Disclosed are high throughput assay systems and methods for identifying agents that alter the level of expression of proteins in mammalian cells, particularly integral membrane proteins.

1. Field of the Invention
The present invention relates to high throughput assay systems and methods for identifying agents that alter the level of expression of cellular proteins, with special emphasis on integral membrane proteins in mammalian cells.
2. Background of the Related Art
The ability to respond to the surrounding environment and the control of entry and exit of molecules through the cell membrane are fundamentally important functions of any mammalian cell. These functions are due, in significant part, to the various proteins that reside, in whole or in part, within the cell membrane.
The cell membrane of mammalian cells is relatively impermeable to water-soluble substances, such as ions, small inorganic molecules, peptides and proteins. To enter and/or influence a cell, such hydrophilic substances must interact with at least one protein (e.g. a receptor, an ion channel or a transporter) that resides in the cell membrane and is exposed, at least in part, on the cell surface to the extracellular milieu. In contrast, lipophilic substances, such as steroids, can diffuse directly through the cell membrane into the cytoplasm where it can then interact with one or more target proteins.
There are two basic responses from a cell when an external stimulatory molecule (e.g. a peptide or an organic or inorganic molecule) interacts with a cell surface protein: (i) an ionic or molecular (or macromolecular) material is vectorally transmitted from the outside of the cell membrane to the cytoplasm inside the cell by transport through the lipid bilayer and vice versa; and/or (ii) a signal is transmitted to the cytoplasm or a protein therein by virtue of a change in the membrane protein, e.g. a change in the conformation of the membrane protein and/or the state of aggregation of the membrane protein.
The transfer of a signal across the cell (signal transduction) begins with the binding of an extracellular substance (ion, small molecule, protein) to an extracellular domain of a protein resident in the cell membrane. Binding of the substance to an extracellular domain of the transmembrane protein causes the protein to change form an inactive to an active form. This active form then stimulates catalytic activity, or some similar such response, that generates a cytosolic signal (which is sometimes in the form of one or more secondary messenger substances in the cytoplasm).
There are two major types of such signal transduction in mammalian cells: (i) the transmembrane protein may have a protein kinase activity in its cytosolic domain, the activity of which is activated when the extracellular substance binds to the transmembrane protein (the kinase then phosphorylates its own cytoplasmic domain, which enables the transmembrane protein to associate and activate another protein, which in turn acts on other proteins and substances within the cell cytoplasm); and (ii) the transmembrane protein may interact with a G protein that is associated with the membrane, which causes the GDP (guanine diphosphate) bound to the G protein to be replaced by GTP, resulting in dissociation of the G protein into monomer and dimmer fragments, one or both of which, in turn, acts upon a target protein (also often associated with the membrane, requiring it too then to act upon yet another target protein, this one in the cytoplasm).
The physical transfer of material across the cell membrane permits a wide range of substances to get into and/or out of a cell, including ions, small molecules (such as sugars and hormones) and macromolecules (such as proteins and enzymes). Three major routes exist for such material transfer(s): (i) proteins resident in the cell membrane may form channels that permit the passage of ions, such as sodium, potassium and chlorine, from the extracellular milieu through the membrane and into the cytoplasm, or vice versa; (ii) proteins resident in the cell membrane may bind small molecules, such as sugars, on one side of the membrane and then release that same molecule on the opposite side of the membrane, thereby acting as transporters; and (iii) proteins resident in the cell membrane may bind small molecules and so trigger the process of internalization, in which the bound protein:molecule pair is brought into the cell by endocytosis (at some point, the protein:molecule pair becomes separated; the protein may then be returned to the cell surface to interact with another small molecule or it may be degraded).
Common features of all these proteins include their relatively, large size, the multiple hydrophobic regions spanning the cell membrane, and hydrophilic extracellular and/or intracellular domains.
With respect to the passage or trafficking of macromolecular substances, proteins begin the pathway that leads to secretion by co-translational transfer directly from ribosomes to the membranes of the endoplasmic reticulum. These proteins are then transferred to the Golgi apparatus, where they are sorted according to their final intended destination and move towards the cell membrane.
More specifically, proteins enter the ER during synthesis and are folded and glycosylated, at least partially. The proteins are then transferred to the cis face of the Golgi apparatus (proteins that are to be resident in the endoplasmic reticuluim are returned to the ER at this time). Further glycosylation occurs as the proteins move through the Golgi stacks from cis to trans. Specific signals cause some proteins to be returned to the ER, some proteins to be retained in the Golgi, some proteins to be transported to endosomes and lysosomes, and some proteins (cell surface proteins) to be transported to and retained in the cell membrane.
Those proteins that are transported to and retained in the cell membrane follow the longest and most extensive trafficking pathway, entering the membranes of the endoplasmic reticulum and subsequently traveling through the membranes of transition vesicles, the Golgi complex and secretory vesicles before reaching their final destination. Among these proteins are active and passive transport proteins and cell surface receptors.
To illustrate the complexity of the trafficking pathway, in epithelial cells lining body cavities, the sorting and distribution mechanism of the ER places different proteins in distinct subparts of the cell membrane. For example, proteins transporting sugars and amino acids in intestinal epithelial cells are distributed to that region of the cell membrane facing the intestinal cavity. MHC molecules and the poly-Ig receptors binding antibodies wind up in segments of the cell membrane of epithelial cells on the side opposite the side facing the body interior.
The following is a table of some known cell surface molecules, receptors and membrane-associated proteins.
