In one embodiment, an apparatus guides movement of a cutting instrument across a first surface of a work piece. The apparatus has a base, a tape-measure mount, and a fence. The base has a substantially-flat lower surface that abuts the first surface of the work piece. The tape-measure mount mounts a tape measure to the base on a first side of the apparatus. The fence is attached to the base, opposite the first side of the apparatus, and has a guiding surface that guides the movement of the cutting instrument across the first surface of the work piece. At least one movable component, other than a tape measure tape, is attached to the base to permit adjustment of a dimension of the apparatus that is used to calibrate the apparatus for use with the cutting instrument.

1. Field of the Invention
The present invention relates to the measurement and cutting of work pieces, and, more specifically but not exclusively, to apparatuses that may be used to guide movement of a cutting instrument, such as a circular saw, across a work piece at a desired measurement from an edge of the work piece.
2. Description of the Related Art
Circular saws can be difficult and dangerous to use for a number of reasons. For example, circular saws typically include a cutting guide that requires the user to stand very close to the circular saw and to lean over the saw in order to view the cutting guide. This is because the cutting guide is conventionally located on the opposite side of the circular saw, away from the user. This further requires the user to place his or her abdomen, waist, leg and/or thigh closer to the circular saw blade, while simultaneously concentrating on keeping the cutting guide on a line that was previously drawn on the work piece, to result in a somewhat even, but not necessarily accurate, cut. As one of Popular Mechanics magazine's top five most dangerous tools, the circular saw's blade travels at 120 miles per hour and is a major cause of injury, especially to "do-it-yourselfers." Although professional carpenters might be more prepared to handle the hazards of using a circular saw due to their experience with the tool, even carpenters suffer from daily fatigue that increases as the long workday progresses, as well as exposure to the elements of a typical outdoor or construction-site work environment. These factors contribute to the likelihood of accidental injury from circular saw use, even among experienced users.
Circular-saw kick-up and kickback can be a dangerous problem. Kick-up occurs when the circular blade of a power saw binds or grabs a work piece being cut, which throws the spinning saw and its cutting blade up toward the user. Similarly, kickback occurs when the circular blade of a power saw binds or grabs a work piece being cut, which throws the spinning saw and its cutting blade back toward the user. Typically, the kick-up and kick-back motion occur together such that the saw is forced away from the surface of the work piece and backward toward the user. The motion of kick-ups and kickbacks can occur so quickly as to make it difficult or impossible for the user to avoid injury. Although various guides for circular saws are known, none of these guides provide protection for the user from kick-ups and kickbacks.
U.S. Pat. No. 7,020,978 to Nelson discloses an adjustable tool guide that provides no protection from circular-saw kickback. This tool guide is used in conjunction with a clamp that holds the tool guide in position over the work piece, so that the user can place both hands on the circular saw. Disadvantageously, this procedure adds an extra step that slows the cutting process, and further, the '978 patent does not specifically address the potential for harm to the user due to kick-up, kickback, or other safety concerns. In practicality, professional users seldom clamp down their smaller work piece and instead usually hold the work piece with one hand while holding the circular saw with the other. This scenario provides little protection from circular saw kick-up and kickback and increases the user's exposure to the moving blade. Further, although the tool guide of the '978 patent has an integrated tape measure with means for adjusting the effective extension length of the tape with respect to the guide, this arrangement can be unreliable because the tape adjustment assembly is pulled against the work piece each time the device is used. This pulling of the tape adjustment assembly promotes and repeatedly increases the potential for inaccuracy due to loss of calibration. To ensure accuracy in the cutting process and subsequent results, the tool guide of the '978 patent must constantly be recalibrated, e.g., by manually verifying the tape adjustment assembly using a second tape measure. Also, since most users do not own multiple circular saws, adjustability of the tool guide can be more of a detriment than a benefit, due to this constant recalibration necessitated by a number of moving parts.
U.S. Pat. No. 6,393,710 to Hastings discloses a combination tape measure and straight-edge apparatus that provides no kick-up or kickback protection from a circular saw. Unless the device is made to be extremely large, passing a circular saw adjacent to the device can be difficult. This is because the tape-measure mounting device is stationary and centrally positioned within the device, thereby providing insufficient clearance for a circular saw motor to pass by the mounted tape measure. The '710 patent provides no means for positioning the tape measure further away from the circular saw in a way that provides the necessary clearance.
U.S. Pat. No. 4,483,071 to Te Kolste also discloses a power-driven circular-saw guide that provides no kick-up or kickback protection. The device of the '071 patent includes a built-in, fully-extended measuring device or rule permanently mounted and extended to the length of the device. The size limitation of the device that is necessary to make the device portable and easy to carry limits the length of material that can be cut, making the cutting of commonly-available building material (for example, 2″×4″ framing lumber in 6- to 16-foot lengths) impractical. The device also includes a wing-nut clamp that needs constant attention to ensure cutting-length accuracy.
U.S. Patent Application Pub. No. 2007/0277389 also discloses an attachable circular-saw guide that provides no kick-up or kickback protection. The device of the '389 application is an attachment to a circular saw that increases the saw's handling weight. Moreover, the '389 application discloses a device for cutting a workpiece at various angles that limits the length of material being cut, making the cutting of commonly-available building material (for example, 2″×4″ framing lumber in 6- to 16-foot lengths) impractical.

Selectively calibrated work piece cutting guide


A transaction terminal is configured with an application that is configured to present a user interface for out-of-band communication with a transaction handler during the processing of a payment transaction. The transaction handler is configured invoke the application in the transaction terminal via transmitting a predetermined code in an authorization response message.

Millions of transactions occur daily through the use of payment cards, such as credit cards, debit cards, prepaid cards, etc. Corresponding records of the transactions are recorded in databases for settlement and financial record keeping (e.g., to meet the requirements of government regulations). Such data can be mined and analyzed for trends, statistics, and other analyses. Sometimes such data are mined for specific advertising goals, such as to provide targeted offers to account holders, as described in PCT Pub. No. WO 2008/067543 A2, published on Jun. 5, 2008 and entitled "Techniques for Targeted Offers."
U.S. Pat. App. Pub. No. 2009/0216579, published on Aug. 27, 2009 and entitled "Tracking Online Advertising using Payment Services," discloses a system in which a payment service identifies the activity of a user using a payment card as corresponding with an offer associated with an online advertisement presented to the user.
U.S. Pat. No. 6,298,330, issued on Oct. 2, 2001 and entitled "Communicating with a Computer Based on the Offline Purchase History of a Particular Consumer," discloses a system in which a targeted advertisement is delivered to a computer in response to receiving an identifier, such as a cookie, corresponding to the computer.
U.S. Pat. No. 7,035,855, issued on Apr. 25, 2006 and entitled "Process and System for Integrating Information from Disparate Databases for Purposes of Predicting Consumer Behavior," discloses a system in which consumer transactional information is used for predicting consumer behavior.
U.S. Pat. No. 6,505,168, issued on Jan. 7, 2003 and entitled "System and Method for Gathering and Standardizing Customer Purchase Information for Target Marketing," discloses a system in which categories and sub-categories are used to organize purchasing information by credit cards, debit cards, checks and the like. The customer purchase information is used to generate customer preference information for making targeted offers.
U.S. Pat. No. 7,444,658, issued on Oct. 28, 2008 and entitled "Method and System to Perform Content Targeting," discloses a system in which advertisements are selected to be sent to users based on a user classification performed using credit card purchasing data.
U.S. Pat. App. Pub. No. 2005/0055275, published on Mar. 10, 2005 and entitled "System and Method for Analyzing Marketing Efforts," discloses a system that evaluates the cause and effect of advertising and marketing programs using card transaction data.
U.S. Pat. App. Pub. No. 2008/0217397, published on Sep. 11, 2008 and entitled "Real-Time Awards Determinations," discloses a system for facilitating transactions with real-time awards determinations for a cardholder, in which the award may be provided to the cardholder as a credit on the cardholder's statement.
The disclosures of the above discussed patent documents are hereby incorporated herein by reference.
In a conventional system for processing payment cards, such as credit cards, debit cards, prepaid cards, etc., a transaction handler is configured to communicate with the acquirer processors of acquirer banks representing the merchants and the issuer processors of issuer banks representing the cardholders. The communications by the transaction handler with the acquirer processors and the issuer processors are based on standardized communication protocols. Such a communication system for a conventional payment card processing network has been adapted for secure and efficient processing of payment card transactions. However, when it is desirable to implement additional services in connection with the conventional processing of the payment card transactions, such a conventional communications system for payment card processing may appear inadequate.

Systems and methods to communicate with transaction terminals


The present invention describes a method and compositions by which introducing PO4−3 ion at particular stage in the preparation of aluminum/zirconium solutions surprisingly results in significantly improved zirconium molecular weight stability.

1. Field of Invention
This invention relates generally to the field of stabilized aqueous aluminum zirconium solutions useful in antiperspirant formulations, methods of making same and compositions thereof.
2. Description of Related Art
Aluminum zirconium chlorohydrate-glycine aqueous solutions are used in various antiperspirant formulations as the active ingredient. It is known that lower molecular weight zirconium polymers are more efficacious than larger molecular weight zirconium polymers. In these solutions and in the formulas (i.e., clear gels) these materials rapidly polymerize, reducing their effectiveness.
The following references are disclosed. U.S. Pat. No. 5,118,497 (Katsoulis), U.S. Pat. No. 5,202,123 (Katsoulis), U.S. Pat. No. 5,225,187 (Carmody), U.S. Pat. No. 5,589,196 (Callaghan et al.), U.S. Pat. No. 5,672,340 (Sun et al.), U.S. Pat. No. 5,770,196 (Callaghan et al.), U.S. Pat. No. 6,403,069 (Chopra et al), U.S. Pat. No. 6,726,901 (Yin et al.), U.S. Pat. No. 6,783,755 (Kajino et al.), U.S. Pat. No. 6,835,374 (Parekh et al.), U.S. Publication No. 2003/0021757 (Carillo et al.), U.S. Publication No. 2003/0211060 (Yin et al.), U.S. Publication No. 2004/00011795 (Li et al.), U.S. Publication No. 2004/022750 (Lee et al.), U.S. Publication No. 2004/0136934 (Carrillo et al.), U.S. Publication No. 2005/0019287 (Li et al.).

