A high speed downlink packet access communication system method that supports a plurality of redundancy variations that are characterized by at least a first parameter that comprises an indicator regarding self-decodability of a corresponding packet and a second parameter that comprises a selection of a particular redundancy version from amongst a plurality of candidate redundancy versions. Pursuant to a preferred approach, and upon determining a need to transmit redundant information as corresponds to a given packet, one automatically selects, for at least one of the first and second parameters, a specific value from amongst a plurality of candidate values and then uses the specific value to transmit the redundant information.

Data transmission, including the transmission of packets of data, comprises a well-understood area of endeavor. In many cases, and particularly when transmitting data via a wireless pathway, not all of the data may be properly received. For example, pathway conditions may be sufficiently poor so as to distort or overwhelm one or more transmission symbols as correspond to the underlying data.
Redundancy encompasses the general area of attempting to avoid or at least ameliorate such problems by transmitting more than just the basic data as described above. For example, by sending an entire message twice, or three times more, one can increase the likelihood that at least one of the transmissions will pass without undue compromise. Such a simplistic technique, of course, would be very consumptive of the communication pathway itself and could greatly reduce the total number of unique messages that could be supported by such a pathway. Consequently various other redundancy schemes have been proposed to increase the likelihood of effecting an adequate exchange of information while simultaneously minimizing usage of the supporting communication resources.
For example, present High Speed Downlink Packet Access (HSDPA) standards specify use of a hybrid-automatic repeat request (H-ARQ) scheme that makes use of a specific rate-matching algorithm. The two fundamental forms of H-ARQ are Chase combining and Incremental Redundancy (IR). The first packet data transmission will typically comprise both information bits and parity bits as correspond to the information bits. In Chase combining, each re-transmission repeats the first transmission or part of it. In IR, each retransmission provides new parity bits from the mother code to build a lower effective code rate, where the effective code rate is determined by dividing the number of unique information bits received by the number of unique information and parity bits received.
For HSDPA, this particular approach permits use of different versions of the H-ARQ redundancy algorithm. In particular, a so-called S parameter is used to indicate whether a given packet is self-decodable by itself and a so-called R parameter indicates the start point for an included stream of parity bits (and thereby in effect comprises a redundancy version selection indicator). Selection of these parameters corresponds to selection of a corresponding H-ARQ redundancy algorithm from amongst a potential plurality of candidates.
These parameters are presently selected on a relatively static basis. While a given user may make a proper (i.e., efficient) selection of these parameters in a given instance, or for a given point in time, transmission conditions can and will change (sometimes quickly and sometimes dramatically). Such changes can quickly render a given choice of parameters sub-optimum. As a result, this capability of selecting a particular approach to redundancy from amongst a plurality of candidate options does not always necessarily lead to an otherwise hoped-for improvement with respect to data throughput or efficiency.
Skilled artisans will appreciate that elements in the figures are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions of some of the elements in the figures may be exaggerated relative to other elements to help to improve understanding of various embodiments of the present invention. Also, common but well-understood elements that are useful or necessary in a commercially feasible embodiment are often not depicted in order to facilitate a less obstructed view of these various embodiments of the present invention. It will also be understood that the terms and expressions used herein have the ordinary meaning as is usually accorded to such terms and expressions by those skilled in the corresponding respective areas of inquiry and study except where other specific meanings have otherwise been set forth herein.

Packet transmission redundancy selection apparatus and method


The present invention is directed to novel nucleic acid and amino acid sequences associated with the metabolism of seed storage compounds in plants. A novel discovery described herein lies in the identification of the nucleic acid sequences that encode the wri1 genetic locus in Arabidopsis thaliana, and lipid metabolism regulator (LMR) polynucleotide sequences contained therein. Preferably, the seed storage compounds are lipids, fatty acids, starches or seed storage proteins.

The study and genetic manipulation of plants has a long history that began even before the famed studies of Gregor Mendel in the 19th century. In perfecting this science, scientists have accomplished modification of particular traits in plants ranging from potato tubers having increased starch content to oilseed plants such as canola and sunflower having increased or altered fatty acid content. With the increased consumption and use of plant oils, the modification of seed oil content and seed oil levels has become increasingly widespread. The seed oil production or composition has been altered in numerous traditional oilseed plants such as soybean (U.S. Pat. No. 5,955,650), canola (U.S. Pat. No. 5,955,650), sunflower (U.S. Pat. No. 6,084,164) and rapeseed (Toepfer et al. 1995, Science 268:681-686), as well as non-traditional oil seed plants such as tobacco (Cahoon et al. 1992, Proc. Natl. Acad. Sci. USA 89:11184-11188).
Plant seed oils comprise both neutral and polar lipids (see Table 1). The neutral seed lipids contain primarily triacylglycerol, which is the main storage lipid that accumulates in oil bodies in seeds. The polar lipids are mainly found in the various membranes of the seed cells, e.g. the endoplasmic reticulum, microsomal membranes and the cell membrane. The neutral and polar lipids contain several common fatty acids (see Table 2) and a range of less common fatty acids. The fatty acid composition of membrane lipids is highly regulated and only a select number of fatty acids are found in membrane lipids. On the other hand a large number of unusual fatty acids can be incorporated into the neutral storage lipids in seeds of many plant species (Van de Loo, F. J. et al. 1993, Unusual Fatty Acids in Lipid Metabolism in Plants pp 91-126 editor T S Moore Jr. CRC Press).
Lipids are synthesized from fatty acids and their synthesis may be divided into two parts: the prokaryotic and the eukaryotic pathway (J Ohlrogge & J Browse 1995, Lipid Biosynthesis Plant Cell 7:957-970). The prokaryotic pathway is located in plastids that are the primary site of fatty acid biosynthesis. Fatty acid synthesis begins with the conversion of acetyl-CoA to malonyl-CoA by acetyl-CoA carboxylase (ACCase). Malonyl-CoA is converted to malonyl-ACP by the malonyl-CoA:ACP transacylase. The enzyme beta-keto-acyl-ACP-synthase III (KAS III) catalyzes a condensation reaction in which the acyl group from acetyl-CoA is transferred to malonyl-ACP to form 3-ketobutyryl-ACP. In a subsequent series of condensation, reduction and dehydration reactions the nascent fatty acid chain on the ACP cofactor is elongated by the step-by-step addition (condensation) of two carbon atoms donated by malonyl-ACP until a 16- or 18-carbon saturated fatty acid chain is formed. The plastidial delta-9 acyl-ACP desaturase introduces the first unsaturated double bond into the fatty acid. Thioesterases cleave the fatty acids from the ACP cofactor and free fatty acids are exported to the cytoplasm where they participate as fatty acyl-CoA esters in the eukaryotic pathway. In this pathway the fatty acids are esterified by glycerol-3-phosphate acyltransferase and lysophosphatidic acid acyltransferase to the sn-1 and sn-2 positions of glycerol-3-phosphate, respectively, to yield phosphatidic acid (PA). The PA is the precursor for other polar and neutral lipids, the latter being formed in the Kennedy pathway (Shanklin and Cahoon 1998, Annu. Rev. Plant Physiol. Plant Mol. Biol. 49:611-641; Voelker 1996, Genetic Engineering ed.: J K Setlow 18:111-13; Frentzen 1998, Lipid 100(4-5):161-166).
Acetyl-CoA in the plastids is the central precursor for lipid biosynthesis. Acetyl-CoA can be formed in the plastids by different reactions and the exact contribution of each reaction is still being debated (J Ohlrogge & J Browse 1995, Lipid Biosynthesis Plant Cell 7:957-970). It is however accepted that a large part of the acetyl-CoA is derived from glucose-6-phospate and pyruvate (i.d. phosphoenolpyruvate) that are imported from the cytoplasm into the plastids. Sucrose is produced in the source organs (leaves, where photosynthesis takes place) and is transported to the developing seeds that are also termed sink organs. In the developing seeds, the sucrose is the precursor for all the storage compounds, i.e. starch, lipids and partly the seed storage proteins. Therefore, it is clear that carbohydrate metabolism in which sucrose plays a central role is very important to the accumulation of seed storage compounds.
Although lipid and fatty acid content of seed oil can be modified by the traditional methods of plant breeding, the advent of recombinant DNA technology has allowed for easier manipulation of the seed oil content of a plant, and in some cases, has allowed for the alteration of seed oils in ways that could not be accomplished by breeding alone. For example, introduction of a Δ12-hydroxylase nucleic acid sequence into transgenic tobacco resulted in the introduction of a novel fatty acid, ricinoleic acid, into the tobacco seed oil (Van de Loo, et al. 1995, Proc. Natl. Acad. Sci USA 92:6743-6747). Tobacco plants have also been engineered to produce low levels of petroselinic acid by the introduction and expression of an acyl-ACP desaturase from coriander (Cahoon et al. 1992, Proc. Natl. Acad. Sci USA 89:11184-11188).
The modification of seed oil content in plants has significant medical, nutritional and economic ramifications. With regard to the medical ramifications, the long chain fatty acids (C18 and larger) found in many seed oils have been linked to reductions in hypercholesterolemia and other clinical disorders related to coronary heart disease (Brenner R. R. 1976, Adv. Exp. Med. Biol. 83:85-101). Therefore, consumption of a plant having increased levels of these types of fatty acids could reduce the risk of heart disease. Enhanced levels of seed oil content also increase large-scale production and thereby reduce the cost of these oils.
In order to increase or alter the levels of compounds such as seed oil in plants, nucleic acid sequences and proteins regulating lipid and fatty acid metabolism must be identified. As mentioned earlier, several desaturase nucleic acids such as the Δ6-desaturase nucleic acid, Δ12-desaturase nucleic acid and acyl-ACP desaturase nucleic acid have been cloned and demonstrated to encode enzymes required for fatty acid synthesis in various plant species. Oleosin nucleic acid sequences from such different species as Brassica, soybean, carrot, pine and Arabidopsis have also been cloned and determined to encode proteins associated with the phospholipid monolayer membrane of oil bodies in those plants.
Although several nucleic acids that are involved in enzymatic steps of the metabolism of lipids, fatty acids and starches have been cloned and identified, there are likely a multitude of such plant nucleic acids that have yet to be identified. Phenotypic analysis of several oilseed plants and other mutated plants has revealed other putative proteins involved in plant lipid metabolism, but the prior art has yet to describe the genomic location of these proteins or the nucleic acids that encode them.
An exemplary study is that of the oilseed plant Arabidopsis thaliana. In 1998, Focks and Benning isolated and characterized a wrinkled mutant of Arabidopsis thaliana designated wri1 (Plant Physiology 1998, 118:91-101). The wri1 mutant has a decreased seed oil content that was speculated to be due to a defect in the seed-specific regulation of carbohydrate metabolism. In the wri1 mutant, the activities of several glycolytic enzymes were reduced and the mutant seeds were impaired in the incorporation of sucrose and glucose into triacylglycerol lipids, while important precursor molecules for plastidial lipid biosynthesis, like pyruvate and acetate, were incorporated at increased rates. This biochemical evidence was interpreted by Focks and Benning as indication that the WRI1 protein could be a regulatory protein governing carbohydrate metabolism during seed development or a hexokinase that may act as a sugar sensor in developing seeds, and thus controlling the activities of several glycolytic enzymes (Plant Physiology 1998, 118:91-101). The wri1 phenotype (wrinkled seeds) has been found in two different allelic Arabidopsis thaliana mutants, namely wri1-1 and wri1-2.
Since the discovery of the wri1 phenotype by Focks and Benning, the Arabidopsis thaliana genome was sequenced in its entirety (The Arabidopsis Genome Initiative 2000 Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 408:796-844). These genomic sequences have been annotated and open reading frames encoding putative proteins have been assigned in an automatic process. Importantly however, this annotation is only based upon homologies with other sequences with known functions, and therefore, in no way identifies the true location, sequence or functionality of an Arabidopsis thaliana nucleic acid sequence. The annotation and assignment of open reading frames also in no way describes the location, function or sequence of the wri1 gene.
Therefore, what is needed in the art is the elucidation of the location and identity of the one or more nucleic acids associated with the wri1 mutation in Arabidopsis thaliana along with an understanding of the functionality of the proteins and protein fragments encoded by those nucleic acids.


