A protective covering for a horse's hoof is provided which comprises a horseshoe having convex and concave edges and a polymeric fiber fabric embedded in a polymeric resin bonded to the horseshoe. The fabric extends beyond the convex edge of the horseshoe. When the shoe is fitted to the horse's hoof, the fabric extends up over the outside of the hoof. The protective covering is secured to the hoof using an acrylic structural adhesive both between the hoof and the shoe and between the polymeric fiber fabric and the outside of the hoof. The polymeric fiber fabric is preferably a polyolefin, and particularly preferred is woven polyethylene. The polymeric resin is preferably polyurethane.

1. Field of the Invention
This invention relates to protective coverings for horses' hoofs, including a method of attaching a horseshoe to a horse's hoof.
2. Description of Related Art
Traditionally, horseshoes have been secured to horses' hoofs by means of nails. The nails are passed through holes in the horseshoe and nailed into the hoof wall of the animal. This method secures the horseshoe quite well and is very useful for horses who tread on soft ground. Such horses need be shod only once every four to eight weeks, this due to continuous hoof growth regardless of shoe wear.
As with many other things, specialized horseshoes have been developed for special purposes. Titanium and aluminum, as well as other alloy-based metal horseshoes, have been developed for lightweight use in the field of horse racing. While such shoes are strong, they are intentionally designed to be as small and lightweight as possible. Frequently, such shoes do not have high abrasion resistance. This, combined with daily workout of horses on abrasive track surfaces, tend to wear out shoes very quickly. Thus, thoroughbreds and other racehorses tend to require frequent shoeing.
For this type of use, the attachment of horseshoes to horses' hoofs with nails can become a problem. Frequent removal and reattachment of shoes makes numerous nail holes in the horse's hoofs. This is a problem for two reasons. First, with numerous nail holes already in the hoofs, it can be difficult to find intact hoof wall into which to nail a new shoe. Second, the abundance of nail holes weakens the hoof wall which can lead to failure of the wall and damage to the horse's hoof and foot.
Noninvasive methods of attachment of hoof coverings have previously been attempted, most often without success. Generally, such methods involve a shoe covering mainly of polymeric material which is glued to a horse's hoof. Often, the glue lacks the strength and resilience necessary to withstand forces transferred through it by a horse. Because of the way in which horses gallop, the entire weight of a horse can at certain times be supported by only a single hoof. Most adhesives do not have the strength, flexibility, and toughness to withstand such forces without breaking.
Furthermore, some hoof coverings, such as that disclosed in U.S. Pat. No. 4,892,150, require special fitting of the shoe to the horse's hoof which can be time-consuming and difficult. Attempting to keep a horse's hoof in the air while a shoe is thermofit to it is difficult since a horse will not generally allow a hoof to be kept off the ground for an extended period of time.
Therefore, it is desired to create a hoof covering which can be quickly and easily attached to a horse's hoof, can withstand the forces generated by a horse at full gallop, and is lightweight enough to be useful for thoroughbred racing.

Protective covering for a horse's hoof and method of attaching

Trustees of the University of Pennsylvania


The present invention relates to a method of treating human immunodeficiency diseases with electroactivated aqueous salt solutions followed by reconstitution of a healthy microflora.

1. Field of the Invention
The present invention relates to a method of treating human immunodeficiency diseases with electroactivated aqueous salt solutions followed by reconstitution of a healthy microflora.
2. Description of the Related Art
Acquired immune deficiency syndrome is a disease of the human immune system. The immunodeficient state is reflected in an inability of the immune system to respond to various antigens. The immunodeficient state may allow for the growth of tumors, due to a defect in the normal antitumor activity of the immune system. The immunodeficient state may also lead to allergic or autoimmune problems. The development of an immunodeficient state is often caused by metabolic disorders. These metabolic disorders may result from diabetes, obesity, artherosclerosis, uremia and attrition.
Irritable colon syndrome is a common aspect of many diseases and is often connected with problems in the immune system. Many diseases that appear unrelated, such as AIDS, chronic renal failure, bacterial endocarditis, and bronchial asthma are related by a unified feature: irritable colon syndrome, a common disruption of the balance of microflora in the intestine and growth of pathogenic bacteria. The disruption of the balance of microflora, followed by disruption of the immune system, determines the onset and course of many diseases.
Thus, novel methods of treatment of immunodeficient states can be achieved through the development of new methods of purifying an organism from pathogenic accumulations, normalizing metabolism, and restoring the healthy intestinal microflora. Such methods would make it possible for a person to control the illness by a natural means.
A number of methods of treating immunodeficient states are known. In one, a hexapeptide drug is administered through hypodermic injections. (Patent of Russian Federation No. 2062096). This drug has shown good results in the treatment of immunodeficient patients with chronic and active persistent hepatitis B, brucellosis and chronic bronchitis.
In another method, patients suffering from AIDS or AIDS-related syndromes are treated by the injection of a pharmaceutical composition containing zidovudin (31-azid-31-deoxythymidine) and inosyplex (paracyd-benzoic acid), possibly in combination with inosinum. (European Patent No. 0362162).
Unfortunately, the positive results obtained through these two methods are accompanied by side effects that can lead to damage of the liver, kidney and heart, resulting in severe complications. In addition, these methods do not restore the healthy microflora of the intestine, which has been disrupted by the disease being treated.
Another method of treating immunodeficient patients uses a solution of water mixed with either sodium hydrocarbonate, alcohol solution of iodine, potassium permanganate or sulficil-sodium. In the course of treatment, the patient takes the mixture orally and by means of rectal or vaginal lavage. (Patent of Russian Federation No. 2077886). This method is based on the removal of pathogenic accumulations and the normalization of the metabolism in a natural way that can be regulated by the patient. However, like the methods described above, this method does not restore the healthy microflora of the intestine.
A method of treating irritable colon syndrome that may also be used to treat immunodeficiencies involves purification of the intestine with enemas. This is followed by the implantation of microflora in the intestine with the help of colonoscopy. Lactobacteria are implanted in the ascending section of the intestine, Bifidobacteria are implanted in the transversal section and colibacteria are implanted in the descending section. (Patent of Russian Federation No. 2092167). Unfortunately, aside from the cleansing enemas, this method does not contemplate removing pathogenic agents from the intestine and thus, is not as effective as it might be.
Another method of treating autoimmune diseases, as well as AIDS, consists of inhibiting, removing or neutralizing a variety of growth factors, antigens or receptors. This treatment comprises either administering the active molecules directly to the patient's blood or removing the patient's blood, treating it, and returning it to the patient. (U.S. Pat. No. 5,888,511).
It is also possible to treat immunological disorders, inflammatory diseases and infections with magnesium gluconate. The magnesium gluconate may be administered alone or in combination with antioxidants or anti-inflammatory agents. (U.S. Pat. No. 5,853,738). Additional methods use pharmacologically accepted salts, such as NaPa alone or in combination with suraminum, interferon or Pag. These agents act directly to suppress the growth of tumor cells and to prevent the onset of problems associated with viral infections. (U.S. Pat. No. 5,877,213).
The inadequacy of the treatment described above is insufficient stimulation of the immune system and a failure to normalize metabolism. Additionally, they do not regenerate the healthy microflora.
Finally, a generalized method of treating viral infections, such as AIDS, herpes and hepatitis, and the accompanying immunodeficiencies has been described. The method is based on a course of therapy consisting of the introduction into the patient of an electroactivated aqueous NaCl solution in an amount that does not exceed the daily requirements for electrolytes and water. Simultaneously, the patient is exposed to dry radon with a frequency of radiation of 17 gHz for 1.5 to 2 minutes. (Patent of Russian Federation No. 2089194). As with the other described methods, this method is problematic because it does not provide sufficient immunostimulation, does not normalize metabolic processes and does not regenerate the healthy microflora.

Method of treatment of human immunodeficiency diseases


A heat pump system includes a heat source unit, a discharge refrigerant communication tube, a liquid refrigerant communication tube, a gas refrigerant communication tube, a first usage unit and a second usage unit. The first usage unit has a first usage-side heat exchanger capable of functioning as a radiator of the heat-source-side refrigerant introduced from the discharge refrigerant communication tube. The first usage unit is capable of performing operation in which an aqueous medium is heated by radiation of the heat-source-side refrigerant in the first usage-side heat exchanger. The second usage unit has a second usage-side heat exchanger capable of functioning as an evaporator of the heat-source-side refrigerant introduced from the liquid refrigerant communication tube. The second usage unit is capable of performing operation in which an air medium is cooled by evaporation of the heat-source-side refrigerant in the second usage-side heat exchanger.

Heat pump water heaters, such as the one described in Japanese Laid-open Patent Publication No. 60-164157 are known which are capable of utilizing a heat pump cycle to heat water. Such a heat pump water heater has primarily a compressor, a refrigerant/water heat exchanger, and a heat-source-side heat exchanger, and is configured so that water is heated by the radiation of refrigerant in the refrigerant/water heat exchanger, and the hot water thereby obtained is fed to a storage tank.


Compositions and methods for conferring tolerance to glyphosate in bacteria, plants, plant cells, tissues and seeds are provided. Compositions include a novel class of EPSPS enzymes, designated Class III, and polynucleotides encoding such enzymes, vectors comprising those polynucleotides, and host cells comprising the vectors. The novel proteins comprise at least one sequence domain selected from the Class III domains provided herein. These sequence domains can be used to identify EPSP synthases with glyphosate resistance activity.

