A method of fabricating an integrated circuit with trenches, without parasitic edge transistors, for isolating FET transistors from each other without degrading the FETs operating characteristics by junction leakage, breakdown or shorting, when a metal silicide is used in the source/drain regions. A silicon wafer is formed with sidewalls on the sides of each area in which a groove is to be etched. In etching the silicon, the sidewalls define the lateral dimension of the trenches. After the trenches are etched, the sidewalls are removed and the trenched are filled with an insulating material using a high density plasma reactor, such as an electron cyclotron resonance (ECR) plasma reactor. This type of reactor simultaneously deposits and sputter etches so that silicon edges at the base of the now removed sidewalls become tapered at an angle of about 45.degree. during deposition. Thus, the profiles of the filled trenches all have tapered tops which reduces the possibility of parasitic edge transistors and any leakage or shorting.

With higher levels of integrated circuits on semiconductor chips, such as silicon, and the need exists for faster transistors in these circuits which can be accomplished by substantially reducing and even eliminating leakage between semiconductor devices in the integrated circuit and/or preventing the formation of parasitic transistors. For example, with trench isolation, an integrated circuit with field effect transistors (FETs), having each of their gates insulated from the silicon body by a gate oxide and positioned between a source and drain in the silicon, must be fabricated to either minimize or eliminate any parasitic edge or corner transistors at the interface of the FET region and the trench at the cross over of the gate electrode. FETs in such integrated circuits without parasitic edge transistors perform at faster switching speed and without the potential of latchup.
Higher levels of integration requires increasing numbers of transistors isolated from each other in essentially the same amount of silicon real estate as lower levels of integration. Trench isolation, in contrast to recessed oxidation isolation, commonly know as LOCOS, is the formation of thin, vertical grooves in the silicon so that the amount of silicon real estate is minimized, thereby leaving more silicon for the semiconductor devices and passive devices. Trenches normally are fabricated by anisotropically etching with a plasma gas(es) to which the silicon is selective to create substantially parallel walls or an U-shape groove deep in the silicon. If desired, V-shaped grooves can be formed by preferential wet etching of the (110) crystal plane of a {100} silicon wafer. Both types of trenches are filled with an insulating material, preferably an oxide of silicon. The walls of the etched silicon can be thermally oxidized prior to filling the trench, if so desired.
Although trench isolation saves silicon for more semiconductor devices and passive devices, this isolation technique produces parasitic transistors due to diffusion of the source and drain impurities of the FET at the edges of the trench. These parasitic transistors are detrimental to the integrated circuit for at least two reasons. They increase the OFF current of the FETs, and they turn on at a lower voltage than the FETs and create a "subthreshold kink" in the current-voltage (I.sub.D -V.sub.G) characteristic curve. As the FETs are designed with smaller and smaller dimensions for higher levels of integration, the applied voltage to the FET is being lowered and the detrimental influence of the parasitic edge transistor on the operation of integrated circuit becomes even greater. One technique for reducing parasitic edge transistors is to round the edges at the top of the groove opening which is filled with insulation and to provide a gate insulation of any potential parasitic transistor which will be thicker than the gate insulation of the FET.
In addition to trying to prevent leakage and/or the formation of parasitic transistors, it difficult to deposit the insulating material into the grooves so that the grooves are completely and uniformly filled in forming the trenches. In addition, when the depth of the grooves are increased, they are more difficult to fill, especially when the aspect ratio of depth to width is 2 to 1 or greater. In using chemical vapor deposition (CVD) to fill the grooves to form the trenches with silicon containing source gases, especially a source gas, such as silane which forms nonconformal silicon oxide, care must be taken during deposition so that the deposited material does not grow shoulders at the top of the grooves which may eventually close off before the bottom of the grooves are filled.

Trench isolation for integrated circuits


The present invention facilitates clock and data recovery for serial data streams by providing a mechanism that can be employed to detect and adjust operation and timing of clocks. The invention employs a differential analog circuit, using current steering logic, to process center and edge samples and identify an average operation of the clocks. The circuit can identify transitions between adjacent center/edge data samples and determine whether an identified transition is early or late for each bit in a set of consecutive bits of a received serial data stream.

With the increased speed of computers and the need for high performance peripherals, the use of high speed serial data communications applications in integrated circuits built to physically interface to any given bus has also increased. In the past, serial communication was typically regulated to relatively slow applications and components such as computer mice, modems, and the like. However, serial communication is now desired and employed in many areas of communication or data transfer. For example, high speed serial communication is employed for communication or data transfer to digital memory, optical communications, hard drive devices, digital video (e.g., digital video recorders), network devices, compact disk drives, digital video disk drives, digital cameras, and many more devices.
There are several common serial communication standards currently available, including USB (Universal Serial Bus) 1.1 that provides communication speeds up to 12 Mbps (Million bits per second), FireWire (IEEE 1394) that operates at 400 Mbps, and USB 2.0 that operates at a maximum of about 480 Mbps. The operational speeds of these standards have increased over time. For example, the speed of USB 2.0 versus USB 1.1 illustrates an improvement of over 40 times. State of the art optical networks used in data communications and telecommunications operates at bit rates up to 40 Gbps (billion bits per second).
Generally, serial communication includes a transmitter and a receiver. The transmitter encodes or modulates a lower speed parallel data bus into a higher speed serial data stream that is then placed on a communication media. The serial data stream travels on the communication media and is then obtained from the media by the receiver. The serial data stream is then processed by the receiver in order to decode or recover the original data and de-serialize the resulting data into a duplicate parallel data bus.
Several techniques exist to encode the serial data and many signaling approaches can be used to transmit the data. Encoding techniques are used to embed a guaranteed density of transitions in the data and to facilitate reconstruction of the parallel data bus at the receiver. An example of these encoding techniques is 8b-10b encoding used on the physical layer in Gigabit Ethernet, PCI-Express, Fibre Channel, and 1394. Another encoding method is referred to as scrambling, which is used in SONET (Synchronous Optical NETwork). At the lowest level, the signaling approach can be as simple as NRZ (non-return to zero) binary, where 0 bit is encoding as one voltage level and a 1 bit is encoding as a different voltage level. Another commonly employed serial encoding/decoding scheme is (Non-Return-to-Zero Inverted) encoded and bit stuffed. NRZI is a data transmission method in which the polarity of the bit is reversed whenever a 0 bit is encountered, and a static voltage level is transmitted whenever a 1 bit is encountered as illustrated in FIG. 1, and designated at reference numeral 110. NRZI thus uses the presence or absence of a transition to signify a bit (indicating a logical 0 by inverting the state). Combined with bit-stuffing, where an extra 0 bit is inserted after every six consecutive 1 bits, this data encoding causes a guaranteed transition every 7 bit times when a data payload would be all 1 bits. Every transition gives the CDR circuit phase information that it uses to align its recovered clock to the phase of the incoming data. The less time between transitions, the less phase error which is to be expected caused by frequency offset. Finally, the data can be transmitted using a multi-level signaling approach where multiple bits are encoding as multiple data levels and transmitted at a lower data rate. For example, if two bits are wished to be transmitted simultaneously at one half the equivalent data rate as the binary approach, four voltage levels can be assigned to the various bit combinations 00, 01, 10, an 11.
The structure of the data stream follows a specific communications protocol, which defines the rules for sending a block of data (each known as a Protocol Data Unit (PDU)) (e.g., 150 of FIG. 2) from one node in a network to another node. The exchanged PDUs comprises three parts: a sync sequence 160, a packet payload (also known as a Service Data Unit (SDU)) 170, and an End of Packet (EOP) 180. The protocol does not define or constrain the data carried in the payload portion 170 of the data block. The protocol does, however, specify the format of the sync sequence.
The incoming data stream may be at a different frequency than the receiving system. Each side can vary from an ideal frequency within a +/−delta range as limited by a ppm tolerance value or jitter tolerance value defined in a respective industry standard. Often, the source and receive frequencies are slightly different. Regardless of the relative source and destination frequencies, the incoming data stream shows all jitter components of an electrical transmission over a bandwidth limited media (e.g., data dependant cycle to cycle jitter).
Several techniques exist to recover and track the possibly asynchronous data at the inputs to a serial receiver. Because of slight variations in timing, operating frequency, and other non-ideal operating conditions present at sending and receiving ends, the recovered clock can become early or late over time. Generally, the recovered data should be obtained from data samples taken at a center of each bit time of an incoming data stream. However, the recovered data can become corrupted as the recovered clocks drift with respect to the data causes data samples to be taken at inappropriate times of the incoming serial data stream. Accordingly, it would be desirable to have systems and/or methods that monitor and correct recovered clock(s) in order to facilitate data and clock recovery of incoming or received serial data streams.
Two primary classes of clock recovery circuits exist: linear and binary (also called bang-bang). A linear clock and data recovery (CDR) circuit attempts to recover the original transmitting clock and data. A conventional CDR circuit attempts to recover the clock and data by utilizing a phase detector (PD) or alternatively a phase-frequency detector (PFD), and source a charge pump followed by a loop filter and the voltage controlled oscillator (VCO) of a phase locked loop (PLL). The phase detector detects the absolute timing error between the current recovered clock and the timing of the ideal clock and together with the charge pump, generates an error signal proportional to the size of the timing error. This error signal is filtered using a loop filter and used to drive the VCO.
A binary clock recovery system recovers the clock by examining the sign of the phase error between the current recovered clock and the data. If the recovered clock is too early, the clock recovery system delays the clock. If the recovered clock is too late, the clock is advanced.