A modulator includes an interferometer waveguide structure formed on an electro-optical substrate, preferably a Z-cut lithium niobate or a Z-cut lithium tantalate. The substrate includes a domain inversion between a region near the first arm and a region near the second arm of the interferometer waveguide structure. In one example, two coplanar strip electrode structures, each extending near at least a portion of the first arm and the second arm, respectively, are electrically coupled to each other.

Mach Zehnder interferometers (MZIs) are used to modulate the amplitude or intensity of an optical signal, for instance in digital and analog communications and electric field sensors. Often, they are fabricated as monolithic devices on either Z-cut or X-cut lithium niobate or lithium tantalate.
A typical MZI includes two arms for dividing an optical input signal into two beams, which are then recombined. In one design, the arms have equal length. During operation, the relative phase of the two beams is controlled by some type of optical phase modulation in one or both arms in order to modulate the intensity of the output signal, which depends on the relative phase of the two beams.
In many applications, the drive voltage of the modulator is of particular interest as it affects link gain, sensor sensitivity, and drive power requirements for high speed, such as ˜40 Gigahertz (GHz) or faster, analog or digital links. Drive voltage sensitivity is characterized by the product between the drive voltage and the length of the device electrodes.
For devices of limited size, such as found in many optical communication applications, drive voltages tend to be relatively high, for example in the 4 to 5 Volt (V) range. On the other hand, low voltages often are desired in analog applications, where switching between the on and off states is characterized by Vπ, π being the total phase shift in the interferometer. As a result, such devices, when packaged, can be relatively long, for example in the 10 to 15 centimeter (cm) range. Generally, a Z-cut substrate is preferred when fabricating devices for which a low Vπ is important. Typical values for the voltage-length(VL) product in such devices are in the 10 to 12 Vcm range.
Since the voltage length product depends on the intrinsic electro-optic coefficient of the material used, considerable effort has been devoted to investigating materials with high electro-optical coefficients. For a given electro-optical material, the voltage-length product depends on the detailed geometric configuration of waveguides and electrodes. Mathematically, this factor can be described by an overlap integral between the electrical and optical fields. It can be shown that the overlap integral is strongly dependent on the exact geometry chosen.
Modulators based on a coplanar waveguide (CPW) electrode structure and having horn arrangement on lithium niobate (LiNbO3) substrates are disclosed in U.S. Pat. No. 6,304,685 B1, issued on Oct. 16, 2001 to W. K. Burns and U.S. Pat. No. 6,356,673 B1, issued on Mar. 12, 2002 to W. K. Burns, to the instant inventor, both applications being incorporated herein in their entirety by this reference. The use of ridge waveguides described in these patents was found to enhance the overlap integral, and to facilitate, simultaneously, velocity matching and near 50 Ohm line impedance.
In the prior CPW arrangement, a voltage is applied to a central hot electrode, which is disposed between two ground electrodes, with the vertical (Z-directed) electrical field component having opposite directions on the two arms of the interferometer. Thus, the phase changes accumulated in the two arms of the interferometer have opposite sign. Since the output of the interferometer depends on the difference of these phase changes, they add to produce the total phase change in the MZI. This is termed a "push-pull" configuration.
In the "push-pull" configuration associated with the CPW arrangement disclosed in U.S. Pat. No. 6,304,685 B1 and U.S. Pat. No. 6,356,673 B1, however, the electrical confinement is such that the overlap efficiency is uneven with respect to the two MZI waveguide arms. It is estimated that while the overlap integral for the waveguide under the central hot electrode contributes a large percentage of about 80% to the total phase change, the overlap integral for the MZI waveguide under the ground electrode contributes relatively little (about 20%) to the total phase changes.
Double coplanar strip (CPS) Mach Zehnder integrated electro-optical modulators are disclosed, for example, in US. Patent Application Publication No. 2003/0002766, by Pruneri et al., published on Jan. 2, 2003. In some of the arrangements shown in this reference, the substrate includes regions with mutually inverted ferroelectric domain orientations and the same drive voltage is applied to neighboring central electrodes. Electrical coupling between the neighboring central electrodes is prevented.
Domain reversal also has been proposed to make zero-chirp interferometers on Z-cut material.

Optical modulator with coupled coplanar strip electrode and domain inversion


The invention provides novel compositions and golf balls formed from those compositions. The compositions generally include a cured blend of an elastomer, a peroxide polymerization agent, a co-agent, and an unsaturated polycarboxylic acid. More particularly, the cured composition includes a cured blend of cis 1,4 polybutadiene, dicumyl peroxide, zinc diacrylate, and fumaric acid. One piece golf balls formed of these compositions have improved durability.