Stabilized aqueous aluminum zirconium solutions


Some embodiments of the present disclosure relate to an integrated circuit (IC) arranged on a semiconductor substrate, which includes a flash region, a capacitor region, and a logic region. An upper substrate surface of the capacitor region is recessed relative to respective upper substrate surfaces of the flash and logic regions, respectively. A capacitor, which includes a polysilicon bottom electrode, a conductive top electrode arranged over the polysilicon bottom electrode, and a capacitor dielectric separating the bottom and top electrodes; is disposed over the recessed upper substrate surface of the capacitor region. A flash memory cell is disposed over the upper substrate surface of the flash region. The flash memory cell includes a select gate having a planarized upper surface that is co-planar with a planarized upper surface of the top electrode of the capacitor.

The semiconductor manufacturing industry has experienced exponential growth over the last few decades. In the course of semiconductor evolution, the minimum feature sizes for semiconductor devices has decreased over time, thereby helping to increase the number of semiconductor devices per unit area on successive generations of integrated circuits (ICs). This device "shrinkage" allows engineers to pack more devices and more corresponding functionality onto newer generations of ICs, and is consequently one of the underlying drivers of the modern digital age. Another advancement that has helped improve the functionality of ICs has been to replace traditional polysilicon gates with metal gates, and to replace traditional silicon dioxide gate dielectrics with so called high-κ dielectrics. Whereas silicon dioxide has a dielectric constant of approximately 3.9, high-κ dielectrics have a dielectric constant of more than 3.9, which helps to reduce gate leakage and allows faster switching for transistors.

Integration techniques for MIM or MIP capacitors with flash memory and/or high-κ metal gate CMOS technology

Taiwan Semiconductor Manufacturing Co., Ltd.


A multi-speed sprocket assembly is provided for engaging a bicycle chain displaceable by a derailleur. The multi-speed sprocket assembly generally includes at least one smaller sprocket and at least one larger sprocket. The larger sprocket includes first and second transitional segments for alternatively receiving a shifting chain segment of the bicycle chain shifting from the smaller sprocket to the larger sprocket. The first transitional segment includes a first run-on ramp configured to receive an outer link plate of the shifting chain segment. The first run-on ramp has a first support point configured to bend the transferring bicycle chain at a first angle to position a first chain roller against a no-load tooth flank of the larger sprocket while a second chain roller rests against a load tooth flank of the smaller sprocket. The second transitional segment includes a second run-on ramp configured to receive the outer link plate of the shifting chain segment. The second run-on ramp has a second support point configured to bend the shifting chain segment at a second angle to position the first chain roller against the no-load tooth flank of the larger sprocket while the second chain roller rests against the load tooth flank of the smaller sprocket.

The present invention relates to bicycles and more particularly to a multi-speed sprocket assembly including a larger sprocket having first and second support points configured to bend a shifting chain segment at first and second angles, respectively.
Typically, a bicycle having a derailleur shifting system includes a drive multi-speed sprocket assembly, a driven multi-speed sprocket assembly and a chain extending therebetween. The derailleur axially moves or shifts the chain between sprockets. To facilitate the shifting of the chain from a smaller sprocket to a larger sprocket, the sprockets may have teeth missing that form missing-tooth gaps and recesses on a face of the larger sprocket facing the smaller sprocket. However, one disadvantage of providing missing-tooth gaps is that if several missing-tooth gaps are disposed on one sprocket, it cannot be ensured that the chain transitional segments from one sprocket to the other sprocket are identical. For example, if the number of teeth of the larger sprocket, including the missing teeth, is not integer divisible by the difference between the tooth number of the larger sprocket and the adjacent smaller sprocket then, in the case of two missing-tooth gaps on the larger sprocket, at least one missing-tooth gap may not be positioned such that it is optimally offset relative to the smaller sprocket.
The chain transitional segment may be defined as the distance between the contact point of the chain roller on the last tooth of the smaller sprocket and the contact point of the chain roller on the tooth of the larger sprocket that follows the tooth gap. An optimum transitional segment exists when the chain roller on the tooth of the larger sprocket is in an optimum support position (AP) which causes the subsequent chain roller to neither "ride" on a tooth tip of the larger sprocket nor swivel excessively farther from the load tooth flank toward the larger sprocket. An optimum transitional segment ensures smooth shifting of the chain from the smaller sprocket to the larger sprocket.
With an optimum transitional segment, the chain engages the sprockets at three points. One chain roller rests against the last tooth of the smaller sprocket, one chain link plate is laterally supported on the run-on ramp on the larger sprocket and another chain roller rests against the no-load tooth flank in the optimum support position (AP) and makes contact with that tooth of the larger sprocket that follows the missing-tooth gap. If the support position is too high relative to the optimum AP or is displaced in the direction of the tooth tips, a noticeable jerk occurs during the shifting process because the chain roller contacts the larger sprocket to far away from the load tooth flank and jerkily compensates for this distance. If the support position is too deep relative to the optimum AP or displaced in the direction of the tooth base, then the shifting process is delayed. Under high load, in particular, there occurs a "riding" of the chain since the chain rollers slip so far in the direction of load that they no longer engage the larger sprocket, but instead only rest on the tooth tips. At the moment when the smaller sprocket releases the chain, the chain snaps, with strong jerks, into the intermediate space on the larger sprocket or causes the corresponding chain rollers to strike against the load tooth flanks. This may result in overload and increased wear on the corresponding components of the drive train.


Serial derivatization by chemical reactions of analytes for mass spectrometry is disclosed. The derivatizations enhance the use of MS techniques for analyzing protein samples, particularly when the sequence of a polypeptide is determined by tandem MS/MS. Accurate mass analysis techniques are described for use in sequencing polypeptides, together with the use of sequencing data in protein analysis.