N-phosphonomethylglycine, commonly referred to as glyphosate, is an important agronomic chemical. Glyphosate inhibits the enzyme that converts phosphoenolpyruvic acid (PEP) and 3-phosphoshikimic acid (S3P) to 5-enolpyruvyl-3-phosphoshikimic acid. Inhibition of this enzyme (5-enolpyruvylshikimate-3-phosphate synthase; referred to herein as "EPSP synthase", or "EPSPS") kills plant cells by shutting down the shikimate pathway, thereby inhibiting aromatic amino acid biosynthesis.
Since glyphosate-class herbicides inhibit aromatic amino acid biosynthesis, they not only kill plant cells, but are also toxic to bacterial cells. Glyphosate inhibits many bacterial EPSP synthases, and thus is toxic to these bacteria. However, certain bacterial EPSP synthases have a high tolerance to glyphosate.
Plant cells resistant to glyphosate toxicity can be produced by transforming plant cells to express glyphosate-resistant bacterial EPSP synthases. Notably, the bacterial gene from Agrobacterium tumefaciens strain CP4 has been used to confer herbicide resistance on plant cells following expression in plants. A mutated EPSP synthase from Salmonella typhimurium strain CT7 confers glyphosate resistance in bacterial cells, and confers glyphosate resistance on plant cells (U.S. Pat. Nos. 4,535,060; 4,769,061; and 5,094,945).
EPSP synthase (Mr 46,000) folds into two similar domains, each comprising three copies of a βαβαββ-folding unit (Stallings et al. (1991) Proc. Natl. Acad. Sci. U.S.A. 885046-5050). Lys-22, Arg-124, Asp-313, Arg-344, Arg-386, and Lys-411 are conserved residues of the EPSP synthase from E. coli (Schönbrunn et al. (2001) Proc. Natl. Acad. Sci. U.S.A. 98:1376-1380). Conserved residues important for EPSPS activity also include Arg-100, Asp-242, and Asp-384 (Selvapandiyan et al. (1995) FEBS Letters 374:253-256). Arg-27 binds to S3P (Shuttleworth et al. (1999) Biochemistry 38:296-302). Variants of the wild-type EPSPS enzyme have been isolated which are glyphosate-tolerant as a result of alterations in the EPSPS amino acid coding sequence (Kishore and Shah (1988) Annu. Rev. Biochem. 57:627-63; Wang et al. (2003) J. Plant Res. 116:455-60; Eschenburg et al. (2002) Planta 216:129-35). He et al. (2001, Biochim et Biophysica Acta 1568:1-6) have developed EPSP synthases with increased glyphosate tolerance by mutagenesis and recombination between the E. coli and Salmonella typhimurium EPSPS genes, and suggest that mutations at position 42 (T42M) and position 230 (Q230K) are likely responsible for the observed resistance. Subsequent work (He et al (2003) Biosci. Biotech. Biochem. 67:1405-1409) shows that the T42M mutation (threonine to methionine) is sufficient to improve tolerance of both the E.coli and Salmonella typhimurium enzymes.
Due to the many advantages herbicide resistance plants provide, methods for identifying herbicide resistance genes with glyphosate resistance activity are desirable.

Identification of a new class of EPSP synthases


A dispenser for storing and sequentially dispensing flexible, disposable lids for cups such as those used with soft drinks, coffee, soups, or the like from a nested stack of lids held in an elongated container by a dispensing rod disposed across one side of its lower end. The dispensing rod projects through a wall of the container and is attached to a turning handle. In resting position, an edge portion of the circular surface of the lowermost lid sits on the dispensing rod, a lip portion of which extends tangentially outward and clockwise. When rotated, the lip portion of the rotatable dispensing rod engages a portion of the outer wall of the lowermost lid, slightly flexing the lid so that it becomes separated from the stack and drops into a catch tray.

Dispensers of many sorts are used by establishments which employ disposable containers such as paper and Styrofoam cups. While dispensers for cups are found in many service settings, dispensers for lids have not come into common use. Disposable lids have generally been presented for use in open, horizontal trays. In such trays, the elongated stack of lids generally rests with its longitudinal axis disposed horizontally within the tray. This presentation makes it difficult to grasp and separate a single lid from the stack. The consumer often must use two hands to obtain a single lid. This process entails the touching and possible soiling or contamination of the remaining lids in the tray. In addition, with frequent handling of the lids, the tray often becomes cluttered with loose lids that have been dislodged from the stack. This messy presentation further impedes the efficient removal of a single lid from the tray. Furthermore, when presented in such open trays, various dirt or food particles, fluids and the like may be accidentally introduced into the tray rendering the entire contents unusable.
In attempts to overcome the problems of open, horizontal trays, some establishments have adopted partially open vertical cylinders or other upright containers. While the potential for accidental spoilage of the entire stack is somewhat reduced by the use of a partially-open, vertical container, the potential for contamination is not substantially reduced. Even when the stack is in such a container with its longitudinal axis disposed vertically within the container so that the top or bottom lid is in a readily hand engageable position, there is no means of preventing the incidental handling and contamination of other lids in the stack.
The lid dispensing device proposed in U.S. Pat. No. 4,643,334 to Steele (1987) facilitates the removal of lids from a partially open vertical container, but does not substantially overcome the problem of contamination mentioned with respect to such containers. In addition, it is limited in application to the dispensing of lids constructed in such a manner that they do not form a substantially interlocked stack. A stack of substantially interlocked lids prevent horizontal movement of individual lids which can only be efficiently removed with a upward or downward motion of the top or bottom lid. This motion is generally difficult to achieve with a partially open vertical container and cannot be efficiently achieved with the device of the aforementioned patent. Because the Steele device can only be used to remove lids through a horizontal motion, it cannot be used for dispensing lids for many types of Styrofoam cups. These cup lids nest in a substantially interlocking stack and are thus unsuitable for use with the Steele device.
The aforementioned problems with the storage and presentation for use of disposable lids in either horizontal or vertical trays often lead establishments to keep the lids behind a service counter. When this practice is adopted, the lids must be dispensed to ultimate consumers by service personnel. This consumes employee time, increases the duration of the service transaction and still poses some contamination and spoilage problems.
Several devices have been proposed to accomplish the serial dispensing of lids from a largely closed container with a dispensing opening. See for example, U.S. Pat. Nos. 5,131,562 to Brown (1992), 5,012,952 to Franz (1991) and 5,038,969 to Berger (1991). However, all of these patents are limited for use with lids of very specific construction. The Brown and Franz devices each rely on the outward flare or flange of a lid to accomplish the dispensing function. Such a flare is frequently not employed in lids designed for use with paper cups. When such non-flared lids with substantially straight walls are nested, they present a stack with a primarily smooth, straight and uninterrupted surface. These characteristics are apt to make the Brown and Franz devices ineffective in dispensing such lids.
The device proposed for lid dispensing by U.S. Pat. No. 5,038,969 issued to Berger is limited to the dispensing of lids with a circular top wall and a downwardly extending annular flange integral with the top wall. In addition, this device is sufficiently complex both in the number of parts and the specifications of their inter-workings so as to make its manufacture expensive relative to the present invention.


A method and circuit for generating a shifted strobe signal for sampling data read from a memory device includes generating an instantiation of a shifted strobe signal by applying both a coarse adjustment delay value and a fine adjustment delay value to a clock. Data read from a predetermined, programmed memory location or locations of the memory device is sampled using the shifted strobe signal. At least one of the applying steps is repeated and the read data is sampled again using the current instantiation of the shifted strobe signal. The process is repeated until the current instantiation of the shifted strobe signal is aligned with a valid data window of the memory device. The method can be used in both single data rate and double data rate applications.

The present invention relates generally to integrated circuits, and more particularly, to a data synchronization circuit that generates a local data strobe signal to synchronize read operations with a processor initiating read operations.
Some flash memory drive suppliers define a valid data window during which data is valid and available for capture. As clock frequencies increase, the valid data window is narrowed. In addition, on-chip variations (OCV), such as process variations, voltage fluctuations, and temperature variations, can cause the valid data window to shift in response to the varying operating conditions.
Flash drive vendors are redefining how the valid data window is determined, moving from a defined window during which data is valid and available for data capture to a floating valid data window that shifts with variations in operating conditions. Since the valid data window shifts with operating conditions, consideration must be given to a technique not only to establish where valid data can be found at one set of operating conditions but also to re-evaluate where valid data can be found as operating conditions change.

Data strobe signal generation for flash memory


The present invention relates to an immunoassay for detection of BNP, proBNP and fragments thereof. Essentially the assay comprises: a) contacting the antigen with a first antibody specific to a fragment corresponding to amino acids 11-22 of BNP, or to a part of this peptide comprising at least three amino acids of said sequence, to obtain a first order immune complex. b) contacting the first order immune complex obtained at step (a) with a second antibody recognizing said first order immune complex, to obtain a second order immune complex, wherein said antibody is unable to recognize free BNP, proBNP or free first antibody; c) Detecting the second order immune complex.

BNP and proBNP are reliable markers of heart failure (HF) widely used in clinical practice. Several types of sandwich immunoassays (conventional assays) utilizing two mono- or polyclonal antibodies, specific to different epitopes of BNP or BNP-fragment of proBNP molecule are described in literature.
BNP molecule is known as an extremely unstable molecule rapidly losing its immunological activity in water solutions. This loss of activity is usually associated with proteolytic degradation of the peptide. Sandwich immunoassays commonly used for qualitative or quantitative antigen immunodetection utilize two or more antibodies specific to two or more different epitopes. The longer is the distance between the epitopes, the higher is the probability that sites of proteolysis would be located between the epitopes of the antibodies, thus increasing the sensitivity of the assay to proteolytic degradation of the antigen. And vice versa, the closer are the epitopes to each other, the smaller is the probability of the proteolytic cleavage of the molecule between the epitopes.
Immunoassay methods for very small molecules have been described, including the application of so called anti-metatype antibodies. Such methods are disclosed, e.g. for detecting digoxin (Self et al., 1994, Clin. Chem. 40:2035-2041), and angiotensin II (Towbin et al., 1995, J. Immunol. Meth. 181:167-176).
However, it is not an easy task to apply this type of method to different analytes, since very specific monoclonal antibodies are required in such a method.

