The present invention concerns a method for the detection of cytosine methylation in DNA samples, wherein the following steps are conducted: (a) a genomic DNA sample, which comprises the DNA to be investigated and background DNA, is chemically treated in such a way that all of the unmethylated cytosine bases are converted to uracil, whereas the 5-methylcytosine bases remain unchanged; (b) the chemically treated DNA sample is amplified with the use of at least 1 primer oligonucleotide as well as a polymerase, whereby the DNA to be investigated is preferred as the template over the background DNA, and (c) the amplified products are analyzed and the methylation status in the DNA to be investigated is concluded from the presence of an amplified product and/or from the analysis of additional positions.

The present invention concerns a method for the detection of cytosine methylation in DNA samples.
The levels of observation that have been well studied due to method developments in recent years in molecular biology include the genes themselves, as well as transcription and translation of these genes into RNA and the proteins arising there from. During the course of development of an individual, when a gene is turned on and how the activation and inhibition of certain genes in certain cells and tissues are controlled can be correlated with the extent and nature of the methylation of the genes or of the genome. Pathogenic states are also expressed by a modified methylation pattern of individual genes or of the genome.
5-Methylcytosine is the most frequent covalently modified base in the DNA of eukaryotic cells. For example, it plays a role in the regulation of transcription, in genetic imprinting and in tumorigenesis. The identification of 5-methylcytosine as a component of genetic information is thus of considerable interest. 5-Methylcytosine positions, however, cannot be identified by sequencing, since 5-methylcytosine has the same base-pairing behavior as cytosine. In addition, in the case of a PCR amplification, the epigenetic information, which is borne by 5-methylcytosines, is completely lost.
A relatively new method that has since been applied most frequently for investigating DNA for 5-methylcytosine is based on the specific reaction of bisulfite with cytosine, which is converted to uracil, which corresponds in its base-pairing behavior to thymidine, after a subsequent alkaline hydrolysis. In contrast, 5-methylcytosine is not modified under these conditions. Thus the original DNA is converted, such that methylcytosine, which originally cannot be distinguished from cytosine by means of its hybridization behavior, now can be detected by "standard" molecular biological techniques as the single remaining cytosine, for example, by amplification and hybridization or sequencing. All of these techniques are based on base pairing, which now is fully utilized. The prior art, which concerns sensitivity, is defined by a method that incorporates the DNA to be investigated in an agarose matrix, through which diffusion and renaturation of the DNA is prevented (bisulfite reacts only on single-stranded DNA) and all precipitation and purification steps are replaced by rapid dialysis (Olek A., Oswald J., Walter J. A modified and improved method for bisulphate based cytosine methylation analysis. Nucleic Acids Res. 1996 Dec. 15; 24 (24): 5064-6). Individual cells can be investigated with this method, which illustrates the potential of the method. Of course, previously, only individual regions of up to approximately 3000 base pairs in length have been investigated; a global investigation of cells for thousands of possible methylation analyses is not possible. Of course, this method also cannot reliably analyze very small fragments of small sample quantities. These are lost despite the protection from diffusion through the matrix.
A review of the other known possibilities for detecting 5-methylcytosines can be derived from the following review article: Rein T, DePamphilis M L, Zorbas H. Identifying 5-methylcytosine and related modifications in DNA genomes. Nucleic Acids Res. 1998 May 15; 26 (10): 2255-64.
The bisulfite technique has previously been applied only in research, with a few exceptions (e.g., Zeschnigk M, Lich C, Buiting K, Dörfler W, Horsthemke B. A single-tube PCR test for the diagnosis of Angelman and Prade-Willi syndrome based on allelic methylation differences at the SNRPN locus. Eur J Hum Genet. 1997 March-April; 5 (2): 94-8). However, short, specific pieces of a known gene are always amplified after a bisulfite treatment and either completely sequenced (Olek A, Walter J. The pre-implantation ontogeny of the H19 methylation imprint. Nat Genet. 1997 November.; 17(3): 275-6) or individual cytosine positions (Gonzalgo M L, Jones P A. Rapid quantitation of methylation differences at specific sites using methylation-sensitive single nucleotide primer extension (Ms-SNuPE). Nucleic Acids Res. 1997 Jun. 15;25 (12):2529-31; WO 95/00669) or an enzyme cleavage (Xiong Z, Laird P W. COBRA: a sensitive and quantitative DNA methylation assay. Nucleic Acids Res. 1997 Jun. 15;25(12): 2532-4) are detected by a "primer extension reaction". Also, detection by means of hybridizing has been described (Olek et al., WO 99/28498).
Urea improves the efficiency of the bisulfite treatment prior to the sequencing of 5-methylcytosine in genomic DNA (Paulin R, Grigg G W, Davey M W, Piper A A. Urea improves efficiency of bisulphate-mediated sequencing of 5′-methylcytosine in genomic DNA Nucleic Acids Res. 1998 November 1;26(21):5009-10).
Other publications, which are concerned with the application of the bisulfite technique for the detection of methylation in individual genes are: Grigg G, Clark S. Sequencing 5-methylcytosine residues in genomic DNA. Bioassays. 1994 June; 16(6):431-6, 431; Zeschnigk M, Schmitz B, Dittrich B, Buiting K, Horsthemke B, Dörfler W. Imprinted segments in the human genome: different DNA methylation patterns in the Prader-Willi/Angelman syndrome region as determined by the genomic sequencing method. Hum Mol Genet. 1997 March; 6(3):387-95; Feil R, Charlton J, Bird A P, Walter J, Reik W. Methylation analysis on individual chromosomes: improved protocol for bisulphate genomic sequencing. Nucleic Acids Res. 1994 February 25;22(4):695-6; Martin V, Ribieras S, Song-Wang X, Rio M C, Dante R. Genomic sequencing indicates a correlation between DNA hypomethylation in the 5′ region of the pS2 gene and in its expression in human breast cancer cell lines. Gene. May 19, 1995; 157 (1-2): 261-4; WO 97/46705, WO 95/15373 and W097/45560.
Another known method is so-called methylation-sensitive PCR (Herman J G, Graff J R, Myohanen S, Nelkin B D, Baylin S B. (1996), Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA. Sep. 3; 93 (18): 9821-6). For this method, primers are used, which hybridize either only to a sequence that is formed by the bisulfite treatment of a DNA that is not methylated at the respective position, or, vice versa, primers, which only bind to a nucleic acid which has formed by the bisulfite treatment of a DNA that is methylated at the respected position. With these primers, amplified products can then be produced, whose detection in turn supplies hints of the presence of a methylated or unmethylated position in the sample, to which the primers bind.
A more recent method is also the detection of cytosine methylation by means of a TaqMan PCR, which has become known as "methyl-light" (WO 00/70090). It is possible with this method to detect the methylation status of individual positions or a few positions directly in the course of the PCR, so that a subsequent analysis of the products is spared.
A review of the prior art in oligomer array production can be taken from a special publication of Nature Genetics that appeared in January 1999 (Nature Genetics Supplement, Volume 21, January 1999), the literature cited therein and U.S. Pat. No. 5,994,065 on methods for the production of solid carriers for target molecules such as oligonucleotides with reduced nonspecific background signal.
Probes with many fluorescent labels have been used for the scanning of an immobilized DNA array. Particularly suitable for fluorescent labels is the simple introduction of Cy3 and Cy5 dyes at the 5′-OH of the respective probe. The fluorescence of the hybridized probes is detected, for example, by means of a confocal microscope. The dyes Cy3 and Cy5, in addition to many others, are commercially available.
Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF) is a very powerful development for the analysis of biomolecules (Karras M, Hillenkamp F. Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons. Anal Chem. 1998 Oct. 15;60 (20): 2299-301). An analyte is embedded in a light-absorbing matrix. The matrix is evaporated by means of a short laser pulse and the analyte molecule is transported unfragmented into the gas phase. The ionization of the analyte is achieved by collisions with matrix molecules. An applied voltage accelerates the ions in a field-free flight tube. The ions are accelerated to a varying extent based on their different masses. Smaller ions reach the detector sooner than larger ions.
MALDI-TOF spectroscopy is excellently suitable for the analysis of peptides and proteins. The analysis of nucleic acids is somewhat more difficult (Gut, I. G. and Beck, S. (1995), DNA and Matrix Assisted Laser Desorption Ionization Mass Spectrometry. Molecular Biology: Current Innovations and Future Trends 1: 147-157.) For nucleic acids, the sensitivity is approximately 100 times poorer than for peptides and decreases overproportionally with increasing fragment size. For nucleic acids, which have a backbone with multiple negative charges, the ionization process through the matrix is essentially less efficient. In MALDI-TOF spectroscopy, the selection of the matrix plays a very important role. For the desorption of peptides, several very powerful matrices have been found, which produce a very fine crystallization. Several high-performing matrices have been found in the meantime for DNA, but the difference in sensitivity has not been reduced in this way. The difference in sensitivity can be reduced by modifying the DNA chemically in such a way that it is similar to a peptide. Phosphorothioate nucleic acids, in which the usual phosphates of the backbone are substituted by thiophosphates, can be converted into a charge-neutral DNA by simple alkylation chemistry (Gut, I. G. and Beck, S. (1995), A procedure for selective DNA alkylation and detection by mass spectrometry. Nucleic Acids Res. 23: 1367-1373). The coupling of a "charge tag" to this modified DNA results in an increase in sensitivity by the same amount that is found for peptides. Another advantage of "charge tagging" is the increased stability of the analysis against impurities, which greatly interfere with the detection of unmodified substrates.
Genomic DNA is obtained by standard methods from DNA of cells, tissue or other test samples.
This standard methodology is found in references such as Fritsch and Maniatis, Molecular Cloning: A Laboratory Manual, 1989.
Accordingly, up until now there have been many methods for methylation analysis in the prior art. The present invention, however, will solve the problem that current methods are unable to solve, i.e., to amplify in a targeted manner a DNA to be investigated that is found in a body fluid or serum, when other, sequence-homologous DNA segments of different origin are also present.
The DNA to be investigated as well as the otherwise present nucleic acids, which are named background DNA below, are usually amplified equally, since the primers used are not able to distinguish between the DNA to be investigated and background DNA. One possibility for distinguishing these DNAs, however, is by the different methylation pattern. A current method is methylation-sensitive PCR, abbreviated MSP (Herman J G, Graff J R, Myohanen S, Nelkin B D, Baylin S B. (1996), Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA. September 3; 93 (18): 9821-6). This method is comprised of several steps. First, a bisulfite treatment is conducted according to the prior art, which in turn leads to the circumstance that all cytosine bases are converted to uracil while the methylated cytosine bases (5-methylcytosine) remain unchanged. In the next step, one now uses primers, which are completely complementary to a methylated DNA converted with bisulfite, but not to a corresponding DNA which was present originally in the unmethylated state. When the PCR is conducted with such a primer, this leads to the fact that the originally methylated DNA is amplified exclusively. It is also possible to use a primer, which, in contrast, amplifies only unmethylated DNA. In this way, if the DNA to be analyzed as well as background DNA are present, the DNA fragments to be investigated will be produced selectively and exclusively, as long as they differ from the background DNA relative to their methylation status in a CpG position. Prior art is now to infer from the detection of such a DNA molecule to be investigated either the methylation state or the presence of a DNA to be investigated, which in turn permits, in principle, a diagnosis, for example, of a tumor disorder in the patient, since it is known, for example, that the serum DNA concentration is in part drastically increased in tumor patients. Only the DNA originating from tumors will be detected in addition to the background DNA. In principle, the analysis of DNA is comparable in other body fluids.
The method that is described here and which is to be considered as the closest prior art, however, has several disadvantages. For example, it is not possible to conclude the quantity present in serum from the detectability of an amplified fragment of the DNA to be investigated. Even minimal quantities of such DNA are successful for obtaining a positive result, which is an advantage, on the one hand, but can also act in a very unfavorable manner, if one wishes to evaluate, for example, the effect of a tumor resection on serum DNA. The greatest disadvantage, however, is that many methylation positions are present, in which the DNA to be investigated and the background DNA differ only in degree. It is obvious that the existing MSP method can only be conducted if one knows that the backbround DNA differs definitively and up to 100% from the DNA to be investigated in the CpG position of interest, if one does not want to risk false positive results. In contrast, it is typical in a tumor tissue that a specific position is present in the methylated state, e.g., in 95% of the tumor cells, in which the otherwise present background DNA, however, is present in the methylated state only to a maximum of 5%, so that it is not possible with the MSP method to produce informative results, since a quantification of the template DNA by means of PCR in principle is not possible or can be accomplished only with increased expenditure. Also, this invention is based on the knowledge that often methylation patterns are present in a DNA fragment, which are typical for a specific type of cell, for example, a tumor cell.
Also, prior art includes a process developed by Epigenomics, which amplifies equally the DNA to be investigated and background DNA after bisulfite treatment and then examines the former CpG positions contained in the fragment by hybridization techniques, and alternatively by means of mini-sequencing or another current method. This has the advantage, that a quantitative pattern is obtained relative to the investigated methylated positions, i.e., the determination of the methylation degree of a multiple number of positions is successfully obtained, which, e.g., makes possible a very accurate classification in the case of solid tumors. The disadvantage of this method, however, is that it cannot supply accurate information in those cases in which the background DNA greatly predominates, since this information is amplified accurately along with the DNA to be investigated and both are analyzed in the mixture. This problem does not exist in the analysis of solid tumors, in which the material to be investigated can be selected in a targeted manner, but the analysis, for example, of serum DNA is made difficult.

