The invention relates to the methods of manufacturing five-carbon sugars and sugar alcohols as well as other compounds derived from pentose-phosphate pathway from readily available substrates such a hexoses using metabolically engineered microbial hosts.

1. Field of the Invention
The present invention relates to the methods of manufacturing five-carbon aldo- and keto-sugars and sugar alcohols by fermentation in recombinant hosts. Especially, the invention is directed to recombinant hosts that have been engineered to enhance the production of the pentose phosphate pathway intermediates, or the production of one or more of xylitol, D-arabitol, D-arabinose, D-lyxose, ribitol, D-ribose, D-ribulose, D-xylose, and/or D-xylulose, and to methods of manufacturing the same using such hosts.
2. Background of the Invention
Five-carbon sugars and five-carbon sugar alcohols have numerous uses as sweeteners. For example, xylitol is widely used as a non-cariogenic alternative sweetener. D-ribulose and D-xylulose, as well as sugar alcohols other than xylitol, also have potential as sweeteners in the form of free monosaccharides or as components of oligosaccharides. In that regard, glucosyl-xylulose, a close structural analog of sucrose, can be easily synthesized from sucrose and D-xylulose (Kitaoka, K., et al., Oyo Toshitsu Kagaku 41(2):165–72 (1994)).
Five-carbon sugars and five-carbon sugar alcohols are also useful for the organic and enzymatic synthesis of pharmaceuticals, functional food ingredients, etc. D-arabinose and D-lyxose are both structurally very close to D-ribose (the natural sugar constituent of nucleosides/nucleotides) and are components of many drugs and drug formulations.
Five carbon sugars and sugar alcohols are useful as carbon sources for the growth of microorganisms such as bacteria and fungi. Additionally, they are useful as biochemical reagents in laboratory assays of the enzymes that use such five carbon sugars and sugar alcohols as substrates, and as standards in the chromatographic analysis of sugars and sugar alcohols.
A sugar is said to be "naturally produced" if it is capable of being enzymatically synthesized by a non-recombinant microbial or animal host. The precursors of naturally produced five-carbon sugars and their corresponding alcohols are often the pentose phosphate pathway (PPP) sugar intermediates. These intermediates, in their 5-phosphorylated or unphosphorylated form, are valuable in and of themselves as chemical precursors of other various useful compounds. These include, for example, nucleotides and riboflavin (derived from the PPP metabolite D-ribose 5-phosphate), and folate, ubiquinone as well as various aromatic amino acids (derived from the PPP metabolite D-erythrose 4-phosphate). These amino acids are in turn precursors for flavonoids and alkaloids. Consequently, methods and hosts that increase the conversion of a raw material such as a hexose sugar into a desired PPP sugar intermediate such as ribose-5-P, ribulose-5-P or xylulose-5-P, and thus also enhance production of a desired downstream metabolite, would be of significant economical value. These compounds can be extracted or isolated or used in vivo or in vitro as is or as precursors in further metabolic/or chemical reactions to manufacture useful products.
U.S. Pat. No. 5,798,237 (Picataggio, S. K. et al.) reports a recombinant Lactobacillus that has been genetically engineered with xylose isomerase and xylulokinase genes to impart the ability to ferment lignocellulosic biomass that contains xylose to lactic acid.
Jeffries et al. have reported the genetic engineering of xylose fermentation in yeast in order to provide for the efficient production of ethanol from xylose. Jeffries, T. W. et al., "Genetic Engineering of Xylose Fermentation in Yeasts," See: calvin.biotech.wisc.edu/jeffries/bioprocessing/xoferm/xoferm.html. Such yeast were identified by their ability to direct carbon flow from the five carbon sugar xylose into the two carbon endproducts alcohol, ethanol, most likely via a pathway that involved the PPP transketolase enzyme acting in a direction that promoted carbon flux away from PPP intermediate accumulation.
Aristidou, A. et al., WO 99/46363 reported that yeast in which the coupling of pyridine nucletide-linked dehydrogenase reactions had been improved by overexpression of NAD glutamate dehydrogenase or malic enzyme not only exhibited a more efficient production of ethanol from xylose but also had an enhanced production of xylitol from xylose.
However, little has been done with regard to modifying microorganisms in the opposite direction, to redirect carbon flow away from glycolysis or away from ethanol production and into the PPP, with accumulation of PPP intermediates and sugars or sugar alcohols derived therefrom. For example, U.S. Pat. No. 5,281,531 (Miyagawa, K. et al.) reports a method of producing D-ribose in a Bacillus host in which the gluconate operon (which encodes the proteins involved in gluconate uptake and metabolism) is partly or wholly modified so as to highly express the gluconate operon. Especially, the gntR gene is deleted or inactivated and the promoter is replaced with another.
D-ribose has been produced from glucose by fermentation with Bacillus subtilis (U.S. Pat. No. 3,607,648). Methods for the production of D-xylulose and D-ribulose by fermentation of glucose with some bacteria isolated from nature have also been described (Canadian patent 840981).
U.S. Pat. No. 3,970,522 (Sasajima, K.-I. et al.) report the production of D-ribose in a strain of Bacillus that has high 2-deoxyglucose oxidizing activity. In one strain, the Bacillus also lacks at least one of transketolase and D-ribulose phosphate 3-epimerase.
Onishi et al. have developed a multi-stage process for the production of xylitol wherein glucose is first fermented with an osmophilic yeast into D-arabitol. Using a different strain D-arabitol is then converted in a second fermentation into D-xylulose. Lastly, using a third strain and in a third fermentation, D-xylulose is reduced to xylitol by fermentation (Onishi, H. and Suzuki, T., Appl. Microbiol. 18:1031–1035 (1969)).
Harkki et al. have developed a one-stage fermentation process to convert glucose into xylitol and were the first to suggest directly modifying the PPP for the production of xylitol from glucose in a single host (U.S. Pat. No. 5,631,150).
Many of the above microbiological methods use strains of bacteria isolated from nature. Most teach no methods of further improving the native abilities the of microorganisms for the production of such sugars or sugar alcohols, or for broadening the spectrum of useful products produced by the fermentation. While the work of Harkki et al. (U.S. Pat. No. 5,631,150) describes some methods of metabolically engineering hosts and methods for the production of xylitol in such hosts, especially by over-expression of the genes of the oxidative branch of PPP, nevertheless, clearly, additional methods for enhancing the metabolic flux through the PPP would be beneficial for production of five carbon sugars as well as any PPP-derived product or product precursor.

Manufacture of five-carbon sugars and sugar alcohols


A toner loading system for use with reprographic machines which reduces powder clouding and minimizes toner spill during loading. A toner cartridge is mountable on a toner housing. The housing includes an opening sized to accept the cartridge. When in a raised position, the cartridge is on top of the housing. When in a lowered position, the cartridge is positioned within the housing through the opening. A removable seal on the bottom of the cartridge includes a long pull tab which can be grasped from above the housing, when the cartridge is lowered, to allow removal of the seal and allow flow of toner from the cartridge to the housing while the cartridge is extended substantially or completely within the housing, thus reducing powder clouding, providing more even toner flow, and reducing mess or spillage. The reduced powder clouding is due to a substantially reduced height from which the toner has to fall when being loaded into the housing.

1. Field of the Invention
The present invention relates to a toner loading system for use with reprographic machines which reduces powder clouding and minimizes toner spill during loading.
2. Description of Related Art
There are known various toner cartridges which can replenish toner to a toner housing of a machine such as a reprographic device. There is a need for such cartridges to be easy to use such that a user can easily replace toner in the toner housing without spilling on the user, on outer surfaces of the toner housing or on other surfaces within the reprographic device. Known cartridges and toner replenishing methods utilize a mechanism which locks or otherwise attaches a toner cartridge onto a top surface of the toner housing. Many have mechanisms to open or close apertures in the top of the toner housing such that toner can enter the housing. Some known cartridges include a removable seal on a lower side of the cartridge. Upon attachment of the cartridge on top of the housing, the seal can be removed and the toner flows down into the aperture of the housing.
However, there are problems with current apparatus and methods. One problem is that toner dust clouding occurs upon releasing of toner from the cartridge. Once the toner cartridge is emptied, there are many instances when upon removal of the cartridge, toner particles which have clouded and become dispersed in the air within the toner housing can escape the aperture of the housing and cause unwanted mess. There is a need for a toner cartridge and a dispensing method which allow for simple replenishment of toner while substantially reducing toner dust clouding.


An account management system has been developed that enables customer or client-related information to be stored, viewed and manipulated in a manner that reflects the relationship among different customers. The account management system includes an account data structure that defines accounts and relates customers to accounts so that the accounts include a group of related customers. In addition, a method of managing an underwriting account for an insurance policy has been developed. In particular, a method comprises the steps of establishing a plurality of participants; assigning each participant of the plurality of participants to an account; establishing business rules at an account level; and providing an underwriting decision for an account based upon the business rules.

Conventional systems for account management generally lack a holistic approach. Such conventional systems have poor customer data integrity and fail to provide adequate customer insight. They may also provide primitive workflows that are primarily manual, and may be lacking in standardization and codified best practices. Often, information is resident in multiple, isolated systems and paper files, and lacks consistent organization. Information formats may be primarily document-based and, therefore, provide little opportunity for digitization. Customer service may be infrequent and may enable poorly managed customer interactions, limited self-service capabilities, and undifferentiated customer and producer servicing approaches. Finally, these systems lack real-time measurement mechanisms for profit and service performance analysis, but instead include highly manual producer management processes.
In the field of insurance underwriting, the systems that support and enable the related activities have a particularly acute problem with regard to account management. In addition to the issues previously discussed, insurance underwriting has several other issues that result from the lack of a holistic approach to account management. For example, insurance underwriting includes tasks, such as the ordering of credit reports or loss control surveys that are reactive in the application/underwriting review process. Additionally, working interfaces with other systems, such as agency management systems, often do not exist. Further, viable data feeds into policy rating/issuance systems are often lacking. As a further complication, underwriting appetites also are not clearly articulated or consistently executed because conventional systems provide limited executional capabilities supporting account and activity management. In addition, they also lack rigorous segmentation methodologies to develop unique approaches to product and underwriting rules.
Accordingly, there is a need for an improved system and data structure for account management.