Proteins are the fundamental biological units of cell structure and are formed from linear sequences of amino acids linked together by peptide bonds. This primary amino acid sequence determines the three dimensional characteristics and the function of the protein. There are twenty common amino acids, each with an amino group, a carbon atom with a unique side chain, and a carboxyl group. During mRNA translation on ribosomes, the peptide bond backbone of a protein is sequentially formed by bonds linking the terminal carboxyl group of one amino acid to the N-terminal amino group of the subsequent amino acid. The resulting linear chain of various amino acids has a first amino acid, the N-terminal amino acid with an amino group, and a final amino acid, the C-terminal amino acid, with a carboxyl group. Although proteins vary in length from a few peptides for peptide hormones to over 1500 amino acids, most proteins are generally about 100 to 300 amino acids long.
Because the structure of proteins is directly related to ultimate physiological function, determining the amino acid sequence of proteins has long been a basic endeavor in biomedical research and medicine. Traditionally, amino acid analysis involved determining a relative percentage of each amino acid present in a digestion of a purified protein and determining of the identity of individual peptide residues using laboratory chemistry. Protein sequencing was a laborious effort involving enzymatic digestions of a large amount of a purified protein into peptide fragments, followed by Edman degradations and alignment of overlapping sequences. Currently, reflecting the growing need for more accurate methods of protein sequencing, tremendous advances have been made in protein sequencing using mass spectrometry (MS). DNA genome sequencing, computer informatics, and sensitive protein analysis methodologies using MS are interfacing with classical protein chemistry to greatly advance the emerging field of scientific research known as proteomics.
Proteomics is the field of protein research that studies the large scale or global analysis of the protein complement of an organism (Aebersold and Mann, 2003, Nature 422:198). Proteomics is uniquely important in research, diagnostic, and clinical applications because it relates information from various technical disciplines, including chemistry, genetics, cell imaging, and chip- or microarray-based protein or DNA analyses, to cell function and physiology. In practice, proteomics requires detailed analyses of complex data for a large number of proteins in a short time period. Parameters of protein analysis include not only primary amino acid sequence, but also deletions, splice rearrangements, polymorphisms, mutations, substitutions, and other post-translational modifications (PTMs), such as phosphorylation, acetylation, nitration, sulfonation, oxidation, methylation, glycosylation, cross-linking. High throughput analysis of proteins and their related forms is critical for research in biology, physiology, and medicine and can be used in clinical diagnostic applications.
Mass spectrometry (MS) is a potentially valuable tool in proteomics because highly sensitive measurements of mass can identify some proteins by their amino acid sequence. (Aebersold and Goodlett, Chem. Rev. 101: 269-295, 2001; reviewed in Mann, et al., 2001, Ann. Rev. Biochemistry 70:437; Kinter and Sherman, Protein sequencing and Identification Using Tandem Mass Spectrometry, Wiley, N.Y., 2000). Because each amino acid or chain of amino acid residues can theoretically be detected by an accurate measurement of its mass, a sufficiently accurate measurement of mass allows the identification of the individual amino acids. When the sample processing and MS techniques are highly accurate, the actual sequence of amino acids that form a polypeptide molecule can be determined. Further, if a highly accurate and reliable method detects a deviation from the known mass for an amino acid, this can indicate that the amino acid has been modified, thus allowing detection of the modifications to protein structure described above that are often highly important in proteomics research, such as deletions, splice rearrangements, polymorphisms, mutations, substitutions, and post-translational modifications.
Mass spectrometry (MS) involves the analysis of ionized analytes in a gas phase using an ion source that ionizes the analyte, a mass analyzer that measures the mass-to-charge (M/Z) ratio of the ionized analytes, and a detector that registers the number of ions at each m/z value. The MS apparatus may also be coupled to separation techniques to improve the ability to analyze complex mixtures. Further, MS instrument combinations can be made to enhance sensitivity and selectivity. A wide range of MS instruments are available for use in protein sequencing. Regarding ion source, electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) are two commonly used techniques to ionize the proteins or peptides for analysis. ESI ionizes the analytes from a solution and MALDI desorbs and ionizes the sample, using a "matrix" that encourages desorption and ionization when exposed to light energy. MALDI produces predominantly singly charged ions from peptides. As described in more detail below, tandem MS/MS is a technique that uses at least two MS components and is a commonly used methodology for MS analysis of polypeptides.
There are several types of mass analysers, including ion trap, time-of-flight (TOF), quadrupole, magnetic sector, and Fourier transform ion cyclotron (FT-MS) analyzsers, each varying in analysis characteristics. These analysers may be run separately or assembled in tandem to maximize sensitivity and strengths of MS analysis. For example, a MALDI ion source is usually coupled to a TOF analyser, but may also be coupled to quadrupole ion-trap and to combined TOF instruments or FT-MS. For example, in TOF-TOF, two TOF sections are separated by a collision cell. In the hybrid quadrupole TOF apparatus, the collision cell is placed between a quadrupole mass filter and a TOF analyser. These examples illustrate how "tandem" mass spectrometry apparatus may be assembled from intact MS apparatus or selected components of the instruments. The fundamental characteristic of tandem MS is the structural information obtained from the fragmentation pattern of the ion. The design of the tandem MS/MS instrument allows versatility and increased sensitivity depending on the goal of the analysis and the chemical composition of the analyte. Of the MS equipment available, MALDI-MS/MS is a preferred method for peptide analysis, although others may be used. Aebersold and Goodlett, 2001; Cramer and Corless, Rapid Comm. in Mass Spectrom. 15: 2058-2066, 2001; see Aebersold and Mann, 2003 for other MS instrument combinations.
Polypeptide analysis by mass spectrometry is facilitated by the ability to obtain an accurate mass measurement of a group of peptides derived from a protein by fragmentation that occurs at specific amino acid sequences after using specific cleavage enzymes for proteolysis. The principle behind protein identification assumes that proteins of different amino acid sequence will, after proteolysis with a defined protease, produce a collection of peptides the masses of which constitute protein mass fingerprints unique to a specific protein. If a sequence database containing the specific protein sequence is searched using selected masses based on the experimentally and accurately observed peptide mass fingerprint, combined with the fragmentation rules of the protease, then the protein is expected to be correctly identified within the database. As described in more detail below, there are several circumstances where the experimentally observed mass spectra do not translate into a correct prediction of the actual protein composition or sequence.
Protein identification by this method involves a few basic steps: (i) Peptides are generated by digestion of the sample protein using amino acid sequence-specific cleavage reagents that allow the residues at the carboxyl- or amino-terminus to be known with a reasonable degree of certainty. For example, the enzyme trypsin leaves arginine (R) or lysine (K) at the carboxyl-terminus of digestion fragments. Accordingly, the N-termini of tryptic peptides (except for the N-terminal one) may be identified as the amino acid following a K or R residue in the protein sequence. (ii) Following digestion, the masses of peptides or polypeptides are measured as accurately as possible in a mass spectrometer. (iii) The experimental protein fragment mass data are run through a computer and compared with data in a computer database and using the rules that apply to the proteolytic method used in the experiment to generate a list of theoretical masses that are compared to the set of measured masses. (iv) An algorithm is used to compare the set of measured peptide masses against those sets of masses predicted for each protein in the database and to assign a score to each match that ranks the quality of the matches. This approach is frequently called "in silico" digestion and the correct protein identification by mass analysis depends on the correlation of the measured masses with corresponding data contained in a database. However, several difficulties exist with this approach. Obviously, for a protein to be identified its sequence has to exist in the sequence database being used for comparison. Also, digests of protein mixtures present a problem for mass analysis because it is not readily apparent which peptides in the complex peptide mixture originate from a specific protein. An increase in accuracy of measurement will decrease the potential error for matching an experimental mass to a corresponding mass in a sequence database, and therefore will increase the stringency of the database search.
If a pure protein is digested, and the resulting peptide masses are compared with the list of peptide masses predicted for that protein, two observations are typically made. First, not all of the predicted peptides are detected. Second, some of the measured peptide masses are not present in the list of masses predicted from the protein. The first problem, the missing masses, is usually due to a number of problems that can occur both before and during mass spectrometric analysis such as poor solubility, selective absorption, ion suppression, selective ionization, very short or very long peptide length, missed or inappropriate proteolytic cleavage or other artifacts that cause sample loss or make specific peptides poorly detected or undetectable by MS. This is a critical drawback because missing peptide masses may contain meaningful biological information. Unfortunately, it is not possible to distinguish between trivial and meaningful missing masses without further experimentation. Therefore, unassigned peptide masses are a significant problem for protein identification by mass analysis and probably the single biggest source of misidentifications or missed identifications.
Fragment ion spectra are generated by a process called collision-induced dissociation (CID) in which the amide bonds of a peptide are broken, followed by recording of the fragment ion spectrum. Cleavage of amide bonds results in b-ions (containing the N-terminal) and y-ions (containing the C-terminal). High quality MS/MS spectra of tryptic peptides typically show prominent b and y-ion series. If only these two ions were produced for every amide bond in a 10 residue peptide, the fragment ion spectrum would contain 18 peaks. Ideally, long stable ion series of predominately either the b or y-type would be recovered. In reality, peptide fragmentation is variable and moiety dependent, which leads to gaps and difficulties in analysis. Determining the identity and sequence of a peptide from its MS/MS spectrum is complicated both by the variety and variability of the fragment ions produced. Factors that complicate interpretation of MS/MS spectra are missing ion subsets, internal rearrangements, subsequent fragmentations, and multiple charge states. Also to be considered are the relationship of fragment ion peak intensity to ion series origin and fragment masses, influence of amino acid residues and their derivatives, on neighboring amide bond cleavages, and the link between amino acid composition and neutral loss fragmentation.
There are currently several approaches to MS protein de novo sequencing that vary with the size and purity of the protein to be analyzed. Although some data have been published, the MS sequencing analysis of partially purified undigested proteins (termed top-down sequencing), or expression analysis of proteins from whole cells, is still technically difficult partly because of the sample complexity (Zabrouskov et al., Mol. Cell. Proteomics 2:1253, 2003; Sze et al., PNAS 99: 1774-1779, 2002).