Prior art golf balls comprise, in general, three types. The first type is the three piece wound ball wherein a vulcanized rubber string is wound under tension around a solid or semi-solid core, and thereafter enclosed in a sheath or covering of tough, protective material. A second prior art golf ball is a one-piece ball formed from a solid mass of moldable resilient material which has been cured to develop the necessary degree of hardness to provide utility. One-piece molded balls do not have an enclosing cover. A third prior art ball is the two-piece ball that includes a solid core and a cover thereon.
The one-piece ball is formed from a combination of materials such as elastomers, fillers and curing agents which are molded under high pressure and temperature to provide a ball of suitable hardness and resilience. One-piece balls are described, for example, in U.S. Pat. No. 3,313,545, U.S. Pat. No. 3,373,123 and U.S. Pat. No. 3,384,612.
While the wound ball has for many years satisfied both the standards of the U.S.G.A. and most golfers, it has several disadvantages. For example, a wound ball is difficult to manufacture due to the number of production steps required and the careful control which must be exercised in each stage of manufacture to achieve suitable roundness, velocity or rebound, "click" and the like. "Click" is the term applied to the sound produced by the ball when dropped on a hard surface or when struck with a golf club. In addition, the cover material for the wound ball has not provided the optimum in adhesion to the wound core and is susceptible to cutting when struck by a golf club.
One-piece and two-piece golf balls, in contrast to wound golf balls, can be produced with an essentially perfect center of gravity and thus, exhibit excellent aerodynamic properties, superior roll and trueness of flight. Such golf balls are highly resistant to cutting and are practically indestructible during use in normal play. These balls return to round even when severely distorted and maintain their superior flight characteristics after extended use. Further, one and two-piece unitary golf balls can be manufactured with better quality than conventional wound balls. One-piece balls also maintain their playing characteristics throughout wide temperature ranges, possess an excellent shelf life, and do not water log. Moreover, if paint on one-piece golf balls becomes worn or damaged, the one-piece balls may be reclaimed by removing or stripping off the old paint and repainting. In contrast, wound balls seldom last long enough to allow repainting.
Although one-piece balls have several distinct advantages, they have not had satisfactory durability due to brittleness. Most one-piece balls do not survive more than about 1000 hits. A need therefore exists for one-piece balls which have high hardness but yet possess improved durability and flexibility to minimize cracking.


A real-time chat and conference contact information manager which, during a real-time online chat, online meeting, or online collaboration session between multiple participants, receives identification items associated with addition of a new participant; stores the received identification data item in a contact record in a local collaboration client contact list; triggered by the storing, extracts a search key value for each data item of the contact record, including at least an email address value associated with the new participant; uses the search key value to search a trusted administered contact information store for corresponding data items; and modifies the contact record to include the corresponding data items from said trusted administered contact information data store.

1. Field of the Invention
This is a continuation of U.S. patent application Ser. No. 11/336,317, filed on Jan. 20, 2006, currently under notice of allowance, which was a continuation of U.S. patent application Ser. No. 10/081,021, filed on Feb. 21, 2002, now issued as U.S. Pat. No. 7,051,049, both of which were filed by Jonathan Samn. This invention relates to technologies and methods for managing personal contact information, and more particularly to management of online personal contact information for real-time online collaboration, conference and message facilities.
2. Background of the Invention
Online collaboration and messaging in real-time has become very popular in recent years. Programs and services such as America Online's ("AOL") Instant Messenger ("IM"), Microsoft's NetMeeting, and Lotus' Sametime are well-known programs and services which allow real-time white board collaboration, chatting, conference sessions and instant messaging via a corporate intranet and/or the Internet.
Using programs and services such as these, a plurality of online users may participate in a joint conference involving text messaging, application program sharing, and real-time photo and video sharing. Many companies have begun to use these services in place of actual face-to-face meetings of personnel which are physically or geographically dispersed.
During these "virtual" meetings, often times one participant will supply other participants with drawings, presentation graphics, and text for discussion. The ensuing discussion between the participants may be logged to a file for later review, which is more convenient than the record keeping mechanisms of actual physical face-to-face meetings. As such, these online virtual meetings and conversations provide advantages over traditional face-to-face meetings, not the least of which are automatic record keeping, reduced travel costs and greater convenience.
Turning to FIG. 3, the arrangement of components of these types of real-time online collaboration systems is shown. A number of collaboration clients (32) are interconnected through a computer network (31). These collaboration clients typically comprise a personal computer equipped with software such as Netscape's Navigator[™], AOL's Instant Messenger[™], or Lotus' Sametime Connect[™]client product. These collaboration clients (32) may also include other computing platforms such as personal digital assistants ("PDA") and advanced web-enabled wireless telephones.
The collaboration clients (32) may interface to the computer network (31) through a number of well-known technologies including, but not limited to, Transmission Control/Internet Protocol ("TCP/IP"), dial-up modems, cable modems, asymmetric digital subscriber line ("ADSL"), or other interface technologies such as wireless interfaces.
Typically, the collaboration client (32) maintains a local contact list (33), such as AOL Instant Messenger's "buddy list" or Netscape Navigators "address book." These contact lists (33) may take the form of simple text files, or as advanced as database files. In some cases, the contact list are stored in proprietary formats.
When an online meeting or collaboration session is established, each new participant may supply the other participants with his or her email address as he or she logs into the session. The other participants may then chose to store that email address in their local contact list. In some cases, such as with the Instant Messenger product, there are other options for users to transmit their entire contact list to other meeting participants.
In general, however, these email addresses as well as any other participant contact information which is exchanged between participants is defined and by the participants themselves. This means that a participant logging in to a virtual meeting may supply accurate and complete information regarding his or her email address and other contact data, such as telephone and company location. However, a participant may choose not to supply some of this information, or may supply incorrect information.
Another method for exchanging personnel information and automatically storing it into such a contact list is called a "vCard". A vCard is a data record that may be attached automatically to an email message, if an email user desires to share his or her vCard with recipients of his or her messages.
A vCard which may contain a number of personal information data items as defined by the sender or originator. This may include email address (e.g. "return email address"), personal or company physical address, telephone numbers, and other descriptive information as defined by the sender.
vCards are an industry standard format data developed by a consortium including Apple, ATT, IBM, and others. Responsibility for maintaining and evolving the vCard specification was assumed by the Internet Mail Consortium ("IMC") in 1996.
By attaching vCards to an email message, a sender may enable the recipient to automatically store information into his or her contact list which is contained in the vCard. For example, a sender of an email message may wish to enable a recipient to automatically store the sender's name, email address, telephone number, position title, and company name into the recipient's address book without having to type it. Upon receipt, the recipient can select an automatic function in his or hers email client software which extracts the information from the attached vCard and stores it into his or her local address book. Later, the recipient may use that information in the address book to address new messages, export to other application programs such as word processors and contact managers, and to load into other databases.
As all of these currently available methods and systems rely on information which is defined and supplied by the sender or the originator of the information, such as a newly joined member of a virtual online conference, these methods and systems are subject to inconsistencies and inaccuracies in the data which may be stored into the recipient's or other participant's address books or contact lists.
For example, one participant in a online conference may supply a full set of information including his name, job title, telephone numbers, and company name. Another participant in the same conference may only supply his email address. When all of the participants in the conference store all of the information supplied by the other participants into their local contact lists, they may later find that their contact list has varying levels of degree of details in the information about each of those participants (and may contain errors).
Later, when one of the participants wants to contact another participant, such as by making a telephone call to that participant, he may or not be able to find that telephone number based upon the information which was or was not supplied by the participant during the online conference.
Therefore, as the vCard industry standard and as the proprietary information standards of the various online conferencing services and suppliers do not assure accuracy or enforce uniformity of detail of the information supplied by online conference participants, the very flexibility of the system becomes a disadvantage of the systems as well.
Therefore, there is a need in the art for a system and a method which allow participants of online conferences and collaboration sessions to automatically store reliable and accurate information regarding the participants of those sessions. There is also a need in the art for this system and method to provide a consistent level of detail of information about each participant so that the participants may rely upon the contents of their local contact list in the future.

Real-time chat and conference contact information manager

International Business Machines Corporation


A vessel for reducing contamination of liquids is formed of a vessel body with an inlet opening and an outlet opening therein. A closing device is attached to the vessel body adjacent the outlet opening. The closing device closes the outlet opening, and includes a normally closed one-way valve which is openable by a predetermined pressure from within the vessel body.