Account level participation for underwriting components


In one aspect the invention discloses a matrix comprising a discrete population of random oligopeptides of the same length, the length being selected from about 4 to about 12 L-amino acid residues, the population comprising at least 10% of all amino acid sequences of the selected length; and a heterogeneous population of antibodies comprising antibodies capable of binding to substantially every member of the oligopeptide population.

The clonal selection theory of Burnet, which explains the general basis of antibody production, has gained virtually complete acceptance. Burnet, M. (1961) Sci. Am. 204:58; Jerne, N. K. (1976) Harvey Lecture 70:93. The theory is based on several premises: (1) as individual cells, i.e., lymphocytes, in the immune system differentiate, each becomes capable of producing only one species of antibody molecule; (2) the entire spectrum of possible antibody-producing cells is present within the lymphoid tissues prior to stimulation by any antigen; that is, the step in which each lymphocyte becomes specified to produce only one type of antibody molecule occurs in the absence of a potential antigen for that antibody; and (3) lymphocytes capable of producing an antibody specific to a particular antigen are induced, by the presence of that antigen, to proliferate and to produce large quantities of the antibody. An enormous range of genetically unique lymphoid cells is present in the lymphoid organs, e.g., the spleen, of each mammal. The spleen can be considered a library of cells, each of which can manufacture a unique antibody, and the library is so large that for any particular antigen, at least one lymph cell exists within the library that is capable of recognizing the antigen and producing antibodies specific to the antigen.
Heretofore, the production of an antibody that will recognize an antigen of interest has required the antigenic stimulation of a laboratory animal. Typically, the antigen is injected into a laboratory animal, and, after a suitable incubation period, a second injection is given. The spleen cells of the animal are then harvested and fused to myeloma cells. When fused to a spleen cell, the myeloma cell confers to the spleen cell its ability to grow in culture. Surviving colonies of fused cells, i.e., hybridomas, are then screened to identify clones that produce antibodies that specifically recognize the antigen. This procedure must be repeated each time it is desired to produce an antibody to a particular antigen. For each antigen of interest, it is necessary to (1) antigenically stimulate an animal, (2) remove its spleen and hybridize the spleen cells with myeloma cells, and (3) dilute, culture, and screen clones for specific antibody production. Though antibodies that recognize the antigen are produced, this technique does not identify the epitope, i.e., the specific site on the antigen that an antibody recognizes; and one cannot direct the development of antibodies specific to a particular predetermined site or region of the antigen. Also, hybridoma techniques are not effective in the direct development of monoclonal antibodies that recognize haptens, i.e., molecules that contain constitute antibody recognition sites, but which do not elicit an antigenic reaction when injected without a carrier into a laboratory animal. Since antigenic stimulation and antibody production are potentially hazardous to the host, the use of human hosts has been precluded in the development of monoclonal antibodies.
The universe of antibody binding specificities may be open or closed. If the universe of antibody binding specificities is closed, then the following basic tenets apply:
a) one can design and prepare any given epitope and isolate any antibody (for example, a monoclonal antibody produced by a member of a random set of hybridomas) from a universe of antibodies without having first immunized an experimental animal with an antigen containing that epitope. A self-addressing sorting scheme can be used to screen to identify the proper paired correspondence between antibody and epitope; PA1 b) the universe of epitopes can be specified in at least a theoretical fashion, and in principle, can be synthesized; and PA1 c) one can independently isolate and identify an antibody-producing hybridoma with the same epitopic specificity as one previously isolated and identified. Such a repeated isolation occurs in a "second hit" experiment, and can be used to estimate the effective size of the universe of antibody specificities. Such an approach is similar in logic to defining a complementation group in genetics. PA1 a) one cannot isolate an antibody specific for an epitope without prior immunization with an antigen containing that epitope; PA1 b) the universe of epitopes cannot be specified or synthesized; and PA1 c) one should not be able to independently isolate more than one antibody with the same target specificity.
Even if the universe of epitopes is large, if it is closed, it can be defined by rules, algorithms or iterative analyses.
In the alternative, if the universe of antibody specificities is open, the following principles apply:
The binding domain of a monoclonal antibody specific to a malaria virus surface protein has been identified as being no larger than 40 amino acids long. Cochrane, A. H. et al. Proc. Natl. Acad. Sci. U.S.A. 79:5651 (1982), inserted a 340 base pair sequence from a Plasmodium knowlesi gene into the pBR322 vector. The engineered vector produced in E. coli a beta-lactamase fusion polypeptide that reacted with a monoclonal antibody specific for a P. knowlesi circumsporozooite (CS) protein. This finding indicated that the binding domain of the monoclonal antibody was limited to a region of the CS protein encoded by the inserted sequence, or approximately 110 amino acids. Lupski, J. R. et al., Science 220:1285 (1983), used the same system and, employing transposition mapping techniques, further localized the binding domain to a 40-amino acid region of the CS protein.
Green, N. et al., published PCT application 84/00687, produced antibodies by inoculating laboratory animals with synthetic peptides. Antibodies produced in response to peptides having a length of 8 to 40 amino acid residues and corresponding to sequences in an influenza virus protein were cross-reactive with the virus in vitro.
Dame, J. B. et al., Science 225:593 (1984), sequenced the CS gene of Plasmodium falciparum and discovered 41 tandem repeats of a tetrapeptide, with some minor variations. Using synthetic peptides of 4, 7, 11, and 15 amino acid residues of the predominant repeating amino acid sequence, Dame et al. then conducted competitive binding assays to determine what length of peptide would inhibit the binding of the CS protein with a monoclonal antibody specific to that protein. Dame et al. found that the synthetic 4 amino acid sequence did not significantly inhibit binding, but the 7, 11 and 15 amino acid sequences did inhibit binding. These results suggest that this monoclonal antibody to the CS protein recognizes a 5 to 7 amino acid sequence comprising the repeating tetrapeptide.
The known crystal structures of the Fab fragment and lysozyme show that there are two contact points on the lysozyme molecule for the antibody combining site, and each contact point spans over about five amino acids. Earlier work on antibody binding to carbohydrate antigens and glycosidase cleavage protection experiments show that 5-6 sugar residues are protected from glycosidase cleavage. Studies with antibody binding to haptens also suggests that antibody sites are small. Peptide competition experiments, also called epitope mapping experiments, show that oligopeptides 4 to 5 amino acids in length can specifically compete for antibody binding.
In addition, linear sequences which differ in only one amino acid, can compete for antibody binding with varying degrees of specificity (see, e.g., Geysen et al. (1986) in Synthetic Peptides as Antigens; Ciba Foundation Symposium 119, R. Porter and J. Wheelan, Eds. (New York, Wiley) pp. 130-149).
While five amino acids is a representative length of peptide sequence which can bind with differential specificity to an antibody, five amino acid residues is not necessarily the size of an immunogenic peptide. Generally, when an oligopeptide is the desired immunogen, it is first conjugated to a larger carrier molecule. The actual operational relationship between the immunizing entity and the binding entity can only be resolved when an in vitro immunization-dependent antibody synthesis system is developed.

Method and means for sorting and identifying biological information


A communication system (10) includes a central terminal (12) and a subscriber terminal (14) that communicate information through an air interface (16). A receiver (22) suitable for deployment in either the central terminal (12) or the subscriber terminal (14) includes a parallel correlator (120), a weighting module (140), and a summer (180) that provide acquisition, equalization, and tracking functions.

A wireless communication system includes a transmitter for encoding or modulating user data for transmission over an air interface to a receiver. In addition to the direct or line-of-sight transmission, the receiver may also detect multipath transmissions caused by reflections from terrain features and man-made objects. For effective communication, the demodulator in the receiver resolves the additive combination of these delayed and attenuated versions of the direct transmission. The degradation of the transmitted signal due to multipath effects may severely limit the performance of a wireless communication system. With increased bandwidth requirements in communications and development of new and more complex modulation techniques, such as quadrature amplitude modulation (QAM), the reduction or elimination of multipath interference becomes more important. Directional antennae placed on the transmitter, receiver, or both may geometrically reduce the number of potential multipath transmissions between the transmitter and the receiver. Also, traditional tapped delay lines or rakes may perform some level of channel equalization to accurately recover the transmitted signal. However, many of these techniques require excess signal to noise levels to resolve multipath interference, which reduces the total available information bandwidth in a wireless communication system.

Multipath equalization using taps derived from a parallel correlator


Systems and methods for evaluating online videos. One method includes receiving a URL; determining a URL type; detecting whether the URL includes one or more videos; determining at least one of a size of the video, a position of the video on a web page of the web page URL, whether the video is set to autoplay, and whether the video is set to mute; computing a score based on one or more of the size of the video, the position of the video on the web page of the web page URL, whether the video is set to autoplay, and whether the video is set to mute; obtaining at least two frames of at least part of the video, wherein each frame is obtained at one or more predetermined intervals during playback of the video; and classifying each detected video based on the at least two frames.