Highly sensitive method for the detection of cytosine methylation patterns


A method of tracking automotive production in the manufacture of automotive vehicles (10) is provided. The method includes manufacturing a plurality of automotive vehicles along an assembly line (12). Each of the plurality of automotive vehicles having a build characteristic (13). The build characteristics varying among the plurality of automotive vehicles. The method includes installing a radio frequency transmitter within each of the plurality of automotive vehicles as they move along the assembly line (16). Each of the radio frequency transmitters generating a unique identifier signal (20). Associating each unique identifier signal with the build characteristics of one of the plurality of automotive vehicles (34). The method includes transferring the plurality of automotive vehicles to a plant storage lot as they exit the assembly line (14). The method includes receiving the unique identifier signals (30). The unique identifier signals are used to determine the identity and location of each of the plurality of automotive vehicles within the plant storage lot (40).

The automotive industry must often manage large inventories of products. These inventories often can include a wide variety of different vehicles. Vehicles are often produced at rates such as forty or sixty vehicles per hour. This produces a continuous stream of new vehicles exiting the assembly line. The storage of these vehicles requires large storage areas. Because of this, automotive plants commonly utilize large parking facilities within the manufacturing plant grounds for storing and sorting vehicles. Additionally, the large number of vehicles is handled by a constant flow of vehicles out of storage to counter the flow of vehicles into storage.
The constant flow of vehicles to and from storage can create difficulties in the management of the inventory. The shipment of the wrong vehicle can create costly and time intensive problems. One known solution to such problems has been to track the individual vehicle through the use of a database. Although the use of such databases allows a general accounting of the inventory stock, it often does not prevent the shipment of the incorrect vehicle. If an incorrect vehicle is loaded by mistake and shipped, not only will the solution involve undesirable cost to fix, but also the resulting inventory within the database will likely be incorrectly reported. This is clearly undesirable.
One known solution to prevent the shipping of incorrect products has been to store differing products in separate areas within the storage area. While this may reduce that shipment of incorrect products, it can also have undesirable consequences. The sorting of vehicles into separate storage areas can increase handling costs and may lead to inefficient use of available storage area. In addition, the rate of vehicles flowing off the production line makes such sorting difficult. Also, the build characteristics of consecutive vehicles coming of the line often varies to fit specific orders. This would further confuse storage sorting. As the percentages of each differing build characteristic fluctuates, differing sized storage areas can be required. In addition, the use of separate storage areas also can become undesirable when the number of different vehicles becomes large. As the number of different build characteristics increases, the cost to sort and store such vehicles can become prohibitive. The cost, manpower, and time required for rearranging the storage area to accommodate fluctuations and large numbers of differing vehicles can be undesirable.
In addition to the problem of shipping incorrect vehicles, the large inventories can create additional problems. One such problem arises when specific individual vehicles with a given build characteristic need to be located. If a batch of vehicles with a particular build characteristic is identified as needing repair or recall, the identification of such vehicles may be difficult, costly, and occasionally impossible. The batch may include different vehicles that may be located in different sections of the storage area. In other situations, the specific vehicles may simply include custom products that need to be identified. Even when the general area of the storage facility can be identified as the location of the specific vehicle (such as by tracing production time), finding the specific vehicle can be difficult and costly.
It would therefore be desirable to have a method of tracking inventory that provided a reliable and accurate way to track the exact contents of an automotive storage facility. In addition, it would be desirable for a method that would reduce the shipments of incorrect vehicles, handle the storage of a wide variety of differing vehicles, and would allow specific individual vehicles of vehicle sub-groups to be quickly and efficiently located.

Method of tracking automotive production


A method and a highway addressable remote transducer (HART) soft modem device for modulating and demodulating analog signals with HART messages are provided. A phase coherent frequency shift keying (FSK) modulator modulates and transmits analog signals with HART messages, and a phase coherent FSK demodulator receives and demodulates the analog signals with the HART messages. The FSK modulator is a digital modulator that outputs 1 or 0 for transmission. With oversampling and low pass filtering, the digital modulation results in low jitter and good signal to noise ratio. The FSK demodulator applies a fast energy detect algorithm and dynamically reduces or increases a clock speed of a central processing unit (CPU) of the HART soft modem device for reducing power consumption of the CPU. Furthermore, the HART soft modem device uses direct memory access (DMA) to further reduce the power consumption, thereby reducing the overall power consumption by around 50%.