Immunoassay kit for quantification of BNP and proBNP


Disclosed are W-position modified cytidine nucleotides of formula (I). Provided herein are methods of chemical synthesis of AP-modified cytidine nucleoside triphosphates and their applications as well as uses of the cytidine analogues for the synthesis of modified nucleic acids. The nucleic acid molecule includes DNA, RNA or a combination of DNA/RNA. One of many applications of modified cytidine nucleotides described herein is enzyme selection, when an enzyme of interest bears an activity of an esterase, amidase, oxidoreductase, lyase, ligase or other enzymatic activity, formula (I) wherein the substituants are as defined in the appended claims.

Oligonucleotides (ONs) are short DNA or RNA molecules which have found use in a wide variety of applications in the field of molecular biology, biotechnology, synthetic biology as well as medicine (diagnostics, antisense technology). ONs comprising natural nucleotides are usually unsuitable for application in the field of medicine due to their poor biostability and resistance to nucleases, e.g., blood serum nuclease. In order to improve ON's characteristics, e.g., stability, resistance, selectivity, catalytic activity, pharmacokinetic or pharmacodynamic characteristics, modified nucleotides are used. Moreover, limited chemical diversity of ONs plays an important role in various applications. As a result, ONs are modified to create a desirable diversity and to improve therapeutic ON's affinity, target specificity and distribution in the body, to control aggregation of ONs or to lower their toxicity.
Affinity and specificity are two major characteristics of any nucleic acid-based assay that determine its efficiency. Generally, sequence specificity and binding affinity anti-correlate with each other meaning that as affinity for the chosen target sequence increases, the likelihood of association with closely related but non-target sequences also increases (Lomakin and Frank-Kamenetskii, 1998). Such anti-correlation points out that the formation of nucleic acid duplexes and triplexes necessary for their functioning were either weak or nonspecific which in turn would contradict the methods and technologies which are based on nucleic acid interactions. This bizarre tendency can be explained using one of the two theories of biomolecular interactions. There are two modes of biomolecular interaction—shape complementarity or steric fit and nucleation-zipping. The shape complementarity concept means that biochemical recognition in enzyme-substrate, antigen-antibody and aptamer-small-molecule complexes is provided by a precise steric fit between surface regions of the binding ligand and the target (Koshland, 1995). The theory of steric fit is therefore considered to confirm the affinity-specificity correlation (von Hippel and Berg, 1986). The mechanism of nucleation zipping appears to be essential for the formation of nucleic acid duplexes and triplexes (Craig, Crothers, and Doty 1971; Alberti et al, 2002). By contrast to the steric fit, a strong zip with one irregular or missing link can still be fastened via bypassing this small mismatched part (Rougee et al, 1992). As a consequence, a problem of affinity-specificity is observed: both complexes correct and mismatched show comparable duplex formation efficiency.
Methods that are based on nucleic acid interactions can be divided into two major groups the one which ignores several mismatches and the other that requires high specificity. For example, genome analysis is a technology which is based on a very high affinity and specificity. Genome analysis is a very important methodology in biochemical and biomedical research area as well as provides knowledge about various pathogens and diseases. The basis of genome analysis is often detection of trace amounts of specific DNA sequences and therefore both affinity and specificity are essential. In order to discriminate between two almost identical DNA sequences (e.g. single nucleotide polymorphism), high sequence specificity factor is the main one. Therefore, it is essential to deal with affinity-specificity problem as a major constraining factor to further develop growing high-throughput technologies such as genome analysis.
Synthesis of modified nucleic acids is a way to reduce affinity-specificity anti-correlation. Compared to natural ONs, modified ONs have certain advantages in affinity and specificity, stability or other characteristics. For example, synthetic DNA-RNA-like polymer peptide nucleic acid (PNA) surpasses DNA properties. PNA does not possess a phosphodiester backbone as it is replaced with pseudopeptide polymer (N-(2-amino-ethyl)-glycine), which contains nucleobases connected to the backbone via methylencarbonyl bond. Compared to natural DNA, PNA shows enhanced affinity and specificity (Ratilainen et al, 2000) as well as it appears to be more stable on various surfaces (Kröger et al. 2002). PNA is uncharged and forms DNA-PNA duplexes without any need for additional ionic strength. As a consequence, contrary to natural ONs PNA easily hybridizes at a low salt concentration (Weiler et al. 1997). Hence favourable conditions for DNA-PNA duplex formation might be optimised by destabilizing DNA-DNA complexes. By doing so, PNA based detection probes would become superior compared to DNA probes (Pokorski et al. 2004).
Similarly to PNA, locked nucleic acid (LNA) also exhibits high affinity and specificity (Braasch and Corey 2001; Petersen and Wengel 2003; Rakesh N. Veedu and Wengel 2010; Veedu and Wengel 2009). The ribose moiety of an LNA nucleotide contains an additional covalent bridge connecting 2′ oxygen and 4′ carbon, thus conformational motion is repressed. As a result LNA possesses higher affinity and specificity for complementary DNA or RNA and forms duplexes more easily. In addition, carbocyclic LNA analogues such as ethylene-bridged nucleic acids (ENAs) are particularly advantageous in terms of resistance to blood serum nucleases, e.g. ENAs can circulate in blood more than 48 h compared to natural ONs (<3 h) or LNAs (>9 h).
In addition to PNA and LNA, other synthetic DNA/RNA-like oligomers show enhanced properties such as resistance to nucleases, stability, synthesis cost or diversity over natural counterparts. These artificial oligomers are morpholino nucleic acids (Summerton 1989), hexitol and 1,5-anhydrohexitol nucleic acids (Lescrinier et al. 2000), tricyclo-DNA (Renneberg and Leumann 2002), unlocked nucleic acids (UNAs) (Langkjaer, Pasternak, and Wengel 2009), arabinose nucleic acids (ANAs), treose nucleic acids (TNAs), etc. (Wilson and Keefe, 2006).
ONs are becoming increasingly important and promising molecular tool with widespread applications as nucleic acid therapeutics in the field of antisense therapy, RNA interference (RNAi), ribozyme or aptamer technology (Sharma, Rungta, and Prasad 2014; Rayburn and Zhang 2008). Antisense therapy and RNAi are very efficient processes regulating gene expression. Broadly speaking, the mechanism of action is based on interaction between synthetic ON and a complementary target messenger RNA (mRNA) so that gene silencing occurs. In order to use synthetic ON as a therapeutic agent it should meet several requirements. First of all, ON should cross cell membrane and specifically interact with its target only. Moreover, ON cannot be toxic to the host cell as well as stay stable both in the intercellular and extracellular environment. It should be noted that the cost of ON synthesis plays an important role. Consequently, ON should be described by superior features such as high affinity and specificity to the target, resistance to intra- and extra-cellular nucleases (endo- and exo-nucleases also). ONs cannot interact with other accessory biomolecules and should exhibit properties needed for trans-membrane transfer. As a result, to improve all this stringent properties and functions of a therapeutic ON a lot attention is being paid to the development of synthetic ONs.
Up to date, antisense ONs can be classified into 3 generations—first, second and third (Sharma, Sharma, and Singh, 2014; Chery, 2016). The first generation antisense ONs were developed to increase resistance to nucleases. The standard chemical modification to synthesize first generation antisense ON is replacement of the oxygen atom of the sugar-phosphate backbone with either a sulphur group (phosphorothioate ON (PS-ON)) (Xie et al. 2012; Rahman et al. 2012; E. De Clercq, Eckstein, and Merigan 1969) or methyl group (methyl phosphonates) (Monn and Schurch 2007; Shoji et al. 1991). These ONs have more resistance to nucleases; carry negative charges that ease their cell delivery and peripheral distribution (Yu et al. 2007). Compared to natural ONs, first generation ONs have advantages, however they still possess poor affinity and specificity.
To eliminate shortcomings of the first generation ONs, second generation ONs were developed. Along with PS backbone, additional modifications of nucleobases and monosaccharides are present in the second generation ONs which help to increase affinity and specificity. The most commonly used second generation modifications are 2′-O-methyl (2′-OME) and 2′-O-methoxyethyl (2′-OMOE) modified ribose (Frank Bennett 2007). Other modifications include changes in C5-position of pyrimidines (Moulds et al. 1995; Flanagan, Kothavale, and Wagner 1996) and C7-position of purines (Buhr et al. 1996). Second generation antisense ONs are reported to have a higher affinity and specificity, better tissue uptake and lower toxicity.
Third generation ONs, for example PNAs, LNAs and phosphoroamidate-morpholino oligomers (PMO) are characterised by modifications of the furanose ring. The modifications were made to improve the nuclease resistance, biostability, target affinity and specificity, and other pharmacokinetic profiles of the third generation ONs.
Similarly to antisense therapy, the most commonly used modifications in RNAi are third generation backbone modifications such as boranophosphates and phosphorotioates as well as substitution of 2′-OH group of monosaccharide with OME-, OMOE-, F-, etc. (Bumcrot et al. 2006).
In addition to the widespread application of modified ONs, modified nucleosides or nucleotides are equally important molecular tools in modern medicine. Modified nucleosides/nucleotides come as one of the forms of reverse transcriptase inhibitors which in turn are a class of antiretroviral drugs. Unlike the natural nucleotides these analogues lack a 3′-OH group and thus act as chain terminators. Hence, viral DNA synthesis is halted. Modified nucleoside/nucleotide analogues are used for the treatment of AIDS and during highly active antiretroviral therapy (HAART). For example, acyclovir is a modified guanine based gold standard antiretroviral drug for the treatment of herpes virus infections (Elion et al. 1977; Schaeffer et al. 1978). 3′-substituted-2′,3′-dideoxynucleosides are used for the treatment of HIV infections (Herdewijn et al. 1987; Balzarini et al. 1988), while L-nucleosides are known as specific hepatitis B virus inhibitors (Bryant et al. 2001). Plenty of other nucleoside and nucleotide analogues are used in the antiretroviral therapy (Erik De Clercq and Field 2006; Hurwitz and Schinazi 2013).
Currently there are three FDA approved ON-based drugs used in medicine. Pegaptanib (Macugen®) is an ON that specifically interacts with vascular endothelial growth factor (VEGF) and is used for the treatment of age-related macular degeneration. It is the first FDA approved polyethylenglycol (PEG)-conjugated aptamer, bearing 2′-F and 2′-O-methyl modifications of pyrimidine nucleotide (Pat. No. US20130142796; Tucker et al. 1999). Fomivirsen (Vitravene™) is a PS-ON which binds to the complementary sequence of the cytomegalovirus (CMV) mRNA. It blocks translation of viral mRNA and thus is used for the treatment of CMV retinitis (U.S. Pat. No. 5,595,978; Marwick 1998). Mipomersen (Kynamro™) is also a PS-ON though with different modifications—2′-OMOE and 5-methylcytosine (Pat. No. US2014243389). Mipomirsen targets mRNA of an apolipoprotein B (apo-B) and therefore apo-B synthesis is inhibited. This artificial ON is used to treat hypercholesterolemia (McGowan et al. 2012). There are many other synthetic ONs which are undergoing clinical trials (Chery 2016).
Ribozymes are RNA molecules that are capable of catalysing biochemical reactions. These catalytic RNA molecules mimic function of enzymes at the nucleic acid level. Since ribozymes are often used in medicine, various modifications are tested to improve ribozyme biostability and resistance to nucleases. In the case of ribozymes, selection of modifications is limited by the fact that catalytic activity can be disrupted. Modification of ribozyme can lead to either damaged or improved catalytic activity (Beigelman et al. 1995).
Aptamers are DNA or RNA ONs that form stable and unique tertiary structure and specifically bind to its target molecules, e.g., proteins, drugs, living cells, small organic or inorganic molecules (Patel and Suri 2000; Sun and Zu 2015). Systematic evolution of ligands by exponential enrichment (SELEX) is an in vitro selection technique for evolving aptamers (U.S. Pat. No. 5,270,163; Tuerk and Gold 1990; Ellington and Szostak 1990). A great interest in SELEX technology induced substantial progress towards more efficient, cheaper and easier-to-handle selection methods (Darmostuk et al. 2015). To obtain an aptamer of various desirable properties, e.g. high affinity to its target or selectivity, random ON library is subjected to repeated rounds of ONs selection and identification. Properties of selected aptamer, for example stability, overall charge of nucleic acid molecule, hydrophobicity or hydrophilicity, lipophilicity, thermostability or resistance to nucleases, can be further improved by post-SELEX technology that utilizes additional chemical modification of the selected ON (Gao et al. 2016; Kusser 2000). Unfortunately post-modification increases the risk to impair the tertiary structure of an aptamer thus changing essential ON characteristics (e.g. affinity, selectivity or catalytic activity) (Avino et al. 2012). To overcome this complication and to expand structural and functional diversity of ONs an alternative strategy referred to as mod-SELEX is performed using a library of ONs with the chemical substitutions already present (Keefe and Cload 2008). Various chemical modifications enrich starting ON pool, however, renders amplification step of SELEX challenging, as modified nucleotides are usually poor substrates for DNA and RNA polymerases (Lapa, Chudinov, and Timofeev 2016). A wide variety of upgraded approaches of conventional SELEX have been developed such as capillary electrophoresis, magnetic bead-based, cell, in vivo, one-round, post-, photo-, in silico, blended, mirror-image or Spiegelmer, chimeric, indirect, crossover, click SELEX, etc. There is no unique SELEX method to fulfil all requirements as each SELEX owns its benefits and drawbacks.