As people increasingly consume content online, i.e., over the Internet, the importance of evaluating and tracking the quality and quantity of that consumption has increased. For example, many Internet entities, such as publishers of online content and online advertisers are now creating and distributing online videos over the Internet. Videos are often either a segment of content requested by an Internet user, an Internet advertisement created by an advertiser (e.g., a video ad similar to a television commercial), or some combination of requested content and a video ad.
Traditionally, advertisers and ad networks had little knowledge of the factors that affect true viewability of an online video: autoplay, player size, and position on the page. This lack of knowledge resulted in 'invalid impressions' which themselves caused a great deal of lost value in video ad buys.
Accordingly, a need exists for systems and methods for evaluating online videos, such as digital videos distributed over the Internet. More specifically, a need exists for systems and methods for evaluating online videos distributed over the Internet, such as for improving advertising metrics.


One exemplary embodiment may include an engine breathing system including an exhaust driven auxiliary air pump to flow air directly into the exhaust side of the breathing system.

FIG. 1 is a schematic illustration of a product or system 10 including a modern breathing system used for a single stage turbocharger. Such a system may include a combustion engine 12 constructed and arranged to combust a fuel such as, but not limited to, gasoline or diesel fuel in the presence of oxygen. The system may further include a breathing system including an air intake side 14 and a combustion gas exhaust side 16. The air intake side 14 may include a manifold connected to the combustion engine to feed air into the cylinders of the combustion engine 12. A primary air intake conduit 20 may be provided and connected at one end to the air intake manifold 18 (or made a part thereof) and may include an open end 24 for drawing air there through. An air filter 26 may be located at or near the open end 24 of the air intake conduit 20.
The combustion gas exhaust side 16 may include an exhaust manifold 28 connected to the combustion engine 12 to exhaust combustion gases therefrom. The exhaust side 16 may further include a primary exhaust conduit 30 having a first end 32 connected to the exhaust manifold 28 (or made a part thereof) and may have an open end 34 for discharging exhaust gas to the atmosphere.
Such a system 10 may further include a first exhaust gas recirculation (EGR) assembly 40 extending from the combustion gas exhaust side 16 to the air intake side 14. A first EGR valve 46 may be provided in fluid communication with the primary exhaust gas conduit 30 and constructed and arranged to flow exhaust gas from the exhaust side 16 to the air intake side 14 and into the combustion engine 12. The first EGR assembly 40 may further include a primary EGR line 42 having a first end 41 connected to the primary exhaust gas conduit 30 and a second end 43 connected to the air intake conduit 20. A cooler 44 may be provided in fluid communication with the primary EGR line 42 for cooling the exhaust gas flowing therethrough.
The system 10 may further include a turbocharger 48 having a turbine 50 in fluid communication with the primary exhaust gas conduit 30 and having a compressor 52 in fluid communication with the primary air intake conduit 20 to compress gases such as, but not limited to, air flowing there through. An air charge cooler 56 may be provided in the primary air intake conduit 20 downstream of the compressor 52. A throttle valve 58 may be provided in the primary air intake conduit 20 downstream out of compressor 52 and upstream of the connection point of the second end 43 of the primary EGR line 42 to the primary air intake conduit 20.
A number of the emission control components may be provided in a primary exhaust gas conduit line 30 typically downstream of the turbine 50. For example, a particulate filter 54 may be provided downstream of the turbine 50. Other emission control components such as, but not limited to, a catalytic converter 36 and a muffler 38 may also be provided downstream of the turbine 50. Further exhaust after treatment devices such as lean NOX traps may also be provided.
Optionally a second exhaust gas recirculation (EGR) assembly 70 may be provided extending from the combustion exhaust gas side 16 at a location downstream of the turbine 50 to the air intake side 14. The second EGR assembly 70 may include a second EGR line 71 having a first end 72 connected to the primary exhaust gas conduit 30 and a second end 74 connected to the air intake conduit 20. A cooler 78 may be provided in fluid communication with the second EGR line 71 for cooling exhaust gases flowing there through. A second EGR valve 76 may be provided and constructed and arranged to control the amount of exhaust gas flowing through the second EGR line 71. An exhaust throttle valve 120 may be provided in the primary exhaust conduit 30 downstream of the connection point of the first end of the second EGR line to the primary exhaust gas conduit 30. The exhaust gas throttle valve 120 may be utilized to control the amount of exhaust gas going into the second EGR line 71.
When such a system 10 includes a particulate filter 54, particulate matter such as, but not limited to soot, is collected in the particulate filter 54. If too much particulate matter is allowed to accumulate in the particulate filter 54, such may adversely impact operation of the system 10 or various components thereof or may adversely impact emissions. The particulate filter 54 may be regenerated to burn off the particulate matter allowing the particulate filter 54 to be used to more effectively collect more particulate matter without adversely impacting the operation of the system 10.
Referring now to FIG. 2, in a system 10 similar to that illustrated in FIG. 1, a second air intake line 122 may be provided and may have a first end 124 connected to the primary exhaust gas conduit 30 and a second open end 126 to draw air from the atmosphere. A blower 127 may be provided in the second air intake conduit 122 to force air into the primary exhaust gas conduit 30 at a location upstream of the particulate filter 54. A burner 128 may also be provided to heat the air flowing through the second air intake line 122 to facilitate regeneration of the particulate filter 54. Such blowers 127 are typically constructed and arranged to provide a pressure ratio of the absolute outlet pressure over the inlet pressure of less than or equal to 1.1.

Exhaust driven auxiliary air pump and products and methods of using the same


A system and method for fabricating an electro-optical hybrid module (100). The electro-optical hybrid module (100) may comprise an electro-optical component, an electronic component (110), a planar light wave circuit (PLC) embedded with at least an optical waveguide (120). The electro-optical component may transmit or receive energy through a micro-folding mirror (160) while the electronic component may amplify and transfer an electric signal to the electro-optical component. The planar light wave circuit may typically provide an opto-electronic signal communication path via the plurality of optical waveguides that may be embedded in the planar light wave circuit.

Optical communication systems may be configured to allow for the propagation of signals between desirable locations. The signals may propagate, through portions of the communication system, along an optical path. An opto-electronic module may typically be used in such optical communication systems such as for example a fiber optic communication system. The opto-electronic module may typically be used for transferring electrical energy and signals to light energy and signals or vice versa. This opto-electronic module may combine optical elements, electrical components, an optical waveguide, and an electrical circuit in order to implement the desired energy transferring capabilities.
Optical fiber may typically be used to guide optical signals in optical communication systems such as for example wavelength division multiplexing (WDM) optical communication systems. There exists a technological limitation in manufacturing a multi-path optical fiber for guiding several optical signals. Currently, a planar light waveguide circuit (PLC) combines several optical units with optical waveguides to be used as part of an optical communication system such as for example WDM. In communication systems incorporating PLC, active devices and optical waveguides may exist as separate entities.
It will be appreciated that for simplicity and clarity of illustration, elements shown in the figures have not necessarily been drawn to scale. For example, the dimensions of some of the elements may be exaggerated relative to other elements for clarity. Further, where considered appropriate, reference numerals may be repeated among the figures to indicate corresponding or analogous elements.

System and method for the fabrication of an electro-optical module


Disclosed are a portable terminal and sliding/swing-type cradling apparatus thereof. The portable terminal includes a first housing, a second housing that slides along the first housing and faces the first housing, and a third housing including a display unit. The third housing is movable from a termination position after sliding along the first housing with the second housing and rotating when the display unit is inclined.

1. Field of the Invention
The present invention relates to a portable terminal which may be a Digital Multimedia Broadcasting phone (DMB phone), a game phone, a chatting phone, a camera phone, an MP3 phone, a cellular phone, a Personal Communication System (PCS), a Personal Digital Assistant (PDA), a Hand Held Phone (HHP), or the like. More particularly, the present invention relates to a portable terminal through which a user can conveniently watch television.
2. Discussion of the Background
In general, a "portable terminal" refers to an electronic device that a user can carry and use to communicate with another user wirelessly. In consideration of portability, the designs of portable terminals have tended not only toward compactness, slimness and lightness, but also toward providing multimedia capabilities to allow the user to pursue a wider variety of functions. In particular, future portable terminals may not only be multi-functional, compact and light, but may additionally be modified to be suitable for functioning in a multimedia environment and for providing internet access and functions. Additionally, such portable terminals may be used by men and women, young and old, anywhere in the world, and may be considered a necessity by users.
Conventional portable terminals may be classified into various types according to their appearance, such as bar-type portable terminals, flip-type portable terminals, and folder-type portable terminals. The bar-type portable terminal has a single housing shaped like a bar. The flip-type portable terminal has a flip panel which is pivotally mounted to a bar-shaped housing by a hinge unit. The folder-type portable terminal has a folder coupled to a single bar-shaped housing by a hinge unit in such a manner that the folder can be rotated in order to be folded or unfolded from the housing.
Further, portable terminals may be classified as neck wearable-type terminals and wrist wearable-type terminals, according to the position or way in which a user wears the terminal. The neck wearable-type terminal is one which a user wears around the neck using a lanyard or necklace, while the wrist wearable-type terminal is one which a user wears around the wrist.
Additionally, portable terminals may be classified as rotation-type terminals and sliding-type terminals according to the way in which the terminal is opened and closed. In a rotation-type portable terminal, two housings face each other and are coupled together. One housing rotates to be opened or closed relative to the other. In the sliding-type portable terminal, two housings are coupled to each other such that one housing slides to be opened or closed relative to the other. The various classifications of portable terminals are easily understood by those skilled in the art.
Further, each conventional portable communication terminal has been converted to allow voice communication as well as high-speed data communication. That is, as consumer demands have increased, various services have been provided using wireless communication technology for transmitting and receiving data at a high speed.
It is a present tendency to have a camera lens mounted to the portable communication terminal and it is possible to transmit image signals and the like. Present portable communication terminals are provided with an embedded or external camera lens module. Therefore, it is possible to conduct image communication with a desired partner or to photograph a desired subject.
However, conventional portable terminals have several problems. A separate cradle must be used to allow a user to watch information displayed on a display unit conveniently. It is well known that a user is more comfortable watching information displayed on the display unit which is cradled and inclined, while facing the inclined display unit. However, unless the conventional portable terminal has a separate cradle, the user watches the inclined body while gripping the body with a hand. While the user may watch images displayed on the display unit without a separate cradle by positioning the terminal on a table, such an arrangement is very inconvenient.
Similarly, in the case of playing a game on the portable terminal, the user has to grip the portable terminal with a hand while pressing buttons with the other hand. Therefore, it may be difficult for the user to play the game.

