Methods and materials are provided for stably introducing any gene into a specific locus in the genome of a microorganism such as yeast without the addition of any drug resistance genes. Specifically provided herein are new genetically engineered inositol-overproducing Saccharomyces cerevisiae strains obtained by using a novel set of yeast integration plasmids that allow the safe, stable, and controlled introduction of homologous as well as heterologous genes into the host genome. In particular, specific loci of the S. cerevisiae yeast genome can be targeted with single or multiple copies of a specific gene that is desired to be expressed or a given set of specific genes that the host can use without the addition of any drug resistance genes. The principles of this new methodology can also be used for the construction of other recombinant yeast and bacterial strains as well as higher eukaryotic cells.

Biosafety of genetically modified microorganisms for uses in human food, animal feed or plant fertilizers is a major issue to be considered in the development and application of emerging biotechnologies. The United States, Europe, and Japan are especially sensitive to the potential biohazards from foods and additives from biotechnological sources. Most of the current recombinant DNA processes use circular DNA molecules called plasmids as cloning vectors to introduce homologous or heterologous genetic information into microorganisms such as bacteria, yeast, plant, and animal cells. Plasmids have the advantage that they exist normally in prokaryotic and lower eukaryotic cells in single or multimeric forms, which means that a certain gene located on such a plasmid could exist in the cell in multicopy form, which may result in a higher expression of the proteins encoded by these genes. In such instances plasmids serve as vectors on which the new genetic property or properties can be engineered and then be subsequently transferred into a host cell. In order to detect whether such a transfer has been successful and also to maintain the plasmid in the transformed cell, the plasmids must also contain a so-called selection gene marker. A selection gene marker is typically a gene that confers resistance to an antibiotic or another substance that kills or prevents the growth of cells that do not contain such a plasmid. A selection marker can also confer other phenotypic traits that can be selected such as the color of colonies, a new enzymatic activity, as well as others.
Plasmid vectors can be replicated in the host cell if they contain autonomous replication sequences recognized by the host DNA synthesis machinery, or if they are able to integrate in the genome of the host cell. The first type of such plasmids, also known as episomal plasmids, can be amplified in large numbers inside a single host cell and their replication is independent of the host chromosomal replication during the cell cycle. The other type of such plasmids, also known as integrative plasmids, can only be replicated and maintained if they are integrated into the host cell genome. Many plasmid vectors used to transform eukaryotic host cells are known as shuttle episomal vectors, meaning that they contain prokaryotic and eukaryotic DNA sequences that allow their episomal amplification in either type of host cells. There are also combinations of prokaryotic-episomal/eukaryotic-integrative shuttle vectors.
The DNA amplification step of all episomal plasmid vectors required to transform eukaryotic cells is preferably carried out in bacterial hosts due to their faster growth rate and ease of purification of the plasmidic DNA. Most plasmids used in molecular biology (such as pBR and pUC-derived plasmids) contain as a selection marker the bacterial drug resistance marker for the ampr or bla gene (See, Sutcliffe, J. G., et al., Proc. Natl. Acad. Sci. U.S.A. 75:3737 (1978), the disclosure of which is incorporated herein by reference). The bla gene encodes an enzyme named TEM-1, which is a widespread plasmidic β-lactamase for narrow-spectrum cephalosporins, cefamandole, and cefoperazone and all the anti-gram-negative-bacterium penicillins except temocillin.
Unfortunately, when using the most common recombinant DNA plasmid vectors to transform microorganisms these drug resistance gene markers are inherently transferred along with the gene or genes that are of interest to the host microorganism. Consequently there is potential for the transfer of bacterial drug resistance genes from a genetically modified organism ("GMO") used as a feed additive to a wild or pathogenic bacteria that is present in the normal intestinal flora of the animal being fed, thereby transforming the normal microbial flora of the animal into new and potentially dangerous antibiotic resistant strains. For example, the TEM-1 enzyme was first reported in 1965 from an E. coli isolate and is now the most common β-lactamase found in enterobacteria. Resistance in more than 50% of Ampr E. coli clinical isolates is due to TEM-1.
The world is currently facing similar problems due to indiscriminant overuse or misuse of antibiotics to treat common human and animal illnesses. This overuse/misuse has created drug resistance in bacterial strains that are no longer responsive to available antibiotics. See, Levy, S. B., Scientific American, March 1998, pp. 46–53, the disclosure of which is incorporated herein by reference. The FDA as well as the World Health Organization (WHO) and European regulatory agencies are concerned about biotechnology-derived products that could lead to the uncontrolled dissemination of drug resistance genes into the environment, hence posing a potential health problem. Therefore, genetically engineered organisms, for example, recombinant yeast containing bacterial drug resistance gene markers are considered potentially biohazardous and could not be used as food or as a feed additive without carrying out a comprehensive health and environmental risk assessment for its use.
Another disadvantage of plasmids that contain bacterial antibiotic selection gene markers for use in human or animal food fermentation is that antibiotics are costly and they must be present in the medium in which the bacterial host has to be cultivated. In response to this problem "food-grade" vectors have been developed. See, for example, U.S. Pat. No. 5,627,072, the disclosure of which is incorporated herein by reference.
In the specific case of yeast, and in particular those of the genus Saccharomyces, a recombinant molecule containing a drug resistance gene marker would not be considered "generally recognized as safe" ("GRAS") by the Food and Drug Administration and would be considered to be a potential biohazard unless a risk assessment is performed on the recombinant yeast. The GRAS classification is important when choosing a microorganism to industrially manufacture a product such as inositol that is also GRAS (see, 21 C.F.R. 184.1370(c)), since a byproduct of the fermentation is the yeast biomass itself or its extract. Therefore, if the yeast biomass is biohazard-free, it can itself be sold for profit as a valuable feed or food additive, which is the case for the genus Saccharomyces. Conversely, a non-GRAS biomass, such as certain yeasts of the genus Candida, for example, Candida boidinii, can be considered biohazardous waste, and therefore such biomass has to be disposed of by costly procedures which add to the production cost and which could potentially impact the environment. Currently, biohazardous biomass has to be either incinerated or disposed of according to the NIH guidelines for the treatment of biohazardous waste. Therefore, having a "GRAS" regulatory status is an important aspect to be considered for a successful industrial biotechnology process.
Fermentation technology can produce many compounds at a lower manufacturing cost than the present chemical technologies, with the added advantage of being environmentally safe. Such an example is the production of inositol and inositol-containing metabolites. Industrial methods to produce inositol have been based on chemical conversion of phytic acid (inositol hexaphosphoric acid ester) to myo-inositol and phosphate using corn mill factory steep water. See, Bartow, E., et al., Ind. Eng. Chem. 30: 300 (1938) the disclosure of which is incorporated herein by reference. The first practical industrial methods, still in use in Asia today, involve the breakdown of phytic acid with high heat, high pressures, and very acidic conditions. See, U.S. Pat. No. 2,112,553, the disclosure of which is incorporated herein by reference. Such processes produce waste products that impact the environment thereby adding to production costs due to the necessity for treatment procedures of such waste byproducts.
Inositol, or more specifically, the most abundant isomer, myo-inositol, is presently used in non-milk based infant formula, premixed vitamin supplements for humans, and is used as feed additive for animals and aquaculture applications. Recently, however, new uses for inositol have been suggested for alternative treatments of human diseases such as diabetes type II, folate-resistant neural tube defects (NTDs), manic depressive disorders, and obsessive compulsive disorders ("OCD's").
Inositol and inositol derivatives can be produced by fermentation of genetically modified yeast. White, M. J., et al., J. Biol. Chem. 266:863 (1991), (hereinafter referred to as "White, et al. (1991)"), and U.S. Pat. Nos. 5,529,912, and 5,599,701, the disclosures of which are incorporated herein by reference, describe genetically modified yeast of the genus Saccharomyces which has a functional stable recombinant DNA sequence that prevents the expression of the OPI1 gene, a negative regulator of phospholipid biosynthesis which results in the overexpression and excretion of inositol. There is described therein a complete deletion of the open reading frame ("ORF") region of the OPI1 gene, which results in the constitutively depression of the gene INO1, the result of which is the overproduction and excretion of inositol and overproduction of inositol-containing metabolites and/or phospholipids. Many of the other coregulated enzymes involved in phospholipid biosynthesis are also expressed at high levels. Using these methods, a diploid Opi− strain with its two endogenous copies of the INO1 gene was constructed accordingly (See, U.S. Pat. No. 5,599,701), designated as the YS2 strain, and was deposited at the American Type Culture Collection located at 10801 University Boulevard, Manassas, Va., under accession number 74033. U.S. Pat. No. 5,529,912 further describes an Opi− diploid S. cerevisiae strain designated as YS3 (ATCC accession number 74034) containing multiple (3–6) copies of the INO1 gene. U.S. Pat. No. 5,296,364, the disclosure of which is incorporated herein by reference, describes a method for increasing production of inositol into the growth media using the S. cerevisiae strains designated as YS2 and YS3.
U.S. Pat. No. 5,618,708, the disclosure of which is incorporated herein by reference, describes mutants of the yeast genus Candida which excrete inositol into the growth media. Some members of the genus Candida, however, are not considered GRAS, as stated above.
However, even though wild type S. cerevisiae is considered a GRAS organism, new genetically modified strains such as the YS3 strain described in White, et al. (1991) and U.S. Pat. Nos. 5,529,912 and 5,599,701 is not considered to be GRAS because it contains bacterial drug resistance gene markers that were inserted in its genome during the insertion of recombinant plasmids carrying extra copies of the INO1 gene.
In order to solve the above-described limitations of the present genetic engineering technology, new recombinant DNA techniques and materials have been developed that allow for genetic metabolic engineering of yeast without adding any heterologous drug resistance genes in the DNA recombination process. They also allow for the stable integration of genes of interest into yeast, such as even more copies of the INO1 gene than has been previously possible, and the integrations are done at different loci in the genome hence increasing the genetic stability of the resulting strain. These novel recombinant strains could be considered GRAS and contain improved nutritional qualities.