Aptamers have been used in numerous investigations, from acting as therapeutics in medicine to various applications in biotechnology, e.g. chromatography, mass spectrometry, capillary electrophoresis, as acoustic, optical or signalling aptamers, etc. (Tombelli, Minunni, and Mascini 2005). However it is believed that the major field of aptamer's application is clinical therapy. Besides clinical therapy, aptamers are used in many other applications; such as detection of viral or bacterial infections (Kiilerich-Pedersen et al. 2013; Rotherham et al. 2012), detection of cancer biomarkers (Chang, Donovan, and Tan 2013), detection of proteins in Western blot (Shin et al. 2010), as capture agents in microarrays and biosensors (Jung et al. 2013; Sosic et al. 2013; Q. Wang et al. 2014), chromatography and surface plasmon resonance (Zhao et al. 2008; H. Chen et al. 2014) or as in vivo imaging agents (Hong et al. 2011).
Three types of nucleotide modifications are used to generate modified aptamers; the backbone, sugar or nucleobase modifications (Wilson and Keefe 2006). Similarly to therapeutic ONs, modification of sugar-phosphate backbone leads to an increased resistance to nucleases. However, the main task is to create three-dimensional architecture alternatives and expand variety. For example, aptamers with an F, NH2 or O-MOE residue at the 2′ position of ribose are used (Wilson and Keefe 2006). To obtain high affinity and specificity aptamers with unique tertiary structure modification of nucleobases is performed. The most common modifications are C5-substituted pyrimidines (e.g. 5-pentynyl-, 5-N-carbamoyl-, 5-borate-, 5-iodo-, 5-tyrosyl-, 5-imidazole-, 5-carboxamide-, 5-naphtylaminocarbonyl-, 5-benzylaminocarbonyl-) and purines bearing various residues at the C7 and C8 positions (Pat. No. US20160215013; Lapa, Chudinov, and Timofeev 2016). There are several reasons to select and modify C5 position of pyrimidines and C7 position of purines. It has been shown that both of these positions orient the modified residue towards the major groove of the double helix; this arrangement is commonly considered to minimize interference with aptamer activity. Moreover, dNTPs with C5/C7 substituents have demonstrated the best compatibility with most RNA and DNA polymerases. As a consequence such modified analogues can be amplified and used in SELEX.
Substitution of C5-position of pyrimidine nucleotide is one of the most commonly used base modifications in aptamer technology. SOMAmers (Slow Off-rate Modified Aptamers) are aptamers that distinguish themselves having very low dissociation rate constants and containing various functional groups at the 5-position of the uracil (J. C. Rohloff et al. 2014; Kuwahara et al. 2006). Functional moieties conjugated at the uracil ring mimic amino acid side chains and thus create unique intramolecular motifs and make direct contacts with proteins. This creates a somamer/aptamer which specifically interacts with extremely hydrophobic or charged molecule, e.g. protein. To increase C5-modified nucleotide repertoire copper(I)-catalysed azide-alkyne cycloaddition or Click chemistry may be applied (Tolle et al. 2015). Click chemistry is based on utilization of 5-ethynyl-dUTP that being a component of an ON may be further modified. This prevents incompatibility of modified substituent and polymerase.
There are several aspects regulating the selection of nucleobase position to be modified. The most important rule is to preserve the Watson-Crick base geometry and complementarity with natural bases. Contrary to modified nucleotides, unnatural nucleotides are not limited to natural pair formation and may generate completely new unnatural base pairs. Thus unnatural base pairs can expand the genetic alphabet by creating a third base pair (next to A:T and C:G) (Yamashige et al. 2012; Seo et al. 2011; Malyshev et al. 2012). Using six instead of four natural nucleotides, unnatural nucleotides could increase the functionality of aptamers by providing additional chemical and structural diversity. It has been demonstrated that during ExSELEX (genetic alphabet Expansion for SELEX) incorporation of unnatural base pairs into starting pool can yield aptamers with greatly augmented affinities to its targets (Kimoto et al. 2013; Georgiadis et al. 2015).
It should be specified that the compatibility of the modified nucleotides and ONs with DNA or RNA polymerases used in the SELEX process is a primary concern (Obeid et al. 2010; Bergen et al. 2012; Lam, Hipolito, and Perrin 2008). It is important that not only modified dNTPs should act as good substrates for polymerases but modified templates must also be further amplified. Since polymerases play a significant role in molecular biology it is obvious that a gold standard for polymerase (thermostability, efficiency, fast synthesis, accuracy, processing power, use of modified substrates) is being searched for. Before starting SELEX process with modified NTPs or dNTPs, commercially available polymerases are tested first. It is known that C5/C7-position of nucleotides are the most permissive sites for modification that are accepted by several known polymerases such as Vent, KOD Dash, KOD XL, Taq DNA and T7 RNA polymerases (Lipi et al. 2016). However, usually these polymerases are efficient only under specific optimal conditions. Investigation of structural and functional properties of polymerases leads to understanding of the nature of interactions between polymerase and its substrate as well as it helps to learn the mechanism of polymerization. Such knowledge in turn becomes a basis for generation of mutant polymerases following rational design principles (Kries, Blomberg, and Hilvert 2013; Khoury et al. 2014). Although rational design is based on the ability to predict crucial amino acids, it does not guarantee polymerase improvement (Samish et al. 2011). An alternative strategy to upgrade proteins known as directed evolution mimics the process of Darwin's natural selection (Jackel, Kast, and Hilvert 2008). Directed evolution is based on repeated cycles of generation of huge molecular diversity and selection of proteins based on the desired properties. Directed evolution is analogous to natural selection since the link between genotype and phenotype is preserved (Leemhuis, Kelly, and Dijkhuizen 2009). So during in vitro evolution specific selection pressure is created, e.g., utilization of modified nucleotides instead of natural ones. In the directed molecular evolution of polymerases, selection by compartmentalized self-replication (CSR) has commonly been used (Pat. No. US7514210132; Ghadessy, Ong, and Holliger 2001). By applying selection pressure, for instance replacing natural nucleotides with various analogues, mutant polymerases that are able to incorporate modified NTPs can be selected and become right for SELEX (T. Chen and Romesberg 2014; Laos, Thomson, and Benner 2014). CSR is based on simple feedback—only genes encoding active polymerases are replicated, whereas inactive variants fail to amplify their own genes and disappear from the gene pool. Using CSR a variety of polymerases have been evolved that differ in substrate specificity: DNA polymerase specific for modified dNTP (Obeid et al. 2010; Bergen et al. 2012; Meek, Rangel, and Heemstra 2016), RNA polymerases capable of incorporation of modified NTP (Chelliserrykattil and Ellington 2004), DNA polymerase acting as RNA polymerase (Xia et al. 2002), polymerase demonstrating DNA and RNA polymerase and reverse transcriptase activities (Ong et al. 2006).
Although CSR is a very powerful method for evolution of polymerases, it lacks versatility for evolution in vitro of other proteins. However insertion of an extra stage into the CSR cycle before the polymerase reaction allows its application to enzymes other than polymerases. Usually, in cooperative/coupled compartmentalized self-replication or otherwise known as compartmentalized partnered-replication (CPR), synthetic circuits are linked to the production of Taq DNA polymerase so that evolved circuits that most efficiently drive Taq DNA polymerase production are enriched by exponential amplification during a subsequent emulsion PCR step (Ellefson et al. 2014). Despite the fact that this approach is especially sensitive, examples of CPR are rare in literature, since it is complicated to design such a cooperative system that links activity of a random enzyme to its amplification by polymerase. DNA binding proteins regulate the majority of cellular processes (e.g. replication, transcription, epigenetic modification, DNA damage repair) therefore investigation of DNA-protein interactions is important for biotechnological progress as well as fundamentally. To investigate interactions between DNA and proteins a cross-linking strategy has been applied that is based on conversion of weak noncovalent interactions to covalent bonds by formation of covalent heteroconjugate. To characterize such conjugates properly DNA-protein complex must be stable, chemical bonds must connect nucleobases and amino acid side chains positioned at small distance only, and covalent complex must preserve native steric shape (Steen and Jensen 2002). Structural analysis of nucleic acid-protein heteroconjugates enables the understanding of cross-linking stoichiometry, finding out the domains of nucleic acid binding proteins and specific amino acid residues that interact with nucleic acid molecule.
Photochemical cross-linking (or photocrosslinking) is one of the most commonly used methods to analyse DNA-protein complexes and mechanisms of interaction. Since native proteins and nucleic acids absorb UV light at 250-280 nm, they can be connected photochemically but still maintain their tertiary structure. However, there are some drawbacks such as low yield and photochemical or oxidative degradation of covalent complex. To bypass such difficulties, photoactive chemical group that absorbs >300 nm UV light is used. This photoactive chemical group is introduced into nucleic acid or protein molecule by several approaches. One strategy allows incorporation of additional hetero-bifunctional photoactive cross-linking agents, e.g. 2-iminothiolane (Wower et al. 1981) or 4-mercaptobutyrimidate (Traut et al. 1973), for joining the DNA-protein complex. In order to apply this strategy, cross-linking agent is delivered after formation of ON-protein complex so that free amino acid side chain groups may interact. When complex is excited at 350-365 nm UV light, formation of covalent bonds occurs. An alternative approach to connect DNA to a protein is to utilize photosensitive DNA or protein analogues. Since both in vivo and in vitro synthesis of ONs is an advanced technology, photoactive group is introduced into nucleic acids more often. There is a vast amount of different photosensitive nucleotide analogues and photosensitive modifications. The most common nucleotide analogues are azido-, thio-, bromo- and iodo-substituted nucleobases bearing nucleotides (Meisenheimer and Koch 1997). Another way to photosensitize nucleotide is by incorporating photosensitive chemical group such as psoralen (S. S. Sastry et al. 1993), diazirine (Shigdel, Zhang, and He 2008) or benzophenone (S. Sastry it Ross 1998).
Benzophenone is probably the most widely used and versatile photophore in organic chemistry, bioorganic chemistry, and material science due to its unique photochemical properties (Sergentu et al. 2014). The efficiency of photosensitization depends on two operations: ability of the agent to acquire and maintain excited triplet state and subsequent energy transfer which is strongly connected to interactions between photosensitive molecule and the surrounding chemical groups. It has been demonstrated that benzophenone absorbs at 365 nm UV light leading to triplet state transition that is characterized by long half-life. As a consequence benzophenone has a wide range of applications as a photoinitiator (Gyorgy Dorman et al. 2016; Khanum, Shashikanth, and Deepak 2004; Ranganatha et al. 2013). Due to its properties benzophenone is used in bioconjugation and immobilization, proteome and interactome profiling, surface and polymer chemistry, DNA photolabelling, etc. (Gyorgy Dorman et al. 2016). Application of benzophenone expanded to in vivo protein labelling by genetically encoding benzophenone-containing amino acid (Chin et al. 2002; Lang and Chin 2014; L. Wang et al. 2001). Moreover, since benzophenone initiates transformations of surface C—H bonds, it is a very important photophore used to develop surface technologies, and applied in biotechnology, optics, electronics and photonics (Turgeon, Harley, and Bailey 2014; G. Dorman and Prestwich 2000).
Benzophenone is activated in a UV range (350-365 nm) that does not damage cells, proteins or nucleic acids. Benzophenone photochemically reacts with sterically accessible C—H bonds found in the sugar-phosphate backbone of DNA or in the side chains of amino acids. As a result, benzophenone has been utilized along with various biomolecules for photoimmobilization of ONs and peptides for creating cell trapping systems (Herman et al. 2011), functionalizing surfaces for the detection of antigens and pathogenic bacteria (Konry et al. 2005) or generating antimicrobial coating for textiles (Dhende et al. 2011). DNA microarrays are a growing field of biotechnology and therefore different immobilization methods are being developed. Photochemical immobilization of ONs onto benzophenone-derivatives coated surface seems to be very promising in this field (Renberg et al. 2009; Marcon et al. 2010). Unfortunately, little is known about ONs bearing benzophenone modification, immobilization or cross-linking with various biomolecules (Nakatani, Dohno, and Saito 1999; Nakatani, Yoshida, and Saito 2002). Such ONs could be synthesized either by chemical pattern or during enzymatic catalysis. As a result benzophenone-modified specific ONs could be immobilized onto different supports and used for detection of complementary sequences in various samples.
Growing technologies of ONs stimulate generation of alternative nucleotide modifications. Although modifications of 05/07/08 nucleotide positions are analysed sufficiently, little is known about substitutions of other nucleotide positions. Furthermore, there still is a need to evolve new polymerases that not only incorporate modified nucleotides during PCR but also are efficient, accurate and productive and would improve mod-SELEX. CSR is a widespread approach to evolve mutant polymerases which incorporate modified nucleotides, yet there is a lack of alternatives to evolution in vitro of other proteins. Moreover, to investigate protein-protein, protein-nucleic acid interactions or to apply immobilization technologies conjugation/cross-linking technologies need to be further improved. The present invention provides knowledge about new nucleotide modifications by introducing N4-modified cytidine analogues and its applications.