High speed early/late discrimination systems and methods for clock and data recovery receivers


The present invention is directed to a method of altering the amount or composition of synovial fluids secreted from joints in a subject in need of such treatment. The method comprises administering to a subject a pharmaceutical composition comprising a P2Y purinergic receptor agonist in an amount effective to alter the amount or composition of synovial fluids. The P2Y purinergic receptor agonist is administered in an amount effective to stimulate secretion of synovial fluid, lubricin, hyaluronic acid, or surface-active phospholipids; to enhance joint lubrication; or to treat osteoarthritis. The pharmaceutical compositions useful in the present invention comprise a P2Y purinergic receptor agonist of Formula I and include, but are not limited to: uridine-, adenosine-, cytidine-5′-di- or triphosphates, dinucleoside polyphosphates, and analogs thereof. The invention is useful for treating conditions associated with reduced joint lubrication and joint stiffness, such as osteoarthritis.

The joint cavity is surrounded by a capsule and held together by ligaments. Synovium lines the joint cavity and is folded upon itself several times to permit considerable motion. The inner portion of the synovium is lined with a layer of synoviocytes, consisting of Type A cells which are involved in phagocytosis and secretion, and Type B cells which are believed to synthesize the hyaluronate of synovial fluid (Bora, et al., Hand Clin. 3: 325-336 (1987)).
Human joints are lubricated by fluid secreted from synovial membranes, which line internal, non-articular joint surfaces. The lubricating properties of synovial fluid have been attributed to a surfactant consisting of surface-active phospholipid (SAPL), the mucinous glycoprotein lubricin, hyaluronic acid (hyaluronan), and water (Schwarz, et al., Br. J. Rheumatol 35: 821-827 (1996), Jay, et al., J. Rheumatol. 27: 594-600 (2000), Marshall, et al., Curr. Opin. Rheumatol. 12: 468-474 (2000), Bora, et al., Hand Clin. 3: 325-336 (1987), Hills, et al., Br. J. Rheumatol. 37: 143-147 (1998), Jay, et al., Connect. Tissue Res. 28: 245-255 (1992), Hills, et al., Proc. Inst. Mech. Eng. 214: 83-94 (2000)). Hyaluronan is a critical constituent component of normal synovial fluid and an important contributor to joint homeostasis. Hyaluronan imparts anti-inflammatory and antinociceptive properties to normal synovial fluid and contributes to joint lubrication, buffering load transmission across articular surfaces and providing a continually replenished source of hyaluronan to articular tissues. (Marshall, Curr. Opin. Rheumatol. 12: 468-474 (2000)).
Joint lubrication is compromised in osteoarthritis (OA) ((Schwarz, et al., Br. J. Rheumatol. 35: 821-827 (1996), Marshall, et al., Curr. Opin. Rheumatol. 12: 468-474 (2000), Hills, et al., Br. J. Rheumatol. 37: 143-147 (1998), Hills, et al., Proc. Inst. Mech. Eng. 214: 83-94 (2000)) and following arthroplastic surgery (Delecrin, et al., Clin. Orthop. 307: 240-249 (1994)). OA is a degenerative joint disease characterized by progressive deterioration and loss of articular cartilage associated with proliferation of new bone and soft tissue in and around the joint. OA can be classified as: (1) primary, in which no underlying cause is apparent; (2) secondary, which is associated with a predisposing factor such as trauma, repetitive stress (occupation, sports), congenital abnormality, metabolic disorder, or other bone/joint disease; and (3) erosive, characterized by hand OA associated with synovitis and radiographic central erosions of the articular surface. Unlike rheumatoid arthritis, a systemic disease simultaneously affecting multiple joints, OA involves only joints that are traumatized or exposed to mechanical abuse. OA develops essentially when the rate of wear exceeds the production of new collagen fibers by chondrocytes. The lipids within the joint, including phospholipid, change in profile shortly after an impact injury leading to eventual OA, whether bone fracture occurs or not (Rabinowitz, et al., Clinical Orthopedics and Related Res. 190: 292-298 (1984)). The following symptoms and criteria are used to establish a diagnosis of osteoarthritis:
Patient History:
Typical symptoms of osteoarthritis include use-related pain affecting one or a few joints with less common rest and nocturnal pain, and brief stiffness after rest or in the morning, lasting less than 30 minutes. Other symptoms include loss of joint movement or functional limitation joint instability, deformity and crepitation ('crackling').
Physical Examination:
Physical examination reveals chronic monarthritis or asymmetric oligo/polyarthritis and firm or "bony" swellings of the joint margins, such as Heberden's or Bouchard's nodes. Patients rarely display synovitis with a cool effusion. On physical examination, crepitance, an audible creaking or crackling of the joints on movement is sometimes detected. Osteoarthritis is also associated with deformity. Patients display restriction of movement, such as the limitation of internal rotation of the hip. Objective neurologic abnormalities are sometimes observed when the spine is involved and affect intervertebral disks, apophyseal joints and paraspinal ligaments.
Laboratory Studies:
Routine laboratory work is normal and conducted to rule out other causes of arthritis such gout, and to detect other primary disorders. Erythrocyte sedimentation rate is normal but is sometimes elevated in patients with synovitis.
Joint Fluid Analysis:
Analysis of the joint fluid provides information about the joint fluid characteristics of osteoarthritis. The joint fluid is normally straw-colored with good viscosity and the number of joint fluid white blood cells (WBC) less than 2000/μL. Analysis of the joint fluid is important in ruling out crystal-induced arthritis or infection.
X-ray Findings:
As the disease progresses and over a long-term duration, radiographic findings include joint space narrowing, subchondral bone sclerosis, subchondral cysts, and osteophytes. Erosions differ from that characteristic of rheumatoid and psoriatic arthritis because they occur subchondrally along the central portion of the joint surface.
When SAPL is injected into osteoarthritic joints, wear associated with OA is successfully reduced (Hills, Proc. Inst. Mech. Eng. 214: 83-94 (2000)). In OA, the concentration and molecular weight of hyaluronan in synovial fluid is reduced by dilution, fragmentation, and production by synoviocytes of hyaluronan of lower than normal molecular weight. Consequently, the homeostatic condition of synovial fluid maintained by hyaluronan is compromised (Marshall, Curr. Opin. Rheumatol. 12: 468-474 (2000)). The outermost lubricating layer of SAPL deposited onto articular cartilage from synovial fluid is deficient in OA (Hills and Monds, Br. J. Rheumatol. 37: 143-147 (1998)). Studies of changes in joint fluid after total arthroplasty in a rabbit model of total knee replacement have shown that joint fluid volume and total protein concentration recovers to normal, but hyaluronic acid concentration and molecular weight are reduced and do not completely recover to normal values (Delecrin, et al., Clinical Orthopaedics and Related Research 307: 240-249 (1994)).
The recognition that synovial fluid hyaluronan in OA is abnormal led to the proposition that removal of pathologic osteoarthritic synovial fluid and replacement with products that restore the molecular weight and concentration of hyaluronan toward normal levels can have a beneficial therapeutic effect. The treatment approach has been termed viscosupplementation (Marshall, Curr. Opin. Rheumatol. 12: 468-474 (2000)). Commercial preparations of hyaluronic acid (Healon), which has joint lubricating qualities, have been used as a viscosupplementation treatment for OA (Jay, et al., J. Biomed. Matl. Res. 40: 414-418 (1998)). However, commercial preparations of hyaluronic acid possess inferior lubricating qualities compared with synovial mucin (Jay, et al., J. Biomed. Matl. Res. 40: 414-418 (1998)). Pharmacotherapeutic agents used to manage arthritis include analgesics, anti-inflammatory drugs, muscle relaxants, and antidepressants. Aspirin is the drug of choice for both anti-inflammatory and analgesic reasons. Other non-steroidal anti-inflammatory drugs may be used and act by inhibiting lipo-oxygenase conversion of cell membrane lipids to arachidonic acid. Topical capsaicin cream may help to relieve hand or knee pain and acts by causing the release of the peptide substance P from sensory neurons. Muscle relaxants are used usually in low doses and include diazepam, cyclobenzaprine, carisoprodol, and methocarbamol. Although corticosteroids are not administered orally, they can be administered intra-articularly to reduce inflammation and on an intermittent basis to avoid acceleration of cartilage breakdown. However, the crystalline preparations of corticosteroids may cause synovitis. Purely analgesic agents and tricyclic antidepressants for depression may also be useful. However, nonsteroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen and indomethacin, and newer NSAIDs with specificity for cyclooxygenase-2 (COX-2 inhibitors), including celecoxib, are known to induce gastrointestinal toxicity (Mundasad, et al., J. Ocul. Pharmacol. Ther., 17(2): 173-179 (2001)).
As described above, pharmacotherapetuic agents commonly used to treat OA may cause adverse side effects, such as the gastrointestinal toxicity, and do not directly improve joint fluid properties or enhance joint lubrication. There exists a need for agents that are both safe and effective in treating OA by enhancing joint lubrication.
P2Y receptor agonists are known to induce the secretion of mucins, surfactant, and water from respiratory epithelial surfaces in the lung (Yerxa and Johnson, Drugs Future 24: 759-769 (1999); Benali, et al., Am. J. Respir. Cell. Mol. Biol. 10: 363-368 (1994); Gobran, et al., Am. J. Physiol. 267: L625-L633 (1994); Knowles, et al., New Engl. J. Med. 325: 533-538 (1991); Lethem, et al., Am. J. Respir. Cell. Mol. Biol. 9: 315-322 (1993)). In addition, P2Y receptor agonists induce tear fluid secretion and improve the lubrication and hydration of the ocular surface in dry eye disease by stimulating the release of mucins and water from the conjunctival epithelium (Hosoya, et al., J. Pharmacol. Exp. Ther. 291 (1): 53-59 (1999); Murakami, et al., Invest. Ophthalmol. Vis. Sci. 41(4): S457 (ARVO Abstract 2423 (2000); Murakami, et al., Curr. Eye Res. 21(4): 782-787 (2000); Shiue, et al., Life Sci. 66(7): PL105-111 (2000); Jumblatt and Jumblatt, Exp. Eye Res. 67: 341-346 (1998)). However, P2Y receptors are not known to have any beneficial affect on the joint or in joint lubrication.
It is also known that P2Y receptor agonists modulate all components of the mucociliary clearance (MCC) system by: (1) increasing both the rate and total amount of mucin secretion by goblet cells in vitro (Lethem, et al., Am. J. Respir. Cell. Mol. Biol. 9: 315-22 (1993)); (2) increasing cilia beat frequency in human airway epithelial cells in vitro (Drutz, et al., Drug Dev. Res. 37(3): 185 (1996)); (3) increasing Cl− secretion, hence, water secretion from airway epithelial cells in vitro (Mason, et al., Br. J. Pharmacol. 103: 1649-1656 (1991); and (4) releasing surfactant from Type II alveolar cells (Gobran, Am. J. Physiol. 267: L625-L633 (1994)). In addition to such actions, P2Y agonists have also been shown to increase intracellular Ca++ due to stimulation of phospholipase C by the P2Y2 receptor (Brown, et al., Mol. Pharmacol. 40: 648-655 (1991); Yerxa and Johnson, Drugs of the Future 24(7): 759-769 (1999)). U.S. Pat. Nos. 5,789,391; 5,763,447; 5,635,160; 5,935,555; 5,656,256; 5,628,984; 5,902,567; 5,292,498; 5,837,861; 5,900,407; 5,972,904; 5,981,506; 5,958,897; 5,968,913; 6,022,527; 6,133,247; and 6,143,279, and PCT International Patents WO97/29756, WO97/35591, WO96/40059, WO97/05195, WO94/08593, WO98/19685, WO98/15835, WO98/03182, WO98/03177, WO98/34942, WO98/34593, WO99/09998, WO99/32085, WO99/61012, WO 00/30629, WO 00/50024, and WO96/40059 disclose beneficial therapeutic effects of dinucleotides and related compounds in sinusitis, otitis media, ciliary dyskinesia, pneumonia associated with immobilization, lung disease, cystic fibrosis, dry eye disease, vaginal dryness, bronchitis, edematous retinal disorders, retinal degeneration and detachment, and gastrointestinal disease.