Smart field data devices in use today are generally Highway Addressable Remote Transducer (HART) enabled. HART is a global standard for sending and receiving digital information across analog wires between smart devices and control or monitoring systems. The HART communications protocol is widely recognized as the industry standard for digitally enhanced 4 milliampere (mA)-20 mA smart instrument communication. Use of the HART based technology is growing rapidly and today most major global instrumentation suppliers offer products with the HART communications protocol. The HART communications protocol enables two-way digital communication with smart instruments without disturbing 4 mA-20 mA analog signals. The HART communications protocol utilizes, for example, the Bell 202 frequency shift keying (FSK) standard of the Bell 202 modulator-demodulator (modem) of Bell System to superimpose digital communication signals at a low level over the 4 mA-20 mA analog signals. This process enables two-way field communication and makes it possible for additional information beyond the typical process variables to be communicated to and from a smart field instrument.
Current deployment of Highway Addressable Remote Transducer (HART) field data devices utilizes a hardware based Bell 202 modem and a separate microcontroller for a HART communications protocol implementation which adds to the total power. One or more HART field data device implementations, for example, a mixed signal microcontroller such as the MSP430 microcontroller, that utilize low power are known in the art. The MSP430 microcontroller utilizes many power saving techniques comprising multiple low power modes (LPMs), for example, LPM1 to LPM3. The current state of the art HART field data device implementations utilize these power saving methods. Although the MSP430 microcontroller can perform direct memory access (DMA) when a central processing unit (CPU) of the MSP430 microcontroller is not on or activated, the HART field data devices that currently exist do not implement this technique. Moreover, the implementations known in the art utilize a poor approximation of the Bell 202 modem and are likely to result in poor performance characteristics in terms of bit error rate and low probability of receiving HART communications protocol messages correctly. Furthermore, combining precise digital signal processing (DSP) algorithms with DMA power saving methods are not implemented in the HART field data devices known in the art.
Highway Addressable Remote Transducer (HART) field data devices are commonly used in industrial automation and control systems. Many of these HART field data devices comprise a microcontroller, a HART modulator-demodulator (modem) compliant to the Bell 202 standard, and an interface arrangement compliant to a conventional 4 mA-20 mA current loop circuit. However, the total component count of the HART modem adds to the overall cost, lowers reliability of the HART modem, and results in higher power consumption. Hence, there is a need for a solution, for example, a soft modem device which eliminates additional components such as modem chips, resistors, capacitors, crystal oscillators, etc., and reduces cost and power. Since the HART communications protocol typically requires less than 1 megahertz (MHz) of central processing unit (CPU) cycles, the HART field data devices allow room for soft modem implementation. A soft modem is a modem with minimal hardware that utilizes a host's resources in place of additional hardware in a conventional modem. Since HART field data devices that utilize Bell 202 modem standards are power sensitive, there is a need for a soft modem implementation of the HART field data device that uses advanced techniques to minimize operating power.
In a typical Highway Addressable Remote Transducer (HART) field data device, modulation is performed via pulse width modulation (PWM). PWM is a modulation technique that controls the width of a pulse based on modulator signal information. Typically, PWM allows control of the power supplied to electrical devices. A conventional PWM modulator utilizes two different frequencies for PWM generation. This type of modulation works well at low baud rates, for example, at 300 bauds in a V.21 or Bell 103 modem, but results in substantial jitter and a lack of phase coherency at higher speeds. Hence, there is a need for a digital modulator with an exact numerical implementation, that outputs 1 or 0 instead of an 8 bit value, that operates at high baud rates, for example 19200 or 9600 samples per second, and that results in low jitter and a good signal to noise ratio. Further, there is a need for lowering power consumption of the HART field data device by incorporating energy detect schemes to reduce the central processing unit (CPU) speed when no HART analog signal is present, using direct memory access which can work without CPU intervention, thereby lowering CPU power consumption, and changing the CPU clock dynamically as the processing demand of the HART field data device increases. Common energy detection methods for detecting a valid signal to enable power savings in a soft modem utilize an averaging and threshold detection method. These energy detection methods, typically, have a longer time constant and are slow to respond. Hence, there is a need for a quick energy detection method with a slower detection of energy decay.
Hence, there is a long felt but unresolved need for a soft modem implementation of a Highway Addressable Remote Transducer (HART) field data device which requires low operating power. Furthermore, there is a need for a method that performs quick energy detection of digitized analog samples and throttling of the central processing unit (CPU) clock of the HART soft modem device based on the energy detection of the digitized analog samples, for reducing power consumption of the HART soft modem device.

Energy efficient highway addressable remote transducer soft modem


A contact assembly including an insulative carrier having a plurality of passages formed therein. A spring contact is positioned in the plurality of passages. The spring contact includes a helical spring and a contact plate affixed to one end of the helical spring. The contact plate has a plurality of portions extending away from the contact plate and extending away from the helical spring.

The invention relates generally to contact assemblies and in particular to a spring-biased, grid contact assembly and method of manufacturing thereof.
Integrated circuits are typically housed within a package that is designed to protect the integrated circuit from damage, provide adequate heat dissipation during operation, and provide electrical connection between the integrated circuit and the leads of a printed circuit board. Several conventional packages are in the prior art including land grid array (LGA), pin grid array (PGA), ball grid array (BGA), and column grid array (CGA).
In integrated circuit (IC) packages, terminal lands are arranged on one major face of the package in a pattern corresponding with mounting pads, or leads, on the surface of a circuit board or the like. The device package is mounted on the circuit board by soldering the terminal lands to the mounting pads. Packages having a pattern of lands distributed over a major portion of one face thereof are called land grid array (LGA) packages. Similarly, packages having small solder bumps arranged in a pattern on one face for forming interconnections with external circuitry are usually referred to as ball grid array (BGA) packages.
In many applications, the soldering of the leads of the IC package to the printed circuit board is undesirable. For example, it is impossible to visually locate a short or ground between the IC package and printed circuit board. Usually, an expensive X-ray technique is required to inspect the connections since the leads are hidden under the package. Further, the increasing number of leads being provided by IC packages makes the soldering of the packages to printed circuit boards more difficult.
Accordingly, in the prior art, an improved connector has been developed which is designed to eliminate the need for the soldering the leads of an IC package to a printed circuit board. One example of a device which satisfied this criteria is the wadded wire of "fuzz ball" socket. The "fuzz ball" socket comprises a non-conductive substrate formed with a plurality of through holes which each house a contact element. The contact elements are formed by forcing a predetermined length of gold plated wire into a through hole such that the wire will bend haphazardly into a jumbled contact that extends through the through hole and resembles a piece of steel wool. To mount an IC package to a printed circuit board, the "fuzz ball" socket is tightly sandwiched between the printed circuit board and the package to tightly secure to the "fuzz ball" socket. It can be appreciated, sufficient pressure must be applied to both the "fuzz ball" socket and the package, respectively, to maintain electrical connections between the lands of the package and the printed circuit board via the "fuzz ball" socket.
As the number of lands and corresponding "fuzz ball" contacts are increased, the pitch between contacts is maintained increasing the module size correspondingly with increased manufacturing problems due to the number of contacts. The placement of individual wires into evermore through holes requires tremendous logistics. Furthermore, "fuzz ball" sockets are relatively expensive due to costly manufacturing including the placement of individual wires into the through holes to form the various "fuzz ball" contacts. Additionally, the great force required to push the ball leads of a BGA package into contact with the "fuzz ball" socket creates wear on the BGA ball leads and increases the likelihood of distorting the ball leads.
Wadded wire contact performance is statistically based due to fabrication techniques. This means that the number of contact points and bulk resistance varies contact to contact which requires testing of every contact to verify performance and higher contact normal force. These contacts are also susceptible to physical handling damage. The spring rate of these contacts is relatively high with a low working range of compressions (i.e. about 3 mils).
Other contact assemblies use shear stamped LGA contacts. Such contacts typically have low compliance or high compression stiffness that requires a high nominal contact normal force to provide enough deflection to accommodate packaging tolerances. Stamped sheet contacts of a leaf spring design result in relatively long parallel contact structures with corresponding high electrical coupling which increases near and far end noise limiting signal integrity at high circuit (i.e. clock) speeds. Furthermore, it is desirable to achieve high contact stress and the connection interface, which results in a more reliable connection. Thus, there is a need in the art for a contact array that provides high contact interface stress with a low connection compression force, which in essence results in a low force.

Contact assembly and method of making thereof

International Business Machines Corporation


A light emitting device is provided, comprising a light emitting diode 10, where the light emitting surface 11 thereof is bound to an optical element 13 by means of a bonding material 12 comprising a phosphate glass or an oxide glass having Tg<250° C. In operation of the device, when the temperature approaches or exceeds Tg of the bonding material, the bonding material gets fluidic and can thus relax any thermally induced stresses between the light emitting diode and the optical element.

Light emitting diodes (LEDs) are currently contemplated as light sources for several different lighting applications, and the use of light emitting diodes is expected to grow in the coming years.
A light emitting diode is typically comprised in a package containing the actual LED-chip comprising the active, light producing, layers, and light extraction optics arranged on the LED-chip. The light extraction efficiency between the chips ant the optics of the package is a major issue with which LEDs are confronted.
A classical approach in this context involves the use of primary extraction optics, e.g. optical domes provided on the LED-chips, which optical domes extract the light based on their refractive properties. The materials of these optical domes are often based on silicones and polymers (such as PMMA). However, these optical domes have limited photo-thermal stability, which limits the power of the used LED-chips, which in turn limits the lumen power of the light-emitting device.
An approach to solve this is to use inorganic optical elements for the extraction of light from LED chips. The material of such optical elements can for example be polycrystalline ceramic materials or glass. Such inorganic optical elements have much higher photo-thermal stability, which allows light emitting devices with high lumen power and output.
However, high power LEDs may dissipate significant amounts of heat, and the radiation may be intense. In this context, the bond between the LED chip and the extraction optics, which forms a junction that couples light from the LED chip to the extraction optics and that physically binds the extraction optics to the LED chip, should itself exhibit high photo-thermal stability, so that it is not the limiting factor in the light-emitting device, and so that it is able to benefit from the high photo-thermal stability of the inorganic extraction optics.
However, as high power LEDs may dissipate a lot of heat in operation, slight differences between the coefficients of thermal expansion for the LED-chip, the bonding material and extraction optics results in build-up of heat induced tensions in the package, eventually leading to breakage of the package. Thus, there is a need for a light-emitting device where the bond between the LED-chip and the extraction optics can withstand the load and stress it is exposed to.

Light emitting device with tension relaxation


A device for producing circularly polarized optical emission includes a light emitting semiconductor heterostructure, further including at least one semiconducting layer; a ferromagnetic contact having a magnetic moment, in electrical contact with a layer of the semiconductor heterostructure; and a contact electrically connected to a different region of the semiconductor heterostructure. This light emitting semiconductor heterostructure may be a light emitting diode (LED), or some other structure. The ferromagnetic contact injects spin polarized carriers (electrons or holes) into the semiconducting device, which recombine with their opposing carriers to produce circularly polarized light. A process for producing circularly polarized optical emission includes applying a bias across a light emitting semiconductor heterostructure having a contact with a net magnetic moment, therby injecting spin polarized carriers into the light emitting semiconductor heterostructure.