An electronic shower temperature display device that connects directly to an existing shower arm and showerhead assembly comprising a sensor coupling unit, panel support bracket, and a display panel assembly. Microprocessor-based circuitry monitors both temperature and the presence or absence of water through the device and the showerhead. The device displays real-time shower temperature on a self-contained unit consisting of a position adjustable display panel. A programmable memory storage system is used for retrieving multi-user temperature settings, whereby provides an audible tone when the desired temperature is arrived at. A programmable temperature scorching setting provides protection from scorching by signaling an audible warning tone when the shower temperature has gone passed a preset temperature. The device displays true water temperature by monitoring temperature and water conductivity inside the sensor-coupling unit.

1. Field of the Invention
The present invention relates to temperature display systems, and more particularly, to a device used to display real-time temperature of water delivered by a showerhead.
2. Description of the Related Art
Several designs for water temperature display systems have been designed in the past. None of them, however, includes a real-time temperature display that is installed directly to an existing shower arm and showerhead, without modification of any in-wall plumbing system. In addition, none of them include an adjustable LCD display panel to provide optimal viewing angles.
Typical shower temperature control systems consist of cumbersome and expensive adaptations that require replacement of existing plumbing systems, including installation of electrical wiring. These modifications are very expensive and time consuming; furthermore, most consumers are not eager to dismantle their bathroom walls or wall tiles for devices that practically have no market presence or time-tested reliability. If the typical shower temperature control system were to fail, the user would have a second expense of having to rebuild the plumbing system back to its originality. Other shower temperature control systems require retrofitting devices that control a mixing chamber and mount on an outside wall, but only when the hot and cold water have a dependent valve control. These devices would not work on typical shower systems that have independent hot and cold controls prior to a mixing chamber.
In addition, other systems fail by displaying water temperature that is nonexistent. When water flow is not present, typical temperature sensors continue to read the internal and external temperatures of the mixing chamber, coupling, and pipes caused by heating retention of the materials. This thermo affect causes these type of systems to display a temperature, even when water is not present or being discharging through the showerhead.
Applicant believes that the closest reference corresponds to U.S. Pat. No. 5,944,255 issued to Shirmohamadi for Shower water automatic temperature controller on Aug. 31, 1999. However, it differs from the present invention because Shirmohamadi teaches a self-contained unit 160 that rapidly and accurately senses, controls and maintains the temperature of water delivered to the user of a shower or bath. The invention allows a user to preset a desired water temperature using a manual control interface 60 and uses a sensor 10 located on (or within) the mixer outlet pipe 20 to measure the temperature of the mixed water being delivered to the user. The sensor produces an input signal that is used by a microprocessor 30 to calculate both derivative gain and proportional gain, and fuzzy logic may also be used by the microprocessor to produce an output signal, such that the system responds quickly and accurately to both quantum temperature changes and to the rate of temperature change. The output signal controls a motor 80 that via the action of gears 90, controls the action of the water mixer valve 110 thus maintaining a constant temperature of water delivered to the user. The invention also allows a number of users to preset temperatures for their own comfort, and to select this preset temperature before entering the shower, so negating the need for manual "trial and error" adjustment. Importantly, the invention is also designed so that any layperson, with no plumbing experience and the minimum of mechanical ability may retrofit the device to an existing water delivery system.
Other patents describing the closest subject matter provide for a number of more or less complicated features that fail to solve the problem in an efficient and economical way. None of these patents suggest the novel features of the present invention. There are no similar water temperature display systems to the best of applicant's knowledge, having a real-time temperature display that is installed directly to an existing shower arm and showerhead, without modification of any in-wall plumbing system and has an adjustable LCD display panel to provide optimal viewing angles.