Joint lubrication with P2Y purinergic receptor agonists


Provided in the present invention are ingenol compounds and a use thereof in preparing an anti-HIV latency drug. In particular, provided in the present invention is a use of ingenol compounds and pharmaceutically acceptable salts thereof for preparing a drug for: (a) intervening with HIV viral latency; (b) activating an HIV virus that has been integrated into mammalian genomes; and/or (c) inducing the expression of the dormant HIV provirus in infected cells. The compounds of the present invention may also be used in combination with antiretroviral drugs to accelerate the removal of latent viral reservoirs.

Acquired immunodeficiency syndrome (AIDS) is a contagious disease that seriously endangers people's life and health caused by HIV infection. According to WHO statistics, there are more than 40 million AIDS patients worldwide, with 5 million new patients each year, while about 3 million deaths each year. At present, the main clinical treatment of AIDS is Highly active antiretroviral therapy (HAART), which not only effectively controls HIV replication, but also rebuilds the immune function of AIDS patients, thereby opening the door of hope for the treatment of AIDS. People have hoped that HAART can completely eliminate HIV in vivo, thereby achieving the goal of completely curing AIDS. However, subsequent practice has shown that although HAART can inhibit viral replication in patients at the largest extent, and reduce plasma viral load to levels not detected by conventional detection methods, there are still viruses in the infected body. Once drug treatment is stopped, the viral load will rebound to the pre-treatment level (Ho, D D Toward HIV eradication or remission: the tasks ahead. Science, 1998. 280: 1866-1867). One of the important reasons that HIV is difficult to be completely eliminated in vivo is that HIV-1 can hide in resting memory CD4+ T cells, which are produced by the transformation of a small number of HIV-infected activated CD4+ T cells. The integrated provirus thereof lacks transcriptional activity and therefore, will not be attacked by the immune system and antiretroviral drugs. Although the infected individual carries a small number of the latent infected cells, the attenuation rate is so slow that it is impossible to completely remove it only by HAART treatment during the individual lifetime. Therefore, HIV latently infected resting CD4+ T cells are the main part of the virus reservoir in the body, and they are also the huge obstacle for the complete elimination of HIV in clinical treatment [Finzi, D. et al. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nature Med. 1999, 5, 512-517]. The molecular mechanism of the formation of HIV-1 latently infected cells is generally considered to be related with the chromatin state at the integration site, the presence of the inhibitory nucleosome nuc-1, the epigenetic modification represented by acetylation, and the host transcription factor such as NF-κ B, the viral transcriptional activator Tat and other factors [Coiras, M., M R et al. Understanding HIV-1 latency provides clues for the eradication of long-term reservoirs. Nat. Rev. Microbiol. 2009., 7:798-812.]. Based on this mechanism, some studies have proposed a therapeutic strategy for clearing latent virus reservoirs, which is to try to induce pro-virus expression of HIV latent-infected cells by drugs, and to re-activate their latent viruses, and at the same time, to combine high-efficiency anti-retroviral therapy with the following method: the activated latent infected cells is killed under the action of the human immune system, so that the removal of the virus reservoir is accelerated (Richman et al. The Challenge of Finding a Cure for HIV Infection, Science, 2009, 1304, 323). Although there are several treatment solutions in the clinic for the strategy, the results are still unsatisfactory, either the activator is ineffective, or it is effective but its toxic side effect is large. However in China, there are still no anti-AIDS new drugs with the independent intellectual property rights available on market. Therefore, it is of great significance to develop new intervention drugs with independent intellectual property rights, safe, effective and inexpensive to eliminate the HIV-1 virus reservoir.
As a unique medical resource in China, traditional Chinese medicine has attracted more and more attention from modern medicine because of the following advantages: wide varieties, wide clinical application, mild effect and few side effects and the like.

Ingenol compounds and use thereof in anti-HIV latency treatment

SHANGHAI XIN HAO BIOLOGICAL TECHNOLOGY COMPANY


The invention relates to thiophene carboxanmides of formula (I), wherein A, R1, R2, R3, n and X are as defined in the specification, processes and intermediates used in their preparation, pharmaceutical compositions containing them and their use in therapy.