1. Field of the Invention
This invention relates to light emitting semiconductor devices and processes, and more particularly to light emitting semiconductor devices and processes that use spin-polarized carriers to produce circularly polarized light.
2. Description of the Related Art
Circularly polarized light, especially modulated (i.e. pulsed) circularly polarized light, is useful in optical switching and optical computing applications.
It is known that a light emitting diode (LED) emits unpolarized light and that a quarter wave plate may be used to filter this light to produce circularly polarized light. However, attaching this additional component on or adjacent to an LED requires an additional manufacturing step, and increases the size of the component.
Skilled practitioners in the art will recognize that FIG. 1 shows a typical known LED structure 10 for producing unpolarized light. This LED structure 10 has at least one n-doped semiconductor layer 12 adjacent to at least one p-doped semiconductor layer 13 to form a p-n junction. This p-n junction is usually disposed on a semiconducting substrate 14. This structure is connected to a voltage source 16 through a pair of electrical contacts 11. Positioned in the path of light emitted from this structure is a quarter wave plate 15.
In operation, when a voltage is applied to this LED structure 10 through the contacts 11, electrons will be injected into the p-n junction from one direction, while holes will be injected into the p-n junction from the opposite direction. These electrons and holes will recombine or decay to produce unpolarized photons. When this unpolarized light passes through the quarter wave plate 15, it emerges as circularly polarized light.

Polarized optical emission due to decay or recombination of spin-polarized injected carriers

The United States of America as represented by the Secretary of the Navy


An improved VI improver and a fluid composition comprising the VI improver. The VI improver is an asymmetric radial polymer comprising a plurality of arms having at least two distinctly different peak molecular weights, which arms are chemically the same. The weight ratio of a longest set of arms and a first set of shorter arms will vary within the range from about 1.2:1 to about 8.0:1. If more than one set of shorter arms is used the ratio of adjacent arms molecular weights will vary within the same range. While the arm might be essentially any polymer, polymers of conjugated diolefins and copolymers of at least one monoalkenyl aromatic hydrocarbon and at least one conjugated diolefin are preferred. Conjugated diolefin homopolymers are preferred and polyisoprene is most preferred.

1. Field of the Invention
This invention relates to an asymmetric polymer and to a composition of matter comprising the same. More particularly, this invention relates to an asymmetric polymer which will alter the viscoelastic properties of a composition of matter comprising the same and to a composition of matter comprising the same.
2. Prior Art
Methods for varying the elasticity of polymers are, of course, well known in the prior art and such methods are taught in U.S. Pat. No. 4,620,048. The invention described in U.S. Pat. No. 4,620,048 has been described by reference to polymeric viscosity index (V.I.) improver additives and patentees clearly indicate that the parameters which affect elasticity of the polymer will interact to affect the viscoelastic properties of a composition containing the polymer. One such parameter is molecular topology. The thrust of the invention described in U.S. Pat. No. 4,620,048 seems to be that mechanical degradation of the polymer may be reduced if the compliance of the polymer is reduced or if the molecular weight of the polymer is narrowed. There is, apparently, no indication in U.S. Pat. No. 4,620,048 that the performance of such a polymer might show even further improvement as a V.I. improver as a result of the improved elastic property, per se, at least in certain cases as when used in a lubricating composition lubricating journal bearings. The thrust of the present invention, then, resides in this latter discovery with the polymer of this invention.
It is well known in the prior art that a reduction in HTHSR viscosity will improve fuel efficiency. This is taught for example in ASTM Data Series Publication, DS62 "The Relationship Between High Temperature Oil Rheology and Engine Operation" published in 1984 and confirmed in the paper by D. C. Olson, SAE Paper, 87128. A mere reduction in HTHSR viscosity will, however, genereally result in an increase in journal bearing wear in an automotive engine.
More recently, it has been established that bearing oil film thickness, which affects bearing wear, is proportionate to both the HTHSR viscosity and the oil elasticity. This is taught in SAE Paper 860376, by Bates et al. This discovery too is confirmed by the aforementioned Olson Paper. It follows from this discovery that improved journal bearing wear could be realized if the oil elasticity could be increased while maintaining the same HTHSR viscosity and improved fuel efficiency could be realized and journal bearing wear maintained with a lower HTHSR viscosity by increasing the oil elasticity. The aforementioned U.S. Pat. No. 4,620,048 does teach that oil viscoelastic properties of an oil can be changed by changing the topology of the polymer added to the oil as can the shear stability of the oil composition. There is, however, no teaching or suggestion in this patent that both fuel efficiency and bearing wear can be improved if the proper topology is selected.
In light of the foregoing, a need remains for a polymer which can be added to an oil and improve the oil fuel efficiency while maintaining or improving journal bearing wear properties.

Asymmetrical radial polymer and composition of matter comprising the same


A tractor balancing device capable of providing vertical support to the frame of a side-mounted bush hog. The balancing device consists of an inflatable and deflatable air bag secured between a platform placed above the right, front axle of a bush hog tractor, and a bracket affixed to the frame of the side-mounted bush hog. The air bag is connected to an air compressor and receives air by means of an air hose. A system of pressure regulation is provided so as to control the level of air pressure within the air bag. If, during operation of the bush hog, either the moment of the bush hog arm or the incline of the surface causes the tractor to tilt in the direction of the bush hog arm, the air bag can be inflated. This stiffens the frame of the bush, preventing it from pivoting and tilting the tractor. The moment applied to the tractor is reduced by virtue of the upward force applied by the air bag onto the frame of the bush hog. The air bag can be deflated when the bush hog is not in use, or when the bush hog tractor is in danger of tilting away from the bush hog arm. Thus, the inflation and deflation of the air bag serves to balance the tractor.

Motorized vehicles are commonly used not only to transport people, but also to lift and carry loads. Many vehicles have within them a mechanism for lifting or carrying objects. For example, some trucks carry a fork lift from the rear bed of the truck. The rear bed of the truck is configured to receive the forks of a fork lift, enabling the truck to transport the fork lift. Also, some tractors carry a side-mounted bush hog consisting of an extendable mechanized arm with a rotating mower blade at the end of the arm. The bush hog has a frame which mounts onto the tractor. This allows the tractor to transport the bush hog and use it to cut vegetation adjacent to a roadway.
There is a danger inherent in the use of lifting or carrying devices on motorized vehicles. That danger occurs when the moment applied to the vehicle from the device being lifted or carried is increased, causing the vehicle to tilt or even fall over. If the moment, or angular force, applied to a truck or tractor by the operation of the lifting or carrying device increases beyond the gravitational force created by the weight of the truck or tractor itself, tilting will occur. In this instance, the weight of the vehicle will not be sufficient to prevent tilting.
Moment is a product of several factors. One factor is the amount of force applied to the lifting or carrying arm. Another variable is the angle at which force is applied to the moment arm. A third factor is the radius away from the object at which the force is applied. A sufficient increase in either the force applied to an object or the distance from an object at which the force occurs will increase the moment and cause rotation in the body securing the lifting device.
In the context of motorized vehicles with a lifting or carrying device, moment will increase when the downward force on the device increases. This occurs when the lifting device attempts to lift a heavier load. Moment will also increase when either the length or the radius of the moment arm increases.
It is critical that a motorized vehicle with a lifting device stay balanced. If such a vehicle becomes too far out of balance, it could tilt over causing damage to the vehicle and, possibly, personal injury. For example, a dump truck which becomes out of balance while dumping a load of dirt into a hole could tilt backwards, causing the truck and the driver to flip into the hole.
In order to avoid tilting, motorized vehicles have employed one of two types of balancing devices. The first type involves a counter-weight attached to the vehicle opposite the lifting device. For example, a weight may be attached to a fulcrum or to the hub of a wheel opposite the lifting mechanism. The utility of a counter-weight is that it increases the gravitational force on the vehicle opposite the lifting mechanism so as to counter-act the angular force applied by the load during lifting. However, the added weight also means that the truck or tractor must be engineered to move a considerably heavier load. This raises the cost of the vehicle and reduces fuel economy. It also makes handling the vehicle difficult in the event of a flat tire or in the event towing is necessary.
The second type of balancing device employs legs extendable from the side of the vehicle in the direction of the lifting mechanism. The legs are usually connected to pads which rests on the ground. The legs provide support to the vehicle to avoid tilting. However, this type of balancing mechanism only has utility when the vehicle is stationary.
The prior art fails to teach a device which can provide additional vertical support for a side mounted lifting or carrying mechanism while the vehicle is moving. Such a device counter-acts the downward force applied at the end of the moment arm without adding additional weight to the vehicle itself. If the vehicle begins to tilt in the direction of the load being lifted, the frame upon which the lifting or carrying device is mounted is adjustably stiffened, thereby accomplishing a balancing of weight. It is an object of the present invention to provide a device for counter-acting the gravitational force applied to a lifting or carry device attached to a motorized vehicle.
It is also an object of this invention to provide a device by which the frame of a lifting device secured to a motorized vehicle may be stiffened relative to the vehicle itself, thereby preventing tilting during operation.
It is an additional object of the present invention to provide a device which will balance a vehicle having a lifting or carrying device while the vehicle is moving.
It is another object of the present invention to secure an adjustably inflatable air bag to both the frame of a lifting or carrying device on a motorized vehicle and an axle of that vehicle in such a manner that inflation of the bag counter-acts the gravitational force applied to the moment arm when the lifting or carrying device is employed.
It is a further object of this invention to place an inflatable/deflatable air bag between the right, front axle of a tractor and a mounting plate attached to the frame of a side-mounted bush hog in such a manner that the air bag may be inflated when the tractor begins to tilt towards the side where the bush hog is mounted, and may be deflated should the tractor begin to tilt towards the opposite side, thereby allowing the tractor to be balanced during operation of the bush hog.