Portable terminal and sliding/swing-type cradling apparatus thereof


A bowling practice device for regularizing and perfecting bowling technique. An aerodynamically designed hollow body includes an outer wall and a cylindrical inner wall. The opposed ends of the outer wall taper to meet the cylindrical inner wall. The outer wall preferably comprises a plurality of foam panels, one of which includes at least two finger holes suitable for personalization to the hand of the bowler.

1. Field of the Invention
The present invention relates to the sport of bowling. More particularly, this invention pertains to a practice assistance device for enabling a bowler to regularize, and thereby enhance the consistency of his arm swing.
2. Description of the Prior Art
The sport of bowling basically requires a single piece of player equipment, namely a spherical ball that is conventionally of rigid material such as polyurethane, hard rubber, even wood. It includes finger holes, preferably suited to the size and style of the bowler, by which the ball is grasped prior to release at the end of a stroke or swing of the bowler's arm.
While neither the bowler's basic equipment nor the object of the sport is, at first glance, particularly complicated, many factors enter into a bowler's awareness as he seeks to "perfect" his game. The skilled bowler will take into account, for example, his location and launch point in relation to the degree of oiling of the lane. Various adjustments reflect many factors, including, for example, the positioning of the pins that remain standing, the thickness and contour of the oil that protects the wooden lane, etc.
Adjustments (w.r.t. launch point, stance, etc.) made for varying lane conditions and the like are most effective when the bowler is able to make such adjustments based upon a predictable stroke of the bowler's arm. Otherwise, adjustments to stance, position and the like are made "in the dark", reflect guesswork and have no particular reliability.
The bowler's stroke represents a composite motion that includes addressing the ball, and striding coordinated with backstroke and follow-through arm swings. The reduction of this relatively-complex sequence into a reliable predictable sequence of motions relies upon repetition. By coupling such repetition with analysis, one can multiply the benefits of repetitive practice of the bowler's stroke.
A number of factors complicate the ability of a bowler to engage in the type of repetition that would result in the grooving of his stroke. The most obvious type of practice requires the bowler to spend many hours by himself at the bowling alley, observing the action of his ball as he plays many practice rounds. In addition to the impracticality of such extensive practice, requiring absence from the home, for the average non-professional bowler, the feedback that he or she receives from such practice is complicated by factors, such as oiling of the boards of the alley, that prevent isolation of the action of the ball to the bowler's stroke. Furthermore, excessive practice with a bowling ball may result in arm strain.


A ballpoint pen 10 includes: a ballpoint pen tip 20 having a writing ball 30 and a holder 21 holding the writing ball 30; a shaft tube 12 to which the rear end part of the ballpoint pen tip 20 is mounted; and ink 40 accommodated in the shaft tube 12. The holder 21 has an ink guiding hole 26 formed from the rear end thereof toward the head end thereof and a ball house 22 formed with the inner circumference near the head end of the holder 21 expanded. The writing ball 30 is formed of a zirconia sintered body with the content of an aluminum element being less than 0.1 weight %, and the ink 40 contains inorganic particles 41.

Although a cemented carbide alloy has conventionally been used as a writing ball for a ballpoint pen, a writing ball made of ceramics has also been used in recent years. The writing ball made of ceramics is less susceptible to corrosion caused by ink and has a feature that there is little wear to a ball receiving seat. For example, JP 59-135195 A discloses a writing ball made of zirconia sintered body ceramics. Moreover, JP 2001-80260 A discloses a writing ball made of a zirconia sintered body, as one of writing balls suitable for ink containing hard inorganic pigment.
In the writing ball described in JP 2001-80260 A, spaces between hard grains composing the writing ball are much narrower if compared with a conventional cemented carbide alloy ball. Therefore, since the fragments of the hard grains exposed on the surface of binder metal combining the hard grains are minute and since the number of the fragments is very small, it is less likely that the fragments will drop from the surface of the writing ball and act as abrasives during writing, preventing the wear of a ball receiving seat. Moreover, since the distances between boundaries of the hard grains are narrow, the edges of the hard grains of the boundaries are less likely to act as cutting blades, preventing wear to a ball receiving seat.


This invention comprises a minimal elastance underwater breathing apparatus UBA) in which the elastance component of UBA impedance is substantially eliminated by forcing the breathing bag to expand and contract in a horizontal plane with small vertical displacements and hence minimal elastance. The invention further includes a servo-mechanism operating with a microprocessor, 3-axis position sensor and rotatable joints which act to keep the breathing bag oriented horizontally no matter what the diver's position. The principles of the present invention may be adapted to existing UBA with redesign and additions.

1. Field of the Invention
This invention relates to the field of underwater breathing apparatus (UBA), more specifically to self-contained, closed-circuit underwater breathing apparatus, which operates without need of air or breathing gas from an outside supply remote from the diver, and wherein carbon dioxide gas (CO.sub.2) generated by a diver is constantly removed and oxygen (O.sub.2) needed for metabolism is constantly supplied.
2. Description of the Prior Art
A closed-circuit UBA is a form of self-contained underwater breathing apparatus (SCUBA) in which a diver's breathing gas is recycled through a closed loop, adding oxygen and removing carbon dioxide gases as needed. The carbon dioxide gas is typically removed by chemical absorption. UBA typically comprise an oxygen supply bottle, a canister containing CO.sub.2 absorbent, a breathing bag or flexible volume element, connecting hoses, a mouthpiece for the diver, and a diluent gas or inert gas bottle. Inert gases such as helium or helium/nitrogen mixtures are often used. Some UBA versions monitor O.sub.2 electronically and add oxygen when inspired O.sub.2 concentrations drop below desired levels. The only mechanical adjustments that can be made by a diver involve the degree of filling of the breathing bags. As ambient pressure changes, for example as the diver goes deeper or rises, the volume of gas within the breathing bag(s) contracts or expands respectively, and diluent gas may be added or dumped, either manually or automatically. Some UBA have a single breathing bag; others have one for the inhalation side and another for the exhalation side of the recirculating loop.
The closed-circuit breathing apparatus and its basic construction and principles of operation have been known for some time (U.S. Pat. No. 3,837,337 to LaViolette, 1974). Improvements to such equipment are always being made for the diving community, which includes military, commercial underwater construction and salvage, and sport divers. For example, improvements in the control of air or breathing gas flow within the apparatus are discussed in U.S. Pat. No. 4,440166 to Winkler, et al, (1984), wherein particularly with respect to emergency mechanical control system in the event that the electronics fails.
The large majority of patents in the art center around the two critical performance factors for UBA, namely CO.sub.2 absorption and O.sub.2 control. Almost none deal with improving or lessening the difficulty of breathing-particularly during arduous exercise or heavy work. Those that do deal only with the fluid mechanical flow resistance and not other sources of impedance or mechanical resistance to breathing arising from the elements in the UBA including tubing or hoses, canister, etc. In general, breathing resistance in a UBA can be significant for the diver; it can reduce his effectiveness or the duration of work capability, and may, more seriously, contribute to loss of consciousness.
The mechanical resistance to breathing on a UBA is complex, because the breathing is sinusoidal or periodic in nature and not a steady flow. In this kind of flow situation dynamic analyses must be employed, such as those common to the art and discussed in detail by R. Peslin and J. J. Fredberg, "Oscillation Mechanics in the Respiratory System, chap. 11 in Handbook of Physiology: vol III, The Respiratory System, A. P. Fishman (ed.), 1987, American Physiol. Soc., Bethesda, Md., and H. D. Van Liew, "The Electrical-Respiratory Analogy when Gas Density is High", Undersea Biomedical Research, vol. 14, no. 2 (1987) pp. 149-160. In a periodic flow, allowance must be made for additional resistances to the motion of the breathing gas. These resistances are termed elastance and inertance and they cause increased energy loss, because the diver must overcome them as well as the resistance due to flow to keep breathing. Inertial resistance or inertance arises from accelerations and decelerations in the gas flow and displaced water due to the periodic nature of the flow. This generally becomes important only at high frequencies that are generally much higher than human breathing patterns, even under sustained work loads. Inertance increases with depth due to the gas density increasing, but rarely contributes to impedance at the breathing frequencies normally used by a diver.
Elastic resistance or elastance arises from pressure changes as a result of flow entering a closed volume or pressure changes as volume changes (in submersed breathing bags for example). Because of the oscillatory or periodic nature of the flow, complex algebra must be used to describe the overall resistance to flow, which is termed the impedance. Therefore; EQU Z=R-(jE/.omega.)+j.omega.I Eqn. 1
where Z is the impedance in units of pressure/flow rate, R is the resistance due purely to flow (the flow resistance) in the same units, E is the elastance in units of pressure/volume, I is the inertance in units of pressure/flow acceleration, and .omega. is the radian frequency in units of reciprocal time. Eqn. 1 applies to a series arrangement of R, E and I, typical of UBA. Impedance is composed of a real part, the flow resistance, and an imaginary part, which is a combination of the inertance and the elastance. The magnitude of Z can be computed by; EQU .vertline.Z.vertline.=.sqroot.[R.sup.2 +(.omega.I-E/.omega.).sup.2 ]Eqn. 2
so that all three components of impedance contribute to overall energy loss in the flow system. The energy loss is reflected in the pressure drop required to cause flow.
The foregoing are terms of the art necessary to understand the present invention, but they do not constitute the invention.
Flow resistance is present at all times by virtue of the flow rate of gas being moved. The pressure drop required to cause flow at a given rate increases with flow rate in a complicated manner when flow resistance is present. Elastance contributes to the impedance at low frequencies which are generally in the range of a diver's breathing frequencies, whether the diver is at rest or working. It is therefore a major part of the impedance of the UBA. As breathing frequency increases the flow resistive part becomes increasingly more important and elastance increasingly less important factor in the pressure required to maintain flow.
Impedance in the UBA adds to the positive and negative respiratory pressures that a diver must generate to breathe. Impedance is generated by the elastance, inertance and resistance in the UBA. Resistance in UBA arises from breathing hoses, valves, changes in flow diameter, the canister and other similar obstructions in the flow path. Resistance is the fluid mechanical cost of moving the fluid at a given rate. The ratio of the pressure required to drive the flow and the volumetric flow rate is termed the flow resistance.
Elastance is the reciprocal of compliance in the system and is derived in UBA primarily from changes in volume of the breathing bag when immersed. If these changes in volume lead to a vertical expansion or contraction of the bag, pressure is altered by hydrostatic forces, wherein the pressure change (.DELTA.P) is given by; EQU .DELTA.P=.rho.g.DELTA.h Eqn. 3
where .DELTA.h is the vertical displacement and .rho. is the density of the ambient fluid, usually water or sea water, and g is the acceleration of gravity. The shape of the bag and its orientation in the water have an effect of the elastance. Reference is made to D. D. Joye, J. R. Clarke, N. A. Carlson and E. T. Flynn, "Formulation of Elastic Loading Parameters for Studies of Closed-Circuit Underwater Breathing Systems", NMRI Technical Report 89--89, Bethesda, Md., 1989 (report available from NTIS, Washington, D.C.). Elastance is inversely proportional to the cross-sectional area that is perpendicular to the vertical direction. If the volume change in the breathing bag had no vertical component, for example if the bag changed shape in a horizontal direction only, there would be no change in pressure due to volume change and hence no elastance (except for some possible hydrostatic change in an uneven bag fill). There are other contributions to elastance in a UBA, for example the volume of internal hoses and containers in the breathing loop, that have an additional, but much smaller, effect.
The force that moves the flow of breathing gas is respiratory pressure. Although the respiratory pressure imposed by UBA elastance can be relatively high at the low frequencies commonly encountered in a diver's breathing pattern, which is typically in the range 5-60 breaths/minute, particularly 10-40 bpm, there have been no efforts to either statically or dynamically reduce UBA elastic impedance to make it easier for the diver to breathe.