Tandem MS analysis of peptides followed by computerized database searching is also common in high-throughput proteomics research. Recent advancements in multidimensional separation technologies and automated data collection and analysis have further increased the throughput of this method for analyzing polypeptides in biological samples. However, a major drawback of this method remains a strict dependence on high quality experimental MS spectra because a theoretical peptide sequence is determined by matching the experimental spectra with the theoretical ones generated in silico. Although more and more genomes of different organisms are being sequenced, the databases still fall short of the entire collection of model organisms currently employed in biological research today. In addition, genome-derived predicted polypeptide sequence information often fails to reliably predict actual polypeptide information due to database errors, imperfect knowledge of transcript splicing (often employed in eukaryotic cells) as well as post-transitional modifications of polypeptides. The number of post-translational chemical and enzymatic modifications known to occur for proteins and peptides continues to increase. Currently, over 200 post-translational modifications of proteins are known. As the variety, breadth and frequency of such modifications are appreciated, the probability of perfect mass spectral matches to database-generated MS spectra must decrease. Thus, these biological processes may greatly hamper database searching and accurate sequence determination of proteins in biological samples.
Recent publications show that improved approaches of MS analysis can identify protein isoforms originating from alternative mRNA splicing, single-point mutations, and co- and post-translational modifications (reviewed by Mann and Jensen, Nat. Biotech. 21: 255-261, 2003) Chemical derivatizations can be combined with affinity chromatography to identify specific amino acid modifications. Esterification of negatively charged amino acid residues before immobilized metal affinity column chromatography followed by MS/MS analysis improved identification of phosphopeptides (Ficarro, Nat. Biotechnol. 20: 301-305, 2002). MacCoss used capillary multidimensional liquid chromatography followed by MS/MS analysis to analyze proteins digested with three different proteolytic enzymes and obtained sequence results for overlapping peptides, which reduced ambiguity in mapping modifications, and detected phosphorylation sites (MacCoss et al., PNAS 99: 7900-7905, 2002). Claverol et al. used a strategy combining gel separated proteins and ESI-MS/MS to determine phosphorylation and saccharidic motifs of casein (Claverol, et al., Mol. Cell. Proteomics 2: 483-493, 2003). Chemically induced protein modifications from toxin exposure were identified using a combination of MALDI-TOF with targeted LC-MS/MS (Person, et al. Chem. Res. Toxicol 16: 598-608, 2003).
Cagney noted their experimental results were typical of peptide MS/MS experiments in that long but incomplete y-ion series were observed (Cagney and Emili, 2002). Most de novo peptide MS/MS spectra are either incomplete, or too complicated to be accurately interpreted for sequencing peptides. This is mainly due to difficulties of directionality (distinction of N-terminal ions from C-terminal ions), low efficiency of fragmentation, internal fragmentation, the presence of different types of ions generated during fragmentation (i.e. types b, y, a, c, x and z), the presence of incomplete set of ions of the b and y series, and their tendency to lose NH3 and H2O groups. These various fragmentation ions can be generated at greatly varying amounts, each with a characteristic ability to be detected in the mass spectrometer. Thus, MS/MS spectra of polypeptides can present as a highly complex series of apparent masses present at greatly varying intensities. Due to the inherent complexity of MS/MS spectral appearance, de novo peptide sequencing has not fully been enabled for polypeptide sequence determination. The presence of sequence errors and compounding factors such as polymorphism, differential splicing, or protein post-translational modifications generate a need for effective de novo sequencing strategies (Cagney, 2002). There would be great advantage to proteomics if the sequence of peptides could be sequentially determined directly by MS/MS spectral analysis.
Attempts at de novo sequencing have focused on addressing the technical difficulties of directionality and labile peptide bonds to simplify or enhance the spectral readout while maintaining accuracy of amino acid definition. Additionally, not all peptides can be resolved due to inherent chemical structure and varied propensity to fragmentation during MS analysis. Several amino acids pose specific difficulties, e.g., isoleucine and leucine have identical masses (isomeric); the masses of lysine and glutamine are similar (isobaric) and difficult to distinguish; the amide bonds linking acidic amino acids aspartic acid and glutamic acid to other amino acids are more labile than other amide bonds, imparting a fragility to the peptide at these sites; the amino acid located just subsequent to the N-terminal amino acid tends to be resistant to fragmentation; and histidine and proline are very difficult to analyze, especially proline adjacent to aspartic acid. Given these technical difficulties and the complex data analysis required, it is not unexpected that faulty or incomplete mass spectral analysis would introduce errors in protein sequences in de novo protein sequencing.
Recently, MS/MS based methods including isotopic labeling and chemical derivatization have improved MS spectral readout (reviewed in Cagney and Emili, 2002). The use of 16O/18O labeling improves identification of y-ions, but also reduces the signal intensity (Munchbach et al., Anal. Chem. 72: 4047-4057, 2000; Uttenweiler-Joseph et al., Proteomics 1: 668, 2001). An alternative approach involves methyl esterification of the carboxyl groups in a peptide (Hunt, et al., PNAS 83: 6233, 1986; Goodlett, et al., Rapid Commun. Mass Spectrom. 15: 1214, 2001.) This reaction increases the mass for aspartic and glutamic acid carboxylic side chains, and also modifies the C-terminal carboxyl group. However, for both isotopic labeling and methylation, the modified spectra must still be compared with the original, underivatized peptide spectra. Accordingly, that chemical labeling of peptides may require additional experimental and computational steps that may slow down high-throughput sequencing. Mass spectrometry (MS) involves the analysis of ionized analytes in a gas phase using an ion source that ionizes the analyte, a mass analyzer that measures the mass-to-charge (M/Z) ratio of the ionized analytes, and a detector that registers the number of ions at each m/z value. The MS apparatus may also be coupled to separation techniques to improve the ability to analyze complex mixtures. Further, MS instrument combinations can be made to enhance sensitivity and selectivity. A wide range of MS instruments are available for use in protein sequencing. Regarding ion source, electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) are two commonly used techniques to ionize the proteins or peptides for analysis. ESI ionizes the analytes from a solution and MALDI desorbs and ionizes the sample, using a "matrix" that encourages desorption and ionization when exposed to light energy. MALDI produces predominantly singly charged ions from peptides. As described in more detail below, tandem MS/MS is a technique that uses at least two MS components and is a commonly used methodology for MS analysis of polypeptides.
Mass spectrometry (MS) involves the analysis of ionized analytes in a gas phase using an ion source that ionizes the analyte, a mass analyzer that measures the mass-to-charge (M/Z) ratio of the ionized analytes, and a detector that registers the number of ions at each m/z value. The MS apparatus may also be coupled to, separation techniques to improve the ability to analyze complex mixtures. Further, MS instrument combinations can be made to enhance sensitivity and selectivity. A wide range of MS instruments are available for use in protein sequencing. Regarding ion source, electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) are two commonly used techniques to ionize the proteins or peptides for analysis. ESI ionizes the analytes from a solution and MALDI desorbs and ionizes the sample, using a "matrix" that encourages desorption and ionization when exposed to light energy. MALDI produces predominantly singly charged ions from peptides. As described in more detail below, tandem MS/MS is a technique that uses at least two MS components and is a commonly used methodology for MS analysis of polypeptides.
Chemical modification of the N-terminus of a peptide before MS analysis has been found to improve MS analysis. The incorporation of a quaternary ammonium group at the N-terminus using the reactive N-hydroxysuccinimidyl ester enhanced sensitivity in MALDI MS (Bartlet-Jones, et al., Rapid Comm. Mass Spectrom. 8: 737, 1994). Cardenas, et al reacted peptides with N-succinimidyl-2-(3-pyridyl)acetate, followed by liquid chromatography separation and analysis by ESI-MS/MS (Cardenas, et al., Rapid Comm. Mass Spectrum. 11:1271-1278, 1997). This reaction modified the N-terminal amino acids and the amino group of lysine. Keough et al. reported the addition of a sulfonic acid group to the N terminus of tryptic peptides increases fragmentation sensitivity and produces much higher fragment ion yields than native peptides. (WO 02/08767; 2003/0032056; WO 02/095419; PNAS 96: 7131-7134, 1999; Rapid Commun. Mass Spectrom 15: 2227-2239, 2001). Destabilization of amide bonds by protonation of amide nitrogen produced extensive fragmentation under MALDI and ESI ionizing conditions (AP MALDI in combination with ion trap MS). The MS/MS spectra of sulfonized peptides containing aspartic, glutamic and oxidized methionine showed more uniform fragmentation along the peptide backbone. Additionally, Keogh, et al. observed the preferential fragmentation on the N-terminal side of proline residues, enhancing recognition of proline.
Chemical modification of the C-terminal amino acid of the peptide before analysis has been found to form longer, more stable series of y-ions. Several methods of C-terminal chemical modification have been reported for lysine. As noted above, trypsin digestion is routinely used in polypeptide analysis by MS to produce fragmentation because the resulting fragment will reliably end in arginine (R) or lysine (K), thus establishing the C-terminal moiety. Although arginine is known to produce an exceptionally strong MS signal, lysine can be difficult to detect. However, lysine can be chemically modified to improve its signal (see Peters, WO 03/056299). This modification distinguishes the mass of lysine from that of glutamine. Cagney and Emili (2002) used a similar approach by differential guanidination of C-terminal lysines followed by LC-ESI-MS/MS analysis (Cagney and Emili, Nat. Biotech. 20: 163-170, 2002). Gu et al (Gu et al., J. Am. Soc. Mass Spectrom. 14: 1-7, 2003) utilized a method incorporating deuterium-labeled (heavy) lysine.
Peters et al. (Peters, et al., WO 03/056299) described a different chemical derivatization method for C-terminal lysine and demonstrated that when the polypeptide's C-terminal lysine was modified by a particular class of reagents, for example 2-methoxy-4,5-dihydro-1-H-imidazole (referred to as "imidazole"), the complexity of the resulting MS/MS spectra was greatly reduced. Peters et al. noted that the y-ion series identification was improved thereby permitting assignment of amino acid sequences more accurately.
Simplification of MS/MS spectra by chemical derivatization of peptides, and the subsequently improved ability to identify the amino acid sequence data, illustrates the potential for developing high quality fragmentation spectra, obtaining long series of complete b, and especially y-ion series, and offers a practical approach to de novo sequencing. An improved resolution in de novo mass measurements increases the accuracy of sequence determination, and decreases reliance on predictive in silico sequence analysis of proteins. However, while chemical modification can increase the reliability and utility of MS analysis and improves the capability for de novo sequencing, several uniquely problematic technical challenges have not been solved and numerous biologically important characteristics of peptides cannot currently be elucidated by existing MS techniques. Moreover, the reliance on computer databases for peptide sequences and protein identification always involves predictions and approximations rather than experimental data, and thereby, increases the possibility for error that cannot be detected from the data. Therefore, ideally, the mass analysis of polypeptides would permit an accurate and reliable polypeptide sequence that would utilize a de novo identification of each amino acid in the peptide.
Given the inherent complexity of peptide fragmentation and the difficulties of MS spectral analysis, a combination of different methods for chemical derivatization of peptides has not been completely developed. For proteomics and analysis of complex mixtures of peptides, it is accepted that only very simple and extremely efficient chemical derivatization steps are compatible with proteomics. If any heterogeneity is introduced by the chemical reaction, the peptide samples become even more complex, thereby complicating the MS analysis and subsequent data processing. (Mann and Jensen, Nat. Biotech. 21:255-261, 2003). Therefore, although chemical derivatization is a known procedure for use in mass spectrometry, the use of multiple discrete derivatization techniques would be expected to introduce significant complexity and complication to a peptide mass analysis and the use of de novo sequencing for a complete determination of the linear amino acid sequence of a peptide is still difficult.