Cells engineered to contain genes of interest


AN LED tube apparatus has a tube body with two opposite ends fixed to a first cap and a second cap. AN LED module is placed in the tube body. The LED module has a driver circuit containing an electronic ballast that generates high frequency electric current. The first cap has two first metal pins to be inserted in a first socket end of a light tube bracket. The first metal pin clutches an end of a leading wire. The leading wire has a protective portion breaking off when the first metal pin is applied with a predetermined range of heat generated by the high frequency electric current when the LED tube apparatus is not operated properly.

Light tube apparatuses are widely used in our daily life. Light tube apparatuses are usually installed to corresponding light tube brackets for connecting to an external power supply like a 110V˜220V power source. There are several standards for defining common light tube brackets for matching different light tubes. For example, T8 light tube is a widely used standard and many places are already installed with corresponding light tube brackets.
Traditional fluorescent light tubes have limited life span. Meanwhile, their luminous efficacy are also not perfect, compared with LED light tubes. Therefore, LED light tubes, when their manufacturing cost are decreasing, are widely used to replace traditional fluorescent tubes.
On the other hand, while considering compatibility of traditional fluorescent light tubes, it would be usually more convenient to design an LED tube that can be directly installed in various settings. For example, users may want to buy an LED light tube from a store and would like to install the LED tube directly to a light tube bracket originally designed for fluorescent light tubes. But, there are various aspects to improve LED light tubes to make such products more reliable and convenient by solving various technical problems.
In such crowded field, it is very beneficial to find out innovative design that may satisfy human needs more perfectly, particularly light tubes are so widely used in daily life.

This patent is subject to a terminal disclaimer.

Tubular lighting apparatus with protection portion


Therapeutic compounds which are cell proliferation modulators, preferably inhibitors. These modulators contain amino acid structures that are arranged as a hydrophilic analog of an alpha-fetoprotein. The modulator may be a peptide itself, e.g., an octapeptide like that of SEQ ID NO: 5; a peptidomimetic; or may be in the form of a pharmaceutically acceptable scaffold, such as a polycyclic hydrocarbon to which is attached the necessary amino acid structures for biological and/or chemical activity. The modulators of the invention are distinguished in one aspect over previous compounds in that they are orally active, and therefore do not have to be injected into the patient. The compositions and methods are useful for reducing estrogen-stimulated growth of cells, and treating or preventing cancer, such as breast cancer. The treatment or prevention methods can include the use of tamoxifen therapy in combination with the peptide therapy.

Every year in the U.S., 180,000 new cases of breast cancer are diagnosed and approximately 60% of these are estrogen-receptor-positive (ER+) (Martin et al. 1994). Moreover, every year there are a substantial number of breast cancer recurrences, and many of these are ER+. Tamoxifen has been the mainstay for medical treatment of ER+ breast cancer and has provided significant clinical benefit (Fisher et al. 1989; Fisher et al. 1998). However, there are a substantial number of ER+ breast cancers that are refractory to tamoxifen due to either intrinsic or acquired resistance. New treatments for these ER+, tamoxifen-refractory breast cancers are needed, and some promising agents are currently being evaluated in clinical trial. Letrozole, which blocks estrogen synthesis by inhibiting aromatase; and goserelin, which stifles ovarian release of estrogen by inhibiting gonadotropin release; are both being tested for this purpose (Goss et al. 2001; Nystedt et al. 2000).
Several population and epidemiologic studies as well as laboratory studies have indicated that alpha-fetoprotein (AFP) interferes with estrogen-dependent responses, including the growth-promoting effects of estrogen on breast cancer (Bennett et al. 1998). For example, Couinaud et al. (1973) have reported that women with AFP-secreting hepatomas develop amenorrhea which self-corrects following removal of the hepatoma, and Mizejewski et al. (1983) have shown that AFP inhibits the responsiveness of the uterus to estrogen. Jacobson et al. (1989) and Richardson et al. (1998) have shown that elevated levels of AFP during pregnancy are associated with subsequent reduction in lifetime risk for breast cancer, and Jacobson et al. have hypothesized that this could be caused by a diminution in estrogen-dependent breast cancers (Jacobson et al. 1989). Sonnenschein et al. (1980) have shown in rats that an AFP-secreting hepatoma prevents the growth of an estrogen-dependent breast cancer in the same rat. Finally, it has been shown that AFP purified from a human hepatoma culture and then injected into tumor-bearing immune-deficient mice stopped the growth of ER+, but not estrogen-receptor-negative (ER−) human breast cancer xenografts in these mice, and did so by a mechanism different from that of tamoxifen (Bennett et al. 1998).
More recently, the active site of AFP responsible for its antiestrotrophic activity has been identified (Mesfin et al. 2000). It consists of amino acids 472–479 (SEQ ID NO: 6, EMTPVNPG), an 8-mer sequence in the 580-amino acid AFP molecule.
Aggregation of proteins and peptides has been seen with full length AFP as well as with subunits of AFP. Wu et al. (1985) showed that AFP tends to form aggregates, which may contribute to its loss of anti-estrotrophic activity during storage. Eisele et al. (2001) reported that oligomers of various sizes formed during storage of a 34-mer peptide (amino acids 447–480) derived from AFP. Similar aggregation behavior has been seen with a number of other protein and peptide pharmaceuticals, including human interferon-γ (Kendrick et al. 1998), human calcitonin (Bauer et al. 1994), insulin (Sluzky et al. 1991), and synthetic β-amyloid peptide (Hilbich et al. 1991; Christmanson et al. 1993; Halverson et al. 1990). Hughes et al. (1996) and Hilbich et al. (1992) reported inhibition of amyloid peptide aggregation by substitution of hydrophobic phenylalanine with hydrophilic threonine or by adding polylysine at the carboxy-terminus of the amyloid peptide.

Alpha-fetoprotein peptides and uses thereof

CLF Medical Technology Acceleration Program, Inc.


A heat slug or spreader is attached directly to a surface of the die in a ball grid array (BGA) package. The heat spreader roughly conforms to the topological profile of the die, underlying substrate, and electrical interconnections between the die and the substrate, such as bond wires. The outer portion of the heat spreader substantially cover the outer portion of the substrate, or alternatively, cover only those portions extending in laterally from the sides of the chip and not the corners. An encapsulant completely covers the heat spreader and die.

In general, semiconductor packages are used to protect a semiconductor die in a package body and to provide connection points for connecting the packaged die to external devices and circuitry. Ball grid array (BGA) packages are currently used to handle the high density and high pin-count of semiconductor die. In a typical BGA package, the semiconductor die is mounted to the top surface of a printed circuit board (PCB) type substrate. The die is wire bonded to electrical traces on the top surface of the substrate. The bond wires and die are then typically encapsulated for protection. Solder balls are bonded to the electrical traces on the bottom surface of the substrate to provide electrical connection to an underlying device, such as a PCB.
During operation of the integrated circuit, heat is generated by the die which must be removed from the package. Many packages use heat dissipation elements, such as heat slugs, heat spreaders, and heat sinks, attached or coupled to the die. These elements can be made of materials, such as aluminum, copper, steel, and alloys, which spread and remove the heat from the device.
With a cavity-down configuration, in which the die face is facing down towards the ball grid array, the die and bond wires are encapsulated in the cavity, and a heat dissipation element is typically attached to the back side of the die to form the top of the chip package. These types of configurations have high package or substrate profiles as well as high assembly costs. With a cavity-up configuration, in which the die face is facing up and away from the ball grid array, a chip lid is secured over the die and bond wires to dissipate heat generated by the circuit. However, these "drop-in" lids result in a high thermal resistance between the die and the heat spreader.
Accordingly, a ball grid array package with a heat dissipating element is desired without the disadvantages discussed above with conventional packages.


A cable foul sensor device for winches includes a flapper plate extending from a cover for the cable drum, and a sensing finger extending along the edge of the flapper plate to terminate above an upper layer of cable wound on the drum. The flapper plate is connected to a pivot member through which an adjustable set screw is mounted. A stationary housing for spring loaded switches is mounted on the cover and includes a contact plate which is depressed downward by the set screw of the pivot member to force the switches to the closed position to provide power for the drum. Upon fouling of the cable at the drum, the cable foul will displace the sensing finger and the flapper plate which will cause the pivot member to pivot away from the actuator plate, thereby permitting the spring loaded switches to bias in the open position to interrupt power to and lock the drum. An audio and/or visual signal is provided to indicate that a cable foul at the drum has occurred.