The NF-κB (nuclear factor κB) family is composed of homo- and heterodimers of the Rel family of transcription factors. A key role of these transcription factors is to induce and coordinate the expression of a broad spectrum of pro-inflammatory genes including cytokines, chemokines, interferons, MHC proteins, growth factors and cell adhesion molecules (for reviews see Verma et. al., Genes Dev. 9:2723–35, 1995; Siebenlist et. al., Ann. Rev. Cell. Biol. 10:405–455, 1994; Bauerle and Henkel, Ann. Rev. Immunol., 12:141–179, 1994; Barnes and Karin, New Engl. J. Med., 336:1066–1071, 1997).
The most commonly found Rel family dimer complex is composed of p50 NFkB and p65 RelA (Baeuerle and Baltimore, Cell 53:211–217, 1988; Baeuerle and Baltimore, Genes Dev. 3:1689–1698, 1989). Under resting conditions NF-κB dimers are retained in the cytoplasm by a member of the IκB family of inhibitory proteins (Beg et. al., Genes Dev., 7:2064–2070, 1993; Gilmore and Morin, Trends Genet. 9:427–433, 1993; Haskil et. al., Cell 65:1281–1289, 1991). However, upon cell activation by a variety of cytokines or other external stimuli, IκB proteins become phosphorylated on two critical serine residues (Traenckner et. al., EBMO J., 14:2876, 1995) and are then targeted for ubiquitination and proteosome-mediated degradation (Chen, Z. J. et. al., Genes and Dev. 9:1586–1597, 1995; Scherer, D.C. et. al., Proc. Natl. Acad. Sci. USA 92:11259–11263, 1996; Alkalay, I. et. al., Proc. Natl. Acad. Sci. USA 92:10599–10603, 1995). The released NF-κB is then able to translocate to the nucleus and activate gene transcription (Beg et. al., Genes Dev., 6:1899–1913, 1992).
A wide range of external stimulii have been shown to be capable of activating NF-κB (Baeuerle, P. A., and Baichwal, V. R., Adv. Immunol., 65:111–136, 1997). Although the majority of NF-κB activators result in IκB phosphorylation, it is clear that multiple pathways lead to this key event. Receptor-mediated NF-κB activation relies upon specific interactions between the receptor and adapter/signalling molecules (for example, TRADD, RIP, TRAF, MyD88) and associated kinases (IRAK, NIK) (Song et. al., Proc. Natl. Acad. Sci. USA 94:9792–9796, 1997; Natoli et. al., JBC 272:26079–26082, 1997). Environmental stresses such as UV light and γ-radiation appear to stimulate NF-κB via alternative, less defined, mechanisms.
Recent publications have partially elucidated the NF-κB activation. This work has identified three key enzymes which regulate specific IκB/NF-κB interactions: NF-κB inducing kinase (NIK) (Boldin et. al., Cell 85:803–815, 1996), IκB kinase-1 (IKK-1) (Didonato et. al., Nature 388:548, 1997; Regnier at. al., Cell 90:373 1997) and IκB kinase-2 (IKK-2) (Woronicz et. al., Science 278:866, 1997; Zandi et. al., Cell 91:243, 1997).
NIK appears to represent a common mediator of NF-κB signalling cascades triggered by tumour necrosis factor and interleukin-1, and is a potent inducer of IκB phosphorylation. However NIK is unable to phosphorylate IκB directly.
IKK-1 and IKK-2 are thought to lie immediately downstream of NIK and are capable of directly phosphorylating all three IκB sub-types. IKK-1 and IKK-2 are 52% identical at the amino acid level but appear to have similar substrate specificities; however, enzyme activities appear to be different: IKK-2 is several-fold more potent than IKK-1. Expression data, coupled with mutagenesis studies, suggest that IKK-1 and IKK-2 are capable of forming homo- and heterodimers through their C-terminal leucine zipper motifs, with the heterodimeric form being preferred (Mercurio et. al., Mol. Cell Biol., 19:1526, 1999; Zandi et. al., Science; 281:1360, 1998; Lee et. al, Proc. Natl. Acad. Sci. USA 95:9319, 1998).
NIK, IKK-1 and IKK-2 are all serine/threonine kinases. Recent data has shown that tyrosine kinases also play a role in regulating the activation of NF-κB. A number of groups have shown that TNF-α induced NF-κB activation can be regulated by protein tyrosine phosphatases (PTPs) and tyrosine kinases (Amer et. al., JBC 273:29417–29423, 1998; Hu et. al., JBC 273:33561–33565, 1998; Kackawa et. al., Biochem. J. 337:179–184, 1999; Singh et. al., JBC 271 31049–31054, 1996). The mechanism of action of these enzymes appears to be in regulating the phosphorylation status of IκB. For example, PTP1B and an unidentified tyrosine kinase appear to directly control the phosphorylation of a lysine residue (K42) on IκB-α, which in turn has a critical influence on the accessibility of the adjacent serine residues as targets for phosphorylation by IKK.
Several groups have shown that IKK-1 and IKK-2 form part of a 'signalosome' structure in association with additional proteins including IKAP (Cohen et. al., Nature 395:292–296, 1998; Rothwarf et. al., Nature 395:297–300, 1998), MEKK-1, putative MAP kinase phosphatase (Lee et. al., Proc. Natl. Acad. Sci. USA 95:9319–9324, 1998), as well as NIK and IκB. Data is now emerging to suggest that although both IKK-1 and IKK-2 associate with NIK, they are differentially activated, and therefore might represent an important integration point for the spectrum of signals that activate NF-κB. Importantly, MEKK-1 (one of the components of the putative signalosome and a target for UV light, LPS induced signalling molecules and small GTPases) has been found to activate IKK-2 but not IKK-1. Similarly, NIK phosphorylation of IKK-1 results in a dramatic increase in IKK-1 activity but only a small effect on IKK-2 (for review, see Mercurio, F., and Manning, A. M., Current Opinion in Cell Biology, 11:226–232, 1999).
Inhibition of NF-κB activation is likely to be of broad utility in the treatment of inflammatory disease.
There is accumulating evidence that NF-κB signalling plays a significant role in the development of cancer and metastasis. Abnormal expression of c-Rel, NF-κB2 or IκBα have been described in a number of tumour types and tumour cell lines, and there is now data to show that constitutive NF-κB signalling via IKK-2 takes place in a wide range of tumour cell lines. This activity has been linked to various upstream defects in growth factor signalling such as the establishment of autocrine loops, or the presence of oncogene products e.g. Ras, AKT, Her2, which are involved in the activation of the IKK complex. Constitutive NF-κB activity is believed to contribute to oncogenesis through activation of a range of anti-apoptotic genes e.g. A1/Bfi-1, IEX-1, XIAP, leading to the suppression of cell death pathways, and transcriptional upregulation of cyclin D1 which promotes cell growth. Other data indicate that this pathway is also likely to be involved in the regulation of cell adhesion and cell surface proteases. This suggests a possible additional role for NF-κB activity in the development of metastasis. Evidence confirming the involvement of NF-κB activity in oncogenesis includes the inhibition of tumour cell growth in vitro and in vivo on expression of a modified form of IκBα (super-repressor IκBα).
In addition to the constitutive NF-κB signalling observed in many tumour types, it has been reported that NF-κB is also activated in response to certain types of chemotherapy. Inhibition of NF-κB activation through expression of the super-repressor form of IκBα in parallel with chemotherapy treatment has been shown to enhance the antitumour effect of the chemotherapy in xenograft models. NF-κB activity is therefore also implicated in inducible chemoresistance.

Thiophene carboxamide compounds as inhibitors of enzyme IKK-2


Disclosed herein is a hula-hoop, which applies pressing force in a vertical direction as well as in a horizontal direction when the hula-hoop is rotated, thus achieving a good exercise effect, and which performs an acupressure action and a compression action using acupressure protrusions. The hula-hoop includes first and second rings (10, 20). Protruding parts (11, 21) and grooves (12, 22) are alternately provided on the first and second rings (10, 20). Streamlined body pressing space (30) is defined between the grooves (12, 22) by attaching inward protruding parts (11, 21) to each other, so that the waist flesh (h) is pinched between the grooves, thus providing pressing force in a vertical direction.

Generally, the term "hula-hoop" refers to equipment for playing or improving health by turning a ring-shaped hoop around the hips, as in a hula-dance. The hula-hoop is used as waist exercise equipment for strengthening the muscles of the waist.
The hula-hoop usually has the shape of a simple ring. In addition, a hula-hoop having on the inner circumferential surface thereof acupressure protrusions has become widely popular.
When the hula-hoop is rotated, the waist is pressed or massaged in a horizontal direction, but no pressing force acts on the waist in a vertical direction.
More improved hula-hoops are disclosed in Korean U.M. Registration No. 20-0210351 and No. 20-0249553. In Korean U.M. Registration No. 20-0210351, two ring-shaped hula-hoops are coupled to each other. Meanwhile, in Korean U.M. Registration No. 20-0249553, a hula-hoop is constructed to have a wavy shape, thus increasing the area of contact with the waist.
The conventional hula-hoops are advantageous in that the area of contact with the body (waist) is increased when the hula-hoop is rotated. However, the conventional hula-hoops are problematic in that no pressing force acts in a vertical direction, but pressing force acts only in a horizontal direction, as in the prior art.

Hula-hoop for pressing flesh of waist in vertical direction


A spring forming machine is provided with closed-loop feedback from sensors which monitor dimensions of the coils and heads of the spring being formed, servo motors which control wire feed speed, coil radius and pitch forming elements, and coiling direction. Video cameras form pictorial images of the spring being formed. The images are digitized and fed to a central computer, along with images from similar machines forming similar springs, which compares the signals, such as photometric images, from the different machines, which represent actual spring dimensions, with a single stored image relating to the desired dimensions, such as head shape, coil diameter, and the positions and angles of bends. Discrepancies are correlated with causation data, such as feed roll slippage or material hardness variations, and adjustment signals are sent to the machines. Machines producing errors are interrogated more frequently by the computer. Large errors or failures to respond to adjustments triggers an alarm.