This patent is subject to a terminal disclaimer.

Serial derivatization of peptides for de novo sequencing using tandem mass spectrometry


Plant stresses such as pest infestations, disease, drought, flood, and excessive temperatures can lead to significant losses of crops each year. There is a continuing need to develop novel plant varieties that are less susceptible to damage or loss by such stresses. The present invention provides for the isolation, characterization and use of an entirely novel class of plant genes, generally designated ROB5. Transgenic plants expressing ROB5 can show a dramatic improvement in their capacity to tolerate a variety of stress conditions. Moreover, ROB5 expression can further lead to marked increases in plant growth rates and plant vigor. The present invention encompasses all such ROB5 genes and peptides encoded thereby, plants expressing corresponding ROB5 constructs, and plant products thereof.

Pest infestation, disease, and adverse environmental conditions can result in severe crop damage or loss. In the Western world, crop devastation can translate into financial ruin for those involved in the agricultural industry. In many other parts of the world the results may be even more drastic including widespread malnutrition and famine. There exists a continuing need to develop plants and crops that exhibit improved resistance to plant stresses, thereby increasing crop yields in adverse conditions and reducing the risk of crop failure. For example, plants with increased tolerance to drought, heat and higher salt conditions may open the possibility of farming in semi-desert climates, where agriculture was previously non-viable. Conversely, the development of novel crops with improved tolerance to cold or freezing temperatures may significantly prolong the growing season in regions with colder climates.
A number of plant genes are known to show increased levels of expression when plants are exposed to stress. Examples include those genes involved in metabolic pathways influenced by abscisic acid; a naturally occurring plant 'growth hormone' that can promote several plant functions including, for example, leaf aging, apical dominance, and seed or bud dormancy. The levels of abscisic acid are known to increase in plants under stress. Moreover, exogenous application of abscisic acid to plants is known to increase tolerance to abiotic stresses including chilling, cold, heat, salt and dehydration (Guy (1990) Annu. Rev. Plant Physiol. Plant Mol. Biol. 41: 187-223.)
Previously, the inventors for the present invention have shown that the application of 75 μM abscisic acid to cell suspension cultures of Bromus inermis can result in increased freezing tolerance, with a corresponding increase and de novo synthesis of a specific set of unknown proteins (Robertson et al. 1987 Plant Physiol. 84: 1331-1337; Robertson et al. 1988 Plant Physiol. 86: 344-347). Additional studies have shown that abscisic acid treated bromegrass cells can exhibit an increased tolerance to heat (Robertson et al. 1994 Plant Physiol. 105: 181-190), and salt (Ishikawa et al. 1995 Plant Science 107: 83-93).
Studies using comparative 2-dimensional gel electrophoresis have indicated that a large number of unknown proteins may be upregulated in response to stress (Robertson et al. 1994). Some of these proteins in the 20-30 kDa size range are cross-reactive with an anti-dehydrin antibody and an antibody (Wcs120) to cold-responsive winter wheat protein. Another group of proteins in the 43-45 kDa range were differentiated from those in the 20-30 kDa range by a lack of cross-reactivity with Wcs120 and poor cross-reactivity with the anti-dehydrin antibody. Moreover, some of the proteins in the 43-45 kDa range were found by microsequencing to have some degree of homology within the initial amino-terminal amino acids.
Despite considerable efforts to engineer genetically modified crops with increased stress tolerance, to date there are little or no such crops on the commercial market. Performance Plants Inc. have reported a drought tolerant canola plant with modified stomatal function that shows 10% increased yield over controls under drought conditions. Transgenic tomato plants (Zhang, H-X and Blumwald, E. 2001. Nature Biotech, 19: 765-768) with enhanced salinity were produced by overexpressing a vacuolar Na+/H+ antiport protein. The freezing tolerance of non-acclimated and cold acclimated canola seedlings can be increased by over expressing CBF (C-repeat/dehydration responsive element binding factor) (Jaglo et al. 2001. Plant Physiol, 103(4): 1047-1053). This work was based on the observation that small increases in freezing tolerance occurred in Arabidopsis seedlings constitutively expressing CBF genes (Gilmour, S. J. et al. 1998. Plant J., 16: 433-442.) Enhanced tolerance to both salt and drought stresses has been identified in transgenic Arabidopsis plants overexpressing vacuolar H+-pyrophosphatase (Gaxiola, R. A. et al. 2001. Proc. Natl. Acad. Sci. USA, 25: 11444-11449). Most transgenic plant work in abiotic stress has been done with Arabidopsis thaliana a non-economic model plant system.
The future prospects of engineering novel plants with an increased capacity to tolerate environmental insults will depend on the availability of critical stress tolerance controlling genes, and knowledge of their functional regulatory properties; The inventors for the present application, and others, have endeavored to decipher the mechanisms of plant stress tolerance in the hope of developing an understanding of the biochemical pathways involved. Nonetheless, the characterization of the genes and proteins involved in plant stress responses presents a number of significant challenges.
There remains a continuing need to develop a better understanding of plant stress responses, so that corresponding methods can be developed to confer advantageous properties to plants. This need extends to the production of crops with an increased capacity to resist damage by both infestation and disease. In addition, there remains a need to develop crops that exhibit resistance to damage by adverse climatic conditions such as excessive temperatures, drought, flood, low levels of nutrients, or high levels of toxins. Even incremental gains in plant stress tolerance may have a significant economic impact in stablizing the quality and supply of grain, oilseed and horticulture. Enhancement of germination, growth and flowering are extremely important in regions that have a short or otherwise difficult growing season.

Plant stress tolerance genes, and uses therefor


An application running on a mobile device presents information about a lighting product, for example, selected from a catalog on a graphical user interface via one or more elements (e.g. a touchscreen) of the mobile device and captures an identification of the selected product. The user interface includes a user selectable indication of a lighting design tool, e.g. a button, icon or other link to the tool. User selection of the tool indicator initiates access to the lighting design tool; and the application passes the identification of the selected product to the lighting design tool. The lighting design tool processes the identification of the selected product and an output of the lighting design tool is presented based in part on photometric information about the selected product automatically retrieved by and populated to the lighting design tool without further manual input to obtain the photometric information about the selected product.

Electrical lighting has become commonplace in modern society. Electrical lighting devices are commonly deployed, for example, in homes, buildings of commercial and other enterprise establishments, as well as in various outdoor settings. Even in a relatively small state or country, there may be millions of lighting devices in use. Lighting design, however, can be very complex and require specialized expertise along with highly customized tools.
Even a single supplier or manufacturer may offer thousands of lighting products for a multitude of lighting applications and/or in a variety of aesthetic styles. For each such product, the manufacturer will have physical and operational data about the product that may need to be considered and processed when a person is deciding whether or how to use each particular product for that person's desired lighting project.
Lighting solutions, particularly in commercial and/or high-end residential spaces, are typically designed by representatives of lighting manufacturers. Such lighting professionals design lighting solutions to meet the needs of current or would-be occupants of the space, but with a particular lighting manufacturer's product line in mind. As such, the current or would-be occupant might have multiple alternative solutions from which to select with the assistance of a lighting designer. Even if initially chosen by a customer, the designer often needs to process information about a product to design an installation to meet building codes and/or customer expectations, e.g. number and arrangement of selected fixtures to achieve desired light levels. Furthermore, lighting installers and/or service technicians are often tasked with ensuring complex lighting solutions are properly installed and functioning optimally, which requires access to product specifications.
However, identifying a particular lighting product, visualizing the particular lighting product within a space, and retrieving detailed information related to the lighting product and the lighting product within the space has remained difficult and often requires transitioning between multiple applications with manual data entry that increases the time involved as well as the potential for error.

Lighting product catalog application with embedded linkage to lighting design tool


A multi-layered conductor structure device has a substrate, a first conductor layer formed on the substrate, which provides an electrode or wiring, and an insulating film covering the first conductor layer and the substrate. On the insulating film, a second conductor layer is formed which comprises an indium tin oxide, and which provides an electrode or wiring. The first conductor layer is formed of an alloy of aluminum with copper, gold, boron, bismuth, cobalt, chromium, germanium, iron, molybdenum, niobium, nickel, palladium, platinum, tantalum, titanium, tungsten, and/or silver.

1. Field of the Invention
The present invention relates to a device having a multi-layered conductor structure including a transparent conductor layer comprising indium tin oxide (ITO), such as a liquid crystal display device, a charge coupled device (CCD), or a photoconductor stacked solid imaging device (PSID).
2. Description of the Related Art
A multi-layered conductor structure device, such as liquid crystal display device, CCD or PSID, is known which has, on a substrate, a first conductor layer which provides an electrode or wiring, an insulating film covering the first conductor layer and the substrate, and a second conductor layer formed on the insulating film and comprising ITO, which provides an electrode or wiring. For such a device, it is required that the first conductor layer have a low resistivity, and also have a high resistance to an etching liquid (a mixed liquid of nitric acid and hydrochloric acid) used for patterning the second ITO conductor layer.
Taking a liquid crystal display device as an example, an attention is greatly attracted to an active matrix type liquid crystal device provided with a thin film transistor (TFT) using an amorphous silicon (a-Si) film, as a switching element. It will be able to realize a large-area, highly fine, and high image quality panel display (a flat television) by constituting a TFT array using an a-Si film which can be produced at a low temperature on an inexpensive amorphous glass substrate.
In order for the active matrix type liquid crystal display device to display highly fine image, and have a large area, and an increased opening ratio of a pixel, it is necessary to make thin and long the signal lines to TFT, i.e., gate electrode wiring (gate line), or data wiring (data line). Further, in order to remove waveform distortion of the pulsed signals, it is necessary to sufficiently lower the resistivity of the wirings. Thus, the wiring materials must have a sufficiently small resistivity. For example, when a reverse stagger type TFT structure wherein a gate line is formed on a glass substrate, on which a TFT is formed by stacking an insulating film and a-Si film, is used, it is required that the gate line have a thin thickness and a sufficiently small resistivity, and can withstand chemical treatments performed during subsequent processes.
More specifically, a liquid crystal display device generally has an ITO electrode as a pixel electrode. In patterning the ITO electrode, an etching liquid for ITO (a mixed liquid of hydrochloric acid and nitric acid) contacts the gate line or the like through pinholes in the insulating film below the ITO. In such a case, the gate line material is corroded by the ITO-etching liquid, leading to the breakage of the gate line, unless the gate line material has a sufficient resistance to the ITO etching liquid.
As a gate line material which satisfies the above requirements to some extent, a metal film such as tantalum or titanium, or an alloy thereof (e.g., an Mo-Ta alloy disclosed in Published Examined Japanese Patent Application (kokoku) 61-48910) has been used. However, in order to realize a large-area, highly fine display device, a material is required which has a smaller resistivity, a good processability, and high resistance to chemicals during chemical treatments, particularly ITO patterning.
As a lower-resistivity material, a metal such as gold, aluminum, copper or platinum is being considered. However, if a storage capacitor line (Cs line) is formed of aluminum or copper, the Cs line would be broken during the subsequent process, since these metals have a poor resistance to etching liquids used to etch ITO, aluminum, silicon oxide, and silicon nitride. Further, gold, copper and platinum has a poor adhesivity with a substrate, often peeling off the substrate.
In the case of stagger type TFT structure wherein source and drain electrode wirings are formed on a substrate surface, the above properties or requirements are required for the source and drain electrode materials. In addition, the similar problems exist on liquid crystal display devices in general, and more generally on a device having a multi-layered conductor structure (including CCD and PSID) in which a conductor layer of ITO and various electrodes or wiring layers are laminated on each other through an insulating film.