1. Field of the Invention
The present invention relates to winches and hoists used in aircraft and in particular, to cable hoist systems adapted for use in a helicopter to sense cable fouling, control the disposition of the cable with respect to the drum, and signal cockpit personnel that fouling has occurred.
2. Description of the Related Art
There are many ways in which a cable can be fouled at the cable drum. For example, cable used with winch drums can be fouled by parting of the cable, kinks in the cable or an excessive amount of slack in a standing portion of the cable. During reeling operations, the cable can become loosened on the drum and foul. A broken strand of wire from the cable will force successive layers of cable out of alignment with respect to the drum, thereby causing the cable to foul on the drum.
In helicopters, a cable is more susceptible to fouling due to the heavy vibrations which occur on the aircraft's fuselage. Exposure of the fuselage to the vibrations requires that the winch assembly and cable be particularly adapted to operate in the "choppy" environment caused during helicopter operations.
It is therefore especially important to be able to sense immediately when a cable has fouled to prevent irreparable damage to the cable and the winch, and harm to personnel in the immediate area if the cable should part. Just as important is that a cable foul sensor device be able to distinguish between the vibrations in the fuselage of the helicopter, and an actual cable foul which will adversely impact on cable operations.
Cable winding safety devices are known in the elevator and well drilling arts. For example, U.S. Pat. No. 641,242 to Sprague discloses a cable winding safety device having a bar which lies parallel with and close to the face of a cable drum so that the space between the cables will be considerably less than the height of the ridges of the drum with the thickness of the cables. When cables climb out of their groove, the bar is forced back to coact with a switch arm above the drum to open the switch and stop the drum.
U.S. Pat. No. 813,451 to Rohlfing et al discloses a safety device for hoisting mechanisms which is used to control or stop the main hoist of the motor when the hoisting limit has been reached. The device consists of a rocking lever disposed at an interior of the drum and from which a trip-pin extends to project out of the drum. A trip pawl is mounted to coact with the other end of a rocking lever and be forced to extend from the drum to contact a switch when the trip-pin has been forced downward against the rocking lever by the cable being wound around the drum and down upon the trip-pin.
U.S. Pat. No. 1,163,165 to Mueller discloses a safety device for elevators consisting of a flexible metal strip, wire or bar arranged in proximity to a cable drum and extending longitudinally along said drum and spaced therefrom. A loose or broken strand of cable will make contact with the safety device for an electro-responsive controlling device to trip the switch controlling the drum.
U.S. Pat. No. 2,019,512 to Stahl discloses a means for preventing reverse winding of a cable on a drum, which device consists of a latch lever having a land stop and a groove stop which ride along the cable and grooves of the drum to actuate a stop switch when the cable has been taken out from the drum, or when a sufficient amount of cable has been wound upon the drum.
U.S. Pat. No. 2,053,976 to Stahl discloses a detent means for cable drums consisting of a recess in the first turn of the guide groove of the drum and in which a detent lever is arranged to lie in the recess and is pivotally carried by means of a pivot pin secured to the body. When the last turn of cable has been unwound off the drum, further movement of the drum will cause the arm to signal all the cable has been unwound.
U.S. Pat. No. 2,489,913 to Logan discloses a hoist control mechanism consisting of a pair of rocker arms which coact with a roller and control cam on the drum to control movement of the drum.
U.S. Pat. No. 3,031,169 to Robinson et al discloses an apparatus for automatically controlling drilling, which consists of an auxiliary control unit operable by valve means to which a pressure line is connected. The auxiliary control unit senses movement of the drum.
U.S. Pat. No. 3,182,961 to Le Bus discloses a combined fleet angle compensator and braking apparatus consisting of an eccentric shaft along which a sheave guard member moves. A braking mechanism is spaced from the eccentric shaft and is provided with a braking plate member adapted to engage the outer periphery of the cable spooled on the drum in the braking position. Upon release of tension in the cable, the braking plate is moved into contact with the outer layer or wrap of cable upon pivotal movement of the arm 24 to prevent slack in the cable from fouling on the drum.
U.S. Pat. No. 3,994,476 to Van Genneup discloses an automatic arrangement for a windlass to prevent unwanted reverse rotation of such windlass. The device consists of a load sensing lever arm, with one end pivotally mounted to the housing and the other end extending to support a pulley for the windlass block and tackle. Brake pressure is applied when the sensing lever succumbs to a particular amount of downward force resulting from the load thereon.
U.S. Pat. No. 4,213,019 to Houp discloses an overhead door cable safety device consisting of a U-shaped monitoring arm disposed in a spaced relationship adjacent to a top of the cable wrapped around a cable drum. Movement of the monitoring arm upward against the biasing of springs closes a switch to signal that the cable has been disengaged, unraveled, or frayed.
U.S. Pat. No. 4,448,394 to LeMoine discloses a high low safety apparatus for drilling rigs consisting of a pair of longitudinally moveable stems at opposed sides of a cable drum, each of the stems having a hemispherical surface which are normally positioned spaced from the cable on the drum. Movement of the hemispherical surface of the stem moves a valve element to allow passage of air through the valve to stop actuation of the drum.
U.S. Pat. No. 5,335,895 to Sell discloses a sensing rope guide for a hoist drum consisting of a split steel ring joined at the top by a steel hinge and held together at the bottom by a spring and bolt which encircle at least a portion of the drum. Steel groove rollers are housed in pockets of the ring to contact a sensing valve. If travel over the ring along the hoist drum is impeded by resistance from a side pull acting on the retainer and arm, or resistance from some other cause acting at some other point on the ring, the groove rollers cam out to actuate the sensing valve and prevent further operation of the hoist in the same direction.
However, among the devices disclosed in the patents above, none are especially adapted for use in aircraft, such as helicopters, and the particular environmental conditions these machines operate in. The heavy vibration of a helicopter fuselage requires the need for a cable foul sensing device which is immediately responsive to a cable foul at the drum, yet will not inadvertently be tripped due to the heavy vibration that the cable drum and cable are exposed to.


A set of pixel regions (P11, P12, P13) having a pixel electrode (12) corresponding to red, green or blue as one unit is arranged periodically in the X direction, and the delta arrangement is constituted by displacing the pixel arrays from each other by a 1/2 period at odd-numbered lines and even-numbered lines in the Y direction. By connecting only the pixel electrode (12) of pixel regions (P12, P22, P32) corresponding to the same color with the same source line (S2), the pixel regions (P12, P22, P32) are placed alternately right and left of the source line (S2). Among pixel regions (P11, P12, P13, . . . ) in the X direction, the relative position of a TFT (11), the pixel electrode (12), a first electrode (C1) and a second electrode (C2) of storage capacitors CS is the same. Among pixel regions (P12, P22, P32, . . . ) in the Y direction along source lines (S1, S2, S3, . . . ), although the relative position of the TFT (11) and the pixel electrode (12) is reversed right and left at each line, the relative position of the first electrode (C1) and the second electrode (C2) of the storage capacitors CS is the same.