Machines for forming coil springs from continuous wire are well known in the prior art. In the manufacture of mattresses and upholstered furniture that use arrays of coil springs, machines have been employed in the prior art that form a plurality of springs from a continuous length of wire. One such machine is disclosed in British Patent No. 1,327,795 to Willi Gerstorfer entitled "Improvements in or relating to Machines for the Manufacture of Compression Spring Strips from Wire, for example for Upholstery Inserts," expressly incorporated herein by reference. The machine of the Gerstorfer patent is operative to manufacture from a continuous length of wire a plurality of interconnected compression springs comprising alternate left and right hand coil springs joined by an integral straight length of wire. The machine of the Gerstorfer patent employs moveable linkages to shift the settings of the machine to coil the continuous wire alternately in first one direction and then the other, with each coiling direction being followed by the feeding of a length of straight wire. The linkages are cam controlled, with the cam shapes determining the pitch and radius of each spring coil and the length of each straight section of wire interconnecting the coils.
In the use of the machine described in the Gerstorfer patent, however, variations in the dimensions and metallurgical properties of the wire affect the dimensions and elastic properties of the coils formed of the wire, causing the spring dimensions to vary from spring to spring and from one coil to another. This variation can be reduced with wire of higher quality and price. In many applications, there is no need to control precisely the quality of the produced springs because the quality of the mattress or upholstery item in which they are used is not materially altered thereby, or because variations in the parameters of the springs can be compensated in assembly done by hand.
With the increased use of robotics and automated assembly of products using coil springs of the type referred to above, variations in the tolerances of the springs, which may be acceptable from the point of view of the quality of the final product, may not be tolerable for use in the automated assembly machinery that tends to rely on the components being in predictable locations and of predictable dimensions. This is particularly true of the relatively rigid straight lengths of wire which interconnect the elastic coils. Thus, there is a need for coil forming machines to accommodate variations in the quality of the wire from which coil springs are formed and variations in other parameters that cause variations in the dimensions or other properties of the manufactured springs, notwithstanding the precise repeatable movement of the coil forming machine elements.
In addition, in the coil forming machines of the prior art, such as those of the Gerstorfer apparatus referred to above, changes in the dimensions or other specifications of the springs being produced requires replacement or readjustment of mechanical machine components. Such a major changeover in the machine configuration, which replacement or readjustment of machine components entails, is time consuming, limits the flexibility of the machine, and adds cost to the use of the machinery for the manufacture of springs of differing specifications. Accordingly, there is a need for a spring forming machine that can more flexibly accommodate the manufacture of springs of differing designs.

Programmable servo-motor quality controlled continuous multiple coil spring forming method and apparatus


An electronic device providing a message service includes: a communication unit configured to exchange a message with another device; a display configured to display a message received from the another device, a message input by the electronic device, and at least one response message generated by the electronic device, all together on a message service screen of the display; and a processor configured to determine whether the received message includes an inquiry, and provide at least one piece of recommended content based on the inquiry in response to the received message being determined as including the inquiry, and transmit the at least one response message comprising the at least one piece of recommended content to the other device.

1. Field
Apparatuses and methods consistent with exemplary embodiments relate to providing content to a user during a conversation by using an electronic device.
2. Description of the Related Art
As the distribution rate of portable terminals has been rapidly increased in recent times, portable terminals have become a daily necessity for contemporary people. The portable terminals provide various functions including not only a voice call service, which is its primary function, but also various kinds of additional services, such as data transferring, etc.
In particular, communication between users has been actively performed by using a smart terminal. With this trend, various technologies configured to provide more convenient environments for such communication have been developed.

Automated generation of recommended response messages


A computer-implemented method for providing a digital road map for testing an at least partially automated vehicle system. the method includes: accessing a database in which are stored permissible characteristics of the road properties for a multitude of road properties; creating at least one road map section by one of the possible characteristics being selected for the road map section for the first of the multitude of road properties, in each particular case in automated fashion from the database; providing the digital road map, the digital road map including the at least one road map section.

Automated vehicle systems must be designed for many different situations. The reliability of such systems poses a significant technical challenge. The relevant safety requirement tests are extremely complex due to the infinitely large range of possible driving situations, and they are hard to represent by real-world tests alone. It is desirable that the tests be appropriately supported by simulations. A particular challenge in such simulations is to ensure the broadest possible and, ideally, also quantifiable coverage of the possible situations.
Road maps for simulative tests of vehicle systems are primarily created by measuring real roads using highly accurate sensor systems and by subsequently manually digitally post-processing the measurement data. Editors, which may be used to manually define maps, constitute another common way to create such road maps. In addition, there are tile-based road editors where pregenerated road elements are provided on square tiles or hexagon tiles, which can be placed against one another manually.
A possible map format for the simulation is OpenDRIVE, which is supported by many common simulation environments. Road maps can also be directly manually specified here using a text editor as XML.
U.S. Patent Application Publication No. US 2017/0316127 A1 describes a method for providing a testing scenario for a driverless vehicle. A specific embodiment provides that the OpenDRIVE file format, which makes possible a logical description of road networks, thereby be used to simulate the driving environment.


New intraocular lenses (IOLs) and methods for producing IOLs. The present methods include a combination of steps which increase the pull strength between the fixation member of the IOL and the optic of the IOL without requiring sophisticated high frequency corona discharge activation or plasma activation of the fixation member. The fixation members are doubly coated with primer components and silicone polymeric material precursor compositions before being secured to the optics. In addition, the optic members employed in the present invention can be formed, for example, molded, without recesses to accommodate the fixation members. Thus, such recesses can be formed and provided with a quantity of the above-noted precursor composition after the optic members are produced. The doubly coated fixation members are then placed in the recesses and secured to the optic members. The present methods are straight forward, easy to practice and are cost effective in producing high quality IOLs.

This invention relates to intraocular lenses (IOLs) and to methods for producing IOLs. More particularly, the present invention relates to relatively straight forward and easy to practice methods for producing IOLs with optics comprising silicone polymeric materials and to such IOLs which have advantageous properties, for example, increased fixation member pull strengths, that is increased bond strengths between the optic of the IOL and the fixation member or members of the IOL.
The use of IOLs to improve vision and/or to replace damaged or diseased natural lenses in human eyes, particularly natural lenses impaired by cataracts, has achieved wide acceptance. Accordingly, a variety of IOLs has been developed for surgical implantation in the posterior or anterior chambers of the eye according to a patient's needs.
Known IOLs comprise an optical lens portion or optic which includes an optical zone, and one or more, preferably two, supporting structures, called fixation members or haptics, for contacting eye tissue to fix or hold the IOL in the proper position after implantation. The optic may comprise a soft, resilient material, such as a silicone polymeric material (in particular, an elastomeric silicone polymeric material) or a relatively hard or rigid material such as, for example, polymethylmethacrylate (PMMA) . The haptics typically comprise a filament constructed of a resilient metal or polymeric substance, such as PMMA, polyimide or polypropylene.
Each of the filament haptics is preferably flexible to reduce trauma to sensitive eye structures and to be yielding during insertion of the IOL. In addition, filament haptics generally have a memory retaining capability, e.g. , springiness, so that after implantation of an associated IOL, the filament haptics automatically tend to return to their normal orientation.
As an alternative to filament haptics, some IOLs are provided with footplate-type haptics. These footplates generally extend radially outwardly from the optic (in the plane of the optic) and terminate in rounded or blunted ends configured for placement in an eye chamber. The materials for such footplates have included soft materials, for example, 2-hydroxyethyl methacrylate or silicone. However, footplate-type haptics are attended by disadvantages, such as the addition of extra material weight to the IOL and reduced flexibility as compared to filament haptics leading to poor fixation and consequent migration or dislocation of the IOL.
Although the filament haptics are preferred over the footplate-type haptics for several reasons, certain difficulties remain. For example, filament haptics and soft or deformable optics tend to be formed from dissimilar materials which do not ordinarily chemically bond together. As a result, filament haptics have been designed having a variety of attachment end configurations or structures, e.g., anchor structures, for providing a physical or mechanical interlock between the haptic and optic. Polypropylene haptics, for example, have heretofore been secured into silicone polymer-based optics by means of a mechanical lock. This lock may comprise a small loop or other anchor formed at the attachment end or lens bonding region of the haptic, which is then placed in a mold. The precursor material of the silicone polymer-based optic is poured into the mold, through and/or around the lens bonding region of the included haptic or haptics, and is then cured. Christ et al U.S. Pat. No. 4,790,846 discloses the molding of an optic around a haptic having a small loop or other anchor to effect a secure haptic connection.
Christ et al U.S. Pat. No. 4,790,846 further discloses a method for making an IOL in which a region of an elongated filament haptic has a different configuration, e.g., a bulbous enlargement, which cooperates with the optic of the IOL to form a mechanical interlock between this different configuration and the optic. If desired, the bulbous enlargement may have its outer surface roughened to improve adhesion of the material of the optic.
Bruns et al U.S. Pat. No. 4,737,322 discloses an IOL including haptics with anchoring struts which are located in the optic and surround or partially surround the center of the optical zone portion of the optic. These struts provide sufficient anchoring of the haptic in the optic to withstand a tensile pull force of from 50 to 115 grams.
Blake et al U.S. Pat. No. 5,104,590 discloses improving the adhesive properties of polypropylene haptics to silicone lenses through surface treatment of the haptic with a combination of a high frequency corona discharge and a silicone primer. Christ et al U.S. Pat. No. 5,147,397 discloses exposing the lens bonding region of a haptic to a plasma at conditions effective to enhance the bondability of the lens bonding region to the optic. While these procedures can be effective in enhancing haptic/optic bond strength, they are relatively sophisticated and are relatively expensive to practice, thus adding to the complexity and cost of producing IOLs. In addition, substantial care must be exercised in controlling the corona discharge and plasma exposing procedures to avoid damaging the relatively fine filament haptics.
It would be advantageous to provide a relatively straight forward and easy to practice method of producing IOLs which effectively enhances the bond or pull strength between the fixation member or members and the optic.