The invention relates in part to a method of maintaining heavy metal homeostasis in healthy humans, comprising chronically administering to healthy humans a pharmaceutical composition consisting of from about 1 mg to less than about 200 mg of Posiphen or a pharmaceutically acceptable salt thereof together with one or more pharmaceutically acceptable excipients, on a once a day basis. By virtue of this method, prophylactic treatment of a potential disease state such as a neurodegenerative disease, cardiovascular homeostasis, cancer, vital organ homeostasis, and the like. The invention also relates in part to a method of restoring heavy metal homeostasis in sick patients, comprising chronically administering to a sick patient a pharmaceutical composition consisting of from about 1 mg to less than about 200 mg of Posiphen or a pharmaceutically acceptable salt thereof together with one or more pharmaceutically acceptable excipients, on a once a day basis. By virtue of this method, treatment of a potential disease state such as a neurodegenerative disease, cardiovascular disease, cancer, vital organ dysfunction and heavy metal dis-homeostasis, and the like.

Neurodegenerative diseases generally affect abstract thinking, skilled movements, emotional feelings, cognition, memory and other abilities. Despite differences in clinical symptoms and disease progression, disorders from this group share key common features: most of them have both sporadic and inherited origins, all of them appear later in life, and their pathology is characterized by neuronal loss and synaptic abnormalities. Until recently, no common molecular mechanism had been identified among these diseases. However, various neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), transmissible spongiform encephalopathies (TSEs), and amyotrophic lateral sclerosis (ALS), have been shown to share a common cause and pathological mechanism—the overexpression, misfolding, aggregation and accumulation of proteins in the brain, resulting in neuronal apoptosis. The hallmark feature of conformational disorders is that a particular protein folds into a stable alternative conformation, which in most cases results in its aggregation and accumulation in tissues as fibrillar deposits. These deposits have similar morphological, structural and staining characteristics. Multidisciplinary studies strongly support this shared cause and pathological mechanism, suggesting that there may be a common therapy for these devastating disorders.
Mutations in the genes that encode the protein components of fibrillar aggregates are genetically associated with the inherited forms of all neurodegenerative diseases. The familial forms usually have an earlier onset and greater severity than sporadic cases and are also associated with a greater amount of protein aggregates (Soto, 2003, Nature Rev. 4:49).
Neurotoxic aggregating proteins have not only a common aggregating pathway, but also common regulatory pathways for their transcription and translation. While their transcription is activated by copper and/or zinc ions (Bush et al., 2003, Proc. Natl. Acad. Sci. U.S.A. 100(20):11193-94), their translation is upregulated by iron and down-regulated by iron regulatory protein 1 (IRP1). Specifically, their mRNAs are regulated via the 5′-untranslated region (5′UTR) of their transcript, which folds into a unique RNA stem loop with a CAGUGN apical loop similar to that encoded in the canonical iron-responsive element (IRE) of L- & H-ferritin mRNAs. IRP1 binds to this IRE stem look and inhibits the translation of the mRNA by the ribosome (Cho et al., 2010, J. Biol. Chem. 285(41):31217).
Examples of neurotoxic aggregating proteins are Aβ (amyloid-β peptide, a fragment of APP), Tau, alpha-synuclein (aSYN), transmissible spongiform encephalopathy (TSE) prions SOD (super oxide dismutase) proteins, huntingtin (HTT), TDP43 and c9orf72.
APP/Abeta
Alzheimer's disease (AD) is the most common progressive dementia associated with aging. The cholinergic system is the earliest and most profoundly affected neurotransmitter system in AD, with substantial losses in the forebrain, cortex and hippocampus, which are critical in the acquisition, processing and storage of memories (Terry et al., 1991, Ann. Neurol. 30:572-80; Giacobini, In "Alzheimer's Disease: Molecular Biology to Therapy"; Becker & Giacobini, Eds.; Birkhauser: Boston, 1997; pp 188-204; Becker et al., In "Alzheimer's Disease: from Molecular Biology to Therapy"; Becker & Giacobini, Eds.; Birkhauser: Boston, 1997; pp 257-66).
The major neuropathological hallmarks of AD are β-amyloid plaques, neurofibrillary tangles, and synaptic loss. In particular, amyloid-β precursor protein (APP) is cleaved into a number of toxic peptides, one of them being amyloid-β (Aβ): a hydrophobic, neurotoxic self-aggregating 40 to 42 amino-acid peptide that accumulates preferentially within senile plaques in the brain. Other peptides are also cleaved from the N-terminus and C terminus end of APPs. These peptides attack multiple pathways of neuronal cell life, leading to synaptic loss and nerve cell death. This sequence of events induces neuroinflammation and leads to cognitive impairment and neurodegeneration.
In an original hypothesis for AD treatment, inhibition of the accumulation of Aβ in the brain could positively affect the course of AD. Recently, this hypothesis has been expanded by recognizing that APP in the absence of trophic factors is shed from the surface of neuronal cells and processed into an amino terminal fragment (N-APP). This fragment binds to DR6 receptors and induces nerve cell death (Nicolaev et al., 2009, Nature 457:981-90). Furthermore, C31 (another factor cleaved from the C-terminus end of APP) has been found to cause nerve cell degeneration and death in tissue culture cells and in transgenic mice (Galvan et al., 2006, PNAS 103(18):7130-35). Overexpression of C31 has been also shown to lead to neuronal degeneration without Aβ toxicity and plaque deposition. In all three cases (cell death triggered by N-APP, Aβ and/or C31 accumulation), reducing APP synthesis could be beneficial to the preservation of brain cells, by reducing the formation of neurotoxic plaque through the Aβ pathway and by inhibiting the formation of nerve cell-killing toxic N-terminus and C-terminus fragments.
Tau
Even though tau is not a member of the iron regulated neurotoxic protein family, it is overexpressed and aggregates in a number of tauopathies. Conditions in which neurofibrillary tangles are commonly observed include: Alzheimer's disease, progressive supranuclear palsy, dementia pugilistica, chronic traumatic encephalopathy, frontotemporal dementia and parkinsonism linked to chromosome 17, Lytico-Bodig disease (Parkinson-dementia complex of Guam), Tangle-predominant dementia, with NFTs similar to AD, but without plaques. Tau deposits tend to appear in the very old, Picks disease and a number of other neuropathies. Tau's fibrillary tangles are found in most neurodegenerative disorders.
DS, APP/Abeta/SOD1
Down syndrome (DS) results when abnormal cell division involving chromosome 21 results in extra genetic material. It is most often caused by a genetic variation known as trisomy 21, wherein there are three copies of chromosome 21 instead of the usual two copies in all cells. Chromosome 21 contains the genes for APP and SOD1. Overexpression of these genes is responsible for the characteristic features and developmental problems of DS, such as physical growth delays, characteristic facial features and mild to moderate intellectual disability.
aSYN
In humans, alpha-synuclein is encoded by the SNCA gene. An alpha-synuclein fragment, known as the non-Aβ component (NAC) of Alzheimer's disease originally found in an amyloid-enriched fraction is shown to be a fragment of its precursor protein, NACP (now referred to as human alpha-synuclein).
PD, aSYN
Parkinson's disease (PD) is a chronic and progressive movement disorder that involves the malfunction and death of neurons in the substantia nigra region of the brain. Some of these dying neurons produce dopamine, a chemical that sends messages to the part of the brain that controls movement and coordination. As PD progresses, dopamine is depleted from the basal ganglia, which results in major disruptions in the connections to the thalamus and motor cortex and leads to parkinsonian signs such as bradykinesia. It has been found that a hallmark of Parkinson's disease—clumps of alpha-synuclein, called Lewy Bodies—are found not only in the mid-brain but also in the brain stem, the gut and the olfactory bulb. Lewy bodies and aSYN aggregates are present in multiple nerves from the periphery to the brain and, while motor symptoms are associated with Lewy bodies in the brain, non-motor symptoms are associated with aggregates in the periphery. In fact, the intestines have dopamine cells that degenerate in Parkinson's, they accumulate aSYN aggregates, which are responsible for the gastrointestinal symptoms that are part of the disease. Non-motor symptoms in general are experienced by all people with PD before any motor sign of the disease appears. Lewy bodies are also found in several other brain disorders, including dementia with Lewy bodies (DLB). Evidence suggests that dementia with Lewy bodies, Parkinson's disease and Parkinson's disease dementia may be linked to the same underlying abnormalities in brain processing of alpha-synuclein. Many of those afflicted with both dementia with Lewy bodies and Parkinson's disease dementia also have plaques and tangles—which are the hallmark of Alzheimer's disease. Thus, there is an inter-relationship between the Parkinson's disease-related protein alpha-synuclein and the Alzheimer's Aβ-amyloid plaque protein.
TSEs
Transmissible spongiform encephalopathies (TSEs, collectively known as prion diseases) are a group of progressive conditions that affect the brain and nervous system of mammals, and include devastating diseases as bovine spongiform encephalopathy (BSE, also known as "mad cow disease") in cattle, and classic Creutzfeldt-Jakob disease, new variant Creutzfeldt-Jakob disease (nvCJD, a human disorder related to mad cow disease), Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia and kuru (CJD) in humans. Mental and physical abilities deteriorate in the afflicted patients, and myriad tiny holes appear in the cortex, causing it to appear like a sponge (hence 'spongiform') when brain tissue obtained at autopsy is examined under a microscope. The disorders cause impairment of brain function, including memory changes, personality changes and problems with movement that worsen over time.
Unlike other kinds of infectious diseases caused by microbes or viruses, the infectious agent in TSEs is a specific protein called prion protein. Misshaped prion proteins carry the disease between individuals and cause deterioration of the brain. TSEs are unique diseases, in that their etiology may be genetic, sporadic or infectious via ingestion of infected foodstuffs and via iatrogenic means (e.g. blood transfusion). Most TSEs are sporadic and occur in an animal with no prion protein mutation. Inherited TSE occurs in animals carrying a rare mutant prion allele, which expresses prion proteins that contort by themselves into the disease-causing conformation.
The degenerative tissue damage caused by human prion diseases (Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, and kuru) is characterised by four features: spongiform change, neuronal loss, astrocytosis and amyloid plaque formation. These neuropathological features have formed the basis of the histological diagnosis of human prion diseases for many years, although it was recognized that these changes are enormously variable both from case to case and within the central nervous system in individual cases.
Transmissible spongiform encephalopathies encompass the following diseases (including natural host and prion name): scrapie (sheep and goats; scrapie prion); transmissible mink encephalopathy (TME) (mink; TME prion); chronic wasting disease (CWD) (elk, white-tailed deer, mule deer and red deer; CWD prion); bovine spongiform encephalopathy (BSE) commonly known as "mad cow disease" (cattle; BSE prion); feline spongiform encephalopathy (FSE) (cats; FSE prion); Exotic ungulate encephalopathy (EUE) (nyala and greater kudu; EUE prion); kuru (human; Kuru prion); Creutzfeldt-Jakob disease (CJD) or Variant Creutzfeldt-Jakob disease (vCJD, nvCJD) (human; CJD and vCJD prions); Gerstmann-Sträussler-Scheinker syndrome (GSS) (human; GSS prion); and fatal familial insomnia (FFI) (human; FFI prion).
SOD1
Superoxide dismutase (SOD1) is an enzyme that in humans is encoded by the SOD1 gene, located on chromosome 21. SOD1 is one of three human superoxide dismutases. It is implicated in apoptosis (programmed cell death) and amyotrophic lateral sclerosis (ALS). The SOD1 gene provides instructions for making an enzyme called superoxide dismutase, which is abundant in cells throughout the body. This enzyme binds to molecules of copper and zinc to break down toxic, charged oxygen molecules called superoxide radicals. The molecules are byproducts of normal cell processes, and they must be broken down regularly to avoid damaging cells. Mutations in the gene for the enzymes superoxide dismutase 1 (SOD1) or copper zinc superoxide dismutase have been found in approximately 15-20 percent of the familial cases of ALS. SOD1 is also pivotal in reactive oxygen species (ROS) release during oxidative stress by ischemia-reperfusion injury, specifically in the myocardium as part of a heart attack (also known as ischemic heart disease). Ischemic heart disease results from an occlusion of one of the major coronary arteries. During ischemia reperfusion, ROS release substantially contribute to cell damage and death via a direct effect on the cell as well as via apoptotic signals. SOD1 is known to have a capacity to limit the detrimental effects of ROS. As such, SOD1 is important for its cardioprotective effects. In addition, SOD1 has been implicated in cardioprotection against ischemia-reperfusion injury, such as during ischemic preconditioning of the heart. Although a large burst of ROS is known to lead to cell damage, a moderate release of ROS from the mitochondria, which occurs during nonlethal short episodes of ischemia, can play a significant triggering role in the signal transduction pathways of ischemic preconditioning leading to reduction of cell damage
HD, htt
Huntington's disease (HD) is a type of dementia caused by an inherited defect in a single gene on chromosome 4. Huntington's disease is an autosomal dominant disorder, which means that a person needs only one copy of the defective gene to develop the disorder. The defective gene codes for a protein known as huntingtin, which in turn leads to brain changes that cause abnormal involuntary movements, a severe decline in thinking and reasoning skills, and irritability, depression and other mood changes. Huntington's disease also causes a decline in thinking and reasoning skills, including memory, concentration, judgment and ability to plan and organize.
TDP-43
Almost all cases of ALS as well as tau-negative frontotemporal dementia (FTD) share a common neuropathology characterized by the deposition of TAR-DNA binding protein (TDP)-43-positive protein inclusions. A hyper-phosphorylated, ubiquitinated and cleaved form of TDP-43 (known as pathologic TDP43) is the major disease protein in ubiquitin-positive, tau-, and alpha-synuclein-negative frontotemporal dementia and in ALS. Elevated levels of the TDP-43 protein have also been identified in individuals diagnosed with chronic traumatic encephalopathy, a condition that often mimics ALS and that has been associated with athletes who have experienced multiple concussions and other types of head injury. Abnormalities of TDP-43 also occur in an important subset of Alzheimer's disease patients.
C9orf72
Mutations of another protein found in many regions of the brain, CRorf72, have been found to be a genetic link between familial frontotemporal dementia (FTD) and ALS. The C9orf72 gene is located on the short (p) arm of chromosome 9 at position 21.2. The mutation of C9ORF72 is a hexanucleotide repeat expansion of the six-letter string of nucleotides GGGGCC. In healthy humans, there are few repeats of this hexanucleotide, but in people with the mutation, the repeat can occur in the order of hundreds. It is known that the mutation interferes with normal expression of the protein made by C9orf72. C9orf72 can cause FTD and/or ALS via accumulation of RNA in the nucleus and cytoplasm which becomes toxic, and RNA binding protein sequestration occurs. A truncated gene that only codes for half of the C9ORF72 protein can also cause the diseases. Additionally, RNA transcribed from the C9ORF72 gene, containing expanded GGGGCC repeats, is translated through a non-ATG initiated mechanism. This drives the formation and accumulation of dipeptide repeat proteins corresponding to multiple ribosomal reading frames on the mutation. GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport.
Despite the attention of many established and new ventures seeking treatment of neurodegenerative conditions and diseases, there is a long-felt need to develop a treatment for human patients to not only treat the symptoms of a neurodegenerative disease (such as Alzheimer's), but also to develop a treatment that can prevent healthy humans from developing such neurodegenerative diseases or treat sick patients to reverse, stop or slow the course of such neurodegenerative diseases.