Minimal elastance, closed-circuit underwater breathing apparatus

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


This invention relates generally to nucleic acid-based diagnostic assays for detecting, identifying and/or quantitating target sequences in a sample. More specifically, the invention utilizes sequential cleavage of nucleic acids to achieve target and signal amplification through cycling reactions.

This invention relates generally to nucleic acid-based diagnostic assays for detecting, identifying and/or quantitating target sequences in a sample. More specifically, the invention utilizes sequential cleavage of nucleic acids to achieve target and signal amplification through cycling reactions.
Nucleic acid hybridization assays are useful in the detection of particular nucleic acid sequences of interest, also referred to as xe2x80x9ctarget sequencesxe2x80x9d. These target sequences may be characteristic of a particular disease-associated gene, or they may be specific for various organisms or cell types. Accordingly, detection and identification of a particular target sequence can provide diagnostically significant information.
The ability to detect target nucleic acid sequences in a sample by hybridization between a target nucleic acid and a complementary xe2x80x9cprobexe2x80x9d nucleic acid is the cornerstone of nucleic acid-based diagnostic technologies. These assays can generally be characterized as either xe2x80x9cheterogeneousxe2x80x9d or xe2x80x9chomogeneous.xe2x80x9d Heterogeneous assays depend on the ability to separate hybridized from non-hybridized nucleic acids. One such assay involves immobilization of either the target or probe nucleic acid on a solid support so that non-hybridized nucleic acids which remain in the liquid phase can be easily separated after completion of the hybridization reaction (Southern, J. Mol. Biol., 98: 503-517 (1975)).
In comparison, homogeneous assays depend on means other than physical separation for distinguishing between hybridized and non-hybridized nucleic acids. The avoidance of a separation step renders homogeneous assays easier to use and, therefore, more desirable. One such homogeneous assay relies on the use of a label attached to a probe nucleic acid that is only capable of generating signal when the target is hybridized to the probe (Nelson, et al., Nonisotopic DNA Probe Techniques, Academic Press, New York, N.Y., pages 274-310 (1992)).
One of the most significant obstacles to the development of nucleic acid-based diagnostic assays has historically been a lack of sensitivity. In particular, when the number of copies of the target nucleic acid in a sample are limited, sensitivity becomes very important. Many strategies have been designed to overcome this obstacle, with variable success. Among the most successful strategies are those that involve either target amplification or signal amplification. Target amplification involves increasing sensitivity by exponentially multiplying the number of copies of target sequences in a sample. Examples of target amplification techniques include the polymerase chain reaction, or xe2x80x9cPCRxe2x80x9d (Saiki, et al., Science 239: 487-491 (1988), and ligase chain reaction, or xe2x80x9cLCRxe2x80x9d (Wu, et al., Genomics 4: 560-569 (1990)).
Another method for increasing sensitivity is to amplify the signal generated by a single target/probe hybridization event. This can be accomplished by using branched probes, each capable of generating multiple detectable signals (Urdea, et al., Clin. Chem. 39: 725-726 (1993)), or by utilizing cycling probe technology or xe2x80x9cCPT,xe2x80x9d which relies on the ability to generate multiple detectable probes from a single target sequence (Bekkaoui, et al., BioTechniques, 20: 240-248 (1996)).
Still another method for increasing the sensitivity of nucleic acid-based diagnostics employs a cascade reaction to amplify signal. U.S. Pat. No. 4,699,876 discloses a heterogeneous assay utilizing a probe with an enzyme activator attached thereto. Once the probe binds to the target and unhybridized probe is removed, the enzyme activator initiates a signal generation cascade that produces amplified signal levels.
Although a variety of assays exist for detecting nucleic acid, the expanding applications of such assays provides a continuous need for further assay innovation to achieve improved sensitivity and ease of use.
Accordingly, the present invention provides a highly sensitive tricyclic assay system for measuring a target nucleic acid from a sample added to an assay medium, comprising:
a) a non-diffusible first probe-reporter complex, wherein the first probe comprises a nucleotide sequence that is complementary to the target nucleic acid, and wherein the fist probe and the target nucleic acid have sufficient complementarity to hybridize to form a first cleavage site;
b) a first cleavage reagent that recognizes and cleaves the first cleavage site thus forming a diffusable probe fragment-reporter complex and releasing the target nucleic acid into the assay medium;
c) a non-diffusible first target mimic that is functionally separated from the probe reporter complex, wherein the first target mimic comprises a nucleotide sequence that is complementary to the probe, and wherein the first target mimic and probe fragment have sufficient complementarity to hybridize to form a second cleavage site; and
d) a second cleavage reagent, which may be the same or different from the first cleavage reagent, that recognizes and cleaves the second cleavage site thus forming a diffusible target mimic fragment and releasing the probe fragment reporter complex into the assay medium;
wherein the target mimic fragment has sufficient complementarity to hybridize to a second probe;
wherein the target nucleic acid after release into the assay medium following cleavage of the first probe remains capable of binding to a second probe; and
wherein the probe fragment has sufficient complementarity to hybridize to a second target mimic.
As used herein, the term xe2x80x9ccomplementaryxe2x80x9d is not intended to be limited to cases in which two nucleic acids that are hybridized are perfectly complementary. Accordingly, when one nucleic acid is referred to as being xe2x80x9ccomplementaryxe2x80x9d to the other nucleic acid, this term is inclusive of pairs of nucleic acids that, when hybridized together, have one (or more) mismatch(es), so long as they have sufficient complementarity to form stable duplexes.
Other aspects of the invention are described throughout the specification and claims.

Nucleic acid hybridization assay utilizing tricyclic target and signal amplification


A device (10) for isolating a surface for welding in an underwater location or in high fire risk areas. The device comprises a housing (27) which is arranged to be mounted on the surface and a sealing means (30) to provide a seal between the housing and the surface. The housing (27) is provided with a sealed inlet (50) for receiving a welding apparatus, a fluid inlet (32) for the passage of gas into the housing, and a fluid outlet (34) for the passage of gas and/or liquid out of the housing. A heating means FIG. 3 is not figure) for providing heated gas to the fluid inlet is also provided. In use, an ingress of heated gas through the fluid inlet (32) facilitates an egress of gas and/or liquid, contained in a space defined by the housing and the surface, through the fluid outlet (34) in the housing. In this way an in situ dry gaseous environment is provided for welding the surface. The heating means (100) is provided upstream and comprises a space with heating elements (120) surrounded by insulation (130) with electrical inlets (122).