FIG. 1 shows a basic structure of a color liquid crystal display using an active matrix substrate. In FIG. 1, on the surface of a substrate 10 are gate lines G0, G1, G2, . . . running in the X direction, source lines S1, S2, S3, . . . running in the Y direction, a plurality of pixel electrodes 12 placed in the positions corresponding to the intersections of the source lines S1, S2, S3, . . . and the gate lines G1, G2, G3, . . . , and a thin film transistor 11 (hereinafter "TFT") connected with each of the pixel electrodes.
In a selection period, that is, a period in which the TFT 11 is on by the signals from the gate lines G1, G2, G3, . . . , the picture signals provided by the source lines S1, S2, S3, . . . are written in a liquid-crystal-capacitance portion CLC consisting of a common electrode 26 formed on an opposite substrate 20, a pixel electrode 12, and liquid crystal 30 encapsulated between the electrodes 26 and 12. In a non-selection period, that is, a period in which the TFT 11 is off, the picture signals written in the liquid-crystal-capacitance portion CLC in the selection period are retained.
Note that in order to achieve a high-quality display, the storage characteristics in the non-selection period need to be good. For that purpose, it will be effective to set up a storage capacitor CS electrically parallel to the liquid-crystal-capacitance portion CLC. As to the storage capacitor CS, it has been proposed that the storage capacitor CS be established between the adjacent gate line and the pixel electrode 12, or that the storage capacitor CS be established between a storage line (not shown in FIG. 1) separately formed and the pixel electrode 12.
The storage capacitor CS formed as was described above, the pixel electrode 12, the TFT 11, and other accompanying wirings and others constitute pixel regions P11, P12, P13 . . . Note that although in FIG. 1 there is no pixel region between the pixel region P11 and a pixel region P31, there can be a pixel region for blue or a dummy pixel region in the area in question.
The opposite substrate 20 has a color filter 21. The color filter 21 generally consists of a red filter R, a green filter G and a blue filter B. A set of the red filter R, the green filter G and the blue filter B as one unit is repeatedly placed in the display area. As the arrangements of the color filter 21, there are a stripe arrangement, a mosaic arrangement or a delta arrangement. FIG. 12 shows a color arrangement pattern according to the delta arrangement, and FIG. 13 shows an example of a color arrangement pattern according to the mosaic arrangement. The delta arrangement or the mosaic arrangement is more advantageous than the stripe arrangement in that a more delicate picture can be obtained than according to the stripe arrangement because each of the color elements is dispersed uniformly in the display area.
FIG. 3A of Japanese Patent Publication No. TOKUKOUHEI 3-64046 and others disclose a liquid crystal display making use of the delta arrangement, and FIGS. 8C to 8F of the same publication and others disclose a liquid crystal display making use of the mosaic arrangement.
In the liquid crystal display using the delta arrangement disclosed in the above-mentioned publication, as shown in FIG. 14, a set of three pixel regions P21, P22, and P23 corresponding to the red filter R, the green filter G, and the blue filter B as one unit is placed periodically in the X direction. Note that the pixel regions P21, P22, and P23 in a pixel array at an even-numbered line are displaced from the pixel regions P11, P12, and P13 or the pixel regions P31, P32, and P33 in a pixel array at an odd-numbered line by a distance corresponding to a 1/2 period of the above-mentioned one unit. Accordingly, between the pixel array at an odd-numbered line and that at an even-numbered line, the center of the pixel regions P11, P12, P13, . . . are displaced right and left by 1.5 pixel pitches.
The pixel region P21 will be explained as an example, because each of the pixel regions has the same basic structure. In the pixel region P21, a source region 111 of the TFT 11 is connected with a source line S1, a gate electrode 113 is connected with a gate line G2, and a drain region 112 is connected with a pixel electrode 12.
In the pixel region P21, a first electrode C1 electrically connected with the drain region 112 of the TFT 11 and the pixel electrode 12, and a second electrode C2 projecting in the Y direction from a adjacent gate line G1 are formed. The first electrode C1 is usually made of a doped silicon film. The first electrode C1 and the second electrode C2 are, as described below, opposed across a dielectric film. The storage capacitor CS is formed as described above between the pixel electrode 12 and the adjacent gate line G1.
Since each of the source lines S1, S2, S3, . . . extends with a crank-like shape in the Y direction, and does not require a complicated color changeover circuit to supply a plurality of color signals with the same source line at appropriate timing, only the pixel electrode 12 in the pixel region corresponding to the same color is connected with the same source line through the TFT 11. Accordingly, the same source line has the pixel regions corresponding to the same color alternately on both sides of the source line at each line. The source line S2, for instance, has pixel regions P12, P22, P32, . . . corresponding to green alternately on both sides of the source line S2. And necessarily, the position of the TFT 11 and the source line is reversed at each line.
As a result, while as to the pixel regions P11, P12, P13, . . . in the X direction along the gate lines G1, G2, G3, . . . , the relative position of the TFT 11, the pixel electrode 12 and the storage capacitor CS (the first electrode C1 and the second electrode C2) is the same, as to the pixel regions P12, P22, P32, . . . in the Y direction along the source line S2, the relative position of the TFT 11, the pixel electrode 12 and the storage capacitor CS is symmetrical horizontally at every line. For example, comparing the pixel regions P11, P12, P13, . . . connected with the gate line G1 with the pixel regions P21, P22, P23, . . . connected with the gate line G2, the relative position of the TFT 11, the pixel electrode 12 and the storage capacitor CS is symmetrical horizontally.
The manufacturing method of the active matrix substrate with the above-mentioned structure will be briefly explained with reference to FIG. 15. FIGS. 15(A), (B) and (C) are a I-I' sectional view, a II-II' sectional view, and a III-III' sectional view of FIG. 14, respectively.
In FIG. 15(A), after a polycrystalline silicon thin film is formed on the substrate 10, a polycrystalline silicon thin film 110 is formed which constitutes an active region of the TFT 11 and the first electrode C1 of the storage capacitor CS by the patterning according to photolithography.
Then a gate oxide 114 and a dielectric film C3 of the storage capacitor CS are formed by thermal oxidation of the polycrystalline silicon film 110. Next, only the polycrystalline silicon film 110 to constitute the storage capacitor CS is selectively doped to form the first electrode C1 of the storage capacitor CS.
Then a gate electrode 113 and the second electrode C2 of the storage capacitor CS are formed of a doped polycrystalline silicon film according to photolithography. At this step, in the pixel region P21, the gate electrode 113 and the gate line G2 are electrically connected, and the second electrode C2 and the adjacent gate line G1 are electrically connected.
Next, a source region 111 and a drain region 112 are formed by implanting ions with the gate electrode 113 used as a mask. And after an interlayer insulating film 115 is formed, a through-hole is made in it.
Then a source terminal 118 and a drain terminal 119 are electrically connected with the source region 111 and the drain region 112, respectively. The source terminal 118 is electrically connected with the source line S1, while the drain terminal 119 is electrically connected with the pixel electrode 12.
As was described above, the TFT 11 and the storage capacitor CS are formed in the pixel region P21, and at the same time, as shown in FIGS. 15(B) and (C), the storage capacitor CS is formed in the pixel regions P11, P12 and P22, too.
When the pattern shown in FIG. 14 is used, however, if the alignment is not obtained along the horizontal direction (in the X direction) in forming each component on the substrate 10 according to photolithography, in the pixel regions P12, P22, P32, . . . in the Y direction along the source line S2, for example, the structure parameter varies at every line.
In other words, in FIG. 16, when the overlap of a formation pattern A1 of a lower polycrystalline silicon film to form the TFT 11 and the first electrode C1 of the storage capacitor CS, and a formation pattern A2 of an upper polycrystalline silicon film to form the gate lines G1, G2, G3, . . . , the gate electrode 113 and the second electrode C2 of the storage capacitor CS is patterned with oblique lines as facing portions C0 of the storage capacitors CS, if the alignment is not obtained along the horizontal direction between the formation pattern A1 of the lower polycrystalline silicon film and the formation pattern A2 of the upper polycrystalline silicon film, the area of the facing portions C0 patterned with oblique lines varies between the storage capacitors CS (ODD) (these storage capacitors are connected with the gate lines G0, G2, . . .) of the pixel regions P11, P12, . . . P31, P32, . . . at odd-numbered lines selected by the gate lines G1, G3, . . . , and the storage capacitors CS (EVEN) (these storage capacitors are connected with the gate lines G1, G3, . . . ) of the pixel regions P21, P22, . . . selected by the gate lines G2, (G4), . . .
Since FIG. 16 shows an ideal example in which the alignment is obtained right and left, the capacitance value of the storage capacitor CS (ODD) is equal to that of the storage capacitor CS (EVEN).
If the alignment is not achieved in the horizontal direction, however, the capacitance value of the storage capacitor CS (ODD) is different from that of the storage capacitor CS (EVEN). For example, if the formation pattern A1 of the lower polycrystalline silicon thin film is displaced from the formation pattern A2 of the upper polycrystalline silicon thin film in the direction shown by an arrow R, the capacitance value of the storage capacitor CS (ODD) increases whereas that of the storage capacitor CS (EVEN) decreases.
As a result, when the N-type TFT is used, because the optimum LC common voltage of the gate lines G1, G3, . . . at odd-numbered lines is higher than that of the gate lines G2, . . . at even-numbered lines, there occurs a difference between the two optimum LC common voltages, and flickers are caused in each gate line.
In order to solve the above-mentioned problems, an object of the present invention is to provide an active matrix substrate which does not produce flickers even when the pixel electrodes in each of the pixel regions connect with the same source line alternately from right and left at every line, by improving the formation pattern of each of the electrodes constituting the storage capacitors.
Another object of the present invention is to provide a high-quality color liquid crystal display using an active matrix substrate formed as described above.

Active matrix substrate and color liquid crystal display


A therapeutic agent for selectively inhibiting amine oxidases associated diseases and conditions in humans includes at least one compound selected from the group consisting of propargylamines, polypropargylamines, homopropargylamines, 4-substituted-2-butynylamines, 2- and 3-halloallylamines, pyrroline derivatives, cycloalkenyl branched primary amines, propargyl diamines, homopropargyl amines and diamines, allenyl amines and diamines, chloroallyl diamines, lysyne analogs, β-haloamines, RF-substituted amines, RCi-substituted amines, and R3Si substituted amines.

There are now known to be three human genes that code for the TPQ-containing amine oxidases, AOC1, AOC2, and AOC3.
AOC1 is the diamine oxidase found primarily in kidney (HKDAO), though it is also expressed in the liver and brain. The enzyme is thought to be involved in the catabolism of histamine and of putrescine and other polyamines, important mediators of nuclear events underlying cell proliferation. This suggests a fundamental role of HKDAO in the regulation of growth. At the same time, the H2O2 and aldehydes resulting from polyamine metabolism have been suggested to contribute to apoptotic cell death in brain injury. The presence of DAO at the interface between rapidly dividing (e.g., epithelial) and quiescent cells suggests that it might be involved in regulating cell division or differentiation at tissue boundaries. Involvement of DAO in the metabolism of histamine implicates its role in the progression of inflammation.
AOC2 is the retina-specific amine oxidase. The function is not yet clear, and there have been no suggestions in the prior art of a possible therapeutic effect of having a specific inhibitor of this enzyme.
AOC3 codes for an amine oxidase, which is also the human vascular adhesion protein (HVAP-1), responsible for the binding of lymphocytes to the endothelial cell surface and the promotion of their transendothelial migration. A number of studies point to this enzyme being a useful anti-inflammatory target. Further, since leukocyte migration from the blood to tissues is a prerequisite for normal immune responses, inhibitors of HVAP-1 will be important for modulating the immune response. This enzyme, responsible for the semicarbazide-sensitive amine oxidase (SSAO) activity in mammalian tissues, is largely associated with the plasma membrane of various tissues, and is particularly high in vascular and nonvascular smooth muscle cells, but is also found in other cell types such as adipocytes, chondrocytes, and odontoblasts. There are several pathological states where increased circulating SSAO activity has been found: diabetes mellitus, congestive heart failure, cerebral infarction, uremia, inflammatory liver diseases (e.g., cirrhosis), obesity, and hyperlipidemia. High levels of SSAO are also found in atherosclerotic plaques, and serum SSAO activity correlates with the severity of atherosclerosis, as well as intima-media thickness and serum cholesterol levels. It has been proposed that vascular SSAO is involved in the regulation of vascular tone, and thus vascular SSAO inhibition may offer a novel mechanism of vasodilation.
The role of SSAO in the pathophysiology of diabetes has been most extensively investigated. Elevated SSAO activity is associated with type 1 diabetes already at first clinical diagnosis, and in type 2 diabetes, particularly in diabetic patients with vascular complications, such as retinopathy and arteriosclerosis. It has therefore been speculated that SSAO may contribute to the development of vascular complications associated with diabetes. SSAO is associated with translocation of the glucose transporter GLUT4 into the adipose cell surface and thereby promotes glucose uptake in adipose tissue and smooth muscle cells. SSAO contributes to elevated formation of cytotoxic metabolites (principally methylglyoxal from aminoacetone, formaldehyde from methylamine, and H2O2 as by-product) that exacerbate advanced glycation of proteins (including crosslinking) and cause endothelial injury of blood vessels, resulting in early development of atherosclerosis and late-stage diabetic complications such as neuropathy, retinopathy, and nepropathy. Thus SSAO inhibitors may be ameliorative in the development of atherosclerosis and diabetic complications. Plasma SSAO activity is elevated in morbidly obese patients, which might contribute to the increased cardiovascular risk associated with obesity. A potent, selective SSAO inhibitor was found to reduce atherogenesis in a genetically obese diabetic mouse strain fed a high cholesterol diet. Furthermore, a recent study showed that an antibody to block VAP-1 in mice prevented diabetes in a subset of nonobese diabetic mice. Interestingly, aminoguanidine, which blocks advanced glycation and reduces nephropathy in animals, is more potent at inhibiting SSAO than its affect on glycation.
In addition to the LTQ-containing lysyl oxidase (LOX), human genes for four LOX-like proteins have been recently identified: LOXL, LOXL2, LOXL3 and LOXL4. In most tissues, LOX is responsible for the lysine-derived cross-links in collagen and elastin, which is the essential step for biogenesis and repair of the fibrillar extracellular matrix. Despite what should be a harmful effect of lysyl oxidase inhibition early in life, there is growing evidence that the enzyme also plays a role in late-onset fibrotic conditions in man.


