rotate around a central axis and includes at least one substrate holder which in turn can be exposed to different coating materials in different positions. In order to accomplish the object of rotating or transferring the test glasses during a period of rotation or transferring of the substrate holder into a new coating position, the invention suggests providing the drive shaft of the plate for the test glasses with a first driving wheel which is coupled with a second driving wheel which in turn is concentric with respect to the center axis; the transmission ratio is selected such that whenever the substrate holder is moved into a different position, a different test glass is transferred into the flow of coating material and into the measuring light beam. The test glass support is necessarily coupled with the carousel of the substrate holder such that a wrong correlation is avoided.

Arrangement for measuring the thickness of thin layers


A left and right wheels drive system includes: first and second drive sources left and right drive wheels; and a gear mechanism interposed between the drive sources and the drive wheels, the gear mechanism including: a pinion set including a plurality of pinion gears installed on one shaft; and an element group linked with the pinion set and includes first, second, third, and fourth elements When the first element is held stationary, the second, third and fourth elements rotate in the same direction. When the first element is held stationary, the second element rotates at a higher speed than the third and fourth elements. One of the first and second drive sources is connected to the first element, and the other is connected to the second element. One of the left and right drive wheels is connected to the third element, and the other is connected to the fourth element.

1. Field of the Invention
The present invention relates to a left and right wheels drive system which can transmit drive torque from two drive sources to left and right drive wheels while a drive torque difference is introduced therebetween, and more particularly to a left and right wheels drive system which is suitable for use in an electric vehicle which employs an electric motor as a drive source.
2. Description of the Related Art
In electric vehicles (also, referred to simply as vehicles), there is a related-art technique in which electric motors (motors) are provided for left and right drive wheels, respectively, and a drive torque difference is introduced between the left and right drive wheels as required by controlling the electric motors independently, whereby the turning moment of the vehicle is controlled (for example, refer to JP-A-8-19110 and JP-A-2005-138824).
However, in a running scene in which the vehicle requires a large total drive torque (a total of the drive torque of the left and right drive wheels) as when the vehicle is accelerated, the drive torque of each of the left and right drive wheels has to be increased, and therefore, it is difficult to apply a large drive torque difference between the left and right drive wheels. Namely, in order to apply the large drive torque difference between the left and right drive wheels, the drive torque of either of the motors has to be decreased. However, when this occurs, the total drive torque of the vehicle is decreased accordingly, and the running performance of the vehicle in acceleration, for example, becomes insufficient.
To improve this problem, as is described in JP-A-2006-117011, a related-art technique is considered in which the turning moment of a vehicle is controlled without decreasing the drive torque of both of left and right drive wheels by providing a steering unit for turning the drive wheels by making use of a torque reaction force of motors. However, this related-art technique calls for complexity and an increase in weight of the system concerned.
On the other hand, JP-A-2008-215519 discloses a related-art technique in which a torque shift can be made between two motors by interposing two differentials each employing a planetary gear mechanism and two reduction gear trains each made up of a combination of gears between output shafts of the two motors. As in this related-art technique, in the event that the torque shift can be made between two motors, a large drive torque difference can be introduced between left and right drive wheels while suppressing the reduction in total drive torque.
As has been described above, according to the related-art technique disclosed in JP-A-8-19110, the large drive torque difference can be introduced between the left and right drive wheels while suppressing the reduction in total drive torque by making use of the torque shift between the two motors. However, it has been desired that a system configuration is developed which can produce a desired drive torque difference between left and right drive wheels while suppressing a reduction in total drive torque with a simpler configuration.

Mitsubishi Jidosha Kogyo Kabushiki Kaisha


The present disclosure relates to compositions for treating CD96 mediated diseases, and related methods.