The mechanical properties of a welded surface formed under "dry" welding conditions is frequently recorded to be greater than or equal to 23% elongation of tensile allweld. This stands in marked contrast to the mechanical properties of a welded surface which is formed under "wet" welding conditions. The elongation of tensile allweld for an underwater welded surface is typically about 7–8% due to rapid cooling of the welded surface through heat dispersion to the surrounding water and a high concentration of hydrogen absorbed into the weld. The underwater welded surface is thus more brittle and weaker than a weld formed on a surface made of the same material under "dry" conditions.
It is known to provide large hyperbaric chambers which are constructed around, so as to fully enclose, an underwater surface which requires welding. Such hyperbaric chambers are large enough to hold a diver and the diver's welding apparatus. In use, the hyperbaric chamber is drained of water and the diver welds the surface under "dry" conditions. The procedure is lengthy, and costly. The hyperbaric chambers are large and cumbersome to operate, and they are frequently oversized for the surface area which requires welding. Not surprisingly, the hyperbaric chambers are very expensive. For a very small welded area, the cost can run into many millions of dollars.
The present invention seeks to overcome at least some of the aforementioned disadvantages.

Device for isolating a surface for welding


Novel CH2 domain template molecules wherein donor loops from a database of domains are transferred to a CH2 domain scaffold. At least one or up to three loops from a donor are transferred to the CH2 domain. The donor loops may be chosen based on length, e.g., the donor loop may have a length that is similar to that of a structural loop in the CH2 domain scaffold.

Immunoglobulins (antibodies) in adult humans are categorized into five different isotypes: IgA, IgD, IgE, IgG, and IgM. The isotypes vary in size and sequence. On average, each immunoglobulin has a molecular weight of about 150 kDa. It is well known that each immunoglobulin comprises two heavy chains (H) and two light chains (L), which are arranged to form a Y-shaped molecule. The Y-shape can be conceptually divided into the Fab region, which represents the top portion of the Y-shaped molecule, and the Fc region, which represents the bottom portion of the Y-shaped molecule.
The heavy chains in IgG, IgA, and IgD each have a variable domain (VH) at one end followed by three constant domains: CH1, CH2, and CH3. The CH1 and CH2 regions are joined by a distinct hinge region. A CH2 domain may or may not include the hinge region. The heavy chains in IgM and IgE each have a variable domain (VH) at one end followed by four constant domains: CH1, CH2, CH3, and CH4. Sequences of the variable domains vary, but the constant domains are generally conserved among all antibodies in the same isotype.
The Fab region of immunoglobulins contains the variable (V) domain and the CH1 domain; the Fc region of immunoglobulins contains the hinge region and the remaining constant domains, either CH2 and CH3 in IgG, IgA, and IgD, or CH2, CH3, and CH4 in IgM and IgE.
Target antigen specificity of the immunoglobulins is conferred by the paratope in the Fab region. Effector functions (e.g., complement activation, interaction with Fc receptors such as pro-inflammatory Fcγ receptors, binding to various immune cells such as phagocytes, lymphocytes, platelets, mast cells, and the like) of the immunoglobulins are conferred by the Fc region. The Fc region is also important for maintaining serum half-life. Serum half-life of an immunoglobulin is mediated by the binding of the Fc region to the neonatal receptor FcRn. The alpha domain is the portion of FcRn that interacts with the CH2 domain (and possibly CH3 domain) of IgG, and possibly IgA, and IgD or with the CH3 domain (and possibly CH4 domain) of IgM and IgE.
Examining the constant domains of the immunoglobulin heavy chains more closely, the CH3 domains of IgM and IgE are closely related to the CH2 domain in terms of sequence and function. Without wishing to limit the present invention to any theory or mechanism, it is believed that the CH2 domain (or the equivalent CH3 domain of IgM or IgE) is responsible for all or most of the interaction with Fc receptors (e.g., Fcγ receptors), and contains histidine (His) residues important for serum half-life maintenance. The CH2 domain (or the equivalent CH3 domain of IgM or IgE) also has binding sites for complement. The CH2/CH3 domain's retention of functional characteristics of the antibody from which it is derived (e.g., interaction with Fcγ receptors, binding sites for complement, solubility, stability/half-life, etc.) is discussed in Dimitrov (2009) mAbs 1:1-3 and Dimitrov (2009) mAbs 1:26-28 and Prabakaran et al. (2008, Biological Crystallography 64:1062-1067). Consequently, CH2 domains have been used as scaffolds as alternatives to full-length antibodies.
Without wishing to limit the present invention to any theory or mechanisms, it is believed that some modifications to the CH2 domain may have only small effects on the overall structure of the CH2 domain (or CH2-like domain), and it is likely that in cases where the modified CH2 structure was similar to the wild-type CH2 structure the modified CH2 domain would confer the same functional characteristics as the wild-type CH2 domain possessed in the full immunoglobulin molecule.
It is known that efficacy of a therapeutic antibody (or fragment thereof) can be limited by an immune reaction. To address such issues, many methods have been used to humanize antibodies derived from a non-human source with the aim of reducing the human anti-murine antibody (HAMA) response, for example. One such method includes CDR grafting wherein CDRs from a non-human antibody are transferred to a human antibody scaffold. This method, however, may result in a reduction in binding to the target antigen, which may be a consequence of the imperfect fit between the antibody scaffold and the CDRs that results in a loss in molecular recognition between the antigen and the "antibody."
Some methods are used with the aim of preserving the surface recognition features of the antigen-antibody interface (Raghunathan, 2009). Rather than simply transferring a CDR amino acid sequence from one antigen binding molecule to replace a structural loop in another immunoglobulin scaffold, these methods take other characteristics of the antigen binding molecule being transferred into account to preserve the three dimensional orientation of the amino acids and their interactions with framework region amino acids. For example, when constructing a humanized antibody, human frameworks are selected based on sequence similarity of the non-human and human frameworks, length of the 3 "CDR" loops, and the sequence similarity of the loop residues.
The present invention features novel CH2 domain template molecules and methods of design of such CH2 domain templates wherein loops from a database of domains (the "donor loops") are transferred to a CH2 domain scaffold ("the acceptor"). The donor loops may be chosen based on length, for example the chosen donor loop may have a length that is similar (but not necessarily identical) to that of a structural loop in the CH2 domain scaffold. The CH2 domain scaffold may be derived from a CH2 domain of human IgG or from a CH2 domain of a different Ig or from a CH2 domain of a different mammal, e.g., macaque.
The CH2 domain has a traditional Ig-fold with a 13 sheet sandwich comprising 3 pairs of β strands. A disulfide bond connects the middle 13 strands. The strands are denoted by A, B, C, D, E, F and G. Intervening loops (sometimes called structural loops) are denoted as BC, DE and FG. As used herein, loops BC, DE and FG will be referred to as L1, L2 and L3 respectively. These three loops bind to the Fc-Gamma receptor when present as part of the Fc dimer. The other three loops, AB, CD and EF bind to the Fc-Rn receptor when present as part of the Fc dimer. While the CH2 domain scaffold is broadly similar to that of an Ig domain, there are variations both in the sequence signatures and structure. One distinct difference in structure is the D strand. This region is a typical beta strand in most Ig domains, but it is a coil in the CH2 domain. This structural difference in the D region may have entropic effects on the L2 loop. The transfer of loops to the CH2 domain can have an effect on the binding and stability of the engineered molecule. Thus, the present invention is different from traditional methods of antibody engineering involving loop grafting (e.g., traditional humanizing of antibodies) and transferring a loop to a variable domain. Referring to the loop transfer from donor molecules to the CH2 domain scaffolds of the present invention, it is difficult to predict what would be a good loop match based on the amino acid sequence of a loop in a typical immunoglobulin antigen binding region (e.g., since there are significant differences in the sequence patterns and structure). The transfer of loops from a donor to an acceptor molecule would affect the binding and stability of the molecule.
In the present invention at least one or up to three loops (e.g., L1, L2, L3, L1 and L2, L1 and L3, L2 and L3, or L1 and L2 and L3) from a donor are transferred to the CH2 domain. Without wishing to limit the present invention to any theory or mechanism, we believe that a careful rational transfer of such compatible structural loops from a selected donor may ensure preservation of the stereochemistry and surface topology of the antigen binding region of the donor molecule. Also, we believe that preservation of interactions among the loops and between the loops and the proximal β strands may lead to molecules that have desirable biophysical and biochemical properties (e.g., stability, solubility). While we believe that compatible loops may help to maintain affinity with the target, we believe variations in loop lengths may provide recognition with different types of antigens.
Any feature or combination of features described herein are included within the scope of the present invention provided that the features included in any such combination are not mutually inconsistent as will be apparent from the context, this specification, and the knowledge of one of ordinary skill in the art. Additional advantages and aspects of the present invention are apparent in the following detailed description.

CH2 domain template molecules derived from rational grafting of donor loops onto CH2 scaffolds


The present invention relates to an image pre-processing method for a pattern detection system, such as a bar code detection system. The method comprises the steps of: detecting a start point and an end point of a pattern on the basis of image data of at least a portion of a captured image, estimating a point spread function from the image data or a modified image data on the basis of the detected start point and the end point, and restoring the image data or the modified image data using the estimated point spread function.