A DMA transfer system includes a multiplexer for multiplexing DMA requests from a plurality of processors, a flag for changing over between an operation in which a stream ID is removed from a data stream before the data stream is transferred to a requesting processor or an operation in which the data stream is transferred to the requesting processor with the stream ID left added on, ID registers the number of which is the same as the number of processors, acknowledge controllers, the number of which is the same as the number of processors and which are provided to correspond to respective ones of the processors, for controlling a DMA acknowledge signal and access control signal to the processors in accordance with DMA acknowledge signals from a DMA controller, and a stream ID detector for comparing stream IDs in the stream ID registers and data streams transferred by DMA, switching between enabling/disabling of the acknowledge controllers based upon the value of the flag and results of comparison, and outputting a data stream.

Examples of prior art wherein data streams of a number of types greater than the number of DMA channels are transferred are disclosed in the specifications of Japanese Patent Application Laid-Open (KOKAI) Nos. JP-A-62-79558, 64-59445 and 2-278361.
In DMA transfer according to the prior art set forth in these specifications, one DMA request signal output from each of a number of data processors which issue DMA requests and one DMA acknowledge signal sent to the data processor are validated so that DMA requests of a number greater than the actual number of DMA channels can be processed.
For example, the specification of Japanese Patent Application Laid-Open JP-A-62-79558 proposes a DMA controller arrangement in which data transfer by a large number of channels is made possible by externally connecting distributing circuits which distribute outputs to any one of a plurality of different peripheral devices, with the number of distributing circuits conforming to the requisite number of channels. More specifically, as shown in FIG. 8, one set of DMA request signals is selected by a DMA request signal selecting circuit 82 based upon a control signal Co, one DMA acknowledge signal is selected from several DMA acknowledge signals based upon the same control signal Co, and processing of DMA requests of a number greater than the number of channels of a DMA controller 81 is executed.
Further, the specification of Japanese Patent Application Laid-Open JP-A-64-59445 discloses DMA transfer control in an adapter designed so as to be capable of processing data requests from a plurality of requesters using a DMA controller having one channel. As shown in FIG. 9, one set of DMA request signals and DMA acknowledge signals is selected by a DREQ arbiter controller 96 from several DMA request signals and DMA acknowledge signals, and processing of DMA requests of a number greater than the number of channels of the DMA controller is executed. That is, data transfer requests DREQ(a), (b), (c), (d) from many requesters are entered into a DMA controller DMAC 95 as one DREQ by the DREQ arbiter controller 96, and ID information is utilized upon being added onto data or an address. For example, at the time of a DMA transfer from an input/output unit to a memory, ID information from the DREQ arbiter controller 96 is written to a local memory 93 via a multiplexer MPX 97 in an initial cycle, and DMA data from a requester that has been selected by the DREQ arbiter controller 96 is written to the local memory 93 via the multiplexer 97 in the next cycle.
As shown in FIG. 10, the specification of Japanese Patent Application Laid-Open JP-A-2-278361 discloses an arrangement in which DMA request input terminals 115 in a DMA controller are equipped with a multiplexer 112 and DMA acknowledge output terminals 116 are equipped with a demultiplexer 113, thereby making it possible to connect a large number of DMA transfer requesting devices while suppressing an increase in the amount of hardware within the DMA controller. One set of DMA request signals and DMA acknowledge signals is selected based upon a value stored in a selection register 114 and processing of DMA requests of a number greater than the number of channels of a DMA controller is executed.


Distribution map data for distributing a map by communication includes road data representing position information on the roads contained in a plurality of compartments and integrating name data for integrating name information for the same roads contained in the plurality of compartments without duplicating them.

Map data used in the related art in a navigation system installed in a vehicle are compiled in information units (layers) each defined in correspondence to a specific map scaling factor, with each layer of data containing information divided in units (meshes) matching a predetermined area range. Road data indicating road shapes, road types and the like, background data indicating the shapes and types of background objects other than roads and name data indicating the names of the roads and the background objects in the road data and the background data are provided in correspondence to each match.

Computer product having distribution map data, distribution map data generating method, distrubution map data generating apparatus and terminal device


Systems, methods, and devices for generating synthetic genomic datasets and validating bioinformatic pipelines for genomic analysis are disclosed. In preferred embodiments, synthetic maternal and paternal datasets with known variants are used with matched normal synthetic datasets to validate various bioinformatic pipelines. Bioinformatic pipelines are evaluated using the synthetic datasets to assess design changes and improvements. Accuracy, PPV, specificity, sensitivity, reproducibility, and limit of detection of the pipelines in calling variants in synthetic datasets is reported.

The background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
All publications herein are incorporated by reference to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.
With the advent of whole genome sequencing (WGS) and next generation sequencing platforms, massive quantities of data are now available for analysis. While the wealth of data is certainly desirable from a clinical perspective, various difficulties have arisen. For example, in most clinical whole genome analyses, it is not uncommon to oversample tumor tissue between 30-100 fold while oversampling matched normal tissue at least 10-30 fold, where most of the genetic information is obtained from sequencing machines in fragments having a size around 100-400 bases. As such, significant computing power is needed to accurately reassemble a genome and identify a change in the genome.
For example, a recent article (BMC Genomics 2014, 15:244) compared various somatic mutation callers using BAM files as input, including MuTect, GATK UnifiedGenotyper with simple subtraction, SomaticSniper, Strelka, and VarScan2. Here, NIST-GIAB (variant set for reference individual NA12878 by the NIST-led "Genome in a Bottle" Consortium) was used as standard for evaluation. Not surprisingly, the sensitivity of some algorithms was higher than that of others using the same standard. While providing some guidance, such analysis will however not allow taking into account variations in the sample, or identification of detection limits as a fixed input set is provided. Further, each algorithm is designed with underlying assumptions that can impact the efficacy of the analysis computing platform.
More recently, BAMBAM was developed (see US20120059670 and US20120066001) that enables detection of changes between tumor and matched normal using incremental and synchronous location guided alignment. Advantageously, such system and method allows for detection of allele specific changes, and enables detection and characterization of small scale (e.g., SNP) to large scale (e.g., intrachromosomal and interchromosomal rearrangements) events. Still further, the statistical base calling approach in BAMBAM allows to accommodate for allele variants as well as artifacts and low-quality reads that are not uncommon in high throughput sequencing. While at least theoretically statistical approaches can be optimized in sequence analysis algorithms, there are no known systems and methods to evaluate changes in or validate existing analysis computing devices that leverage various computer implemented algorithms or new algorithms.
Thus, there remains a need for systems and methods to evaluate or validate performance of a specific genetic analysis tool, especially where analysis is genomic analysis.


This invention relates to acellular-based therapies for decreasing the level of regulatory T cells (Treg) and/or increasing the level of pro-inflammatory T cells (Th17) to favor immune stimulation. To provide these therapeutic effects, an allogeneic leukocyte population is contacted with another leukocyte population and the acellular components produced are isolated. The leukocyte populations are contacted so as to allow pro-inflammatory allo-recognition. Acellular-based preparations and processes for achieving therapy are also provided.

Failure of an animal's immune system to recognize and destroy abnormal cells arising from normal progenitor cells can result in uncontrolled growth and formation of tissue masses that may cause significant morbidity and mortality in the absence of ineffective therapeutic interventions. This is commonly exemplified, but not limited to, cancer cells caused by spontaneous genetic mutation and deletions or exposure to environmental agents leading to similar genetic and cellular changes. Currently, most therapeutic drugs consist of chemical cytotoxic agents targeting proliferating cells, of which the cancer cells are preferentially affected due to their higher mitotic rate, but with limited direct specificity towards the cancer cells.
New approaches attempt to overcome the lack of specificity of cytotoxic drugs by inducing (in vivo or ex vivo) a target cell antigen-specific response by clonal expansion of a subset of reactive leukocytes from the affected individual or animal. This can be done by isolating either the "target cell" (e.g. cancer cell) itself or by molecular mimicking of a target cell antigen. However, this approach is expensive and may or may not effectively stimulate the desired pro-inflammatory state in vivo. Moreover, in some cases, infective agents (e.g. viruses and parasites) may be established and persist in a subject due to a failure of the subjects immune system to effectively respond to the infective agent/organism via a pro-inflammatory mechanism. Indeed, in many cases the infective organism may actively exert an anergic effect yielding a decreased ratio of Treg to pro-inflammatory cells.
It would be highly desirable to be provided with an acellular-based preparation capable of inducing a state of immune stimulation by decreasing the ratio of the level of regulatory T cells (such as Treg) to pro-inflammatory T cells (such as Th1 and Th17). The acellular-based preparation could induce an immune stimulation either by decreasing Treg levels, increasing pro-inflammatory T cell levels or both. These preparations could be useful for treating, preventing and/or alleviating the symptoms associated to a condition associated with a low or inappropriate immune response (e.g. anergy or tolerance for example), such as a proliferation-associated disorder (cancer for example) or an infection (a parasitic infection for example).