Prevention or treatment of disease states due to metal dis-homeostasis via administration of Posiphen to healthy or sick humans


The present invention relates to an electronically monitored mechanical pipette which includes a transducer assembly for monitoring the rotational movement of a volume delivery adjustment mechanism of the pipette. The transducer assembly preferably includes at least two Hall-effect transducers spaced 90 rotational degrees apart from each other and sense the magnetic field of an annular magnet attached to the delivery adjustment mechanism. The Hall-effect sensors produce sinusoidal signals which are 90.degree. out of phase from each other when the magnet rotates relative thereto. The two out of phase sinusoidal signals are processed by an electronics assembly of the pipette to determine the absolute position of the volume delivery adjustment mechanism and compute a fluid volume delivery setting of the pipette. The transducer assembly in conjunction with the electronics assembly monitors both the number of revolutions of the volume delivery adjustment mechanism from an initial zero position, but also the position of the volume delivery adjustment mechanism within a revolution.

1. Field of the Invention
The invention relates generally to an electronically monitored mechanical pipette. More specifically, the invention relates to a transducer assembly for monitoring the position of a volume delivery adjustment mechanism of the pipette, and for signalling the electronic system of the pipette of the changing volume delivery setting.
2. Prior Art
Mechanically operated micropipettes are well known in the art as exemplified by U.S. Pat. No. 4,909,991 to Oshikubo. In such prior art devices, the volume of liquid to be dispensed by the pipette is generally indicated to the operator by means of a mechanical display. The display commonly consists of a set of rotary drums driven by a gear mechanism attached to the actuating shaft of the pipette, such that rotation of the actuating shaft causes the drums to rotate to display a new setting. However, due to unavoidable mechanical wear and tear on pipettes, the amount of fluid actually being delivered by a pipette may not actually correspond to the volume being indicated by the mechanical display. Further, accuracy may degrade over time as the actuating elements, such as the shaft, gears, and rotary drum, wear out.
Electrically driven pipettes are also well known in the art as exemplified by U.S. Pat. No. 4,905,526 to Magnussen, Jr. et al. This type of instrument commonly includes an electronic display for displaying the volume of fluid to be dispensed by the pipette, and an actuator generally comprising an electric drive mechanism, such as a stepper motor. The stepper motor generally drives a rotor, which is attached by a threaded screw to an actuator shaft, the threaded screw changes the rotational motion of the motor into linear motion of the actuator shaft. The shaft thereafter drives a piston to displace fluid for pipetting. Although electrically operated pipettes have some advantages over mechanically operated pipettes, they nevertheless suffer from several drawbacks. Mainly, the enlarged size of an electrically operated pipette, due to the need to accommodate the electric driving mechanism, and the added electronic hardware, make the device very difficult to handle for the operator. Further, monitoring the position of the electric motor for purposes of ensuring desired fluid delivery volume can lead to less than desired delivery accuracy.
Electrically monitored mechanical pipettes are also known in the art as exemplified by U.S. Pat. No. 4,567,780 to Oppenlander et al. This type of instrument generally includes a plunger having an adjustable stroke length which is generally adjusted by rotating the plunger itself. The electrical monitoring system monitors plunger rotation and electronically displays the volume delivery setting corresponding to the plunger position. The device continuously monitors the plunger position and volume delivery setting of the pipette by means of a potentiometer. Although this device overcomes several of the disadvantages of mechanical and electrical pipettes, it nevertheless fails to completely resolve the problem of high power demands during operation. Further, the use of a potentiometer to monitor the position of the plunger is sometimes not desirable.
Electrically driven pipettes which include a transducer assembly are also well known in the art as exemplified by U.S. Pat. No. 4,821,586 to Scordato et al. This instrument uses a Hall-effect transducer to indicate when the volume delivery adjustment mechanism thereof is in its "home" position, and therefore ready to be set to a desired volume delivery setting. However, the volume delivery setting is calculated based on the number of pulses applied to the windings of an actuation motor, which in turn determines the number of steps a threaded element rotates through a set of threads of known pitch. This indicates the distance the plunger moves longitudinally from the "home" position, thus determining the stroke of the piston and the volume of fluid which will be aspirated into the tip of the pipette. Although the electrically driven pipette uses a Hall-effect switch to assist in positioning the volume delivery adjustment mechanism, it nevertheless suffers from several drawbacks. Mainly, the Hall-effect transducer is used only as a "switch" to indicate a "home" position from which a volume delivery setting can be made, instead of directly monitoring the entire range of movement of the volume delivery adjustment mechanism and thereby directly indicating all positions of the mechanism to the electronic assembly of the unit. Therefore, fluid delivery setting cannot be determined directly from the output of the Hall-effect transducer.