Device having a multi-layered conductor structure


Each of image display apparatus, an image display method and a computer program is arranged to select one of a first display mode of displaying an image of an image signal having a first aspect ratio in the image display area and a second display mode of displaying an image of an image signal having a second aspect ratio in the image display area, superpose a character signal upon the image signal having the first aspect ratio in response to a character display command, change the second display mode to the first display mode, when the character display command is input while the second display mode is selected, and display an image of the image signal having the first aspect ratio, on which the character signal is superposed, in the image display area.

1. Field of the Invention
The present invention relates to an image display apparatus, an image display method and a computer program, and more particularly to technologies suitable for displaying an image of video signals having character signals superposed thereon, such as characters and icons, in a video display area having an aspect ratio different from that of the image.
2. Related Background Art
As an image is captured in a 16:9 video mode with a video camera using a DV (Digital Video) format, video signals in upper and lower areas of an image pickup element of 4:3 aspect ratio are cut off and an image elongated in a vertical direction is output.
When this image is reproduced by a wide television having an aspect ratio of 16:9 widely used nowadays, the image is elongated in a horizontal direction and displayed correctly on the screen of 16:9.
During capturing and reproducing by a video camera, an image can be confirmed on a liquid crystal panel of the video camera. However, a liquid crystal panel is generally has a half line structure having an aspect ratio of 4:3 and has about 225 horizontal lines. The technologies proposed in Japanese Patent Application Laid-Open No. H07-294883 devises a liquid crystal drive circuit to realize wide display by thinning out video signals (horizontal lines) at a ratio of one per four scan lines when an image of 16:9 of the NTSC specifications is displayed on the liquid panel. With this liquid crystal driving method, the wide display can be realized only by modifying a liquid crystal driver circuit without dealing with signals to be input to the liquid crystal panel, so that this method is available to various systems.
This liquid crystal driving method is, however, associated with the problem that characters, icons and the like superposed on video signals are lost due to thinning-out of video signals. For example, as shown in a menu screen 40 shown in FIG. 4, a horizontal line of a character display is thinned out and it becomes very hard to recognize this character.
Similarly, when an image of the PAL specifications is displayed on a liquid crystal panel of the NTSC specifications, video signals are thinned out at a ratio of one per six scan lines. This poses the problem that a portion of a character is thinned out and it becomes hard to recognize it. To avoid this, Japanese Patent Application Laid-Open No. H09-322025 proposes the technologies of preventing a portion of a character, an icon and the like from being lost by controlling a thinning-out operation of video signals if a character and the like are superposed upon thinning-out lines.
However, the technologies proposed in Japanese Patent Application Laid-Open No. H09-322025 cannot deal with a high thinning-out ratio. When a 16:9 image of the PAL specifications among other images is to be displayed on a panel of the NTSC specifications, video signals are required to be thinned out at a ratio of 8:3 in order to display an original image thinned out at a ratio of 6:1 as the 16:9 image. A new approach to this high thinning-out ratio has been desired. Characters on the menu screen 40 shown in FIG. 4 for performing a variety of settings of the video camera, among other screens, are difficult to be recognized and users feel inconvenient.

Image display apparatus, image display method and computer program


A sizing plate for sizing a native valve annulus in a patient's heart for either valve replacement or repair during a minimally invasive surgical procedure is shown and described. The sizing plate is generally shaped such that it corresponds to the shape of the native valve annulus. Additionally, a thickness of the sizing plate is such that it can be inserted through a space between the ribs of the patient during the procedure. The sizing plate includes two keyways extending though the plate separated by a bridge. The keyways are sized and shaped such that they are adapted to be engaged by a minimally invasive surgical tool such as a laparoscopic grasper. The keyways in conjunction with the bridge facilitate manipulation of the sizing plate by the grasper from an external location.

A heart valve can become defective or damaged, such as resulting from congenital malformation, disease, or aging. When the valve becomes defective or damaged, the leaflets may not function properly. One common problem associated with a degenerating heart valve is an enlargement of the valve annulus (e.g., dilation). Other problems that may result in valve dysfunction are chordal elongation and lesions developing on one or more of the leaflets. Adverse clinical symptoms, such as chest pain, cardiac arrhythmias, dyspnea, may manifest in response to valve prolapse or regurgitation. As a result, surgical correction, either by valve repair procedures or by valve replacement, may be required.
Surgical reconstruction or repair procedures may include plication, chordal shortening, or chordal replacement. Another common repair procedure relates to remodeling of the valve annulus (e.g., annuloplasty), which may be accomplished by implantation of a prosthetic ring to help stabilize the annulus and to correct or help prevent valvular insufficiency which may result from defect or dysfunction of the valve annulus. Properly sizing and implanting the annuloplasty ring may substantially restore the valve annulus restored to its normal, undilated, circumference. In other situations, the valve can be replaced. During valve replacement procedures, the valve annulus is sized so as to select an appropriately sized replacement valve.

Annuloplasty sizers for minimally invasive procedures

The Trustees of the University of Pennsylvania


In one embodiment, a system comprises a memory and a memory controller that provides a cache access path to the memory and a bypass-cache access path to the memory, receives requests to read graph data from the memory on the bypass-cache access path and receives requests to read non-graph data from the memory on the cache access path. A method comprises receiving a request at a memory controller to read graph data from a memory on a bypass-cache access path, receiving a request at the memory controller to read non-graph data from the memory through a cache access path, and arbitrating, in the memory controller, among the requests using arbitration.

A coherent memory system in a computer typically includes a high-capacity off-chip external memory coupled with a relatively smaller internal on-chip memory cache. The cache mirrors a portion of the data stored in the off-chip memory. A cache controller directs read requests of addresses of the external memory to the cache when the cache has copies of the data corresponding with those addresses. A read request to access the cache can be serviced with a lower access time than a read request to access the off-chip external memory.
In a coherent memory system with an external memory and a cache, the external memory and the cache remain coherent. In such a coherent memory system, the data stored in the cache either matches the copy of the data at an address in the external memory or is an updated version of the data for that address. Writes to external memory addresses are first written to the cache. Later, a hardware mechanism copies the data from the cache to the external memory under certain conditions.
A typical computer system generally tightly couples the cache with the external memory within a single memory sub-system. Upon any read request, the cache controller determines if the cache is storing the data at the requested address of the external memory. If the cache is storing the data, the memory sub-system reads the data directly from the cache. If the cache is not storing the data, the request is forwarded to the external memory.
The cache stores recently accessed data or likely-to-be accessed data in a plurality of "cache lines," which are minimum units of storage within the cache. However, storing data in the cache that is eventually not used or is used infrequently is inefficient and detrimental to overall system performance because the cache capacity is significantly smaller than the capacity of the external memory. The memory sub-system passes a requested read address to the cache controller. If the controller indicates data for the external memory that is present in the cache, the version of the data in the cache is returned. If the data for the requested external memory address is not in the cache, a scenario known as a "cache miss," the memory sub-system directs the read request to the external memory. In the "cache miss" scenario, the memory subsystem copies large quantities of sequential data bytes to a "cache line" within the cache. Typical cache systems anticipate that a read request to a particular external memory address is followed by a read request to the next higher external memory address. Caching data for sequential memory addresses allows subsequent sequential read requests to the memory sub-system to access data stored in the faster cache instead of requiring additional read requests to access data in the external memory.

System and method to provide non-coherent access to a coherent memory system


The present invention relates to improved radiotracer imaging agent compositions, which comprises 18F-labelled biological targeting moieties, wherein impurities which affect imaging in vivo are identified and suppressed. Also provided are radiopharmaceuticals comprising said improved compositions, together with radiofluorinated aldehyde compositions useful in preparing said radiotracer compositions. The invention also includes methods of imaging and/or diagnosis using the radiopharmaceutical compositions described.

WO 2004/080492 discloses a method of radiofluorination of a vector which comprises reaction of a compound of formula (I) with a compound of formula (II):
or a compound of formula (III) with a compound of formula (IV)
wherein:                R1 is an aldehyde moiety, a ketone moiety, a protected aldehyde such as an acetal, a protected ketone, such as a ketal, or a functionality, such as diol or N-terminal serine residue, which can be rapidly and efficiently oxidised to an aldehyde or ketone using an oxidising agent;        R2 is a group selected from primary amine, secondary amine, hydroxylamine, hydrazine, hydrazide, aminoxy, phenylhydrazine, semicarbazide, and thiosemicarbazide and is preferably a hydrazine, hydrazide or aminoxy group;        R3 is a group selected from primary amine, secondary amine, hydroxylamine, hydrazine, hydrazide, aminoxy, phenylhydrazine, semicarbazide, or thiosemicarbazide, and is preferably a hydrazine, hydrazide or aminoxy group;        R4 is an aldehyde moiety, a ketone moiety, a protected aldehyde such as an acetal, a protected ketone, such as a ketal, or a functionality, such as diol or N-terminal serine residue, which can be rapidly and efficiently oxidised to an aldehyde or ketone using an oxidising agent;to give a conjugate of formula (V) or (VI) respectively:
                wherein X is —CO—NH—, —NH—, —O—, —NHCONH—, or —NHCSNH—, and is preferably —CO—NH—, —NH— or —O—; Y is H, alkyl or aryl substituents; andthe Linker group in the formulae (II), (IV), (V) and (VI) is selected from:
wherein n is an integer of 0 to 20; m is an integer of 1 to 10; p is an integer of 0 or 1; Z is O or S.
WO 2006/030291 discloses a method for radiofluorination comprising reaction of a compound of formula (I):
wherein the vector comprises the fragment:
with a compound of formula (II):
wherein:n is an integer of 0 to 20;m is an integer of 0 to 10;Y is hydrogen, C1-6alkyl, or phenylto give a compound of formula (III):
wherein m, n, and Y are defined as for the compound of formula (II) and the vector is as defined for the compound of formula (I).
Glaser et at [Bioconj. Chem., 19(4), 951-957 (2008)], describe the synthesis of 18F-labelled aldehydes, including 18F-fluorobenzaldehyde, and their conjugation to amino-oxy functionalised cyclic RGD peptides.
Speranza et at [Appl. Rad. Isotop., 67, 1664-1669 (2009)] describe an automated synthesis of [18F]-fluorobenzaldehyde ([18F]-FBA) using a TRACERlab™ apparatus. A hand-made purification device is used to purify the [18F]-FBA. Speranza et at describe the fact that cartridge purification is preferred over HPLC purification for automated synthesizer apparatus syntheses. Their cartridge methodology, however, suggests that dichloromethane or chloroform are the best solvents for [18F]-FBA purification. Both solvents have unsuitable toxicological properties for in vivo use, and are immiscible with water. The method is therefore unsuitable for radiopharmaceutical preparations.
Battle et at [J. Nucl. Med., 52(3), 424-430 (2011)] disclose monitoring anti-angiogenic therapy with [18F]-fluciclatide:

Battle et at mention that the [18F]-FBA used was purified by diluting with water, and trapping on a solid-phase extraction (SPE) cartridge. Impurities such as precursor, DMSO, Kryptofix-222 and hydrophilic by-products were said to be eluted to waste, and the [18F]-FBA subsequently eluted with ethanol. The present inventors have, however, found that using a C18 SPE cartridge only some of the precursor is eluted to waste, and the remainder co-elutes when the [18F]-FBA is eluted with ethanol.
There is therefore still a need for alternative methods of labelling biological targeting moieties with 18F.
The Present Invention.
The present invention provides improved 18F-radiolabelled biological targeting moiety (BTM) compositions, derived from the conjugation of 18F-labelled aldehydes. To aminooxy- or hydrazine-functionalised BTMs. The invention is based on detailed analyses of the impurities present in such aldehydes, and an understanding of how they may be carried through into the radiolabelled BTM product—plus how best to suppress all undesired impurity species. Many of these impurities were not recognised in the prior art, and hence such prior art agents contained undesirable species which would adversely affect the imaging characteristics.
In addition, the improved compositions of the present inventions can be achieved in shorter preparation times, which minimises any loss of 18F (half-life 109 minutes) radioactive content during the preparation and purification steps prior to use. The compositions of the present invention can be obtained using methodology which is amenable to automation on a commercial automated synthesizer apparatus—an advantage over prior art HPLC methods (which cannot be automated in this way). Automation confers improved reproducibility, as well as reduced operator radiation dose.
In addition, the higher radiochemical yield and purity of the product means that less functionalised BTM need be used in obtain the same amount of radioactive product. Since the unlabelled BTM will compete for the same biological site in vivo, lowering the amount of functionalised BTM present helps preserve the efficacy of the radiolabelled product. In addition, since the BTM may be e.g. a complex polypeptide or protein which is expensive and time-consuming to obtain, that is an important efficiency of time/materials.
The present invention provides compositions wherein the concentration of the desired 18F-radiofluorinated BTM is enhanced by a factor of about 40, while the chemical impurities are reduced by about 99% (ie. by a factor of about 100).


An amplification circuit includes a first power supply; a first bipolar transistor whose collector is connected to the first power supply; a first resistor one terminal of which is connected to an emitter of the first bipolar transistor; a second bipolar transistor whose collector is connected to the other terminal of the first resistor; a second power supply; a third bipolar transistor whose collector is connected to the second power supply; a second resistor one terminal of which is connected to an emitter of the third bipolar transistor; and a fourth bipolar transistor whose collector is connected to the other terminal of the second resistor. An emitter of the second bipolar transistor is directly connected to an emitter of the fourth bipolar transistor, thereby becoming an output terminal.

The present disclosure relates to an amplification circuit.
For example, an output stage of a circuit which amplifies an audio signal or the like is configured by a circuit in which an NPN type transistor and a PNP type transistor are connected in a push-pull shape. A technology of improving a sound quality of an audio signal without using a resistor (appropriately referred to as an emitter resistor) which is connected to the emitter of each transistor of the push-pull circuit is described in Japanese Unexamined Patent Application Publication No. 2004-297746.


Provided is a use of an miRNA of an Epstein-Barr virus (EBV), more specifically, EBV miR-BART4-5p, miR-BART4-3p, miR-BART1-5p, miR-BART15-3p, miR-BART5-5p, miR-BART5-3p, miR-BART16-5p, miR-BART16-3p, miR-BART17-3p, miR-BART21-3p, miR-BART18-5p, miR-BART7-5p, miR-BART9-5p, miR-BART22-5p, miR-BART20-3p, miR-BART13-5p, miR-BART13-3p, miR-BART2-3p, and mimics thereof for promoting apoptosis or inhibiting cell growth.

Apoptosis is an important process in normal development and functioning of multicellular organisms. Physiological apoptosis plays an important role in various normal processes, however, abnormal apoptosis causes various diseases (Science. 267, 1456-1462 (1995); Biochem Biophys Res Commun. 266 (3), 699-717 (1999)).
For example, inhibited apoptosis may cause a cancer, an autoimmune disease, an inflammatory disease, and a virus infection. On the other hand, excessive apoptosis may cause a degenerative neurologic disease or a cardiac disease. Thus, as regulation of apoptosis in a concerned tissue or cell is very valuable, a substance promoting apoptosis is useful for preventing and treating an autoimmune disease, a lymphoproliferative disease, an inflammatory disease, and a virus infection and a substance inhibiting apoptosis is useful for preventing and treating a degenerative neurologic disease or a cardiac disease.
MicroRNAs (miRNAs) are non-coding RNAs formed when a long hairpin type transcript produced in a cell is cleaved by enzymes named as Drosha and Dicer into 19 to 25 nt. miRNAs have a base sequence which is incompletely complementary to a 3′ untranslated region of a target gene mRNA, and thus inhibit translation. However, miRNAs have a fully complementary base sequence, and thus induce mRNA degradation.
In 2004, a first case of a virus that EBV expresses its own viral miRNA was reported. Afterwards, 25 pre-miRNAs were discovered. Among the pre-miRNAs, 22 pre-miRNAs produced from a BART transcript were largely divided into Cluster 1 and Cluster 2, and were expressed in most of the EBV-related tumor or cell strain.
miR-BART5-5p, which is expressed in a EBV-infected cell, was reported to inhibit expression of PUMA, which is a pro-apoptotic protein, to increase a rate of cell survival rate (J Exp Med. 205(11), 2551-2560 (2008)). On the other hand, it was reported that, while LMP1, which is an oncogenic EBV protein, induces cell growth and transformation at a low LMP1 expression level, LMP1 inhibits cell growth at a high LMP1 expression level, and miR-BART1-5p, 16-5p, and 17-5p inhibit an LMP1 expression to decrease apoptosis (Proc Natl Acad Sci USA. 104(41), 16164-16169 (2007)). It was reported that miR-BART22-3p inhibits expression of LMP2A, which is known to be necessary to maintain EBV latency, and, although miR-BART22-3p does not affect cell growth or apoptosis, miR-BART22-3p may promote immune evasion (Neoplasia. 11(11), 1174-1184 (2009)). It was reported that miR-BART2-5p targets BALF5, which is an EBV DNA polymerase, to contribute to maintenance of EBV latency and, at the same time, targets MICB, which is a ligand of a natural killer cell, to evade an immune response by the natural killer cell (Nucleic Acids Res. 36(2), 666-675 (2008); Cell Host Microbe. 5(4), 376-385 (2009)). It was reported that miR-BART6-5p targets Dicer, which is related with miRNA biogenesis, and contributes to maintenance of EBV latency (J Biol. Chem. 285(43), 33358-33370 (2010)). Recently, it was proved through a luciferase reporter assay that miRNAs of BART Cluster 1 and Cluster 2 inhibit expression of Bim, which is a pro-apoptotic gene, and reduce apoptosis, but the specific BART miRNA having such functions was not identified (Virology. 412(2), 392-400 (2011)). As described above, EBV BART miRNAs are known to promote cell growth and inhibit apoptosis.

Composition for promoting apoptosis or inhibiting cell growth, comprising epstein-barr virus microrna

Catholic University Industry Academic Cooperation Foundation


A method and system for determining the geolocation--i.e., the latitude, longitude, and altitude--of a stationary RF signal emitter from two or more moving observer aircraft. The observers receive signals from the emitter and the system measures the phase difference between the signals. The observers then perform pulse time of arrival (TOA) measurements over a predetermined clock interval, and calculate the time difference of arrival (TDOA) of corresponding, same-pulse, emitter signals. Based on geometric relationships, the system creates a series of circular lines of position (LOPs) for each observer, and computes hyperbolic LOPs based on the TDOA calculations. The system determines emitter location from the intersection of the hyperbolic LOPs and the circular LOPs.