Acellular pro-inflammatory compositions, process for making same and methods of using same


A bias circuit for obtaining accurate on-chip time constants and resistances. The bias circuit includes a constant-g.sub.m bias circuit and feedback loop circuit. The constant-g.sub.m bias circuit has a mos transistor device and a variable resistor device which are arranged so that the trandsconductance of the transistor device is dependent upon the resistance of the resistor device. The constant-g.sub.m bias circuit generates a bias output signal that is a function of the trandsconductance of the transistor device. The feedback loop circuit includes signal generation means responsive to the bias output signal for generating a signal that is a function of the bias signal. The loop circuit further includes a comparison means for comparing the generated signal to a known external frequency reference, and an output that is operatively connected to the variable resistor device for adjusting the value of the variable resistor device until the generated signal matches the external reference signal. Also provided is a variable resistor device for use in a loop circuit (including the present bias circuit). The resistor device includes an analog-controlled resistor device and a digitally-controlled resistor device. The analog-controlled resistor device is adjusted in response to variations occurring in a control signal between a maximum voltage and a minimal voltage. The digitally-controlled resistor is adjusted in discrete steps whenever the control voltage reaches the maximum or minimum voltage, after which the control voltage is forced to a value approximately half-way between the minimum and maximum voltage.

The present invention relates to the field of integrated circuits, and in particular to a bias circuit for obtaining accurate on-chip time constants and conductances, and a variable resistor circuit for use with a bias circuit.
Generally, it is difficult to realize precise and consistent on-chip impedances levels in an integrated circuit. On-chip impedances are typically realized by transistors biased in the triode region, or by on-chip resistors. When a MOS transistor is used to approximate a resistor, variations in drain-source conductances makes impedance levels difficult to predict. Drain-source conductance can vary as a result of a number of different factors, with the temperature dependence of carrier mobility being a major factor. The resistivity of on-chip resistors can vary as a result of a number of different factors, including manufacturing process fluctuations which affect carrier concentrations, and also the temperature dependence of carrier mobility. The impedance of "identical" on-chip resistors can easily vary by 30% from wafer to wafer at room temperature, and can vary by over 100% with temperature changes.
The difficulty in predicting impedance levels in integrated circuits affects, among other things, the predictability of the gain of an integrated circuit as such gain is often determined by the ratio of transistor transconductance to the conductance of on-chip resistors.
In many integrated circuits which make use of MOS technology, the speeds realized by the circuits are dependent on the ratio g.sub.m /C (where g.sub.m represents the proportionality between the drain current and gate-source voltage of a MOSFET transistor in the active or saturation region and C=the value of an on-chip capacitor). However, as mentioned above, drain-source conductance can vary with temperature fluctuations, thus making on-chip time constants difficult to accurately predict control. The unpredictability of time constants makes it difficult to accurately predict the speed of an integrated circuit as the speed of the circuitry is directly proportional to the time constants which are realized by the circuit. The unpredictability of time constants also makes it difficult to accurately predict the frequency response of integrated filters as such response is dependent on the time constants.
There are a number of bias circuit designs which attempt to provide predictable and stable transistor transconductances. For example, J. M. Steininger, "Understanding Wide-Band MOS Transistors," IEEE Circuits and Devices, Vol.6, No.3, pp.26-31, May 1990, discloses a constant-g.sub.m bias circuit in which transistor transconductances are matched to the conductance of a resistor. Examples of constant-g.sub.m bias circuits can also be seen in J. Ryan et al., "A Magnetic Field Sensitive Amplifier with Temperature Compensation," ISSCC Digest of Technical Papers, pp. 124-125, February 1992; and D. Johns and K. Martin, "Analog Integrated Circuit Design", Wiley, 1997. The disclosures of the above three references are hereby incorporated by reference.
The basic principle of operation of the constant-g.sub.m bias circuits disclosed in the above references is that such circuits make the gate-source voltage difference of two different sized transistors having the same (or proportional) drain currents equal to the voltage across a resistor also having the same or a proportional current. This results in a transistor transconductance that is proportional to the inverse of the resistor value with the proportionality factor being highly predictable and process and temperature independent. However, as mentioned above, precise on-chip resistances are difficult to achieve, with the result that the absolute value of transistor transconductance can not be precisely pre-determined and controlled when an on-chip resistance is used.
It is therefore desirable to provide a circuit which allows accurate on-chip time constants and conductances to be precisely obtained and controlled independent of temperature, power supply, and process variations. In this respect, a circuit having an on-chip impedance solution and transistor transconductances that can be precisely predicted and controlled substantially independent of temperature, power supply and process variations is required. It is also desirable to provide a low noise variable resistor device which can be used as an on-chip impedance solution with a loop circuit for achieving a broad range of resistances.

Obtaining accurate on-chip time-constants and conductances


A semiconductor package structure includes a semiconductor component, a substrate, solder bumps, underfill, a buffer means, and solder balls. The substrate is under the semiconductor component. A joint area is formed between the first surface of the semiconductor and the upper surface of the substrate. Several solder bumps are disposed in the joint area, for electrically connecting the semiconductor component and the substrate. The underfill is filled in the joint area, for coating the solder bumps and tightly jointing the semiconductor component and the substrate. The buffer means is situated in the jointing area, for buffering the underfill to be confined in the joint area. Several solder balls are disposed on the lower surface of the substrate.

1. Field of the Invention
The invention relates in general to a semiconductor package structure, and more particularly to a semiconductor package structure formed by flip chip jointing technique.
2. Description of the Related Art
In the past few years, as the electronic products are developed toward being thin and small, multi-functioned, and high-speed, high-density and high input/output semiconductor package structures are required increasingly. For this reason, the flip chip package structure is now widely applied in the high-performance products and portable electronic products. In addition that the interface jointing paths can be reduced in the flip chip package technique to provide an excellent electrical feature, the whole package structure scale can be reduced meanwhile the multi-input/output pins requirement can be achieved by a suitable chip layout.
In the flip chip package structure, the surface of the chip, having solder bumps is directed to the substrate and the chip is jointed to the substrate directly via the bumps, different from the conventional wire bonding or tape automated bonding (TAB). The present flip chip jointing technique is mostly applied in the flip chip on board (FCOB), in which the chip is directly disposed on the substrate, or the flip chip in package (FCIP), which collocates the package structure CSP, BGA, or MCM, such as FC-CSP, FC-BGA, or FC-MCM.
Referring to FIG. 1, a lateral view of the conventional flip chip package structure is shown. Several solder bumps 104 are disposed on the first surface 102a, and form as bonding joints in the solder reflow process to electrically couple the semiconductor component 102 and the substrate 106. Solder balls 108 are disposed on the lower surface 106b of the substrate 106 for electrically coupling the flip chip package structure and the exterior circuits. The stress generated at the bonding joints for the flip chip expands when hot and shrinks when cold will damage the joints and reduce the reliability on the bonding of the semiconductor component 102 and the substrate 106. Therefore, an underfill process is generally used to fill underfill 110 in the region between the semiconductor component 102 and the substrate 106. By using the underfill 110 to tightly joint the semiconductor component 102 and the substrate 106, the stress at joints can be reduced as scattered to the underfill 110, and the ability of resisting the thermal fatigue at the joints can be improved.
In the conventional underfill process, the underfill 110 is filled in through one side or two sides of the semiconductor component 102, and distributed between the semiconductor component 102 and the substrate 106 by capillarity. Therefore, the upper surface of the substrate 106, contacting with the underfill, has to be larger than the lower surface of the semiconductor component 102 contacting with the underfill. That is, the area of the substrate 106 surrounded by the side surfaces 106p is larger than the area of the semiconductor component 102 surrounded by the side surface 102p, so the substrate 106 can provide enough space for the underfill flow. After the underfill 110 coats all the solder bumps 204 and fills in the region between the semiconductor component 102 and the substrate 106, and a part of the side surfaces 102p, the flip chip package structure 100 is put in an oven where the underfill is heated for solidification. However, in the process as the underfill is flowing or is being heated, the underfill will usually overflow and pollute the substrate 106. Especially when the size of the substrate is limited, such as the upper surface of the substrate is limited about equal to the lower surface of the semiconductor, in the process as the underfill is flowing or being heated, the substrate can not provide enough space for the underfill to flow. Therefore, the underfill will overflow to pollute the substrate, or even overflow to the solder balls on the lower surface of the substrate, thereby damaging the whole product.
Referring to FIG. 2, a lateral diagram of another conventional flip chip package structure is shown. The flip chip package structure 200 includes a semiconductor component 202, solder bumps 204, a substrate 206, solder balls 208, underfill 210 and dams 212. As shown in FIG. 2, several solder bumps 204 are disposed on the first surface 202a of the semiconductor component 202. The solder bumps 204 are jointed to the first surface 202a in the solder reflow process so that the first surface 202a of the semiconductor component 202 can be electrically coupled to the upper surface 206a of the substrate 206 via these solder bumps. The underfill 210 is used for coating the solder bumps 204 and tightly jointing the semiconductor component 202 and the substrate 206. The dam 212 projects from the upper surface 206a of the substrate 206. Due to the dam design, in the underfill process when the underfill 210 is filled in the region between the semiconductor component 202 and the substrate 206, and a part of the side surfaces 202p, the underfill overflow issue can be solved through the blocking of the dams 212.
However, in FIG. 2, in addition that the upper surface 206a of the substrate 206 has to be larger than the first surface 202a of the semiconductor component 202, the inner surface 212p of the dam 212 has to be outside the area on the substrate 206 projected by the first surface 202a of the semiconductor component 202, so that the substrate 206 can provide enough space for the underfill 210 flow. As a result, when a vertical view of the second surface 202b of the semiconductor 202 is taken, the underfill 210 and the dams 212 can be seen to surround the semiconductor component 202 layer by layer, which will influence the appearance of the flip chip package structure 200. Moreover, for the dams has to project from the substrate 206, which will increase the size of the substrate 206, such design cannot be applied to the flip chip package structure in which the lower surface of the semiconductor is almost equal to the upper surface of the substrate.