Transducer assembly for an electronically monitored mechanical pipette


An automated optimization system for generating multiple alternative training and transition plans for airline pilots which include a recall of furloughed pilots, and limits to deviation of pilot start bid periods for training assignments from a specific bid period, wherein such plans are cost optimized to track payroll costs of pilots recalled from furlough, and the combined time for solving an MIP Model representation and generating such plans therefrom is less than one hour.

Numerous systems have been developed to overcome the complexity of determining when training and transition is to occur, and for which crew members, at which locations, at what times, and with an appropriate allocation of training resources including equipment and instructors.
The prior art systems have included both manual and automated systems with response times ranging from days, to weeks, and even months. Further, such systems have tended to implement a decision making process for providing a single solution, rather than a dynamic, adaptive, decision support system providing alternative solutions for evaluation by a strategic planner. In addition, such prior systems have been represented by models which either are too complex for commercial software solution, or have simplifying assumptions that make them too unrealistic for practical use. Prior systems also have generally been too costly in employee and equipment resources. See "Decision Support Systems-An application in strategic manpower planning of airline pilots" by Peter J. Verbeek, European Journal of Operational Research 55 (1991), pages 368-381, Elsevier Science Publishers B. V. While the Verbeek article does not disclose a decision support system, it does describe the enormous complexities which must be addressed in designing such a system to accommodate the large numbers of constraints and variables that are required for a solution to be realistic. Verbeek also referred to his own mixed integer model which was admittedly too complex for solution with commercial software, and thus too costly in time.
From the above it may be discerned that the problem of pilot staffing and training is one of the most complex and costly problems facing the major airlines. If not managed effectively, an airline cannot survive, not to mention profit, in the competitive air transportation market.
By way of example, Continental airlines provides both domestic and international service to more than 100 destinations around the world. They operate 325 aircraft of nine different fleet types to fly 1400 daily flights. Their 5000 pilots are stationed at three domestic and two international crew bases. At least twice a year Continental conducts a system bid award. These awards provide an opportunity for pilots to use their seniority to increase their pay and improve their work schedules by changing their position (base, fleet, and status), and a way for the airline to adjust staffing levels in response to retirements, attrition, and changes in their business plan. In an average system bid award, 15-20% of the airline's pilots receive new positions. The problem of taking the pilots who have received new positions, and finding a training class for each pilot requiring training, an advancement date for each pilot changing position without training, and a release date for each pilot leaving the airline, is a very large NP-hard problem to attempt to solve. Additional complexity for Continental comes from the facts that: pilot positions are interrelated; the timing and number of training classes is variable; minimal length student training schedules must be generated using limited resources; and numerous complicating regulations and business rules related to each pilot's seniority, flight history, and current and future position must be considered.
Continental manpower planners with expert knowledge took more than two weeks to manually generate a single, partial, sub-optimal training plan for ensuring adequate staffing levels with no detailed consideration of costs.
In contrast to the above prior art systems and methods, the system disclosed in related U.S. patent application Ser. No. 10/054,343, and assigned to the assignee of the present invention, is a realistic representation of the real world problem as evidenced by its implementation by Continental Airlines. The system is modeled so efficiently that it can be solved in under an hour. An hour is a huge improvement over the time required by the prior art systems, and is a very reasonable amount of time for a planning problem as complex as the one addressed in the generation of training and transition plans for all pilots of an entire airline.:
In response to a system bid award, the system manages large volumes of data, and employs state-of-the-art optimization modeling and solution techniques, to efficiently allocate human and training resources and attain optimal operational and cost effective performance. A training and transition plan is generated by the system which establishes the timing and number of pilot new hires, training assignments, advancements, and releases. The plan also provides the number of pilots whose training or release should be postponed, and the flow of pilots across different positions in a manner that ensures adequate staffing levels, minimum cost, and efficient utilization of training resources.
After an initial training and transition plan is established, crew planners often face changes in the airline operating environment which necessitate changes to the original plan. For example, in the event of a new bid award which occurs only a couple times each year, pilots may be scheduled for training and transition without regard to any existing plan. Events such as the following, however, often lead to changes in training and transition plans on as small as a monthly basis to maintain staffing levels: new market opportunities, the acquisition and retirement of aircraft and training resources, opening and closing sub-bases, and modification to the number of hours to be flown from different pilot positions to allow the airline to take advantage of business opportunities. Upon the occurrence of such change events, crew planners want to make as few adjustments as possible to the current training and transition plan to avoid disrupting the schedules of a large number of pilots.
The invention is an improvement over the system of U.S. patent application Ser. No. 10/054,343, and was created to overcome the challenges of timing the recall of pilots who have been furloughed from an airline, and also to limit any effect on current training and transition plans during the process of building a new plan.
Pilots who have been furloughed by the airline by contractual agreement must be brought back to the airline in seniority order, and must be brought back before any new pilots are hired by the airline. Two constraints are included in a mixed integer programming model (MIP Model) of the invention to determine when furloughed pilots will be recalled, and to ensure that contractual obligations are met in doing so. Two additional constraints are included to limit the percentage of pilots whose start bid periods are moved out of the bid period of the current plan, and to limit the total percentage of pilots whose start bid periods are either moved into or moved out of the bid period of the current plan.
Prior to the invention, crew planners used manual methods to provide solutions in overcoming the furloughed pilot recall and limited effect problems. Such manual methods were too time consuming for consideration of solution costs. Emphasis was placed mainly on staffing levels. Rather than hours to days being consumed in reaching a manual solution, the invention makes possible multiple alternative solutions in under one hour which address change events giving rise to a need to recall furloughed pilots, or to a need for limited start bid period changes to a current training and transition plan. In addition to the time savings, the solutions derived by this invention are optimized against the airline's costs while maintaining ideal staffing levels.

Integrated decision support system for optimizing the training and transition of airline pilots


Oil-in-water dispersions of .beta.-carotene and other carotenoids that are stable against oxidation, even in the presence of polyphosphates, especially sodium hexametaphosphate. These oil-in-water dispersions are typically prepared by contacting a water-dispersible beadlet comprising at least about 5% colloidal carotenoid with the water phase to form droplets of the carotenoid that are in intimate contact with sufficient oil phase such that the carotenoid is stable against oxidation, even in the absence of an effective antioxidant such as ascorbic acid. The oil-in-water carotenoid dispersions of the present invention are especially useful in dilute juice beverages for providing vitamin A fortification and color, as well as other oil/water food and beverage products where vitamin A fortification and/or color are desired.

A particularly useful source of coloring agents for a variety of foods and beverages are the carotenoids. The carotenoids include carotene, lycopene, bixin, zeaxanthin, cryptoxanthin, lutein, canthaxanthin, .beta.-apo-8'-carotenal, .beta.-apo-12'-carotenal and can provide color pigments ranging from yellow to red. An especially important member of the carotenoid class of compounds is .beta.-carotene. .beta.-carotene is not only useful as a colorant (typically yellow, orange and especially red in color) but also provides a valuable source of vitamin A. For this reason, .beta.-carotene is often included in foods and beverages as a colorant, especially where vitamin A fortification is needed or desired.
One particular food system that .beta.-carotene has been included in for both vitamin A fortification and color are dilute juice beverages. Dilute juice beverages often have a cloudy or opaque appearance by incorporating a beverage emulsion. These beverage emulsions can be either flavor emulsions (i.e., provide the beverage with flavor and cloudiness) or cloud emulsions (i.e., provide primarily cloudiness). Both types of beverage emulsions comprise an oil phase that is dispersed in a continuous water phase, i.e., they are "oil-in-water" emulsions. This oil phase is typically uniformly dispersed in the continuous water phase in the form of fine droplets that give the beverage its cloudy or opaque appearance.
Dilute juice beverages that are intended to be stored without refrigeration (e.g., at ambient temperatures), pasteurization or aseptic packing typically need an antimicrobial preservative. Dilute juice beverages, when exposed to food spoilage microorganisms, can provide a hospitable environment for rapid microbial growth. Such exposure can result from accidental contamination of the dilute juice beverage during manufacturing or packaging. Food spoilage microorganisms can then rapidly proliferate by feeding on nutrients provided by various components (e.g., the juice itself) of the dilute juice beverage.
Preservatives, such as sorbates, benzoates, organic acids, and combinations thereof have been used in dilute juice beverages to provide some degree of microbial inhibition. At levels effective to inhibit microbial growth, some of these preservatives can contribute off-flavors to dilute juice beverages. Accordingly, it has been recently suggested to include certain food grade polyphosphates (especially sodium hexametaphosphate) to enhance the potency of these preservatives at lower levels in dilute juice beverages. See U.S. Pat. No. 5,431,940 (Calderas), issued Jul. 11, 1995, which discloses the use of polyphosphates, such as sodium hexametaphosphate, in combination with sorbate preservatives, such as potassium sorbate, in dilute juice beverages having relatively low water hardness.
Adding .beta.-carotene to dilute juice beverages so that it is well dispersed, as well as providing vitamin A activity and desirable color, has been found not to be an easy proposition. The carotenoids, including .beta.-carotene, are relatively insoluble in water and have relatively high melting points. They are also highly sensitive to oxidation, especially in the presence of water. To make it more water-dispersible, .beta.-carotene is often formulated as a water-dispersible beadlet. These beadlets can be made by dissolving .beta.-carotene in a water-miscible organic solvent, mixing the dissolved .beta.-carotene with an aqueous solution of a swellable colloid (typically gelatin), precipitating the .beta.-carotene in a colloidally dispersed form and then drying the colloidal dispersion. See, for example, U.S. Pat. No. 3,316,101 (Borenstein), issued Apr. 25, 1967 and U.S. Pat. No. 4,522,743 (Hom et al), issued Jun. 11, 1985. See also D. Horn, "Preparation and Characterization of Microdisperse Bioavailable Carotenoid Hydrosols," Die Angewandte Makromolekulare Chemie 166/167, (1989), 139-153; H. T. Gordon and J. C. Bauernfeind, "Carotenoids as Food Colorants," CRC Critical Reviews in Food Science and Nutrition, 18, (1982), 59-97; H. Klaui and J. C. Bauernfeind, "Carotenoids as Food Colorants," Carotenoids as Colorants and Vitamin A Precursors, Chapter 2, (1981).
Even when added as a water-dispersible beadlet, it has been found that .beta.-carotene can still be very sensitive to oxidation in dilute juice beverages that contain sodium hexametaphosphate such that vitamin A activity is rapidly lost and color changes over time, especially when the beverage is subjected to light stress. This has particularly been found to happen when the dilute juice beverage is formulated by dispersing the .beta.-carotene beadlets in water, and then blending this dispersion with the other dilute juice beverage ingredients such as sodium hexametaphosphate. The inclusion of antioxidants such as ascorbic acid has been suggested as a way to prevent the oxidation .beta.-carotene. See U.S. Pat. No. 3,886,294 (Emodi et al), issued May 27, 1975 (use of ascorbic acid as antioxidant for carotenoid coloring compositions); and U.S. Pat. No. 5,153,012 (Ohtaka et al), issued Oct. 6, 1992 (use of a mixture of vitamins C, B.sub.2 and E to stabilize .beta.-carotene even under ambient conditions to minimize its loss from the beverage.) However, even when an antioxidant such as ascorbic acid is included, it has still been found that the .beta.-carotene is rapidly oxidized in dilute juice beverages that contain sodium hexametaphosphate such that vitamin A activity is lost and color changes over time.
The concentration of .beta.-carotene in the water-dispersible beadlet has also been found to be important to the oxidative stability of the .beta.-carotene when formulated in dilute juice beverages that contain sodium hexametaphosphate. For example, when the water-dispersible beadlets contain about 10% .beta.-carotene, it has been found that vitamin A activity and color is rapidly lost over time in such dilute juice beverages containing sodium hexametaphosphate. By contrast, when water-dispersible powders containing only about 1% or 2.5% .beta.-carotene are used, vitamin A activity and color is maintained over time in such dilute juice beverages, even when sodium hexametaphosphate is present. Unfortunately, to provide equivalent vitamin A activity and color, significantly more of these 1% or 2.5% .beta.-carotene powders would need to be included in the dilute juice beverage which increases the processing cost, the ingredient cost, and complexity in formulating the beverage. Furthermore, these 1% or 2.5% .beta.-carotene powders are generally not as physically stable (i.e., they cream more readily) compared to the 10% .beta.-carotene beadlets.
Accordingly, it would be desirable to be able to formulate dilute juice beverages that (1) can be formulated with water-dispersible beadlets containing high concentrations of .beta.-carotene; (2) provide adequate vitamin A activity and color over the expected storage and use life of the beverage; (3) allow the use of preservative systems that contain polyphosphates, especially sodium hexametaphosphate.