Subject matter of the invention is a vessel for reducing contamination in the treatment of liquids, said vessel having an inlet and an outlet opening; the latter opening can be closed in a special way.
In many fields of application, the treatment of liquids requires particular care with respect to actively avoiding contamination which could adversely affect the environment. This applies particularly to noxious liquids, but also to liquids which are used or generated in the analysis of components. The treatment steps to prepare a sample liquid for an analysis are usually carried out in the same laboratory or even the same room as the analysis itself. The use of aerosols, for example, often leads to heavy contamination of the environment with sample components; this in turn interferes with the analysis of components of other samples. An erroneous result can have terrible consequences for the patient, especially when analyzing components in the field of medical and clinical diagnostics.
Analyses that are based on the detection of nucleic acids in a sample have recently been introduced as diagnostic tools owing to their relatively high specificity. These tests are a considerable technical challenge since the contents of nucleic acids and especially the nucleic acids to be detected is a very small one while nucleic acids having similar sequences and other components which may interfere with the determination are also present in the same sample. Experience has shown that amplification procedures which have recently become more and more popular are used to produce a multitude of identical nucleic acids dependent on the presence of certain nucleic acid sequences to be tested; this greatly improves the sensitivity of the test, allowing to even detect individual nucleic acids. The risk involved in the possible high sensitivity of the tests is that contamination of other samples even with only one single nucleic acid from the environment can cause, i.e. simulate, a positive result. When using nucleic acid tests, it is therefore necessary to avoid in a particularly effective manner already the generation of contamination, i.e. the release of nucleic acids from a sample or a reaction mixture into the environment.
When preparing samples for the analysis of components, especially nucleic acids, methods have recently been used where the sample liquid and the components to be analyzed contained therein are subject to a treatment in the vessel wherein liquid is introduced into the vessel through an inlet opening and removed again through an outlet opening after undergoing one or several treatment steps. Such vessels are commercially available in the form of columns containing materials for the separation of components from the liquid, an example being the QlAamp Kit manufactured by Qiagen. These vessels are contained in another vessel, so that liquid which may leak is released into this second vessel and not into the environment. This kind of liquid treatment is, however, complex and requires a corresponding second vessel. Moreover, these vessels are used in the centrifuges in order to transfer the liquid into the second vessel.
DE-A-4020442 describes a system wherein a rigid seal which seals the surface of blood sample vessels is pierced open with the aid of device that is equipped with a needle. Said needle can be covered by a protective cap. A separate tool is, hence, necessary to open and close the vessel.
DE-A-4124577 describes a reagent bottle whose bottom side is closed with a screw cap.
U.S. Pat. No. 3,706,305 describes a container where liquids can be transported with the aid of needles which pierce a membrane.
U.S. Pat. No. 3,601,152 discloses a valve where an elastic piece is completely removed from a projection. Said projection has no lateral openings.
The use of such a valve to avoid contamination has not yet been described.
DE-C-4214634 describes a pipetting aid to absorb liquids, said aid comprises an elastic hollow body and several valves for the in- and outlet of air.
DE-C-4204554 describes an ampoule for liquids where an inlet opening is opened by piercing a plastic membrane using a tip that is integrated in a funnel. The removal of liquid cannot be accomplished by applying pressure differences
DE-A-3139702 describes a vessel for handling paste-like sample material. The outlet openings are closed by means of snap-tops.
U.S. Pat. No. 4,956,298 describes a separation or reaction column that can be emptied via centrifugation. The outlet opening is closed with the aid of a snap-top that has to be mechanically removed.
U.S. Pat. No. 3,799,426 describes a container which is provided with a projection at its top; said projection prevents the vessel from falling through an apertured plate.
EP-A-0 561 003 describes a vessel for receiving liquids wherein the liquid is passed through several membranes when entering the vessel. An elastic seal of the outlet opening is not proposed.
EP-A-0 182 370 describes a blood storage device having a blood intake tube; said blood intake tube can be tightly sealed with a cap that is placed on the tube. An opening with the aid of pressure differences is not proposed.
U.S. Pat. No. 5,139,742 describes a device which comprises two pieces that can be brought into a position to allow the passage of liquid. The outlet opening in this element is not elastically closed with the aid of another element. The opening of the liquid passage is not accomplished with the aid of pressure differences.
DE-A-4021355 describes a blood removal device that is closed with the aid of a pierceable elastic plate. The device is opened with the aid of a hollow needle. However, the closure is provided to allow liquid to be taken into the device. To accomplish this, a vacuum is generated via another opening.
DE-A-2442149 describes a vessel for removing blood followed by a centrifugation procedure where the outlet opening is closed with the aid of a stopper. In order to open the outlet opening, the stopper must be manually removed.
DE-A-2328718 describes a disposable syringe where a screw cap is used to close an outlet opening.
DE-A-1541115 describes a disposable syringe where a semi-spherical cap is used to close the inlet opening.
U.S. Pat. No. 5,003,988 describes an apparatus for the detection of biological substances where liquid is pressed through a cylindrical opening.
DE-a-3639949 describes a method of separating long-chain nucleic acids with the aid of a filter material where the sample is made to pass through this filter material. The device used is a cartridge that is not opened by applying pressure.
U.S. Pat. No. 5,221,483 describes a device for filtering liquids wherein the liquid is passed through a porous filter and/or membranes. Inlet or outlet openings are not opened by applying pressure.
Leonhardt et al. (Amicon Biosolutions, 4/1994, pp 2-7) describe a system for the ultra-filtration of liquids wherein the liquid is transported across a filter by means of centrifugation.
Quiagen News, No. 1/94, pp 1-20, describe a system where liquids can be drawn through vessels. The outlet openings of these vessels can, however, not be reversibly opened or closed. Said literature reference also describes a vessel for cleaning nucleic acids wherein the liquid is passed through a filter material by means of centrifugation. Again, the outlet opening is not opened by applying pressure.
The latter vessel is also described in Quiagen News 2/94, pp 1-14.
It was, hence an object of the present invention to improve currently known methods for treating liquids by providing a new vessel.

Vessel for reducing contamination in the treatment of liquids


Systems and methods for detecting annotation digital ink strokes and further associating annotation digital ink strokes with word digital ink strokes are presented. Ink strokes are captured on a writing surface and then classified as words or annotations. Annotations are then anchored to corresponding words. When words are relocated or edited on the writing surface, the anchored annotations are also relocated and may even be reshaped according to the changes in the anchored words.

Computer users are accustomed to using a mouse and keyboard as a way of interacting with a personal computer. While personal computers provide a number of advantages over printed documents, users often continue to perform certain functions using printed paper. Some of these functions include reading handwritten documents. In the case of annotations, the printed document assumes a greater significance because of the annotations placed on it by the user. One of the difficulties, however, with having a hand-written document is a later need to have the content entered back into the electronic form of the document. This requires the original user or another user to wade through the handwritten content and enter them into a personal computer. In some cases, a user will scan in the handwritten content and the original text, thereby creating a new document. These multiple steps make the interaction between the printed document and the electronic version of the document difficult to handle on a repeated basis. Further, scanned-in images are frequently non-modifiable. There may be no way to separate the handwritten content from the original text. This makes using the handwritten content difficult. Accordingly, an improved way of handling handwritten content is needed.
Tablet PC's are increasingly being used to capture and display handwritten content. In the context of taking notes during a meeting, for example, a Tablet PC presents less of a barrier between individuals than does a laptop computer. Tablet PC's also allow for capturing of handwritten notes so that Tablet PC users are able to take notes in their own handwriting, in an unobtrusive manner similar to taking handwritten notes with a pen and paper.
Tablet PC's capture and display digital ink. The term "digital ink" refers to one or more strokes that are recorded from a pointing device, such as a mouse, a stylus/pen on a digitizer tablet, or a stylus/pen on a display screen integrated with a digitizer tablet (e.g., a touch-sensitive display screen). As used herein, the term "ink" is shorthand for digital ink.
Documents displayed on writing surfaces of tablet PCs may be annotated by a user. Correspondingly, annotations such as underline and blobs are often incorporated within the document. For example, a user may underline a few words in a document to emphasize the words underlined. Thus, extraction of handwritten annotations plays an important role in document processing.

Annotation detection and anchoring on ink notes


A combined holder and support for receptacle such as drinking cups, cans, bottles, mugs comprising a flexible, resilient blanket having insolation qualities, wrapped in various diameter cylindrical open ended chambers adapted to releasably hold the receptacle and a thin and narrow elongated vertical support adapted to be bendable by hand into an L-shaped configuration and including velcro strips on the back face of the vertical support and inner surface of the blanket to support the blanket at various heights relative to the L-shaped configuration. Velcro strips at opposite ends of the blanket secure the blanket in the cylinder. The upper end of the vertical support is bendable to various configurations to accommodate the shape of the support to which it is being supported. Velcro strips at the bottom or top of the vertical support can be included to support the holder to a vertical or horizontal support or an aperture at the top end can be utilized to suspend the holder from a projection formed on a vertical support.