Intraocular lenses and methods for producing same


A multi-computer system includes a chassis and a plurality of computers within the chassis operable independent of one another. Each computer has a plurality of subassemblies. The subassemblies of different computers are physically grouped together within the chassis based upon at least one of size, function or configuration.

Many of today's applications require extremely large computing and memory capacity. As a result, larger and larger computer systems are commonly being used in such applications. However, because such larger computer systems have many more system components and much more complex system components, such larger computer systems are more vulnerable to breakdown or failure. As a result, many applications alternatively use a multitude of independently operable computer systems since simultaneous failure of all of the computer systems is generally unlikely and since the use of multiple computer systems enables repair or servicing of a single computer system while the other computer systems continue operation. Unfortunately, multiple independent computer systems require large amounts of space which is frequently not available in either the rack or other structure supporting the individual computer systems or in the general floor space containing the multiple independent computer systems.

Hewlett-Packard Development Company, L.P.


Ease of processing and exchange of information and data between different programmatic schema and memory stores is described. A common indexing system or coordination language based on the natural number node-labeled tree data structure provides a common programming element for use at the base of all container-oriented manipulation.

1. Field of the Invention
The present invention generally relates to information technology. More specifically, the present invention relates to querying, processing, and exchanging data using different data stores, applications, and processors.
2. Description of the Related Art
Computers have made dramatic advances in their ability to store, process, and communicate information. This rapid advancement in computer science is, in large part, a credit to breakthroughs in chip design, software programming, and networking technologies. Notwithstanding these advances, there is a continued—and increasing—need for the storage of more data in less space and the processing of more information in less time and with increased accuracy. The ability to process information within a computer system (including the storage and transmission of that information) is largely governed by two factors: processor speed and the number of logical or computational steps required for the processing of that information (or any particular segment thereof). While clock speeds of processors continue to increase, the number of processing steps required to accomplish certain natural tasks is logically determined and often with stringent limitations.
Computer programming involves manipulating data structures and their component data using algorithmic instructions written in languages utilizing precise and pre-defined processing rules. Certain processes are fundamental yet inherently complex. With respect to these processes, no amount of ingenuity can reduce the associated complexity or number of steps beyond a certain threshold. In this regard, computational complexity in the 21st century may be analogized to the 19th century's physical problem of friction with the dawn of the machine age where physical scientists had to learn how to reduce or disperse friction in order to move objects efficiently. Similar understandings and planning are now necessary to minimize the computational complexity associated with constructing and managing data.
Until recently, there has been no known data structure that could be used as a base for other container data structures. In particular there was no binary representation for the node-labeled tree data type. The node-labeled tree data type is a data type of increasing importance as interactions with the likes of the World Wide Web continue to grow. For example, the Extensible Markup Language (XML) standard has become an increasingly popular language based on the node-labeled tree data type since presentation of the World Wide Web Consortium specification (XML 1.0) in 1998.
Notwithstanding the growing popularity of XML, there has been (and remains) a continued drive to construct separate programming languages that are designed to fit naturally into different cognitive application areas. The Structured Query Language (SQL) developed by International Business Machines in the 1970s is an example of a programming language for relational databases, finite tables, and two dimensional sequences. C, developed in 1972 by Bell Telephone Laboratories for the Unix operating system, is a general-purpose, block structured, procedural, imperative computer programming language that handles strings and one dimensional sequences. Prolog is a further example of a logic programming language developed in the 1970s and associated with user interfaces and artificial intelligence applications and otherwise capable of handling finite sets and trees.
Multiple languages frustrate processing and interchange of information. Differences in data type and associated programming language create bottlenecks in the exchange and analysis of data and information derived from the same. There is a need for a processing model that allows for ease of processing and interchange of information between various data stores utilizing disparate data types and programming languages. As eighty percent of data is semi-structured and heaps, strings, and trees are the fundamental atomic data structures of this semi-structured data, there is a need for a single underlying data index system or coordination language that could represent and coordinate programming activity between and within different data types.

Representing finite node-labeled trees using a one bit encoding


A stay dry collar is provided to prevent wetting of a customer's clothing around the collar during shampooing or other beauty salon operations. A thermoplastic polymer sheet having moisture barrier properties is provided with score lines defining an inverted V-shaped configuration. The score lines arranged in the inverted-V permit separation of the sheet along the scores to define a center tuck flap and left and right tie panels. After separation, the central tuck panel may be tucked between the customer's clothing and the customer's skin. The left and right tie panels may be gathered together, brought to the other side of the person's neck and then tied to secure the stay dry collar in place. The central tuck panel has a length sufficient to provide meaningful three-sided protection for preventing undesirable wetting of a customer's garments during and after shampooing or during other beauty treatments. The stay dry collar is intended for sanitary, one time disposable use and reduces the expense associated with extra towels and laundering of the towels in beauty salon operations.

The present invention generally relates to the art of salon shampooing and other beauty treatment procedures. More particularly, it relates to a new and improved disposable stay dry collar which is specially designed to prevent undesirable wetting of a customers garments during and after shampooing or other beauty treatment operations.
Nowadays, almost all styling and beauty care operations begin with a thorough shampooing. When hair is washed in a beauty salon, the customer sits in a chair which reclines rearwardly toward a shampooing sink. The sink is provided with a front dugout section to receive the customer's neck so that the head and hair extend into the sink basin. A spray nozzle connected to a flexible hose is manipulated by the operator to wet and rinse the customer during shampooing. In order to thoroughly rinse the customer's hair, the operator frequently extends the nozzle into the sink and directs the flow of water against the back of the customer's head and neck area to thoroughly rinse shampoo or other chemical treatments from the customer's head.
Various devices have been used to cover the customer in an attempt to prevent water from splashing or dripping onto the customer's clothes or the chair. Frequently, a towel is tucked into the customer's collar. However, cotton towels are wetted during the shampooing and rinsing operations. The cotton towel material may actually wick and transmit water from the sprayer nozzle and customer's hair toward the customer's clothing thereby wetting the customers garments. Another shortcoming of using a towel as a wetness barrier is that a number of towels must be used which must be properly laundered. This leads to an extra expenditure of time, energy and money, which is undesirable.
Another method which has been used to cover a customer in an attempt to prevent water from splashing or dripping from the hair onto the customer, the customer's clothes and/or the shampooing chair, has been a plastic or vinyl cape or drape which is placed over the customer and secured to the customer's neck prior to shampooing. These vinyl drapes typically have a cotton tape edge binding which touches the neck of the customer's skin in use. To provide for customer comfort, these drapes are relatively loosely secured about the neck area so that they do not provide a water tight seal at the skin of the customer's neck and accordingly, ingress of water or other chemicals is possible. Moreover, the cotton tape along the neck engaging edge of these drapes can also provide a wicking action which actually transmits the water toward the customers clothing disposed under the drapes, which is undesirable.
A new and improved cape having a separate back splash guard panel is described in U.S. Pat. No. 4,709,420. The splash guard panel prevents splashing through the open back portion of the cape below the neck line during shampooing. However, this shampoo cape still has a neck portion provided with a cotton binder so that it suffers from the same drawbacks mentioned above.
Generally, vinyl drapes are intended to be used over and over again. Reuse of the drapes raises health concerns with respect to the transmission of disease. Accordingly, these drapes should be used once and laundered between uses, which dramatically increases the cost to the salon owner. The drapes are too expensive to be treated as disposable items.


This invention relates to a method for the production of D-(−)-3-hydroxybutyric acid, comprising the step of culturing a recombinant strain containing genes phbA, phbB, ptb and buk by fermentation. Preferably, the recombinant strain is a strain of E. coli. The method of the invention is simple, avoiding the technique of degrading polymer to produce D-(−)-3-hydroxybutyric acid. The present method also provides improved efficiency, lowers the complicated requirement for facilities as used in traditional chemical synthesis, simplifies the complicated technique flow, and omits the complicated chiral separation step. Therefore, the present method greatly reduces the costs associated with D-(−)-3-hydroxybutyric acid production. Also, with this invention, the problems such as environmental pollution of chemical synthesis and chiral separation are overcome.