Oil-in-water dispersions of .beta.-carotene and other carotenoids stable against oxidation prepared from water-dispersible beadlets having high concentrations of carotenoid


A control apparatus controlling charge and discharge of a lithium-ion secondary battery includes a temperature sensor obtaining the temperature of the lithium-ion secondary battery and a controller. The controller controls the charge and discharge of the lithium-ion secondary battery to maintain the temperature obtained by the temperature sensor at a level lower than an upper limit temperature allowed in the lithium-ion secondary battery. The controller estimates the amount of precipitation of lithium in the lithium-ion secondary battery and reduces the upper limit temperature in accordance with an increase in the amount of precipitation.

According to a technique described in Patent Document 1, an upper limit electric power to which charge and discharge of a secondary battery are allowed is set in accordance with the temperature of the secondary battery. The charge and discharge of the secondary battery are controlled such that the electric power of the secondary battery does not exceed the upper limit electric power.

Control apparatus and control method for lithium-ion secondary battery


A rocker-recliner chair comprising a base for standing on the floor and having a pair of side rails, rocker cams seated for rocking motion backward and forward on the side rails, a cross tube assembly disposed above the base and having side plates and cross tubes, a reclining linkage mechanism having a pair of base plates adjustably connected to the cams for backward and forward adjustment with respect to the cams, adjustable connections joining the cross tube assembly to each base plate of the mechanism for enabling the cross tube assembly to be moved forward and backward with respect to the mechanism, a chair frame having a seat, backrest and footrest carried by the mechanism and movable between upright and reclined positions with respect to the base, and a stabilizing spring assembly connected between the cross rail assembly and the base for biasing the rocker cam, linkage mechanism and chair frame to an upright position on the base.

Rocker-recliners conventionally employ rocker cams having curved lower surfaces that rest on a fixed base and in turn carry the reclining mechanism which supports the seat, back rest and foot rest of the chair. A rocker blocking assembly connected to the reclining mechanism and the base prevents the cams from rocking on the fixed base when the chair is moved from the upright to a reclining position. When the rocker blocking assembly is inactive (when the chair is in the upright position), the rocking motion is controlled by spring assemblies conventionally connected between the rocker cams and the base. The various connections between the mechanisms, cams, spring assemblies and base are not susceptible to convenient adjustment to compensate for differences in the center of gravity of the chair caused by different chair styles, e.g., chairs with heavy or lightweight backs and deep or short seats, and by different body sizes of the people occupying the chair. Typical examples of prior art rocker-recliners are shown in the U.S. Pat. Nos. 3,537,747, 3,730,585 and 4,519,647.
One important object of the present invention is to provide an improved rocker-recliner that enables the spring assemblies to be adjusted forward and backward independently of the reclining mechanism and rocker cams.
Another important object of the present invention is to provide a rocker-recliner that enables the rocker cams to be adjusted forward and backward independently of the reclining mechanism and spring assemblies.
Yet another object of the present invention is to provide a method of connecting the various components of a rocker-recliner together in a fashion that is suitable for use with either a metal or wood base and wood, plastic or metal rocker cams.
Another object of the present invention is to provide a spring assembly which maintains the preload applied to the springs when the location of the spring assembly is adjusted.
To accomplish these and other objects, in accordance with the present invention, the base plates of the reclining mechanism are adjustably connected to and supported on the upper horizontal surface of the rocker cams so that the cams can be moved forward or backward with respect to the mechanism and the seating components of the chair carried by the mechanism. A cross tube assembly is also adjustably connected between the base plates of the reclining mechanism, and the spring assemblies in turn are connected at their tops to the cross tube assembly. The lower ends of the spring assemblies are connected at a fixed position to the base. With these adjustments, the balance of the chair may easily be changed by moving the cams and/or the spring assemblies with respect to the mechanism.
These and other objects and features of the invention will be better understood and appreciated from the following detailed description of two embodiments thereof read in connection with the accompanying drawings.

Rocker assembly for rocker-recliner chairs


Wire bonds connect current-carrying edges of high-frequency planar conductors to other electrical devices. In one embodiment, planar transmission lines are interconnected using two wire bonds. One bond wire extends from an edge of a first center conductor to a corresponding edge of a second center conductor, and a second bond wire extends from the other edge of the first center conductor to the other edge of the second center conductor. Embodiments include center conductors at different heights and having different widths, and different electrical devices, such as semiconductor integrated circuits. In a particular embodiment, ball bonding is used. In some embodiments, a tack bond is included after a ball bond to allow closer attachment of the bond wire to the edge of the conductor.

Microwave integrated circuits ("MICs") typically consist of a number of separate high-frequency components, such as thin-film or thick-film transmission lines, semiconductor integrated circuits ("ICs"), active or passive electronic devices, and printed wiring boards ("PWBs"). MICs may also include surface-mount devices, integrated subcomponents, and grounding structures. The devices are electrically interconnected using a variety of techniques.
Microstrip and coplanar transmission lines are examples of planar transmission lines often used in MICs. In a microstrip transmission line, a center conductor is separated from a ground plane by a selected thickness of dielectric material to obtain a characteristic impedance of the transmission line. Fifty ohms is an example of a characteristic impedance often used in MICs. In a coplanar transmission line, ground planes extend along each side of a center conductor to obtain a characteristic impedance. In both cases, center conductors of adjacent transmission lines are typically connected together using one of four bonding methods: 1) a single wire bond between the center conductors of each transmission line, 2) parallel wires bonded symmetrically between the center conductors of each transmission line, 3) mesh bonding between the center conductors of each transmission line, and 4) ribbon bonding between the center conductors of each transmission line. Each of these bonding methods is also used to connect planar transmission lines to other devices.
At microwave frequencies, a single wire bonded between center conductors of adjacent transmission lines results in a signal discontinuity. In other words, the desired characteristic impedance is not maintained across the bond wire. The impedance of the bond wire is usually higher than 50 ohms, which is frequently the characteristic impedance of the transmission lines. The discontinuity leads to scattering and reflections of the incident signal, which degrades the performance of the MIC. Multiple bond wires create a similar discontinuity, but not as severe as a single bond wire.
Mesh and ribbon bonds have a lower impedance than a single bond wire or even multiple bond wires of similar length. However, mesh and ribbon bonds still present an impedance discontinuity. Unfortunately, mesh and ribbon bonds are more difficult to fabricate than wire bonds. Mesh bonding is a manual bonding process that uses fragile pieces of fine metal mesh that must be carefully handled by a skilled operator to avoid tearing. Ribbon bonding can be manual or automatic. Manual ribbon bonding can be as difficult as mesh bonding. Automatic ribbon bonding cannot easily adjust the ribbon width, and is not as flexible of a manufacturing process as wire bonding.

Electrical interconnection for high-frequency devices