There are numerous types of container holders disclosed in the literature and that are available that serve to hold drinking cups. Some of these containers are characterized by the fact that they are capable of being suspended and that they afford insulation qualities to either keep the liquid in the container cool or hot. Others provide means for suspending a drinking cup to a ledge or a platform such as are available in automobiles, boats and other vehicles. While others merely are capable of being hand held by the user and serve to keep the liquid in the container as close to the original temperature as possible over as long a period of time as possible.
For example, U.S. Pat. No. 4,181,765 granted to Harmony on Jan. 1, 1980 and entitled "Insulator for Canned Drinks" discloses an elongated sheet or blanket that is wrapped around a receptacle that has overlapping ends with a strip of adhesive to secure it in place. The insulator holds a drinking cup or can adapted to be hand carried.
U.S. Pat. No. 4,634,089 granted to Wright et al and entitled "Universal Cup Holder" discloses a two arm configuration attached to a back support defining an open channel cylinder receptacle adapted to receive different sized containers. The support structure in addition to the two arms consists of a back vertical member and a bottom horizontal member, each being adaptable to accept a strip of Velcro material.
U.S. Pat. No. 3,698,675 granted to Lerew et al on Oct. 17, 1972 entitled "Portable Holder" is a unitary rigid body defining a cylindrical cavity closed on the bottom for holding a container and a vertical back plate that includes an offset end portion that is adaptable to engage the back of a chair or the like to support the container holder.
U.S. Pat. No. 4,951,910 granted to March on Aug. 28, 1990 and entitled "Vertically Adjustable Velcro Strap Drink Holder" discloses a drink holder that includes a vertical L-shaped back with an offset to be attached to a ledge or the like for holding it in place and a complementary flat plate with a Velcro strip on its back face to engage a complementary velcro strip on the front face of the vertical member. This allows the two members to be mounted in different vertical positions to accommodate different sized containers. A pair of straps with Velcro strips extend laterally from the vertical back and are inserted between the two members and attached to one to hold the drink container that rests on the horizontal extension of the L-shaped back.
U.S. Pat. No. 4,915,337 granted to Iwasaki on Apr. 10, 1990 entitled "Flexible Cup Holder" discloses a flexible unit that includes a relatively narrow rigid U-shaped back with a horizontal and vertical flexible straps that engage the cup for support.
U.S. Pat. No. 4,708,273 granted to Grant on Nov. 24, 1987 entitled "Container Holder" discloses spaced closed and open hoops, a horizontal bottom support and a tab that is adapted to fit over the belt of the user. The container fits into the aperture formed by the spaced hoops and rests on the bottom support to be removed by the user to drink from the container.
Many of these configurations of container holders include various means for suspending a drinking cup at various locations. Some are for suspending the cup to the belt of the user and others are capable of being suspended in various types of vehicles. While they are, more or less, adequate for the particular purpose for which they have been designed they include certain deficiencies in a number of different respects. For example, some can only be utilized specifically for a single purpose for which they were designed. That is to say that the holder for the belt is limited to one who happens to be wearing a garment that will accommodate that particular unit. Other holders have brackets that are only capable of engaging certain configurations for supporting the holder. Many of the heretofore known holders that are adapted to be suspended in a moving vehicle are susceptible of swinging or swaying such that the contents can spill from the container chafe or mar the adjacent surface.
The container holder and support of my invention is characterized as being flexible and capable of many uses. That is to say, that it has many types of applications, as for example, it can be utilized to hold the container in various locations in an automobile, boat or other such vehicle. The back vertical support is made from material that is pliable yet sufficiently rigid to support the drinking cup. Consequently it can be bent at will with little effort by the user to be suspended at various types of supports and locations. As for example, it fits over the window slot or well or the back of the seat of an automobile or other type vehicle. It can also be bent to fit the belt of the user, or a hole in the top of the vertical back allows it to be supported to a nail, hook or the like in a vertical wall or door. Locating Velcro strips to the bottom of the horizontal portion of the bracket and the location where it will rest supports the drinking cup in the holder on any horizontal ledge.
The insulated blanket container holder can be detached from the holder and be hand held. It is contemplated within the scope of this invention that the blanket is a flat, flexible and resilient sponge material that is sufficiently long so that the ends overlap each other to form an open-ended chamber. Various sizes predicated by the amount of overlap will accommodate different sizes of drinking cups. Velcro strips at the edges will hold the blanket in the selected size to accommodate the drinking receptacle and allow the user to remove it as the need requires.
The holder support bracket is a substantially narrow thin flat elongated member that is fabricated from a pliable yet sufficiently sturdy material that allows the user to bend the member into various shapes to complement the support to which it is being attached. The holder support element, like the blanket container holder, carries attaching means for holding the container holder in position and for being attached to the various supports. In one of the embodiments it is contemplated that a hole at the proximal end of the holder support element allows the support to be held by a conventional nail or projection attached to the wall or the like. It is further contemplated by this invention that the outer surface of the blanket is adaptable of having indicia, logos printed thereon or having various colors for enhancing its appearance, identifying the owner of the holder, for advertising or for other like purposes.

Adjustable multi-purpose drink holder with detachable insulator blanket


The purpose is to provide selective PDE IV inhibitors which have a potent anti-asthmatic profile with excellent safety. A compound of the formula (1):

PDEs are enzymes which hydrolyze intracellular cyclic AMP (cAMP) and intracellular cyclic GMP (cGMP) and widely distributed in vivo in various tissues and organs. Up to now, it has been known that PDEs are classified into 7 isoenzyme families, i.e., type I to VII PDEs (PDE I to VII), according to their properties. Among them, PDE IV is known to be an enzyme which is predominantly present in airway smooth muscle cells and a wide variety of inflammatory cells, i.e., neutrophils, eosinophils, lymphocytes, etc. and selectively breaks down cAMP. In addition, it has been known that an elevation of cAMP levels in airway smooth muscle cells leads to relaxation of the airway smooth muscles. An increase of cAMP levels in inflammatory cells has also been known to suppress an activation of inflammatory cells, including, for example, a release of cytotoxic proteins from eosinophils, etc.
Therefore, if PDE IV predominantly located in airway smooth muscle cells and inflammatory cells is inhibited by inhibitors selective for said isozyme form, an elevation of cAMP levels would be induced in such cells. As a result, it would be expected to elicit bronchodilator actions via relaxing airway smooth muscles and anti-inflammatory actions through suppressing inflammatory cell activation. Such selective inhibitors of PDE IV would be expected to become excellent anti-asthmatic agents and therapeutic agents for chronic obstructive pulmonary disease (COPD).
Up to now, it has been known that a xanthine derivative theophylline, a catechol derivative rolipram, and the like, are inhibitors of PDE IV. Theophylline inhibits PDE in various tissues due to its non-selectivity for individual isozymes, thereby exerting not only a bronchodilator activity to be targeted but also extra actions on heart, CNS, etc. Although rolipram is observed to be selective for PDE IV, it is easily transferred into the CNS due to its property of being absorbed. Therefore, rolipram has a drawback that it has adverse central side-effects effects such as an emetic action.
Over the past decade, many pharmaceutical companies have focused on the inhibition of PDE IV for the treatment of asthma. The biological studies on the PDE IV isozyme and the structure-activity relationship of said inhibitors have recently been reviewed in the literature. In such processes, it has been pointed out that in general the therapeutic utility of selective PDE IV inhibitors, such as the prototypical agent rolipram, have been hampered by nausea and emesis limiting their therapeutic potential (J. Med. Chem., 41: 2268 to 2277 (1998)).
Under these circumstances, in order to find out pharmaceutical drugs having an excellent anti-asthmatic efficacy via minimizing undesirable side-effects in tissues and organs other than bronchial smooth muscles and inflammatory cells, various PDE IV inhibitors have been screened and examined.
For instance, with an aim at inhibitors with improved selectivity for PDE IV, various compounds including diazepinoindoles (JP, A, 10-507447 (1998)), tri-substituted phenyl derivatives (JP, A, 10-504530 (1998), JP, A, 10-503174 (1998), JP, A, 10-503173 (1998), etc.), naphthalene derivatives (JP, A, 10-226647 (1998)), etc., have been proposed.
Besides these, for the purpose of developing not only anti-asthmatics but also pharmaceutical agents for preventing and treating a wide range for diseases, PDE IV-inhibitory compounds having a naphthyridine ring have been proposed in JP, A, 7-10875 (1995); WO 96/6843, A1; JP, A, 11-106385 (1999); etc.
Such compound groups are, however, unsatisfactory in view of solving the aforementioned problems. There is still a demand for anti-asthmatics which exert more selective PDE IV-inhibiting actions and have advantageous properties from aspects regarding both of efficacy and safety.