Disclosed is a pedestal apparatus having an antenna attached thereto capable of biaxial motion. The pedestal apparatus according to one embodiment may comprise: a body; a first drive unit, arranged on the lower part of the body, for transmitting driving power; a second drive unit, arranged on the lower part of the body, for transmitting driving power; a first drive gear arranged on the upper part of the body and receiving driving power from the first drive unit; a second drive gear arranged on the upper part of the body opposite the first drive gear, and receiving driving power from the second drive unit; and a driven gear which rotates by receiving driving power from the first and second drive gears, and to which an antenna is connected, wherein the antenna can move biaxially in accordance with the rotational directions of the first and second drive gears.

An antenna, which is provided on a movable body such as a flight vehicle, a body of a motor vehicle, and a hull of a ship, is a device for receiving a signal from a satellite and transmitting a signal to the satellite. Because the antenna receives the signal while tracking the satellite regardless of a position of the antenna, a pedestal apparatus for supporting the antenna is provided to prevent a loss of the signal caused when the movable body sways. That is, the pedestal apparatus supports and fixes the antenna and may rotate in accordance with the motion of the movable body so that the antenna transmits and receives the signal to/from the satellite.
The pedestal apparatus may infinitely rotate as a rotating plate of the pedestal apparatus rotates about an axis perpendicular to the floor, and as a result, a slip ring and a rotary joint need to be mounted to essentially prevent a power cable and an RF signal cable from being twisted. In the slip ring, because mechanical objects in the form of brushes are in contact with each other and rotate in a high-voltage/high-current state, there is a limitation in terms of a life span of components. In particular, the rotary joint for transmitting and/or receiving RF signals is a significantly high-priced component. In a case in which the number of components is increased to implement the infinite rotation of the pedestal apparatus, costs may be greatly increased and a capacity of a bearing and a capacity of a drive motor may be increased.
For example, Korean Patent Application Laid-Open No. 10-2011-0024441 discloses a pedestal apparatus.

Pedestal apparatus having antenna attached thereto capable of biaxial motion


A method of controlling a wind turbine that includes at least one rotor shaft and at least one blade operatively coupled to the rotor shaft includes measuring a first wind turbine operational condition that is representative of a blade deflection value and generating a first operational condition signal based on that first wind turbine operational condition. The wind turbine also includes a drive train including at least one rotor shaft and an electric generator. The method also includes measuring at least one second wind turbine operational condition and generating at least one second operational condition signal. The method further includes changing the blade deflection value by changing the second operational condition.

The subject matter described herein relates generally to wind turbines and, more particularly, to a wind turbine and a method of controlling at least one wind turbine within a wind turbine farm.
Generally, a wind turbine includes a rotor that includes a rotatable hub assembly having multiple blades. The blades transform wind energy into a mechanical rotational torque that drives one or more generators via the rotor. The generators are sometimes, but not always, rotationally coupled to the rotor through a gearbox. The gearbox steps up the inherently low rotational speed of the rotor for the generator to efficiently convert the rotational mechanical energy to electrical energy, which is fed into a utility grid via at least one electrical connection. Gearless direct drive wind turbines also exist. The rotor, generator, gearbox and other components are typically mounted within a housing, or nacelle, that is positioned on a base that includes a truss or tubular tower. At least some of the known wind turbines are physically nested together in a common geographical region to form a wind turbine farm.
In at least some known wind turbines, combinations of local air conditions and wind turbine operational conditions cooperate to induce deflections of one or more of the rotating rotor blades. Some of such blade deflections may be sufficient to reduce a distance between the rotating blades and the truss or tubular tower, thereby increasing a probability of contact between the two. Such contact may increase operational maintenance and replacement costs, decrease electric power generation during associated maintenance outages, and decrease expected life spans of the blades and the truss or tower. In some of the known wind turbines, blade deflection sensors are installed on each of the blades to provide indications to operators of existing blade deflections. However, installation of blade deflection sensors increases capital costs of wind turbine construction and operational maintenance costs, including preventative maintenance and calibration activities.

Wind turbine farm and method of controlling at least one wind turbine


A thrust reverser for a long duct mixed flow fan jet engine having a nacelle formed by a fixed forward structure surrounding the fan, a rear fixed structure and a translatable inner and outer cowl therebetween, the nacelle surrounds the engine and forms a long by-pass duct therewith, a common actuator fixed to the translatable cowls to simultaneously displace them over the rear structure, blocker doors coupled to the inner translating cowls for deployment during thrust reversal into the by-pass duct into a blocking position to divert the airflow through the cascades placed into an opening uncovered when the translatable cowls are axially displaced.

Conventional thrust reversers for aircraft gas turbine engines are provided for deflecting the by-pass airflow or exhaust gases or the combination of both in a generally forward direction upon landing of the aircraft for assisting in braking the aircraft. The thrust reversing arrangement is typically designed to translate from a stowed position, wherein it is aerodynamically blended with a conventional nacelle surrounding the engine, to a deployed position wherein the gas or airflow is turned forwardly as it is blocked and turned by the deployed reversing arrangement. Early thrust reversers were applied to the exhaust gas nozzles and became known as the core thrust reversers. Later with the advent of the turbofan engine, thrust reversers were applied to the bypass duct of the engine and became known as the fan thrust reversers. Such thrust reversers have been in the form of blocking doors which are circumferentially distributed and capable of being selectively pivoted so as to block-off the rearward flow of the by-pass air and turn it outward by the use of the so called cascades which are louvered structures mounted in the cowl upstream of the blocker doors. Of course, simultaneously with the actuation of the blocker doors the outer cowl surface must also be opened so that the reversed airflow could pass to the outside through the cascades.
Such reversing arrangement is disclosed in U.S. Pat. No. 3,541,794 issued Nov. 24, 1970 to Everett A. Johnston, David F. Howard, Hans Bollenbacher and Henry H. Carl and assigned to the assignee of the present application, and is incorporated herein by reference. Such referenced patent, however, discloses a short duct separate flow turbofan engine and its thrust reversing arrangement, which due to its shorter cowling structure requires only the opening of a single cowling structure, which is the combination of an inner and outer bondment into a single translating cowling member.
Another reversing arrangement is disclosed in U.S. Pat. No. 4,278,220 issued Jul. 14, 1981 to Everett A. Johnston and Edward W. Ryan and assigned to the United States of America represented by the Administrator of the National Aeronautics and Space Administration, Washington D.C., and is incorporated herein by reference. Such referenced patent discloses a long duct turbofan engine with an improved thrust reverser having a blocker door with an overhead linkage disposed in the outer nacelle structure. It is, however, provided with a single translating cowl member, and the outer wall of the fan duct is formed solely by the blocker door in stowed position and, as its continuity, by the rear fixed structure.
The problems are, however, different in some long duct mixed flow (LDMF) propulsion system, wherein a relatively long fixed rear structure is present, which prevents the above-noted combination of the inner and outer bondments into a single translating member.
The teachings of these patents are specifically intended to be incorporated herein by reference for enabling one skilled in the art to understand the present invention without the disclosure of extraneous material.

Thrust reversing arrangement for a long duct mixed flow exhaust turbofan engine


A copolyamide composition prepared from hexamethylene diamine and either mixtures of adipic acid and terephthalic acid, or mixtures of adipic acid, terephthalic acid and isophthalic acid, has a melting point below 320.degree. C., a glass transition temperature between 100.degree. C. and 120.degree. C. and physical properties similar to nylon 66.