Advanced Semiconductor Engineering, Inc.


A session established for an application is suspended from an instance and later resumed on the server or a different server. When a session is suspended, its state is captured and persistently stored as a session image in a data repository, and the session is terminated. When the session is resumed, a new session is established on an instance, the session image of the session to resume is retrieved from the repository and restored to the newly established session. The suspension and resumption of a session may be initiated by an application, which may request the suspension and resumption of a session.

Many enterprise data processing systems rely on multi-node database servers to store and manage data. Such enterprise data processing systems typically follow a multi-tier model that has a multi-node database server in the first tier, and one or more computers in the middle tier and outer tiers.
FIG. 1 depicts multi-node database server mds11, which is implemented on multi-tier architecture 10. A server, such as multi-node database server mds11, is a combination of integrated software components and an allocation of computational resources, such as memory, a node, and processes on the node for executing the integrated software components on a processor, the combination of the software and computational resources being dedicated to performing a particular function on behalf of one or more clients. Resources from multiple nodes in a multi-node computer system can be allocated to run a particular server's software. A particular combination of the software on a node and the allocation of the resources from the node is a server that is referred to herein as a server instance or instance. Thus, a multi-node server comprises multiple server instances that can run on multiple nodes. Several instances of a multi-node server can even run on the same node.
A database server governs and facilitates access to a particular database, processing requests by clients to access the database. A multi-node database server, such as multi-node database server mds11, comprises multiple "database instances", each database instance running on a node. Multi-node database server mds11 governs access to database db11. A multi-node database server can govern and facilitate access to one or more databases.
The middle-tier of multi-tier architecture 10 includes middle-tier computer cmp11 and the outer-tier includes user computer cmp12. User computer cmp12 executes browser br11, which interacts with an end-user. The end-user's interaction with browser br11 causes the browser to transmit requests over a network, such as the Internet, to middle-tier computer cmp11. The request causes a process client cl11 on middle-tier computer cmp11 to execute application appl11. Execution of application appl11 by the client cl11 causes client cl11 to connect to multi-node database server mds11. For example, application appl11 may be an order entry application that is configured to receive order requests from browser br11. Data for the order entry application is stored in db11. To process the requests, execution of application appl11 by client cl11 causes client cl11 to connect to database db11. Once connected, client cl11 issues database statements to retrieve and manipulate data stored in database db11.
The tier that directly connects to a server, relative to other tiers in a multi-tier architecture, is referred to herein as containing the client of the server. Thus, client process cl11 is referred to herein as the client of multi-node database server mds11.
An application, as the term is used herein, is a unit of software that is configured to interact with and use the functions of a server. In general, applications are comprised of integrated functions and software modules (e.g. programs comprised of machine executable code or interpretable code, dynamically linked libraries) that perform a set of related functions.
An application, such application appl11, interacts with a multi-node database server mds11 via client-side interface component intcomp11. Execution of application appl11 by client cl11 causes client cl11 to execute client-side interface component intcomp11 to interact with multi-node database server mds11. Application appl11 includes invocations of routines (e.g. functions, procedures, object methods, remote procedures) of client-side interface component intcomp11. Applications are typically developed by vendors and development teams different from those that develop servers and interfaces to servers, such as multi-node database server mds11 and client-side interface component intcomp11.
In order for a client to interact with multi-node database server mds11, a session is established for the client on a database instance of multi-node database server mds11. A session, such as a database session, is a particular connection established for a client to a server, such as a database instance, through which the client issues a series of requests (e.g., requests for execution of database statements).
For each database session established on a database instance, session state is maintained for the session. Session state includes the data stored for a database session for the duration of the database session. Such data includes, for example, the identity of the client for which the session is established, and temporary variable values generated by processes and database components executing software within the database session. A database component is a set of software modules that provide specialized and related functions for a database server, and shall be described later in greater detail. An example of a database component is a Java execution engine.
The beginning and end of a session demarcates a unit of work. Often, the beginning of a database session corresponds to an end-user establishing an interactive session with an application via, for example, a browser, and ends when the end-user logs off. Thus, the beginning and ending of the database session depend on application logic and end-user action, and may not be controlled by a server on which the session is established.
Client-Side Interface Components
Client-side interface components, such as client-side interface component intcomp11, are software components that reside and are executed on the same computer of a client of a server, and that are configured to provide an interface between the client and the server. The client-side interface component intcomp11 is configured for performing the detailed operations needed to interface with multi-node database server mds11. For example, an application appl11 invokes a function of client-side interface component intcomp11 to establish a connection to multi-node database server mds11. The client-side interface component then handles the details of a connection on a particular instance of multi-node database server mds11. To make requests of multi-node database server mds11, such as a request for execution of a query, application appl11 is configured to invoke functions of client-side interface component intcomp11, which then transmits a request for the same to the node and database instance on which the session is established.
Client-side interface component intcomp11 may generate and/or access state that is hidden from other software modules, that is, is not or may not be referenced and accessed by other software modules, and in particular, by application appl11. Such state is referred to as being internal or private to client-side interface component intcomp11.
For example, to create a database session on a multi-node database server mds11, application appl11 invokes a routine of client-side interface component intcomp11. The client-side interface component establishes a database session on a particular database instance within multi-node database server mds11, and stores details about the database session within internal data structures or objects. Such data structures and objects define, for example, the session established for an application, and specify such values as a session id that identifies a session on a database instance, the name of the database instance, and a network address and port number for the connection to the database instance.
Such details of the session are not returned to application appl11, nor may application appl11 access the details. Instead, what is provided to application appl11 is an "external identifier" for the session, such as a value that internal data of client-side interface component intcomp11 maps to the session, or a reference to an object generated by client-side interface component intcomp11 to store some details of the session in private attributes of the object that are inaccessible to application appl11. In this way, application appl11 does not "know" of the specific details of the session that has been established for it; however, application appl11 has the information needed to be able to identify to client-side interface component intcomp11 the particular session that has been established for application appl11. Note that a session id that is internal to a client-side interface component relative to an application that uses the interface is referred to herein as an internal session id.
Calls
A call is a request made by a client to a server to execute a task. Typically, a call is made by a process executing an invocation of a routine in a software module. The invocation causes the process to execute the routine (such execution may itself entail calling and executing other routines), and then to return to execute the module to a point at or just beyond the invocation (or some other designated point e.g. exception handler).
A call causes the calling process or remote process to execute the called routine, which may cause calling and execution of other routines. The call terminates when the call returns. Operations, which are carried out as part of execution of a called routine, are referred as being made within the call.
For example, to make a call to multi-node database server mds11, application appl11 makes a call of a function of client-side interface component intcomp11. In response to the invocation, client-side interface component intcomp11 executes the call, which entails client-side interface component intcomp11 modifying and accessing "local" data stored in the memory of client computer cmp12 by client-side interface component intcomp11, and client-side interface component intcomp11 making multiple remote procedure calls to a database instance within multi-node database server mds11, the multiple remote procedure calls including a first remote procedure call and a second remote procedure call. In response to the first remote procedure call, the database instance performs various operations. The modification and access of the local data, the multiple remote procedure calls, and the various operations performed by the database instance, are referred to as being performed within the "application call" made by application appl11. The various operations performed by the database instance while executing the routine invoked by the first remote procedure call (which may entail execution of other routines) are referred to herein as being made within the first remote procedure call, within a client-side call because the first remote procedure call was made by the client-side interface component intcomp11, and within an application call because the remote procedure call was made by client-side interface component intcomp11 while executing a routine called by application appl11. An application call or client-side call may both be referred to herein as a client call.
Sessions Often not in-Use
Sessions are used by applications to execute application calls. Most application actions, which include application calls, are made in response to end-user activity. End-user activity can occur in bursts, resulting in periods of inactivity between the bursts. During these periods of inactivity, the sessions are not being used by the application for which they were established.
Sessions, even sessions not in current use, consume resources of a database server. At a given moment, significant portions of a database server's resources are allocated to sessions that are not currently being used by the application.
It is possible to de-allocate resources allocated to a session by terminating the session. However, session state, being treated as transient state by a database server, is not preserved by the database server after termination of the session. Therefore, a session established for an application cannot be terminated until the application no longer needs the session state. The inability to preserve session state after termination impairs important database server capabilities.
Debugging Capability is Impaired
An important capability is providing information about transient session state for purposes of debugging. When debugging, it is useful to know the session state that exists when a bug occurs or to simulate running the software under the same or similar session state under which the bug occurs. Because session state of a session cannot be preserved, such information is not available to those debugging a bug nor may software be easily run under the same or similar session state.
Often, debugging requires the expertise of a database server vendor's experts or other outside experts. Because session state of a session cannot be preserved, this information cannot be kept for later examination by the experts or even transported to the expert's location where the expert could examine the session state and/or simulate the bug.
Applications and End-Users Unable to Terminate Sessions to Conserve Resources
When a database session is not in use depends largely on client-side behavior, and, in particular, the behavior of applications and end-users. Applications and the end-users may know what sessions are not in use. However, an application and end-user cannot request that such sessions be terminated to conserver resources because the sessions' state may be needed later—there is no capability that allows an application or end-user to request to terminate a session and preserve its state in a way that allows the session to be restored and continued when later needed.
Based on the foregoing, it is clearly desirable to provide approaches to terminate a session on an instance and preserve the session's state in a way that allows the session to be later resumed on the instance or a different instance, particularly in response to a request of an application or end-user to do so.