Abstract: wherein A is methylene, lower alkylmethylene, carbonyl, etc., Y is a 5- or 6-membered heteroaryl group containing one or two heteroatoms selected from nitrogen, sulfur and oxygen, Z is i) a fused ring in which any of 5- or 6-membered heteroaryl groups is fused to a benzene ring, or ii) a phenyl group which may be unsubstituted or optionally substituted with one or more members selected from the group consisting of nitro, amino, an amino nitrogen-containing group, etc., provided that when A is methylene, Y is a 5- or 6-membered heteroaryl group selected from the group consisting of pyrrolyl, pyridyl, etc., and Z is a phenyl group which may be unsubstituted or substituted, the substituent on said phenyl group is amino, or an amino nitrogen-containing group; or a pharmaceutically acceptable salt thereof, possesses excellent PDE IV inhibition and is useful as a pharmaceutical drug, preferably an anti-asthmatic, etc.


The present invention relates to a process for making single or multiple planar array five layer membrane electrode assemblies utilizing array assemblies, as well as the array assemblies themselves, comprising proton exchange membrane (PEM), catalyst coated membranes (CCM) and gas diffusion layers (GDL), as well as gas diffusion electrodes (GDE) for use in fuel cells, wherein the process is practical, efficient and scalable.

Electrochemical cells generally include an anode and a cathode separated by an electrolyte. A well-known use of electrochemical cells is in a fuel cell (a cell that converts fuel and oxidants to electrical energy) that uses a proton exchange membrane (hereafter "PEM") as the electrolyte, for example direct methanol fuel cells. In such a cell, a reactant or reducing fluid such as methanol is supplied to the anode, and an oxidant such as oxygen is supplied to the cathode. The methanol electrochemically reacts at a surface of the anode to produce hydrogen ions and electrons. The electrons are conducted to an external load circuit and then returned to the cathode, while hydrogen ions transfer through the electrolyte to the cathode, where they react with the oxidant and electrons to produce water and release thermal energy.
Generally, within the fuel cell, the structure consisting of the PEM typically having its surfaces coated with a catalyst/carbon/binder layer and sandwiched between two microporous conductive layers (which function as the gas diffusion layers and current collectors) is known as the membrane electrode assembly (MEA).
Generally within the art, the process of making an MEA is well established, such that individual MEA's are produced manually or by automated processes. In the manual processes, each gas diffusion electrode and/or gas diffusion layer is individually applied for each element of the array. The disadvantage of such processes include, inter alia, a great degree of difficulty in aligning the elements by hand, which makes the process very time consuming and very expensive to implement. Furthermore, technologies developed to make conventional non-array MEA's cannot be readily extended to produce arrays due to the small dimensions, accurate alignment requirements and the electrical isolation between the array elements.

Process for making planar framed membrane electrode assembly arrays, and fuel cells containing the same


A manufacturing method for imprinting stamper is disclosed. The manufacturing method includes forming a plurality of concave patterns on an insulation layer, forming a stamper by filling copper in the concave patterns, separating the stamper from the insulation layer, providing roughness on the surface of the stamper, can separate the stamper from the insulation layer, can prevent the deformation of the stamper and can manufacture pluralities of stampers repeatedly.

1. Technical Field
The present invention relates to manufacturing method for imprinting stamper.
2. Description of the Related Art
Among the fabricating method of the printed circuit board, the imprinting method uses a stamper having convex pattern protruded on the surface of it corresponding to the circuit pattern. The stamper is imprinted on to the insulation board, so that concave pattern is formed corresponding to the circuit pattern. And by filling conductive material in the concave pattern, a board having circuit pattern is formed.
The conventional imprinting stamper is manufactured from nickel stamper formed by nickel plating on the silicon master having a plural grooves, the nickel stamper is separated from the silicon master. And DLC (Diamond Like Carbon) coating, C4F8 coating or SAM (Self-Assembled Monolayer) coating is conducted on the silicon master for easy separation from the silicon master.
As described above, the conventional stamper takes coating process for easy separation from the silicon master. Therefore, the manufacturing process takes much time and the manufacturing cost is increased. In addition, the separation between the stamper and the silicon master is not smooth, so that faulty of the stamper is occurred. And the separation is conducted repeatedly, the faulty is occurred more frequently.

Manufacturing method for imprinting stamper


This variable resistance element is provided with a variable resistance film, a first electrode, which is disposed in contact with one surface of the variable resistance film, and a second electrode, which is disposed in contact with the other surface of the variable resistance film. The first and the second electrodes have corner portions, respectively, and the distance between the corner portions of the first and the second electrodes is set equal to the shortest distance between the first and the second electrodes. Furthermore, the variable resistance element has a third electrode, which is disposed on the one surface of the variable resistance film.

With respect to a semiconductor device (especially, a silicon device), integration and power reduction of a device have been advanced owing to miniaturization (scaling law; Moore's law), and progress in integration and power reduction at a pace of 4-fold per 3 years has been made. However, the gate length of a MOSFET (Metal Oxide Semiconductor Field Effect Transistor) has recently reached 20 nm or less bringing substantial cost increase of a lithography process (device price, and mask set price), and a physical limit of a device dimension (operating limit, or variation limit), and improvement of the device performance by an approach different from the past one depending on the scaling law has come to be sought-after.
A programmable logic device which is reprogrammable called as FPGA (Field Programmable Gate Array), which may be positioned in an intermediate category between a gate array and a standard cell, has been recently developed. With a FPGA, customers themselves can conduct an arbitrary circuit configuration after production of a chip. A FPGA has variable resistance elements, so that customers themselves can establish at their arbitrary electrical connections of wiring. By use of a semiconductor device mounting such a FPGA, the degree of freedom of a circuit can be improved. Examples of a variable resistance element include a ReRAM (Resistance Random Access Memory) using a transition metal oxide, and a solid electrolyte switch or an atomic switch using an ion conductor.
Patent Literature 1 and Non Patent Literature 1 disclose a constitution, an operation, and a crossbar switch in the case of a 2-terminal type switching element (variable resistance element), which regulates the conduction state between two electrodes placed sandwiching an ion conductor (a solid in which an ion can move freely by application of an electric field, or otherwise).
Non Patent Literature 1 discloses a switching element utilizing metal ion movement in an ion conductor and an electrochemical reaction. A switching element disclosed in Non Patent Literature 1 is configured with an ion conductive layer, and a first electrode and a second electrode placed such that the two face each other sandwiching the ion conductive layer. Among these, the first electrode functions as a supplier of a metal ion to the ion conductive layer. The second electrode does not supply a metal ion to the ion conductive layer.
The operation of the switching element will be described briefly. When the second electrode is grounded and a positive voltage is applied to the first electrode, a metal of the first electrode dissolves as a metal ion into the ion conductive layer. Then, the metal ion in the ion conductive layer deposits as a metal in the ion conductive layer and the deposited metal forms a metal-bridge (also called as filament, or conductive path), which connects the first electrode with the second electrode. Due to the electrical connection of the first electrode and the second electrode with the metal-bridge, the switch is put into an ON-state. Meanwhile, in the ON-state, if the first electrode is grounded and a positive voltage is applied to the second electrode, a part of the metal-bridge breaks. As the result, the electrical connection between the first electrode and the second electrode is broken, and the switch is put into an OFF-state. In this regard, at a stage prior to complete breakage of an electrical connection, electrical properties start changing such that the resistance between the first electrode and the second electrode increases, the interelectrode capacitance changes, or the like, and finally the electrical connection breaks. Further, in order to change the OFF-state to an ON-state, the second electrode is grounded again, and a positive voltage is applied to the first electrode.
The switching element is characterized in that the size is smaller than a semiconductor switch (MOSFET, etc.), and the ON-resistance (resistance in an ON-state) is low. Therefore, the switching element is considered to have promise for application to a programmable logic device. Since the conduction state (ON or OFF) of the switching element can be maintained as original without applying a voltage, an application as a nonvolatile memory element is also conceivable. For example, a memory cell containing a selective element such as a transistor and a switching element is used as a basic unit, and a plurality of the memory cells are aligned in each of a longitudinal direction and a cross direction. By the alignment, an optional memory cell can be selected among a plurality of the memory cells by means of a word line and a bit line. Thus, a nonvolatile memory can be realized, in which the stored information of either of "1" or "0" can be read from the state of ON or OFF of the switching element by sensing the conduction state of the switching element of the selected memory cell.

Variable resistance element, semiconductor device having variable resistance element, semiconductor device manufacturing method, and programming method using variable resistance element


The invention relates to diagnostic methods for assessing the need of a subject for treatment with an anti-oxidant, or alternatively, for determining the utilization efficiency and ultimate effectiveness of anti-oxidant therapy in subjects having been treated with antioxidants. More specifically, the methods of the present invention are particularly useful in prophylactic assessment of individuals at risk for developing diseases or conditions in which oxidative stress plays a role, such that an appropriate therapeutic regimen can be prescribed for that individual, thus leading to alternative therapies and/or life style changes. The invention further relates to methods for assessing the need for, the utilization efficiency and the effectiveness of therapy in subjects having received therapy with specific antioxidant and immune enhancing formulations. Kits are also provided for measuring the levels of markers of oxidative stress and immune cell numbers.