1. Field of the Invention
The present invention relates to copolyamides from aliphatic diamines, particularly hexamethylene diamine and either mixtures of adipic acid and terephthalic acid, or mixtures of adipic acid, terephthalic acid and isophthalic acid. In particular, it relates to copolyamides having a melting point(T.sub.m) below 320.degree. C., a glass transition temperature(T.sub.g) between 100.degree. C. and 120.degree. C., and mechanical properties similar to nylon 66.
2. Description of the Prior Art
100% hexamethylene terephthalamide(6T) polymer has a high T.sub.g and also a T.sub.m (about 370.degree. C.) too high for it to be melt processed. While replacing a portion of the terephthalic acid with isophthalic acid lowers the T.sub.m while preserving the high T.sub.g, the resulting 6T/6I (hexamethylene terephthalamide hexamethylene isophthalamide) copolymer has less crystallinity. Accordingly, copolyamides obtained from 66 (hexamethylene adipamide), 6T, and 6I in various ratios have been developed and applied in different industrial fields. For example, Japan Patent No. 46-18809 (71018809) discloses a copolyamide obtained from 10-50 wt% of hexamethylene adipamide(66), 10-50 wt% of hexamethylene terephthalamide (6T) and 10-55 wt% of hexamethylene isophthalamide (6I). The copolyamides are suitable for use as fibers.
Japan Laid open Patent No. 52-85516 (77085516) discloses a copolyamide fiber which is obtained from 20-70 wt% of hexamethylene adipamide(66), 15-45 wt% of hexamethylene terephthalamide (6T) and 15-35 wt% of hexamethylene isophthalamide (6I).
Japan Patent No. 46-28218 (71028218) discloses a complex polyamide fiber which is manufactured from a copolyamide prepared from 10-80 wt% of hexamethylene adipamide(66), 10-50 wt% of hexamethylene terephthalamide (6T) and 10-55 wt% of hexamethylene isophthalamide (6I).
U.S. Pat. No. 4,238,603 discloses a copolyamide fiber which is obtained from 2-15 wt% of hexamethylene adipamide, 45-68 wt% of hexamethylene terephthalamide, and 30-40 wt% of hexamethylene isophthalamide.
Japan Pat. No. 68-067801 discloses a fiber prepared from a copolyamide consisting of 10-80 wt% of hexamethylene adipamide, 10-65 wt % of hexamehtylene terephthalamide, and 10-55 wt% of hexamethylene isophthalamide.
U.S. Pat. No. 4,218,509 discloses a copolyamide fiber which is manufactured from at least 50 wt% of hexamethylene adipamide, 20-40 wt% of hexamethylene terephthalamide, and 2-20 wt % of hexamethylene isophthalamide.
U.S. Pat. No. 4,521,484 discloses the synthesis of copolyamide filaments which are manufactured by using at least 60 wt% of hexamethylene adipamide, 15-30 wt% of hexamethylene isophthalamide and 5-10 wt% of hexamethylene terephthalamide.
U.S. Pat. No. 4,603,166 and U.S. Pat. No. 4,603,166 disclose crystalline copolyamides having high heat deflection temperature, which are prepared from hexamethylene diamine, adipic acid, terephthalic acid and isophthalic acid at a mole ratio of about 100:5-35:65-95: 0-25.
U.S. Pat. No. 4,246,395 discloses a fiber-forming polyamide consisting of 5-20 wt% of hexamethylene adipamide, 40-75 wt% of hexamethylene terephthalamide and 20-40 wt% of hexamethylene isophthalamide. The fiber-forming polyamide has a melting point below 320.degree. C., a glass transition temperature above 115.degree. C. and good thermal stability.
U.S. Pate. No. 4,268,661 discloses copolyamides having a glass transition temperature of 140.degree. C.-170.degree. C. The copolyamides are suitable as engineering plastics and are manufactured from 0-15 mole% of hexamethylene adipamide, 0-50 mole % of hexamethylene terephthalamide and 50-100 mole% of hexamethylene isophthalamide.
Japan Patent Nos. 60-32980(94-32980) and 60-32979(94- 32979) disclose crystalline polyamides for injection molding. The polyamides comprise 30-95 wt% of hexamethylene adipamide, 0-40 wt% of hexamethyene terephthalamide, and 5-30 wt% of hexamethylene isophthalamide.
Japan Patent No. 31-26725 discloses aromatic copolyamides which are produced by polymerizing adipic acid, terephthalic acid, isophthalic acid and hexamethylene diamine in the presence of sodium hypophosphite.
Japan Patent No. 3007761 discloses polyamides prepared from (a) a dicarboxylic acid consisting of 0-70 mole% of adipic acid, 30-100 mole % of terephthalic acid, and 0-40 mole % of isophthalic acid and (b) hexamethylene diamine. The polyamides thus prepared are highly resistant to heat, water and chemicals and have high mechanical strength.
German Patent DE 3506656(1986) discloses copolyamides prepared from adipic acid, terephthalic acid, isophthalic acid and hexamethylene diamine with a weight ratio of adipic acid to mixture of terephthalic acid and isophthalic acid of 30-51:48.5-70. The weight ratio of terephthalic acid to isophthalic acid is 48.5-60:40-51.5. The copolyamides have higher T.sub.g and lower water absorption.
European Patent No. 121984 discloses a copolyamide comprising (A) hexamethylene adipamide, (B) hexamethylene terephthalamide and (c)hexamethylene isophthalamide wherein the mole ratio of the dicarboxylic acid moieties in (A), (B) and (C) is 5-35:5-35:60-90. An injection molding composition comprising the above copolyamides and 10-60 wt% of glass fibers or beads and/or mineral or graphite fibers has a heat deflection temperature of 240.degree. C.-305.degree. C.
Japan Laid Open Patent No. 6-287299 discloses a continuous process for preparing copolyamides. The copolyamides comprise the following recurring units: ##STR1## wherein the weight ratio of (I)/(II) is 55-80/20-45, (I)/(III) is 20-80/20-80 and (I)/(IV) is 55-90/10-45. The copolyamides are heat resistant and have lower water absorption.
Japan laid open Patent No. 06-287,300 discloses a copolyamide comprising the same recurring units (I), (II), (III) and (IV) and having the same weight ratio of (I)/(II), (I)/(III) and (I)/(IV). The copolyamide is crystalline and heat resistant.
European Patent No. 0 409 666 A2 discloses a polyamide composition comprising the following recurring units: ##STR2## wherein the mole ratio of the dicaroxylic acid moieties in the A, B, and C units is about 0.5-49.5/0-20/0.5-49.5 and wherein R is a divalent radical comprising ##STR3## and --(CH.sub.2).sub.6 -- in a mole ratio of about 0.5-50/49.5-0. The polyamide compositions have a glass transition temperature of 90.degree. C. or greater and an oxygen transmission rate of about 2.0 cc-mil/100 in.sup.2 -day-atm or less.
European Patent No. 0 291 096 discloses a novel crystalline copolyamide having high heat deflection temperature. The copolyamide comprises the following recurring moieties: ##STR4## wherein the mole ratio A:B:C is 60-90:35-5: 35-5.

Copolyamide composition with a high glass transition temperature

Industrial Technology Research Institute


There is provided a fluorine-containing copolymer having an aliphatic monocyclic structure in the polymer trunk chain which has a number average molecular weight of from 500 to 1,000,000 and is represented by the formula (Ma):-(M1)-(M2a)-(N)—  (Ma)in whichthe structural unit M1 is a structural unit derived from an ethylenic monomer having 2 or 3 carbon atoms and at least one fluorine atom, the structural unit M2a is at least one structural unit which introduces an aliphatic monocyclic structure in the polymer trunk chain and is represented by the formula (a):