Bar codes have been used in a wide variety of applications as a source for information, for instance for product identification and pricing. A bar code is a set of binary numbers and typically consists of black bars and white spaces, or black and white squares. One-dimensional barcodes are typically consisted of black and white lines, while two-dimensional barcodes are arrays of black and white squares or hexagons or ellipses. Usually the standard classical devices utilized for bar code detection use laser beams (for example, dedicated devices used in supermarkets and stores). Since many mobile devices are already equipped with cameras, it also is possible to arrange bar code detection in these devices.
The physical dimension of the bar codes to be detected varies quite a lot. Bar codes that have low information density on a large area can be detected easily with a normal camera phone. This is because, for such bar codes, the distance between the printed bar code and the lens of the camera must be long in order to include the complete bar code in the viewfinder. In this case the image containing the bar code is situated in the in-focus range of the camera and the quality of the captured image is typically good enough for detection. On the other hand, for the bar codes printed on small areas—even if they have low information density—the distance between the printed code and the camera must be very short. This is due to the fact that for such small codes, the resolution of the printed bar code, situated in the in-focus range of the camera, is around the maximum resolution of the optical system of the camera phone. In order to deal with this problem, the bar code is captured at a distance that is much shorter than the focal distance of the camera. However, when a bar code is captured at a very short distance, the captured image is highly influenced by the distortions of the optical system and sensor of the camera (out of focus). Typically, the captured image is distorted by: sensor noise added to the captured image, optical blur and vignetting that are due to the optical system of the camera (lenses). An example of such an image captured using a short distance between the camera and the printed bar code is depicted in FIG. 1. It is likely that bar code detection applied directly to this image will fail due to the amount of blurring and, therefore, pre-processing is desirable.
One way to improve the quality of the captured image for small bar codes is to use lenses with a very short focal distance that introduce very little blur in the captured image. However, using such a lens requires additional external attachments to the mobile phones, and can cause discomfort and annoy the users. Also, this will add more costs.
IEEE publication "Bar Code Recovery via the EM Algorithm", William Turin and Robert A. Boie, IEEE Transactions on Signal Processing, Vol. 46, No. 2, February 1998, pages 354-363, discloses a bar code recovery method based on the statistical expectation-maximization (EM) algorithm. In this method a bi-level bar code is blurred and fitted to the input line. The point spread function (psf) is assumed to be gaussian and the positions of the bar code edges are assumed to be unknown. The parameter of the psf is also assumed to be unknown. The maximum likelihood approach is used to find the position of the bar code edges. This reference is limited to describe a solution for situations where the amount of blur is small. For medium and highly blurred images there are no examples in the referred paper that illustrate the performance of that method. Moreover, the method mentioned in this reference is derived for bar code detectors based on infrared sensors and the model of such sensors is used in the derivation of the algorithms and methods. In addition to that, the algorithm proposed in the above paper has a large computational complexity that makes it unsuitable for implementation in mobile devices.


Systems and methods for digital detection of an analog tomographic signal are described. The methods include receiving an amplitude-modulated analog signal containing tomographic information, the analog signal having a modulation frequency, fλi; and converting the analog signal into a digital signal at a sampling frequency, fs, to produce a number of samples, K. The digital signal is multiplied by an in-phase reference signal to obtain an in-phase signal component, the in-phase reference signal having the frequency, fλi; and the digital signal is multiplied by a quadrature reference signal to obtain a quadrature signal component, the quadrature reference signal having the frequency, fλi. The in-phase signal component and the quadrature signal component are passed through the K-point averaging filter. A signal amplitude is computed based on the filtered in-phase signal component and the filtered quadrature signal component, the signal amplitude being representative of the tomographic information.

This invention relates in general to optical tomography, and in particular to systems, methods and apparatuses that perform digital detection for use in optical tomography.
Optical tomography, or optical tomographic imaging, is often performed by measuring the amplitude attenuation of light that has been passed through tissue. Propagation of injected photons is determined by the spatially-varying absorption and scattering characteristics of the tissue being probed. In biological tissues, scattering interactions are often the principal mechanisms affecting the light trajectory. As a result of this highly scattering nature, these photons do not navigate in a straight procession but rather diffuse throughout the medium. The photon flux exiting the tissue at any single point is the net effect of the incident light source, and discrete absorption and scattering interactions throughout their pathlength. By illuminating several locations around the tissue of interest, and detecting transmitted and back-reflected intensities at multiple positions along the surface, one can generate tomographic images, similar to X-ray computed tomography. The transmitted intensity measured along the target surface maintains the same frequency with respect to the source, however, it will exhibit an amplitude attenuation and an induced phase shift. This amplitude attenuation and phase shift provide spatial information regarding the absorption and scattering distribution inside the tissue. In continuous wave imaging, the light is either illuminated at a constant amplitude or modulated by a low frequency sine wave (up to a few kHz), and the decay in amplitude relative to the incident source is measured. If the illuminated source is modulated, then a synchronous or homodyne detection technique is often employed to extract the zero-frequency amplitude information. This method requires generating a reference signal whose frequency is equal to and phase locked with the input waveform. Multiplying the input waveform by its reference signal produces an output waveform that is a composite of two independent contributions; one component located at zero-frequency and the other component straddling twice the modulation frequency. This resulting mixed signal is then sent through a low-pass filter to eliminate the higher frequency component, leaving only the remaining DC constituent whose amplitude is directly proportional to the amplitude of the detected optical signal. By imaging with multiple wavelengths, the spectral information is increased allowing investigators to formulate qualitative assessments of hemoglobin parameters such as oxyhemoglobin and deoxyhemoglobin, or quantitative valuations of additional physiologic chromophores. Each wavelength must be modulated at distinct frequencies and/or phase in order to isolate the individual signals and their respective amplitudes.
Almost all continuous wave optical tomography systems currently cited in literature perform any relevant signal conditioning and data processing through analog techniques. Analog systems are used to collect, condition, and possibly filter the incident signal. For those instruments that modulate the intensity of their light source, analog phase-sensitive lock-in methods are usually employed to extricate the optical signal obscured by noise of potentially greater magnitude.
Such analog detection systems, however, suffer from a number of deficiencies and limitations. More specifically, for example, analog phase sensitive detection has many problems associated with it that adversely affect their performance and restrict subsequent applications. Some primary deficiencies include, for example, signal drift, output offsets, gain error, limited dynamic reserve, and harmonic rejection. Additionally, external parameters such as temperature or age contribute to analog noise and, consequently, measurement uncertainty. Furthermore, analog processing is notably sensitive to component tolerances thereby limiting functional utility. Finally, when the digital timing signals share a backplane with analog data signals, coupling can occur, causing fluctuations along the analog lines. A direct consequence of these undesirable attributes is that the instrument noise floor is elevated, causing a reduction in the detection sensitivity, diminished dynamic range for the overall system, and a slowing of the data acquisition. Analog detection systems suffer from other deficiencies and limitations, as well.
There is a need for detection systems for optical tomography that are better than existing detection systems.

Systems and methods for digital detection of a tomographic signal

The Trustees of Columbia University in the City of New York

The Research Foundation of State University of New York


To provide a message image display device enabling a user to grasp a content of each message image when a plurality of message images are displayed. A display control unit (76) causes a display unit (82) to display a screen including a plurality of message images. A remaining-time-information storage unit (74) stores remaining time information corresponding to each of the message images. A judging unit (78) judges whether display of at least a part of the message image is limited by one or more other message images. A remaining-time-information updating unit (80) updates the remaining time information according to the judgment result made by the judging unit (78). The display control unit (76) limits display of each of the plurality of message images according to the remaining time information stored corresponding to the message image.

There is known a message image display device that displays a plurality of message images. Examples of such a message image display device include a game device that displays a plurality of game characters and displays, in positions corresponding to display positions of the respective characters, with balloon images representing lines of the characters.
[Patent Document 1] JP 2003-952 A

Message image display device, message image display device control method, and information recording medium


A method for prediction of electrical characteristics of an electrochemical storage battery and includes determining a functional relationship between a state of charge value which is related to a first parameter for a storage battery and a second state of charge value which is related to a second parameter for the storage battery for a second phase of use of the storage battery. The method also includes determining at least one characteristic variable from the reference of the functional relationship for the second phase to a state characteristic variable profile for a previous first phase of use of the storage battery. The method further includes predicting electrical characteristics of the storage battery utilizing a functional relationship between the characteristic variable and the electrical characteristics.