It is generally recognized that many disease processes are attributed to the presence of elevated levels of free radicals and reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as superoxide, hydrogen peroxide, singlet oxygen, peroxynitrite, hydroxyl radicals, hypochlorous acid (and other hypohalous acids) and nitric oxide.
In the eye, cataract, macular degeneration and degenerative retinal damage are attributed to ROS. Among other organs and their ROS-related diseases include: lung cancer induced by tobacco combustion products and asbestos; accelerated aging and its manifestations, including skin damage and scleroderma; atherosclerosis; ischemia and reperfusion injury, diseases of the nervous system such as Parkinson disease, Alzheimer disease, muscular dystrophy, multiple sclerosis; lung diseases including emphysema and bronchopulmonary dysphasia; iron overload diseases such as hemochromatosis and thalassemia; pancreatitis; diabetes; renal diseases including autoimmune nephrotic syndrome and heavy metal-induced nephrotoxicity; and radiation injuries. Diseases of aging and chronic emotional stress also appear to be associated with a drop in glutathione levels, which allows ROS to remain active.
Certain anti-neoplastic drugs such as adriamycin and bleomycin induce severe oxidative damage, especially to the heart, limiting the patient's exposure to the drug. Redox-active metals such as iron induce oxidative damage to tissues; industrial chemicals and ethanol, by exposure and consumption, induce an array of oxidative damage-related injuries, such as cardiomyopathy and liver damage. Airborne industrial and petrochemical-based pollutants, such as ozone, nitric oxide, radioactive particulates, and halogenated hydrocarbons, induce oxidative damage to the lungs, gastrointestinal tract, and other organs. Radiation poisoning from industrial sources, including leaks from nuclear reactors and exposure to nuclear weapons, are other sources of radiation and radical damage. Other routes of exposure may occur from living or working in proximity to sources of electromagnetic radiation, such as electric power plants and high-voltage power lines, x-ray machines, particle accelerators, radar antennas, radio antennas, and the like, as well as using electronic products and gadgets which emit electromagnetic radiation such as cellular telephones, and television and computer monitors.
Mammalian cells have numerous mechanisms to eliminate these damaging free radicals and reactive species. One such mechanism includes the glutathione system, which plays a major role in direct, destruction of reactive oxygen compounds.
Perhaps one of the most important contributions of glutathione to mammalian health is its participation in the proper functioning of the immune system to respond to infection or other types of trauma. It is known that weakening of the immune system caused by infection or other traumas occurs concurrently with depletion of glutathione in body tissues. It is known, also, that such weakening can be reversed by replenishing the body's level of glutathione by intracellular synthesis. It is believed that glutathione accomplishes its salutary effects by protecting immune cells against the ravages of oxidizing agents and free radicals.
Until recently, the lack of specific and dependable methods for evaluating oxidant stress in vivo made it very difficult to establish a cause and effect relationship between free radical-generating agents or conditions and disease pathology. Furthermore, the various treatment strategies with anti-oxidants have been difficult to monitor due to the lack of techniques sufficiently sensitive to reliably provide an index of oxidative damage in vivo.
For example, there is currently substantial evidence that oxidation of LDL occurs in vivo, and results of animal studies suggest that this may lead to the formation and build up of atherosclerotic plaques. Although epidemiological data support a role for antioxidants in the prevention of clinical events, intervention trials thus far have given mixed results (Steinberg D, Witztum J L. Lipoproteins, lipoprotein oxidation, and atherogenesis. In Chien K R, ed. Molecular Basis of Cardiovascular Disease. Philadelphia, Pa.: W.B. Saunders Co., 1998:458-475). This may be due, in part, to the fact that until now techniques to adequately provide an index of in vivo lipid peroxidation have not been available, which could be used to design and monitor effective antioxidant intervention trials to adequately test the oxidation hypothesis.
Furthermore, there are no set measures to identify high-risk groups that would theoretically benefit most from antioxidant therapies or interventions. Additionally, there are no reliable means to measure or determine the effectiveness of such interventions in vivo. In the absence of such methodology, current (and future) clinical trials testing natural (or synthetic) antioxidants, which utilize clinical endpoints, may give incorrect conclusions regarding the role of antioxidants in specific disease states. This is a possibility because of the inclusion of populations that would not be expected to benefit from antioxidant supplementation, and/or because the dose or agent yielded insufficient antioxidant protection.
It is with respect to the development of more sensitive and accurate assays for assessing the need for intervention with anti-oxidant therapy and for monitoring the effectiveness and utilization efficiency of novel anti-oxidants that the current invention is directed.

Methods of assessing the need for and the effectiveness of therapy with antioxidants


A parallel kinematic machine has a parallel kinematic mechanism including an end effecter and a parallel link mechanism. A numerical control device controls a position and orientation of the end effecter based on kinematics of the parallel kinematic mechanism. A posture setter sets an adjustment tool on the end effecter in a known posture in a reference coordinate system defined outside the parallel kinematic mechanism based on a measurement method. A data acquirer acquires data in accordance with a measurement method selecting code for designating the measurement method used by the posture setter in setting the adjustment tool in the known posture, and defines a correlation between kinematic parameters for the parallel kinematic mechanism and the reference coordinate system. A calculator calculates the kinematic parameters based on the acquired data by using a relational expression describing forward kinematics of the parallel kinematic mechanism.

1. Field of the Invention
The present invention relates to a parallel kinematic machine, and a calibration technology of identifying kinematic parameters in the parallel kinematic machine.
2. Description of the Related Art
A parallel kinematic mechanism which is provided with a base and an end effecter connected parallel to each other by plural driver shafts has higher rigidity and accuracy in posturing than a mechanism which is provided with a cantilever. The Stewart platform is a typical example of the parallel kinematic mechanisms. The Stewart platform has straight driver shafts or struts which are expanded or contracted to control the posture including a position and an orientation of an end effecter. For the highly accurate posturing, however, it is necessary to calculate accurate kinematic parameters such as the length of a strut, coordinates of a joint connecting a strut and a base, and a joint connecting a strut and the end effecter. This operation is known as parallel kinematic mechanism calibration, which is studied by various research institutes of the industry, the government, and the academy.
Generally, such calibration requires solution of multiple simultaneous equations whose number is the same as those of the parameters. To this end, it is necessary to place the end effecter in a determined position and a determined orientation, and determine all or a part of position coordinates (X, Y, Z) and orientation coordinates (A, B, C) in the determined state.
Japanese Unexamined Patent Publication No. 2002-91522 discloses a technology whereby the end effecter is moved in a circle in a given posture, and a radial error in the locus of the circular movement is measured by a range meter of a double ball bar (DBB) system, and kinematic parameters are then calculated based on thus-obtained measurement values in order to determine position coordinates and orientation coordinates. Also, Japanese Unexamined Patent Publication No. 2003-200367 discloses a technology that multiple simultaneous equations are separated into eleven or more equations showing relationships between the end effecter position and the kinematic parameters, and one equation showing a relationship between the end effecter orientation and the kinematic parameters, and these equations are solved to calculate kinematic parameters to execute calibration.
Both of the prior art documents, however, employ small scale kinematics to identify kinematic parameters. It is difficult to analytically solve kinematics problems, particularly, forward kinematics problems. The small scale kinematics, which is also called as differential kinematics or displacement kinematics, is one of the academic fields studying an arithmetic approach of solving these problems. In the small scale kinematics, nonlinear equations describing the forward kinematics are differentiated by the respective kinematic parameters to calculate linear expressions that satisfy relations between errors i.e. small scale displacements of kinematic parameters, and errors i.e. small scale displacements of position coordinates so as to analytically solve the linear expressions. In other words, the small scale kinematics deals with a mathematical expression between an error of a certain numerical value, and an error of another numerical value.
However, it can be seen that the former prior art document refers to the fact that at least one kinematic parameter cannot be acquired. Also, the technology of the latter prior art document requires measurement after posturing, and in particular requires at least one measurement in the posture that involves difficult measurement. Also, the small scale kinematics employed in both of the prior art documents has a difficulty in suppressing numerical errors concerning the relational expressions on small scale displacement. Accordingly, in the case where gravity deformation or a like factor is inevitably involved particularly in use of a large-sized machine tool, convergence in numerically identifying kinematic parameters is poor, which obstructs accurate identification of the kinematic parameters.