A stencil printer apparatus for depositing a solder paste onto the surface of the electronic substrate, comprising a frame, a stencil coupled to the frame, the stencil having a plurality of apertures, a dispenser coupled to the frame, the stencil and the dispenser being configured to deposit the solder paste onto the electronic substrate, an imaging system constructed and arranged to capture an image of the electronic substrate, and a controller coupled to the imaging system and configured to control movement of the imaging system to capture the image. The imaging system comprises a camera element configured to capture the image of at least the portion of the surface of the electronic substrate, and a first illumination element comprising a long-wavelength light source configured to illuminate at least the portion of the surface of the electronic substrate by generating long-wavelength light. Other embodiments and methods are disclosed.

Circuit board manufacturing operations typically involve a stencil printer used to print solder paste onto a circuit board. Typically, a circuit board having a pattern of pads or other conductive surfaces onto which solder paste will be deposited is delivered into the stencil printer and one or more small holes or marks on the circuit board, called fiducials, is used to align the circuit board with a stencil or screen of the printer prior to the printing of solder paste onto the circuit board. After the circuit board is aligned, the board is raised to the stencil (or in some configurations, the stencil is lowered to the circuit board), solder paste is dispensed onto the stencil, and a wiper blade (or squeegee) traverses the stencil to force the solder paste through apertures formed in the stencil and onto the board.
In some prior art stencil printers, a dispensing head delivers solder paste between first and second wiper blades, wherein during a print stroke one of the wiper blades is used to move or roll solder paste across the stencil. The first and second wiper blades are used on alternating boards to continually pass the roll of solder paste over the apertures of a stencil to print each successive circuit board. The wiper blades are typically at an angle with respect to the stencil to apply downward pressure on the solder paste to force the solder paste through the apertures of the stencil. In other prior art stencil printers, the dispensing head is pressurized to force solder paste through the apertures, and the wiper blades are employed to scrape excess solder paste from the stencil during a print stroke.
After solder paste is deposited onto the circuit board, an imaging system is employed to take images of areas of the circuit board and/or the stencil for, in certain instances, the purpose of inspecting the accuracy of the deposit of solder paste on the pads of the circuit board. Another application of the imaging system involves the aforementioned aligning of the stencil and the circuit board prior to printing in order to register the openings of the stencil with the electronic pads of the circuit board. Such imaging systems are disclosed in U.S. Pat. Nos. RE34,615 and 5,060,063, both to Freeman, which are owned by the assignee of the invention and hereby incorporated herein by reference. Some improved imaging systems are disclosed in pending application Ser. No. 11/272,192, entitled IMAGING SYSTEM AND METHOD FOR A STENCIL PRINTER, filed on Nov. 10, 2005, to Prince, which is owned by the assignee of the invention and is hereby incorporated herein by reference.
Consistent modeling of solder paste on a substrate, e.g., the circuit board, is required to facilitate the optimum two-dimensional imaging performance of the vision system, as well as subsequent inspections based on these images, irrespective of variations in geometry, definition, or general qualities of the deposit being imaged. Well-defined solder paste deposits have nearly vertical sides and relatively flat top surfaces that are perpendicular to the optical viewing axis (i.e., an axis generally perpendicular to a plane of the circuit board). Finely textured paste surfaces having this generally perpendicular orientation may be imaged with relative consistency using traditional illumination techniques that illuminate surfaces with on-axis white light. With on-axis illumination, the strongest components of scattered light from the top surface of the solder paste deposit are directed back along the optical viewing path and are collected by the imaging system.
In contrast, when on-axis illumination strikes a surface that is not generally perpendicular to the angle of incidence, the strongest components of scattered light from the surface are directed away, or off-axis, from the optical or on-axis viewing path and are not collected by the imaging system. Specifically, the sloped sides and irregular top surfaces of poorly shaped solder paste deposits are less efficiently illuminated and therefore more difficult to view using only on-axis illumination only.
With white light, a range of wavelengths of visible light is reflected either on-axis or off-axis from the surface (i.e., depending on the shape of the surface). Such white light is generally strongly reflected on-axis by pads having no solder paste deposits because such pads typically are clean and perpendicular to the viewing path. However, recent use of sacrificial and protective coatings to keep the pads of a substrate clean has decreased the level of on-axis reflection from pads having no solder paste deposits. This decrease in reflection makes differentiation between pads without solder paste deposits and with solder paste deposits more difficult.

Single and multi-spectral illumination system and method


An ergonomic work station for computer components or for other purposes that is especially adapted for use by an individual having decreased mobility due to back pain or other conditions. The work station includes a base that extends beneath a chair or bed. A support arm has counter weight on a first side of a pivotal mount and a work table on a second side of the pivotal mount. The support arm may be pivoted to place the table in a work position in front of a user or in vertical position to permit unobstructed egress from or ingress to the chair or bed. The counter weight allows for the support arm to be easily pivoted from the work position to the vertical position by application of only very light pressure.

Many occupations require a worker to spend long periods of time in front of a computer screen. Problems associated with repetitive motion injuries due to computer keyboard or mouse manipulation may result in injuries to a computer user. A well known injury associated with repetitive motion is carpal tunnel syndrome. Injuries and discomfort may be minimized by proper positioning of a user with respect to a work object. Ergonomic designs for chairs and work stations have attempted to address these problems.
For an individual who experiences back pain, however, the simple act of sitting upright for long periods of time may result in debilitating discomfort. Further, the simple act of entering or exiting from a typical computer work station requires that a user bend his or her body in ways that may be uncomfortable or impossible for an individual experiencing back pain.
Some inventors have attempted to address the needs of individuals who, for whatever reason, are unable to sit in front of a computer. For example, U.S. Pat. No. 4,848,710 to Newman teaches a "Support Device" wherein a personal computer may be used by a person lying on a bed. The support body can be mounted on the bed itself, or on a base running on wheels beneath the bed.
Another example is U.S. Pat. No. 5,630,566 to Case for a "Portable Ergonomic Work Station". Case teaches a portable workstation that includes a variety of adjustable support elements that may hold and support computer components.
U.S. Pat. No. 6,286,794 to Harbin for an "Ergonomic Computer Mounting Device Permitting Extensive Vertical, Horizontal and Angular Ranges of Motion" teaches a column having a tilt and swivel mechanism for mounting a computer monitor thereon. The tilt and swivel mechanism is slidably mounted in a vertical track and a counterweight is provided to assist in vertical adjustment.
Other inventors have attempted to design systems for use with a chair or recliner. For example, U.S. Pat. Nos. 4,880,270 and 5,056,864 to Cooper for a "Work Station System" includes a chair having a carriage secured thereto. A surface for supporting an input device and a keyboard are attached to the carriage. The chair is rockable about a horizontal axis, but the spatial distance between the surface for supporting an input device and the seated operator remain constant, as does the spatial distance between the surface for supporting the visual display and the seated operator.
U.S. Pat. No. 5,779,305 to Hocking teaches "Work Stations" having a chair and a means to support pieces of equipment such as a personal computer, a printer and the like. The station has at least two upright stanchions that project upwardly in a substantially parallel manner from a base. Sleeves are engaged on the stanchions. Support members for the pieces of equipment are attached individually or in combination to a sleeve or sleeves so the support members will extend from the sleeves in a direction substantially normal to the longitudinal axis of the stanchions.
U.S. Pat. No. 5,967,599 to Cauffiel for a "Cabinet and Table Assembly for Use with Seating Apparatus" teaches a table that can slide between extended and retracted positions relative to a chair and may also be horizontally pivoted between a working position and an out-of-the-way position.
U.S. Pat. No. 6,102,476 to May et al. for a "Computer Furniture with Integrated Computer" teaches a chair with a monitor support and a keyboard support mounted on a horizontal arm that is pivotally attached to the left armrest.
U.S. Pat. No. 6,425,631 to Lin teaches a "Computer Chair Assembly" having a chair with two armrests, wherein a pivot shaft is disposed on one of the armrests. A horizontal rod is supported on one end by the pivot shaft and on a second end by rollers and a support. The horizontal rod supports an article support frame that may be pivoted in front of or away from a user seated in the chair.
None of the above references are ideal for use by an individual experiencing severe back pain. For example, none of the references teach a vertically pivoting member that permits a user to easily access a bed or chair wherein the pivoting member may be manipulated with fingertip pressure due to counter-weighting of the pivoting member. Additionally, it is desirable for a work station system to provide the above benefits in combination with structure that is adjustable in multiple ways to locate work pieces in an ergonomic orientation with respect to a user.