D-(−)-3-hydroxybutyric acid
is a very valuable intermediate in fine chemical industry, which can be directly used as drug for treating various diseases (Russia Patent 2096035-C1, U.S. Pat. No. 5,112,865, WO00/28985). The traditional methods for the production of D-(−)-3-hydroxybutyric acid (3HB) are chemical synthesis, and a process involving obtaining the 3HB degrading from its polymer poly-D-(−)-3-hydroxybutyric acid (PHB) which is synthesized by bacteria. Both of these two methods relate to very complicated techniques, require a complex chiral separation process to get the target compound, and require large production input, leading to much higher costs of D-(−)-3-hydroxybutyric acid production. On the other hand, environmental pollution also exists in the process of chemical synthesis and chiral separation. Therefore, there still exists a demand for new methods for the production of D-(−)-3-hydroxybutyric acid, which methods are cost-effective and avoid the chiral separation process.
It has been known that β-ketothiolase encoded by gene phbA (or pbaA) catalyzes two acetyl-CoAs into acetoacetyl-CoA; and that acetoacetyl-CoA reductase encoded by gene phbB (or phaB) catalyzes acetoacetyl-CoA into D-(−)-3-hydroxybutyryl-CoA. The combined use of gene phbA and gene phbB in a bacteria can lead to the production of hydroxybutyryl-CoA. Gene ptb and gene buk encode phosphotransbutyrylase and butyrate kinase, respectively. Enzymes encoded by these two genes can catalyze hydroxybutyryl-CoA into D-(−)-3-hydroxybutyric acid in bacteria. Thus, the inventors attempted to use the combination of these four genes to produce D-(−)-3-hydroxybutyric add via a one-step method in engineered bacteria, and succeeded finally.

Method for the production of D-(-)-3-hydroxybutyric acid by recombinant


The present invention provides a system and method for segmenting spaces. The system may provide an aluminum extrusion system for supporting rigid and flexible panels. The aluminum extrusion system may comprise a custom designed aluminum extrusion that may mount flexible or rigid substrates with interlocking bases and connectors. The system is constructed and arranged to be capable of temporary and permanent installation, and is structurally sound, and safe. The system is design to be capable of effectively blending with the existing décor. The aluminum extrusion system provides a method for segmenting space to maximize the functional space which may be utilized, in a way that is attractive, functional, temporary or permanent, and portable.

The present invention relates to building materials, and more particularly to a system and method for segmenting spaces. and supporting various substrates in a modular, attractive and easy to use system.
Current options regarding segmented spaces are limited.
Previous systems do not provide complete systems that may be installed in permanent, temporary or movable manner.
Previous systems do not provide sufficient flexibility or ease of installation. Previous systems do not provide a complete, structurally sound system with securely mountable components. Previous systems are further unattractive and are functional only for small areas. Previous systems are not adjustable in size, and do not blend with existing décor.
Existing systems are usually designed for only one type of substrate, and require precise sizing of substrates such as fabric to get a tight smooth fit. Also, existing systems are not easy to adapt to various installation situations, and are designed for a more industrial look and have many different parts causing confusion in assembly.
Existing systems do not provide sufficiently attractive or sufficiently safe options to segment both large and small private or public spaces. Previous systems further disrupt existing décor.
As can be seen a solution is needed to these problems.


A method for forming a superjunction transistor device includes: forming a plurality of semiconductor layers one on top of the other; implanting dopant atoms of a first doping type into each semiconductor layer to form first implanted regions in each semiconductor layer; implanting dopant atoms of a second doping type into each semiconductor layer to form second implanted regions in each semiconductor layer. Each of implanting the dopant atoms of the first and second doping types into each semiconductor layer includes forming a respective implantation mask on a respective surface of each semiconductor layer, and at least one of forming the first implanted regions and the second implanted regions in at least one of the semiconductor layers includes a tilted implantation process which uses an implantation vector that is tilted by a tilt angle relative to a normal of the respective horizontal surface of the respective semiconductor layer.

A superjunction device, which is often also referred to as a compensation device, includes a drift region with a plurality of regions of a first doping type (conductivity type) and a plurality of regions of a second doping type (conductivity type) complementary to the first doping type. In some publications, the first doping type regions are referred to as drift regions and the second doping type regions are referred to as compensation regions.
The drift region of a superjunction device can be formed by epitaxially growing several semiconductor layers one on top of the other on a substrate by selectively implanting dopant atoms of the first doping type and doping atoms of the second doping type into each of the semiconductor layers, and by a temperature process in which the implanted dopant atoms diffuse in the semiconductor layers such that the regions of the first doping type and the regions of the second doping type are formed. This type of process is sometimes referred to as multi-epi-multi-implant (MEMI) process.
A superjunction device may include a plurality of transistor cells, with each transistor cell including a first doping type region or a section of a first doping type region and a second doping type region or a section of a second doping type region. "The pitch" of a superjunction device is the center distance between two neighboring first doping type regions or between two neighboring second doping type regions. The specific on-resistance RON. A of a transistor device is given by the on-resistance multiplied with the area of a semiconductor body in which the transistor device is implemented. One way to increase the specific on-resistance is to increase the number of transistor cells per unit area. Increasing the number of transistor cells is equivalent to reducing the pitch.
In an MEMI process, the dopant atoms implanted into the individual semiconductor layers diffuse in a vertical direction (which is a direction in which the semiconductor layers are formed one on top of the other) so that the dopant atoms of the first doping type form the first regions and the dopant atoms of the second doping type form the second regions, wherein each of these first and second regions extends across the semiconductor layers in the vertical direction. Diffusion of the dopant atoms, however, is not restricted to the vertical direction, but also includes diffusion in a horizontal direction. The thicker the individual semiconductor layers, the farther the dopant atoms have to diffuse in the vertical and horizontal direction. Reducing the pitch requires reducing the diffusion in the horizontal direction and, consequently, in the vertical direction. This may be achieved by reducing the thickness of the semiconductor layers.
When implanting dopant atoms using an implantation angle of 0°, channeling effects may occur. Such channeling effects, at the same implantation energy, may cause a variation of the implantation depth. The thinner the semiconductor layer in a MEMI process, the greater the impact of channeling effects on a doping profile of the first and second regions may be because the reduced thermal diffusion required with thin semiconductor layers has the effect that the doping profile is very similar to the (varying) implantation profile.
There is therefore a need for an improved method for producing a drift region of a superjunction device.

Method for forming a superjunction transistor device

Infineon Technologies Dresden GmbH & Co. KG


The invention relates to a permanent percutaneous electric connection device intended to be fixed in an osseous structure of a patient to electrically connect an internal entity (150) located inside the body of the patient to an entity external to said body. The device encloses electric connection means running from a first connector to be connected to the external entity to a second connector to be connected to the internal entity. The device has an extension member (120) extending from a socket of the first connector. The extension member is designed for full osseous burial into the osseous structure with its free end (121) being substantially flush with the surface of said osseous structure. The device also comprises an electric connection member (130) comprising the second connector securely fastened to the free end of the extension member (120).

The substantial development made in electrical equipment designed to be installed inside the body of a patient to rectify failure of a natural organ already implies a capability for transmitting electric power required by this equipment, from a source of external power to the interior of the body if that quantity of energy is too important to be delivered by implanted batteries.
Contactless power-supply techniques using power transmission via transformer already exist. For instance, WO 2004/052455 discloses a device for transcutaneous energy transmission, i.e. a contactless transmission of energy without traversing the skin. Such device is designed to be fixed onto the osseous surface and is not adapted for intra-osseous burial.
Power-supply techniques via percutaneous cranial implants are also known. Electric connectors can be inserted in the abutments to which cables or electric linking ribbons leading to electric power consumer equipment are connected.
U.S. Pat. No. 5,904,646 discloses in particular a percutaneous socket enabling an electric connection between an apparatus implanted in the body of a patient, and an external apparatus such as a power supply. This percutaneous socket is fixed onto the surface of an osseous wall by means of osteosynthesis screws, with all the pieces making up the socket and the cables being therefore submuscular or subcutaneous. However, such an arrangement of the socket is not very reliable and vulnerable to infections propagated from percutaneous passage.
Patent FR 03-04063 also discloses a permanent percutaneous electric connection device, provided to electrically connect an internal entity to a human or animal body with an entity external to said body, this device comprising a plate support provided to be impacted in a bone of said body, and percutaneous means of electric connection which comprise (i) fixed means of electric connection integrated into the plate support, and (ii) removable means of electric connection provided to be coupled electrically to said fixed means of electric connection and connected respectively to supple electric linking means.
Entity located inside the body or internal entity here means any electric consumer apparatus or producer of electric power, arranged or not to receive a command or control signal, and/or any equipment for measuring or sensing provided for generating electric signals.
Entity external to the body or external entity means any equipment near or distant from the body, provided to supply electric power and/or command or control signals, or to receive signals generated by any sensor or electric apparatus inside the body and/or electric power generated by equipment inside the body.
Such a permanent osseointegrated percutaneous electric connection device has a high level of security and reliability which makes it eligible for demanding uses, especially in cardiology and neurology.
In particular, such permanent percutaneous electric connection devices allow a soft tissue reduction around the percutaneous abutment, which reduces risks of infection, especially at the level of the percutaneous passage. However, even though the risk of infection at the level of the percutaneous passage is reduced, it still exists, and the devices of the prior art are not adapted to limit or even stop the propagation of infectious agents. In particular, known permanent percutaneous electric connection devices have no means provided for limiting or preventing any risk of propagation of infectious agents along the electric cable or electric cables connecting the percutaneous socket to the internal apparatus.
An aim of the present invention is therefore to propose a permanent percutaneous electric connection that can be osseointegrated, adapted to soft tissue reduction and can be easily connected and disconnected to a cervical cable.
More precisely, an aim of the present invention is to propose a permanent percutaneous electric connection device designed to be osseointegrated in an osseous structure of a patient, ensuring increased reliability, and reducing the propagation of possible infectious agents.
To make the osseointegration possible, the device must be solidly implanted with precision in a complementary cavity, preferably made in an osseous wall, for example in the thickness of the cranium at a distance from the dura mater, in order to realize what is referred to the "primary stabilization", without which the osseointegration process cannot start. That device setting up must respect certain established surgical principles, indispensable to osseointegration: preparation of the osseous cavity as least traumatic as possible, abundant irrigation with saline serum with minimal heating of the bone, adequate primary stabilisation of the implanted device.