CD96/TACTILE ("T cell activation increased late expression") is a cell surface receptor in the immunoglobulin superfamily, which is expressed mainly on T cells, natural killer (NK) cells, and natural killer T (NKT) cells. CD96 belongs to a family of receptors, which includes CD226 and TIGIT ("T cell immunoreceptor with Ig and ITIM domains") that are known to interact with nectin and nectin-like ligands. CD155/NECLS ("nectin-like protein-5") is the primary ligand for all three receptors (CD96, TIGIT and CD226). TIGIT binds to CD155 with higher affinity (3.15 nM) than CD226 (119 nM), and CD96 binding is intermediate (37.6 nM) (Martinet L. & Smyth M. J. Nat Rev Immunol. 2015 Apr.; 15(4): 243-54). Besides CD155, both TIGIT and CD226 also bind another ligand CD112 with much reduced affinity. Recently a new receptor CD112R was discovered that also binds to CD112 (Zhu Y., et al. J Exp Med. 2016 Feb 8; 213(2): 167-76).
Among the receptors in this axis, CD226 (DNAM-1) is one of the major activating receptors for NK cells. CD226 has been reported to potentiate NK cell cytotoxicity against cancer cells, and is critical for tumor immunosurveillance (Lakshmikanth T., et al. J Clin Invest. 2009; 119(5): 1251-63; Chan C. J., et al. J Immunol. 2010; 184(2): 902-11; Gilfillan S., et al. J Exp Med. 2008; 205(13): 2965-73; Iguchi-Manaka A., et al. J Exp Med. 2008; 205(13): 2959-64). Conversely, both CD96 (Chan C. J., et al. Nat Immunol. 2014; 15(5): 431-8) and TIGIT (Lozano E., et al. J Immunol. 2012; 188(8): 3869-75) are known to dampen immune responses through inhibition of NK and/or T cell function. TIGIT expression has been associated with T cell exhaustion (Lozano E., et al. 2012; Kurtulus S., et al. J Clin Invest. 2015; 125(11): 4053-62) and NK cell exhaustion (Zhang Q., et al. Nat Immunol. 2018; 19(7): 723-32), and several anti-TIGIT antibodies are in clinical development.
Overall, there is considerably more literature and mechanistic understanding on CD226 and TIGIT relative to CD96. CD226 does not have a classic ITAM motif as in other immune activating receptors. Upon ligand binding and receptor dimerization, it conducts a positive signaling through a series of phosphorylation events including PKC and Vav1 proteins. The cytoplasmic tail of TIGIT contains an ITT motif and a classic inhibitory ITIM motif. Upon CD155 binding, tyrosine phosphorylation of the ITT motif occurs, and immune inhibitory signaling is transduced downstream involving SHIP1. In contrast, no signaling for CD96 has yet been elucidated. It is known that there is a potentially inhibitory ITIM motif in the cytoplasmic tail of CD96, as well as a potentially activating YXXM motif that is present in multiple immune activating receptors (e.g. ICOS and CD28) (Georgiev H., et al. Front Immunol. 2018; 9: 1072).
Although CD96 was discovered over 25 years ago (Wang P. L., et al. J Immunol. 1992; 148(8): 2600-8), little was known about the function of CD96 other than the fact that it is a member of the immunoglobulin family that shares the ligand CD155 with CD226 and TIGIT (Fuchs A., et al. J Immunol. 2004; 172(7): 3994-8). Subsequent publications linking CD96 to cancer centered mostly on CD96 as a leukemia stem cell (LSC) marker. The first paper indicating CD96 as a potential immuno oncology target was published by the lab of Professor Mark Smyth in 2014; CD96 was shown to compete with CD226 for CD155 binding in NK cells and CD96 negatively regulated production of pro-inflammatory cytokines including IFNγ (gamma) in mice after activation by LPS (Chan C. J., et al. 2014). CD96 knockout mice as well as anti-CD96 antibody-treated mice were less susceptible to MCA-induced sarcoma formation (Id.). In the same study, CD226 or CD155 blockade resulted in a worse outcome, and this is postulated to be due to the loss of the CD155:CD226 activatory pathway (Id.).
Subsequently, further in vivo studies supporting the inhibition of CD96 for cancer treatment have been published (See, e.g. Blake S. J., et al. Cancer Discov. 2016; 6(4): 446-59; Brooks J., et al. 2018; 78(2): 475-88; Harjunpää H., et al. Oncoimmunology. 2018; 7(7): e1445949). Accordingly, a need exists for improved antigen binding proteins and fragments thereof that target CD96 for use in the treatment of disease. Such compositions and related methods are provided in the present disclosure.

GlaxoSmithKline Intellectual Property Development Limited