1. Field of Invention
This invention uses multiple observers to passively determine range and bearing to an RF emitter. In particular, it employs ambiguous emitter wavefront phase change measured at each of at least two moving aircraft, and pulse time of arrival measurements made between two platforms to perform the geolocation.
2. Description of Related Art
Applicant's copending application entitled, "COMBINED PHASE-CIRCLE AND MULTIPLATFORM TDOA PRECISION EMITTER LOCATION," filed on even date herewith and assigned to present assignee, the entire disclosure of which is hereby incorporated by reference in this specification, discloses a method for reducing the geometrical dilution of precision (GDOP) degradation experienced when using multiplatform circular lines-of-position for precision emitter location. This was accomplished by combining the circles-of-position (COPs) generated by interferometer phase difference measurements made by one moving platform with hyperbolic lines-of-position (HLOPs) generated by pulse time difference of arrival (TDOA) measurements between two observers. This combined technique overcame low-frequency limitations in the phase-circle-only approach and reduced sensitivity to time of arrival (TOA) measurement errors compared with TDOA-only geolocation. The use of measurements made by a fully resolved short baseline interferometer (SBI) on the moving platform was a key element of the method. For example, the SBI angle-of-arrival (AOA) measurements made by two separate platforms were used to provide an initial coarse location of the emitter. This coarse location was accurate enough to verify that TDOA measurements between observers were being made on the same pulse of the emitter signal. The SBI was also used in more fundamental ways to generate the phase circles, or COPs, as discussed briefly below.
The COPs were produced from long-baseline interferometer differential phase measurements by the method described in the applicant's U.S. Pat. No. 5,526,001. Resolving ambiguous LBI phase requires simultaneously measuring fully resolved phase with the SBI, using the technique disclosed by Kaplan in U.S. Pat. No. 4,734,702.
In this approach for generating phase circles, requirements on the system phase measurement's repeatable accuracy were reduced. This reduction occurred because any fixed-phase bias error present during the receiver dwell at the first observation point canceled when forming the phase difference at the second observation point. Thus, the LBI baseline did not require calibration. Also, constant antenna phase mistrack errors and receiver calibration phase-bias errors canceled and had no impact on COP accuracy. But as a consequence of this method, the LBI measured only angle change, and not AOA. The SBI not only predicted angle change to resolve the LBI, but also provided the measure of AOA required to correct for variable bias errors.
Variable bias errors, i.e., those that remain constant during a receiver dwell but vary from one receiver dwell to another, greatly impact COP precision and, hence, location accuracy, and must be reduced. The most significant variable bias error is due to changes in a scanning radar's electromagnetic wave polarization caused by the observer detecting different emitter sidelobes in different receiver dwells. This dwell-to-dwell polarization change affects the LBI antenna phase mistrack, and can cause in the differential phase measurement an error of five electrical degrees or more. Since the error is constant between all signal pulses used to form the phase difference between dwells, it cannot be reduced by averaging, as can thermal noise and quantization errors. The method to reduce this error disclosed in applicant's copending application, entitled, "COMBINED PHASE-CIRCLE AND MULTIPLATFORM TDOA PRECISION EMITTER LOCATION," contemplates producing a table from antenna polarization response measurements on the observing aircraft for different signal angles-of-arrival. The SBI AOA measurements made when LBI phase differences are formed are then used to access this table for calibration data that corrects the LBI measurements.
Hence, for resolving the long-baseline interferometer, correcting the variable phase bias errors, and confirming the TDOA measurement, the SBI forms an intrinsic part of the approach given in applicant's copending application entitled, "COMBINED PHASE-CIRCLE AND MULTIPLATFORM TDOA PRECISION EMITTER LOCATION." However, many aircraft used to passively locate emitters do not currently have an SBI available. Furthermore, because of weight, cost, and airframe limitations, it may not be feasible to add an SBI to the existing electronic surveillance measurement (ESM) system. Therefore, it is desirable to have an alternative approach to implementing a combined COP-HLOP location technique that preserves the method's GDOP reduction, improved low-frequency performance, and reduced need for TDOA accuracy, while requiring only two antenna elements. This requires that alternatives be found to resolve the phase ambiguity and correct the phase polarization error.
One alternative approach to differentially resolving the LBI is disclosed in applicant's U.S. Pat. No. 5,343,212, and discussed in connection with phase-circle generation in U.S. Pat. No. 5,526,001. A set of emitter positions is postulated, and each used to establish a hypothesis test. The hypothesis test generates a set of potential emitter locations, resolves the LBI in a manner consistent with each of these assumed locations, and utilizes a sequential check over a number of measurements to determine the actual emitter location from the set. While robust, this method requires multiple receiver dwells to eliminate the incorrect emitter locations. In many multiplatform geolocation situations that are tactically important, the emitter may transmit for no more than ten seconds and the number of phase difference measurements made in that interval can be severely limited. Such a small number of measurements may not be sufficient for the hypothesis test to generate a single unambiguous phase circle.
This invention overcomes the limitations of using an SBI or hypothesis test to resolve the LBI at the expense of requiring at least two moving observers to separately generate multiple phase circles from the ambiguous LBI differential phase measurements. A phase circle is produced for each possible ambiguity resolution of the differential measurements. This is illustrated in FIG. 3 for the scenario shown in FIG. 2 208. The COPs 300, 301 and 302 are derived from the ambiguous phase measurements made by observer 308, corresponding to aircraft 206 in FIG. 2 208, while COP 304, 305 and 306 are generated from the ambiguous phase measurements made by aircraft 307 (205 in FIG. 2). COP 301 and 305 are the true emitter circles-of-position, and this is determined by the common intersection 309 with the TDOA hyperbola limb 303. In this example the TDOA is measured between platforms 307 and 308, but other observers could be used. Thus the invention does not attempt to correctly resolve the phase difference measurement ambiguities before generating the phase circles, and hence does not have the problem with sparse data that can degrade the hypothesis test method. In fact, the phase difference ambiguity is not resolved before the emitter is located. This creates difficulties in correcting the LBI phase measurements for variable bias error and overcoming this difficulty is a key aspect of the invention.
The use of the TDOA measurement in conjunction with the ambiguous phase measurements to locate the emitter and then the use of emitter location to resolve the differential phase should be compared with methods that use TDOA to directly resolve the LBI. Cusdin et al. in U.S. Pat. No. 4,797,679 provide an approach representative of such direct techniques. The LBI used in Cusdin's method must be phase calibrated, and the TDOA measurement is made on the same platform between the two antennas used to measure LBI phase. Also the TDOA measurement must be nearly simultaneous with the phase measurement. Cusdin's is thus intrinsically a single platform technique that associates resolved LBI phase with emitter signal AOA. For multiplatform geolocation the resolved AOAs on two platforms could be intersected, as shown in FIG. 1a. In this figure 160 and 161 represent the AOA, while 178 and 179 are the wedge shaped AOA errors, and 162 the uncertainty these errors create in the emitter location. This region of uncertainty grows quickly with range, but an advantage the method does have is that the observers 163 and 165 obtain the range estimate in a single observer dwell.
By contrast to the direct ambiguity resolution of calibrated LBI phase measurements by TDOA in a single receiver dwell, the method disclosed here uses uncalibrated LBI baselines that are differentially resolved across receiver dwells. Hence, as noted above, AOA is not measured and at least two separate receiver dwells made seconds apart, indicated by the moving observer at 165-166 and at 167-168, are required. Also the LBI ambiguities for the phase measurements made on at least two aircraft must be simultaneously resolved, in effect, by locating the emitter utilizing TOA measurements made on separate platforms rather than across the LBI baseline. The TOA measurement does not have to be time coincident with the LBI phase measurements, nor, as emphasized above, do the observers making the TOA measurements have to be the same as those making the differential phase measurements. Thus this invention is intrinsically a multiplatform technique.
The association of the LBI differential phase measurements with COP 169 and 170 in 174 FIG. 1a rather than the LBI phase with AOA 160 and 161 (173 FIG. 1a) provides a substantial reduction in GDOP compared with a multiplatform application of Cusdin's method. Although the magnitude of the COP error region does have a range dependence since it is ultimately based on the bearing subtended at the emitter, the excursions caused by one sigma error variations indicated by 175 and 177 are the same at each point on the respective COPs 169 and 170. Further, since the TDOA measurement is made between platforms rather than between two antenna on a single platform, it provides a third LOP 171 (with range independent one sigma error 175) which greatly reduces the GDOP, as indicated by the emitter location error region 172.
FIG. 1b is a top level block diagram of the invention, illustrating how ambiguous LBI and TDOA measurements are used to geolocate the emitter in the manner indicated by 174 FIG. 1a for the FIG. 2 208 scenario, producing the COP and HLOP as shown in FIG. 3. Aircraft 307 in that figure corresponds to observer 100 FIG. 1a. The system on aircraft 308 corresponds to 102 and is identical to 100. Hence only the utilization of system 100 will be described in detail in the following summary. The central computing site 103 could be located on either aircraft, or on both, or on a third platform.
The operation of these particular features and other aspects of the invention, such as the method for reducing the impact of variable bias errors without making SBI measurements, are presented in more detail in the summary that follows.

Multiplatform ambiguous phase circle and TDOA protection emitter location


A surveillance system having two specialized surveillance cameras with corresponding specialized illuminators is provided in a dual compartment container that eliminates internal light reflection problems by separating each camera and corresponding illuminator while combining each camera with an alternate illuminator, rendering the system more accurate, yet more compact and suited to unobtrusive placement. Considerable heat is generated by the specialized illuminators, requiring a heat sink to preserve illuminator life expectancy and to prevent the adjacent cameras from being adversely affected by the heat. Another feature enabling the system to work in its compact form despite the heat from the illuminators is that the protective case itself is adapted to be a heat sink for the illuminators.

This invention relates to security cameras and the obtaining of optimal images under varying ambient light conditions. In some circumstances, it is most effective to obtain visible light images. In other situations, such as poor visibility due to smoke or fog, infrared images give the best information about people and objects in the surveillance situation. Versatility and adaptability of the security system to varying conditions is desired.
With security cameras it is usual to place a protective translucent pane or dome over the camera and illuminator, to guard it against the elements or intentional damage by intruders or others who do not wish to be observed.
The combination of versatile camera systems with protective cases has resulted in many such security systems being bulky and difficult to place in a discreet, unobtrusive way.