The present invention relates to a method for prediction of electrical characteristics of an electrochemical storage battery.
It may be desirable to determine or to predict at any given time the state of an electrical storage battery, such as the state of charge or the heavy-current load capability. By way of example, the capability of a starter battery to start a motor vehicle with an internal combustion engine is governed by the state of charge and the state of aging and by the characteristic drop in capacity of the battery, since the current level which can be drawn from the starter battery and the power which can be emitted are limited. It is particularly important to determine the state of charge and the starting capability of a starter battery in situations in which, for example, the engine is operated intermittently hence, in this case, the vehicle power supply system together with its loads is still operated during times in which the engine is switched off, even though the generator is not producing any electrical power. In situations such as this, the monitoring of the state of charge and of the starting capability of a storage battery must ensure that the energy content of the storage battery always remains sufficient to still start the engine.
Widely differing methods are known for measurement of the state of charge and for determination of the load behavior of storage batteries. For example, integrated test equipment (amp-hour (Ah) meters) is used for this purpose, with the charging current being taken into account, and possibly with an assessment using a fixed charging factor. Since the usable capacity of a storage battery is highly dependent on the magnitude of the discharge current and the temperature, even a method such as this does not allow a satisfactory statement to be produced about the usable capacity which can still be drawn from the battery.
By way of example, in the case of a method for measurement of the state of charge, DE 22 42 510 C1 discloses the assessment of charging current by means of a factor which is itself dependent on the temperature and on the state of charge of the battery.
DE 40 07 883 A1 describes a method in which the starting capability of a storage battery is determined by measurement of the battery terminal voltage and of the battery temperature, and by comparison with a state of charge family of characteristics which is applicable to the battery type to be tested.
DE 195 43 874 A1 discloses a calculation method for the discharge characteristic and remaining capacity measurement of a storage battery, in which the current, voltage, and temperature are likewise measured, and with the discharge characteristic being approximated by means of a mathematical function with a curved surface.
DE 39 01 680 C1 describes a method for monitoring the cold starting capability of a starter battery, in which the starter battery is loaded with a resistance at times. The voltage which is dropped across the resistance is measured, and is compared with empirical values in order to determine whether the cold starting capability of the starter battery is still sufficient. The starting process is in this case used to load the starter battery.
Furthermore, DE 43 39 568 A1 discloses a method for determination of the state of charge of a motor vehicle starter battery, in which the battery current and the rest voltage are measured, and are used to deduce the state of charge. The battery temperature is also taken into account in this case. The charging currents which are measured during different time periods are compared with one another, and are used to determine a remaining capacity.
DE 198 47 648 A1 describes a method for learning a relationship between the rest voltage and the state of charge of a storage battery in order to estimate the storage capability. A measure for the acid capacity of the electrolyte in the storage battery is determined from the relationship of the rest voltage difference to the amount of current transferred during the load phase. This makes use of the fact that the rest voltage for the higher state of charge ranges which are relevant for practical use rises approximately linearly with the state of charge.
One problem of determining the state of an electrochemical storage battery using known methods is that wear occurs in particular while rechargeable storage batteries are being discharged and charged, as well as while they are being stored without any load, and the conventional methods do not take account of all the relevant wear factors.
In the case of lead-acid rechargeable batteries, the wear relates on the one hand to corrosion phenomena, which reduce the voltage level when heavy electrical loads are applied, and on the other hand to changes in the morphology and the chemical composition of the active substances. Furthermore, parasitic reactions such as electrolysis and corrosion of gratings, or else simple vaporization, lead to a loss of water from the electrolyte. In the case of a rechargeable battery with liquid electrolytes, this is evident in a reduction on the electrolyte level. Parts which were previously covered with electrolytes in consequence become exposed, and this can lead to a change in the corrosion behavior in these areas. Furthermore, acid stratification can occur by the acid falling in layers on the base of the storage battery, which leads to an increase in the acid capacity in the lower area and to a reduction in the acid capacity in the upper area. In the case of rechargeable batteries with solid electrolytes (e.g., so-called sealed rechargeable batteries), in which the electrolyte is immobilized, for example, by means of a glass fiber mat or a gel, the saturation level of the electrode set (which comprises the porous electrodes and microporous separators and/or a gel) falls with the electrolyte. This is evident, inter alia, in an increased internal resistance and, in some cases, in a reduced capacity. Furthermore, as the electrode set dries out to an increasing extent, the rate of the parasitic oxygen circulation rises, which, in the case of rechargeable batteries of this type, on the one hand reduces the water loss by electrolysis, but on the other hand can reduce the charging efficiency and can increase the heating of the rechargeable battery during charging.
In both situations, the rest voltage of the rechargeable battery for a given degree of discharge (DoD) rises, because the loss of water (WL) with the amount of sulfuric acid unchanged leads to an increased concentration of the dilute sulfuric acid electrolyte, and the rest voltage (U00) rises strictly monotonically with the acid concentration, by virtue of the electrochemical relationships.
Accordingly, it would be advantageous to provide an improved method for prediction of electrical characteristics of an electrochemical storage battery.

Method for prediction of electrical characteristics of an electrochemical storage battery


It is an object of the present invention to provide a polylactic acid composition having excellent crystallinity, wet heat stability and melt stability. It is another object of the present invention to provide a molded article which is obtained from the polylactic acid composition and excellent in appearance and color. The present invention is a composition and molded article thereof which comprises a polylactic acid (component A), a carbodiimide compound (component B) and a phosphoric acid ester metal salt (component C).

In recent years, biodegradable polymers which are decomposed in the natural environment have been attracting attention and investigated worldwide for global environmental protection. Polyhydroxy butyrate, polycaprolactone, aliphatic polyesters and polylactic acid are known as the biodegradable polymers. Since polylactic acid is obtained from lactic acid obtained from a raw material derived from living organisms and a derivative thereof, it is an environment-friendly polymer material having high bio safety. Therefore, use of polylactic acid as a general-purpose polymer is now under study, and its application to medical goods such as surgical suture threads, sustained-release capsules and reinforcement materials for broken bones as a stretched film, fiber or injection molded article is being investigated.
However, polylactic acid has a low crystallization rate and its use as a molded article obtained by crystallization is limited. For instance, it takes long to injection mold polylactic acid because its molded product must be crystallized, and a heat treatment may be required after molding.
Further, polylactic acid has low wet heat stability that it is easily decomposed by water at a high temperature.
To improve the crystallization rate of polylactic acid, a method in which a crystallization nucleating agent for promoting crystallization is added has been studied, and the crystallization rate has been improved to a certain extent. For example, it is proposed to use a phosphoric acid ester metal salt in combination with polylactic acid and it is disclosed that the salt is effective for the crystallization of the resin (patent document 1). However, when the phosphoric acid ester metal salt is used, a new problem occurs that wet heat stability becomes worse. Further, the addition of the phosphoric acid ester metal salt may greatly reduce the molecular weight.
As an alternative method, it is proposed to add an inorganic filler such as a glass fiber. However, when the inorganic filler is used, the specific gravity of the obtained molded product increases. Further, when it is burnt or scrapped, a large amount of the residue is produced, thereby impairing one of the features of environment-friendly polylactic acid. It is also proposed to add a natural organic filler such as wood powder or kenaf to polylactic acid (patent document 2). However, a cellulose-based filler has low heat stability at the molding temperature of polylactic acid by its nature and deteriorates and decomposes in a molding machine at the time of molding. Therefore, it cannot be used to manufacture a high-quality molded article stably.
As for the improvement of the wet heat stability of polylactic acid, various stabilizers such as hindered phenols are proposed but not satisfactory in the improvement of the wet heat stability of polylactic acid.
It is also proposed to improve the wet heat stability by modifying the terminal group of the molecule of polylactic acid which involves in wet heat decomposition. For example, an epoxy compound (patent document 3), carbodiimide compound (patent document 4), and oxazoline, oxazine and aziridine compounds (patent document 5) are proposed. The wet heat stability of polylactic acid is improved to a certain extent by using the above terminal group modifier. However, the terminal group modifier plasticizes a resin and deteriorates its crystallinity. The additive itself has low heat resistance, thereby deteriorating the color of the resin significantly at the time of molding and reducing its value as a commercial product.
Meanwhile, it is known that stereocomplex polylactic acid is formed by mixing together poly(L-lactic acid) and poly(D-lactic acid) in a solution or molten state (patent document 6 and non-patent document 1). This stereocomplex polylactic acid has a melting point of 200 to 230° C. which is higher than those of poly(L-lactic acid) and poly(D-lactic acid) and high crystallinity.
However, the stereocomplex polylactic acid does not show the single phase of stereocomplex polylactic acid and is a mixed-phase composition having the phases of poly(L-lactic acid) and poly(D-lactic acid) (may be referred to as "homo phase" hereinafter) and the phase of the stereocomplex polylactic acid (may be referred to as "complex phase" hereinafter). According to the DSC measurement of the stereocomplex polylactic acid, a low melting point crystal melting peak at a peak temperature of 190° C. or lower corresponding to the melting peak of a homo-phase crystal and a high melting point crystal melting peak at a peak temperature of 190° C. or higher corresponding to the melting peak of a complex-phase crystal are observed.
Since the stereocomplex polylactic acid has the complex phase and the homo phase, it has a defect that the heat resistance of the stereocomplex polylactic acid is hardly obtained fully. To obtain the heat resistance of the stereocomplex polylactic acid, the stereo crystal rate (S) defined by the following equation (a) must be not less than 80%.S=[ΔHmsc/(ΔHmh+ΔHmsc)]×100  (a)
In the above equation (a), Hmh is the crystal melting heat of a crystal melting peak at a temperature lower than 190° C. corresponding to the melting of a homo-phase crystal observed in the DSC measurement, and ΔHmsc is the crystal melting heat of a crystal melting peak at a temperature of 190° C. or higher corresponding to the melting of a complex-phase crystal observed in the DSC measurement.
To cope with this problem, the use of a crystallization nucleating agent such as a phosphoric acid ester metal salt is proposed, and a heat-resistant composition containing no homo-phase crystal but containing only a complex-phase crystal having a crystal melting point of 209° C. and a molded article thereof are proposed (patent document 1).
Even the stereocomplex polylactic acid containing a crystallization nucleating agent such as a phosphoric acid ester metal salt does not still solve a molecular weight reduction problem which occurs in the above-described poly(L-lactic acid) and poly(D-lactic acid) and has a defect that it is difficult to retain its physical properties due to a great reduction in weight average molecular weight. The stereocomplex polylactic acid is classified into a group of aliphatic polyesters and has a defect that it is readily hydrolyzed by moisture as a feature of the aliphatic polyesters like poly(L-lactic acid) and poly(D-lactic acid). Therefore, the improvement of the wet heat resistance of the stereocomplex polylactic acid is desired.    (Patent Document 1) JP-A 2003-192884    (Patent Document 2) JP-A 2005-2174    (Patent Document 3) JP-A 2002-115121    (Patent Document 4) JP-A 11-80522    (Patent Document 5) JP-A 2002-30208    (Patent Document 6) JP-A 63-241024    (Non-patent Document 1) Macromolecules, 24, 5651 (1991)