The present invention relates to a novel fluorine-containing unsaturated cyclic compound, a novel fluorine-containing polymer having an aliphatic monocyclic structure in its trunk chain, and a chemically amplifying photoresist composition which is obtained from the fluorine-containing polymer, is excellent in transparency and possesses improved dry etching resistance.
As a result of an increasing necessity for high integration of a large scale integrated circuit (LSI), microfabrication technology is required for photolithography. In order to satisfy such requirements, there have been tried to use, as exposure light sources, a deep ultraviolet, a KrF excimer laser beam (wavelength: 248 nm) and a ArF excimer laser beam (wavelength: 193 nm) which have a wavelength shorter than conventional g-rays (wavelength: 436 nm) and i-rays (wavelength: 365 nm). Those light sources are put into practical use.
Recently a process using a F2 laser beam (wavelength: 157 nm) having a wavelength in a vacuum ultraviolet region has been studied in an ultra-microfabrication technology and is considered promising as an exposure technology aiming at a technology node of 0.1 μm.
On the other hand, in the pattern formation, a chemically amplifying resist which becomes advantageous in transparency, resolution, sensitivity and dry etching resistance in cases of energy rays having various wavelengths has been studied. The chemically amplifying resist means, for example, in case of a positive resist, an energy-sensitive composition comprising a resin being soluble in an alkali developing solution and having an introduced substituent which has an effect of inhibiting dissolution of the resin but is deprotected due to action of an acid, and a compound which generates an acid by irradiation of energy rays such as light and electron beam (hereinafter referred to as a photoacid generator). When the composition is irradiated with light or electron beam, an acid is generated from the photoacid generator, and by heating (post-exposure bake, which may be hereinafter referred to as "PEB") after the exposure to light, the substituent which has been giving a dissolution inhibiting effect on the resin is deprotected due to action of an acid. As a result, the exposed portion becomes soluble in alkali, and by treating the exposed portion with an alkali developing solution, a positive resist pattern can be obtained. In that case, the acid acts as a catalyst and exhibits its effect in a very small amount. Also action of the acid becomes active by the PEB and a chemical reaction is accelerated like a chain reaction, and thus sensitivity is enhanced.
Examples of conventional resins for chemically amplifying resist are phenol resins in which a part or the whole of hydroxyl is protected by a protective group such as acetal or ketal (KrF resist), methacrylic acid resins in which an acid-labile ester group is introduced to carboxyl (ArF resist) and the like.
However those conventional resist polymers have strong absorption in a wavelength range of a vacuum ultraviolet region and have a significant problem that transparency against F2 laser beam having a wavelength of 157 nm which is studied in a process for ultra fine pattern is low (an absorption coefficient is high). Therefore for exposing with F2 laser, it is necessary to make a resist film thickness very thin and it is substantially difficult to use the polymers as a single layer F2 resist.
R. R. Kunz, T. M. Bloomstein, et al. suggest in Journal of Photopolymer Science and Technology (Vol. 12, No. 4 (1999) 561–569) that fluorocarbons have good transparency at 157 nm as compared with other various materials and have possibility of use as a F2 resist.
However in that literature, there is only description that existing fluorocarbon polymers are high in transparency at 157 nm, but there is no description as to preferable structure of fluorine-containing polymers. Also, for example, with respect to a fluorine-containing polymer having functional group necessary for a positive type or negative type chemically amplifying resist, neither evaluation of transparency nor synthesis of the polymer was made. Moreover the literature does not suggest a fluorine-containing base polymer material being preferable as a chemically amplifying resist and a preferable resist composition obtained therefrom at all, and there is found no possibility of forming a F2 resist pattern by using a fluorine-containing polymer.
Thereafter A. E. Feiring, et al. of E. I. du Pont de Nemours and Company disclosed in WO00/17712 pamphlet (published Mar. 30, 2000) that a specific fluorine-containing polymer is useful for F2 resist application.
That pamphlet describes the use of a fluorine-containing polymer having a structural unit of fluoroolefin and a structural unit having a polycyclic condensed structure which is mainly a structural unit derived from norbornene.
Also an acid-labile (acid-decomposable) functional group necessary for a positive type resist is introduced to the fluorine-containing polymer by copolymerizing a conventional acrylic, methacrylic, norbornene or vinyl ester monomer with a monomer having an introduced acid-labile (acid-decomposable) functional group.
Further thereafter A. E. Feiring, et al. of E. I. du Pont de Nemours and Company disclosed in WO00/67072 pamphlet (published Nov. 9, 2000) that a fluorine-containing polymer having —C(Rf)(Rf′)OH or —C(Rf(Rf′)O—Rb is useful for F2 resist application.
In that pamphlet, a structural unit of norbornene in which —C(Rf)(Rf′)OH or —C(Rf)(Rf′)O—Rb is bonded through a part of —CH2OCH2— is disclosed. Further there is disclosed norbornene derivatives having —C(Rf)(Rf′)OH or —C(Rf)(Rf′)O—Rb as an example of a fluorine-containing polymer to be used for a resist.
However in those patent publications, there is no description as to the use of a fluorine-containing copolymer comprising a structural unit of fluoroolefin and a structural unit having an aliphatic monocyclic structure in its trunk chain, and further there is no description as to an aliphatic monocyclic structure to which a functional group necessary for a resist is introduced.
Further Katsuyama, et al. of Matsushita Electric Industrial Co., Ltd. proposed a method of forming a pattern with exposure light having a wavelength of from 1 to 180 nm using a resist material containing halogen atom, etc. (JP2000-321774A published Nov. 24, 2000). However there is disclosed only a methacrylic resin having a structural unit of methacrylic acid ester having —CH2CF3 group and —CH(CF3)2 group in its side chain as a base resin having halogen atom for a resist, and neither a resin containing fluorine atom in its trunk chain nor a polymer having an aliphatic monocyclic structure in its trunk chain is disclosed. Also there is disclosed no polymer which has, in an aliphatic monocyclic structure, a functional group and is capable of working as a chemically amplifying resist (positive type or negative type).
There is generally known that dry etching resistance of a polymer is enhanced by introducing a norbornene backbone to the polymer. However transparency, particularly transparency in a vacuum ultraviolet region of conventional norbornene derivatives cannot be said to be sufficient.
The present inventors have found that fluoroolefins represented by tetrafluoroethylene have good copolymerizability with unsaturated compounds (monomers) of aliphatic monocyclic structure, and a novel fluorine-containing polymer was obtained. It has been considered that dry etching resistance of monocyclic compounds was insufficient as compared with compounds having polycyclic condensed structure. However the present inventors have found that the copolymer which is obtained in the present invention and comprises fluoroolefin and an unsaturated compound (monomer) of aliphatic monocyclic structure has dry etching resistance higher than that of an unsaturated compound having polycyclic condensed structure, for example, norbornene.
Also it was found that transparency in a vacuum ultraviolet region is excellent as compared with the use of norbornene.
Also studies have been made as to introduction of an acid-reactive functional group necessary for a resist, and as a result, it was found that in addition to the fluoroolefin and unsaturated compound (monomer) of aliphatic monocyclic structure, a specific ethylenic monomer having an acid-reactive functional group has good copolymerizability, which made it possible to introduce an acid-reactive functional group to a polymer. Further the present inventors have found a fluorine-containing polymer in which an acid-reactive functional group is introduced directly to a monocyclic structure and also a novel unsaturated compound of monocyclic structure having an acid-reactive functional group and partly having fluorine atoms. The copolymer comprising such a novel unsaturated compound of monocyclic structure and a fluoroolefin exhibits excellent dry etching resistance and high transparency when used for a resist.

Fluorine-containing polymer, resist composition prepared from same and novel fluorine-containing monomer

Abstract: wherein R1 is at least one hydrocarbon group selected from the group consisting of a divalent hydrocarbon group having 1 to 8 carbon atoms and constituting a ring which may be further substituted with a hydrocarbon group or a fluorine-containing alkyl group and a divalent hydrocarbon group having ether bond which has the sum of carbon atoms and oxygen atoms of 2 to 8, constitutes a ring and may be further substituted with a hydrocarbon group or a fluorine-containing alkyl group; R2 is an alkylene group which has 1 to 3 carbon atoms and constitutes a ring; R3 and R4 are the same or different and each is a divalent alkylene group which has 1 or 2 carbon atoms and constitutes a ring; n1, n2 and n3 are the same or different and each is 0 or 1, the structural unit N is a structural unit derived from a monomer copolymerizable with the monomers to introduce the structural units M1 and M2a, andthe structural units M1, M2a and N are contained in amounts of from 1 to 99% by mole, from 1 to 99% by mole and from 0 to 98% by mole, respectively. The fluorine-containing polymer possesses excellent dry etching resistance and transparency in a vacuum ultraviolet region.


The present invention relates to a device designed to accompany the playing of a guitar or other non-percussion instrument, which provides the capability for a musician to accompany his own playing of the guitar or other non-percussion instrument with a device which produces percussion while in simultaneous use with the guitar or other non-percussion instrument. The present invention is generally comprised of a member which mechanically strikes upon a sound-producing base, by means of an actuation device that is triggered by a mechanical or electrical impulse, initiated by the instrument player and transmitted by a triggering mechanism to the actuation device.

Percussion instruments are well known in the art, as are percussion instruments designed for foot operation. Also known in the art is the use of various percussion instruments in accompaniment of a musical guitar or other non-percussion instruments.
However, there is nothing currently known in the art which provides the capability for a musician to accompany his own playing of a guitar or other non-percussion instrument with a device which produces percussion while in simultaneous use with the guitar or other non-percussion instrument.
Accordingly, it is an object of the present invention to provide a musical accompaniment device which allows a musician to accompany his own playing of a guitar or other non-percussion instrument with percussion.
It is another object of the present invention to provide a musical accompaniment device which produces percussion while in simultaneous use with the guitar or other non-percussion instrument.
It is another object of the present invention to provide a mechanical musical accompaniment device which is attached to a guitar or other musical instrument to produce a tapping sound to accompany the music produced by that instrument.
It is another object of the present invention to provide a mechanical musical accompaniment device which is attached to a guitar or other musical instrument in such a manner as to utilize the acoustic characteristics of the instrument to which it is attached.

R.D. #1, Box 284-B, Kittanning Hollow Rd.


A surface inspection apparatus and method increase wafer productivity, wherein to increase an efficiency of the surface inspection apparatus to detect defects during a scanning of the wafer surface, a scanning speed for a subsequent defect detection is varied according to an increase/decrease of defect density represented on a plurality of images acquired successively. When the density of defects is reduced, the scanning speed increases and a level of a skip rule increases, and when the density of defects increases, the scanning speed decreases and a level of the skip rule decreases to precisely detect defects, thereby increasing reliability, throughput, and productivity.

The recent integration increase of semiconductor devices causes an operation defect of semiconductor devices due to a minute defect that was not such a serious problem in the past, but has a very bad influence upon reliability of the semiconductor devices with a high degree of integration. Defects generated in semiconductor device manufacturing processes may be, for example, foreign particles, a void, dislocation, a stacking fault, an interface fault and the like.
Generally, a surface fault is inspected and measured before or after unit processes of a semiconductor device are performed. A research and development for surface inspection apparatuses to rapidly and precisely detect defects has been actively progressing. It can be understood that the reliability of semiconductor devices depends upon the accurate performance of such surface inspection apparatuses.
Most surface inspection apparatuses employ a bright field optical system for acquiring an image from light reflected from the wafer surface by directing light of a high illumination onto the wafer surface. The bright field optical system uses the reflected light to reproduce an image of the surface. Meanwhile, when employing a dark field optical system using light scattered from defects it is difficult to reproduce an actual image of the wafer surface. Thus, the bright field optical system may be the best way to detect defects on the wafer surface on which various kinds of patterns are formed.
The surface inspection apparatus employing the bright field optical system performs a line scan for a wafer surface by using an image acquisition system, such as a CCD (Charge-coupled device) or TDI (Time Delay Inspection) sensor, so as to detect defects present on an entire face of the wafer. A wafer surface defect detection using such surface inspection apparatus is performed by selecting and sampling a selected area, except for a given portion according to a given skip rule. This is why a defect detection time is long when performing a precise defect inspection for an entire face of a wafer using the image acquisition system of high sensitivity. Thus, a testing throughput decreases.
For example, the TDI sensor uses a swath sampling with a constant scan line interval. A swath sampling of about 25% for the entire face of a wafer is performed according to a skip rule, thereby shortening the defection detection time and thereby increasing a testing throughput.
In the surface inspection apparatus and method described above, however, a throughput can be just enhanced by reducing a scan measurement area when applying a given skip rule, such as swath sampling, but a large amount of defects cannot be detected by an increased skip rule and, thus, a reliability of the defect detection decreases.
Furthermore, when a large amount of defects concentrated mainly on a partial surface, such as an edge portion of a wafer cannot be completely detected, errors in semiconductor manufacturing processes occur and, thus, a production yield decreases.

Apparatus and method for inspecting a surface of a wafer