Percutaneous power delivery system for permanently implanted medical devices and manufacturing method


A kick down and kick up catamaran assembles by hand with holes in main spar and stern spar ends receiving threaded rods extending vertically from the side-by-side hulls, secured in place with hand knobs. A bow spar with a line to the mast lifts the mast to vertical and is then secured between the hulls. A mast operationally rests with its proximal end alongside the main spar, held in place by an easily removable cord that wraps the main spar and slips into a mast slot opening at the mast proximal end. A trampoline stretches between the main and stern spars providing a platform on which the operator sits, tightened by a plurality of adjustable straps between the trampoline and the stern spar.

1. Field of the Invention
This invention relates to catamarans, and more specifically to a catamaran characterized by facile assembly and kick down by hand and employing an underwater relief-tolerant rudder.
2. Prior Art
It is well known to have catamarans comprising a pair of parallel hulls, a mast supported by a main spar between the hulls, and platform between the hulls on which to ride. It is also well-known to have retractable rudders on sailboat sterns operated by a tiller that avoids damage to the rudder when it might impact an underwater object or change in underwater relief. It is also known to have retractable rudders that lift completely out of the water. For catamarans, it is also known to operate the tiller of each rudder from a common helmsman position.
The present invention presents such a catamaran that can be assembled from components without tools using only hand-turned knobs and straps. Likewise, the catamaran can be broken down quickly and easily without tools for ease in assembly and disassembly for convenient transport of the vessel. Assembly can be easily done by one person, including raising and lowering the main mast with a sail attached. It also presents a rudder useful on each hull of such a catamaran that lifts and lowers to track underwater terrain or objects automatically but can be lifted completely out of the water by a single helmsman by simply pulling back on an arm linked to both tillers.


The invention relates to an insulator for an electrical conductor provided with an outer shield, especially a so-called coaxial cable or shielded twin cable, in order to achieve an insulation at the shield that insulates against DC and low frequency AC signals transforming through the conductor and that includes a first and a second element (3,4) formed from electrically conducting material that by means of a dielectric (5) are electrically insulated and delineated from one another. and that are intended to be connected between an interruption at the shield or between the shield and an external earth connection. To achieve an insulator of the type that uses a standard type of capacitive element, that is simple and cheap to produce at the same time having small dimensions, the elements (3,4) are, according to the invention, arranged with one or several continuous openings running through them for passing the conductor through the elements and the delineation between the elements defined by means of the dielectric (5) is crossed by one or more discrete capacitive elements (6) that are electrically connected between the first and second elements.

The present invention relates to an insulator for an electrical conductor provided with an outer shield in order to achieve an insulation at the shield that insulates against DC and low frequency AC signals transforming through the conductor according to the introduction to claim 1.
When electrical conductors with an external earth, for example in the form of shielding, so-called coaxial cables intended for high frequency carrier waves are connected to audio/video equipment or to equipment for telecommunication, problems of circulating earth currents frequently arise. These currents originate from differences in AC potentials between the respective points of connection of the conductors to the equipment, which leads to disturbances in the form of humming noise and disturbing signals. Such currents occur, for example, between the exchange and transmission sections of telecommunications equipment as the likelihood of differences in earth potential is great in such electrical equipment as they are located at a large distance from one another.
To avoid such said problems, it is known to provide the conductor with an insulation that blocks DC signals and low frequency AC signals but that allows the passage of more highs frequency AC signals, which in the majority of cases means signals with frequencies that exceed 50 Hz. Such insulated conductors are commonly provided with an interruption that has a capacitive junction so that DC signals and low frequency AC signals cannot pass, whereby the point at which the capacitive connection is arranged is commonly accommodated in a metallic housing that is similarly connected to earth to prevent surrounding electromagnetic radiation from affecting the signal that is led through the conductor and, conversely, to prevent the signal being transferred in the conductor from affecting nearby equipment.
Despite a number of the insulators so far known forming excellent connections for transferring high frequency signals,.and having fully satisfactory insulation against DC and low frequency signals, there is a need to both reduce the costs of manufacturing and the size of these. One reason that contributes to why known insulators have such -bulky dimensions is that the capacitive element itself constitutes a significant portion of the total dimension of the insulator. This is mainly due to the electrical functions of the capacitive element and its general construction in which the ability to accommodate electrical charges, the so-called capacitance, is proportional to the outer surface of the electrodes and the dielectric constant of the sandwich. Insulators known to date that use standard types of capacitive element, such as condensers of the monolithic ceramic type, are mounted on a pattern card, which has the disadvantage that the insulator becomes much too bulky to be useful in practice. Compare, for example, the earthing insulator known from U.S. Pat. No. 4,987,391 (Kusiak, Jr.). To reduce the outer dimensions of the insulator, it is known to use capacitive elements that have been designed to suit the body of the insulator and its function. For example, an insulator that uses specially formed capacitive elements arranged following one another in. a row and where each one has a ring-like shape with a hole in the center arranged so that the individual electrical conductors that are arranged in the coaxial cable can pass through the insulator body is known from U.S. Pat. No. 4,559,506 (Capek). Despite this type of insulator having succeeded in reducing the outer dimensions, it is far too costly to manufacture due to the specially formed capacitive elements that have to be used with it.
One main objective of the present invention is thus to achieve an insulator of the type described in the introduction that uses a standard type of capacitive element, that is simple and cheap to produce at the same time as it only has small dimensions. A second objective of the present invention is to achieve an insulator that is shielded against electromagnetic radiation.
These objectives are achieved in the insulator according to the invention having the features stated in the claims.

Insulator for an electrical conductor provided with an outer shield


A method of interrupting a job currently in the process of being printed from a print queue of a multifunctional printing system with an interrupt job having its origin in one of a first service or a second service is provided. The job currently in the process of being printed includes a page boundary, a set boundary and a job boundary. Additionally, the first service includes a first input device disposed locally with respect to the multifunctional printing system and communicates with a first memory section having one or more jobs developed with the first input device, while the second service includes a second input device disposed remotely of the multifunctional printing system and communicates with a second memory section having one or more jobs developed with the second input device. The method includes selecting a job from one of a first memory section and the second memory section. The job is designated as an interrupt job and transmitted to the print queue. When the interrupt job is from the first memory section and a preselected condition is met, it is inserted at one of the page boundary and the set boundary. When the interrupt job is from the second memory, it is inserted into the print queue at the job boundary.

This invention relates generally to a multifunctional printing system with interrupt capability and, more particularly to a job interrupt system which permits management of a print queue in such a manner that a job currently in the process of being marked can be interrupted by at least one interrupt job selected from a plurality of job input sources. Additionally, the system can be programmed in such a manner that the at least one interrupt job is prohibited from interrupting the job currently in the process of being marked unless the at least one interrupt job complies with a predesignated priority status. Finally, the system permits a job currently in the process of being printed from the print queue to be interrupted so that at least a first interrupt job and a second interrupt can be printed ahead of the interrupted job, in sequence, even when printing of the first interrupt job is completed prior to delivery of the second interrupt job to the print queue.
Electronic printing systems typically include an input section, sometimes referred to as an input image terminal ("IIT"), a controller, and an output section or print engine, sometimes referred to as an image output terminal ("IOT"). In one type of electronic printing system, manufactured by Xerox.RTM. Corporation, known as the DocuTech.RTM. electronic printing system, a job can be inputted to the printing system from, among other sources, a network or a scanner. An example of a printing system with both network and scanner inputs is found in the following patent:

Job interrupt system for multifunctional printing system