Parallel kinematic machine, calibration method of parallel kinematic machine, and calibration program product


A flexible, software configurable DDR read data path structure provides independently programmable sample stage and sample cycle capability. It also provides the capability to independently delay a read sample stage clock to support a wider range of data and data strobe (DQS) arrival times over a broad frequency range and subsequent sample stages to compensate for any resultant read cycle compression within any source synchronous interface. An SDRAM timing register is used to control read data path structure by changing bits in the register.

1. Field of the Invention
The invention relates generally to a read data path structure in a double data rate (DDR) source-synchronous interface and, more particularly, to a software configurable read data path structure in a double data rate (DDR) synchronous dynamic random access memory (SDRAM) interface.
2. Description of the Related Art
Double Data Rate (DDR) synchronous dynamic random access memory (SDRAM) provides source synchronous read data in that a read data strobe (DQS) is propagated with read data. DDR read data is initially sampled in the DDR DQS clock domain and must be synchronized to the DDR memory controller internal clock domain for transfer. The DDR read data and DQS are propagated from the DDR memory to the DDR memory controller and derived from the DDR memory clock input, which is typically generated by the DDR memory controller and re-buffered and distributed either on-chip or off-chip. Thus, there is a potential for a widely varying range of read data and read DQS arrival times, across different implementations, relative to the memory controller""s fixed internal clock domain(s).
Therefore, what is needed is a flexible DDR read data path structure to support a wide range of read data and DQS arrival times, adaptable to different implementations.
The present invention provides a read data path structure in a double data rate (DDR) source-synchronous interface such as a DDR synchronous random access memory (SDRAM) interface. The read data path structure comprises a first stage comprising a first flip-flop (FF) and a transparent latch (XL). The read data path structure also comprises a second stage comprising a second FF and a third FF. The input of the second FF is connected to the output of the first FF, whereas the input of the third FF is connected to the output of the XL.
The read data path structure further comprises a third stage comprising a fourth FF and a fifth FF. The input of the fourth FF is connected to the output of the second FF, whereas the input of the fifth FF is connected to the output of the third FF.
Additionally, the read data path structure comprises a first multiplexer having at least one input connected to the output of the first FF, at least one input connected to the output of the second FF, and at least one input connected to the output of the fourth FF. The first multiplexer is controlled by at least two bits of an SDRAM timing register.
The read data path structure further comprises a second multiplexer having at least one input connected to the output of the XL, at least one input connected to the output of the third FF, and at least one input connected to the output of the fifth FF. The second multiplexer is controlled by the at least two bits of the SDRAM timing register.

Method and apparatus for sampling double data rate memory read data

International Business Machines Corporation


Described herein are compounds, pharmaceutical compositions and methods for treating pathogenic cell populations. The compounds described herein include conjugates of tubulysins and vitamin receptor binding ligands. The conjugates also include a releasable bivalent linker.

The mammalian immune system provides a means for the recognition and elimination of tumor cells, other pathogenic cells, and invading foreign pathogens. While the immune system normally provides a strong line of defense, there are many instances where cancer cells, other pathogenic cells, or infectious agents evade a host immune response and proliferate or persist with concomitant host pathogenicity. Chemotherapeutic agents and radiation therapies have been developed to eliminate, for example, replicating neoplasms. However, many of the currently available chemotherapeutic agents and radiation therapy regimens have adverse side effects because they work not only to destroy pathogenic cells, but they also affect normal host cells, such as cells of the hematopoietic system. The adverse side effects of these anticancer drugs highlight the need for the development of new therapies selective for pathogenic cell populations and with reduced host toxicity.
Researchers have developed therapeutic protocols for destroying pathogenic cells by targeting cytotoxic compounds to such cells. Many of these protocols utilize toxins conjugated to antibodies that bind to antigens unique to or overexpressed by the pathogenic cells in an attempt to minimize delivery of the toxin to normal cells. Using this approach, certain immunotoxins have been developed consisting of antibodies directed to specific antigens on pathogenic cells, the antibodies being linked to toxins such as ricin, Pseudomonas exotoxin, Diptheria toxin, and tumor necrosis factor. These immunotoxins target pathogenic cells, such as tumor cells, bearing the specific antigens recognized by the antibody (Olsnes, S., Immunol. Today, 10, pp. 291-295, 1989; Melby, E. L., Cancer Res., 53(8), pp. 1755-1760, 1993; Better, M. D., PCT Publication Number WO 91/07418, published May 30, 1991).
Another approach for targeting populations of pathogenic cells, such as cancer cells or foreign pathogens, in a host is to enhance the host immune response against the pathogenic cells to avoid the need for administration of compounds that may also exhibit independent host toxicity. One reported strategy for immunotherapy is to bind antibodies, for example, genetically engineered multimeric antibodies, to the surface of tumor cells to display the constant region of the antibodies on the cell surface and thereby induce tumor cell killing by various immune-system mediated processes (De Vita, V. T., Biologic Therapy of Cancer, 2d ed. Philadelphia, Lippincott, 1995; Soulillou, J. P., U.S. Pat. No. 5,672,486). However, these approaches have been complicated by the difficulties in defining tumor-specific antigens.
Tubulysins are a group of potent inhibitors of tubulin polymerization. Tubulysins are useful in treating diseases and disease states that include pathogenic cell populations, such as cancer. Two particular species of mycobacteria synthesize tubulysins in high titer during fermentation. One species, Archangium gephyra, produces as the main component factors tubulysins A, B, C, G, and I, each of which is characterized by a including the tubutyrosine (Tut, an analog of tyrosine) residue. In contrast, another species, Angiococcus disciformis, produces as the main component factors tubulysins D, E, F, and H, each of which is characterized by a including the tubuphenylalanine (Tup, an analog of phenylalanine) residue. Such bacterial fermentations are convenient sources of tubulysins.

Binding ligand linked drug delivery conjugates of tubulysins


Disclosed is a shaft inserted member into which a shaft is inserted in a relatively movable manner, and a locking mechanism provided in the shaft inserted member. The tip portion of the shaft includes a locking step portion formed by providing an annular groove or a ring-shaped projection portion. The locking mechanism includes at least two locking pieces arranged around the shaft at an equal interval. The shaft is stopped from slipping off by a tip portion of each of the tip locking portions abutting on the locking step portion. The locking piece can receive the force in a pulling direction in a length direction of the locking piece, whereby a load can be reduced. That is, sufficient strength can be maintained.

In JP 58-27453 Y, there is disclosed a structure (hereinafter referred to as a first conventional structure) in which a shaft, which is bifurcated and can be tapered by narrowing down a space therein, is elastically returned after passing through a hole in a body and is stopped from slipping off by a slip-off stopping lock provided at a tip portion thereof.
In JP 3796051 B, there is described a structure (hereinafter referred to as a second conventional structure) in which a shaft is provided with an arrowhead shaped engaging projection part at a tip thereof, and by closing a slit formed inside the engaging projection part, the shaft is configured to pass through an axis insertion hole in an elastically returnable manner.
Furthermore, in JP 4548911 B, there is introduced a structure (hereinafter referred to as a third conventional structure) in which a mushroom-shaped motor shaft has an abutting end part and a small-diameter shaft, and the abutting end part thereof is supported by a thrust washer. At this time, inside a small-diameter groove part surrounding the small-diameter shaft in a circumferential direction, there is a clip facing to stop the abutting end part from slipping off.
This clip includes four extension parts projecting out from a tubular base part toward a center in a transverse direction (a shaft-crossing direction). Each of the extension parts is elastically deformable, and by a tip of each of the extension parts, a space having a smaller diameter than that of the abutting end part is partitioned at the center.
Each of the extension parts, being pushed against the abutting end part, is deformed to allow for passage of the abutting end part, and is elastically returned after the passage so as to be engaged when the abutting end part is pulled up.
In other words, it is configured not to be engaged when it is supported by the thrust washer.
There are problems with the conventional structures, which are discussed as follows.
Since the shaft is bifurcated (and there is a wide space between the bifurcated parts) in the first conventional structure, there is a fear that overall shaft strength may be insufficient. It has a disadvantage in that the shaft may easily slip off in a case where one of the bifurcated parts of the shaft is damaged
The engaging projection part according to the second conventional structure is divided into two parts by the existence of a slit. Therefore, similar to the problem in the first conventional structure, there is a problem of insufficient strength and in that it may easily slip off.
The clip according to the third conventional structure is not related to a rotation of the shaft in the first place. The thrust washer is playing that role.
Therefore, there is a problem in that the number of components is increased.
Furthermore, it is necessary for the clip projecting in the transverse direction to receive a force from the shaft in a direction of pulling out with a thickness direction thereof.
There remains a need for improved shaft slip-off stopping structures and switches having such structures.

Shaft slip-off stopping structure and switch having the same