EGFRepidermal growth factor receptorβ-adrenoreceptorGPCRGABAaRGABAa-gated ion channelnAChRACh-gated ion channelP-glycoproteinmembrane channelKir2.2ion channelMCRmelanocortin receptorhERGion channelA4TM4 familyAbc2ABC transporter; multi-tm; mdr subfamilyAcPLrequired for IL-18 receptor signaling. Contains two IgdomainsAF1qfused to MLL in some leukemiasAlpha-6 integrincomplex with NAG-2Alpha-9 integrinMediates cell-cell and cell-extracellularmatrix interactionsART-4Adenocarcinoma antigen recognized by T-lymphocytesB29Ig superfamilyBAP31potential membrane proteinBeta ig-h3TGF-beta induced; may be associatedwith microfibrils and the cell surfaceBgpdMay play role in self-renewal/diff. of epitheliaCatechol-O-membrane-bound form; inactivates catecholaminemethyltransferaseneurotransmittersCD9TM4; with CD19 in multimolecular B1-integrincomplex, also NAG-2CD19Ig domains; B-cell growth regulationCD27receptor for CD70; TNFR-family; apoptosisCD31/PECAM-1adhesion moleculeCD34"Stem cell antigen"CD37TM4 on B-cellsCD48ligand for CD2CD53TM4 superfamily; high in Burkitt lymphoma cell linesCD54/ICAM-1adhesion moleculeCD59complement inhibitory proteinCD69Involved in lymphocyte proliferationCD87/PAR2Urokinase plasminogen activator receptorCG1Possible TM4 cell surface proteinCoronin-2WD40 domainDPH2Lsingle tm; ovarian ca. suppressorDR5Death receptor for TRAIL; apoptosis-inducingEBI17-tm receptorEBI3contains FnIII domainEP2 or -4prostanoid receptorEvi2BImplicated in leukemogenesisFC gamma R IAntibody Fc receptorFZD4Frizzled 4; receptor for Wnt family ligandsFlk-2receptor tyrosine kinase; differentially expressedFlotillinBAND7 familyGITRglucocorticoid-induced; TNFR family; apoptosis assocGluR3Glutamate ReceptorGlypicanMajor heparan sulfate proteoglycanGPCROrphan G-protein coupled receptorGPR-9-6/CCR9orphan 7-tm hormone receptorHEM-1TM4 familyHepatocytemembrane-bound formGF activatorinhibitorIB3089APutative transmembrane proteinICAM-2Intercellular adhesion moleculeIL-2-gammacommon chain for IL2 and 4 and 7 and 13IL-3-betacommon to IL3 and 5 RIL-3RHematopoietic growth factor receptor associatedwith survival and differentiationIL-4-alphamature form includes IL2 gamma chainIL-6RHematopoietic growth factor receptorIL-7RB-cell growth factorJTBCell surface protein; rearrangedin a jumping translocationL-selectinlymphocyte homing moleculeLAPTm5may have functional role in embryogenesisLigatintrafficking receptor for phosphoglycoproteinsLOX-1Lectin-like oxidized low-density lipoprotein receptorLSM-1interacts with CD45 on lymphocytesLymphotoxin-b Rposs. function in immune developmentMac-2MamaScavenger-like Cys-rich domainMb-1supposedly B-cell restricted; CD3-likeMcp-1chemokine RMDC15metalloprotease-disintegrin; tm glycoproteinMEGF9EGF repeatsMIP-1aRchemokine RMitsugumin 23TM4 protein on ER and nuclear membranesMP709 tmNAG-2Surface TM4 protein similar to CD53;forms complexes w/integrinsNET-4TM4 proteinNET-6TM4 proteinNeuropilinSemaphorin III receptor; also binds VEGFNHE-1sodium/hydrogen antiporterNotch-1Required for the correct differentiation of many tissuesPAR-1 or -2Plasminogen activator receptorperlecanbasement membrane heparan sulfate proteoglycanPft27Putative 7-tm receptorPIRA-1Ig-like; suggested immune regulatory roleProstaglandin E R7-tm receptorProtocadherin-2CExpressed in developing brainRPTP-sigmareceptor tyrosine phosphatase; contains Fn III domainsSelenoprotein RPutative; contains domain of unknown functionSemaphorin BGrowth cone guidance proteinSIMstromal cell protein; TM4 surface RSmoothenedRecptor for Sonic Hedgehog; 7-tmSortilinneurotensin R (NT converting enzyme is in stroma)Stromal CellPotential TM4 cell surface proteinProteinSYBL1synaptobrevin-likeTLR2Toll-like receptor 2TLR4Toll-like receptor 4TSA-1 (Sca-2)Thymic shared antigen; also called Ly-6ETspan6TM4 superfamily; unknown function
The identification of compounds that alter the level of expression of one or more of these proteins is therefore quite important from a number of different perspectives and with a number of goals in mind. For example, identifying a compound that alters the level of expression of a particular protein may lead to the discovery of new therapeutic agents. Alternatively, such an identification may lead to the discovery of the cause or pathway of a defect or disorder. In that way, entirely new areas of research are opened up, as well as a wealth of previously-unknown targets for potential therapeutic intervention.
Moreover, the identification of compounds that alter the level of expression of one or more of these proteins should include compounds that directly or indirectly affect the level of protein expression. A compound that alters the level of expression of an integral membrane protein may do so directly, for example, by binding directly to the protein and inhibiting trafficking. Alternatively, a compound may alter the level indirectly, for example by acting on one or the chaperones that facilitate transport and integration of membrane proteins in the cell membrane or by acting on a protein that degrades the target membrane protein.
There therefore exists a need in the art for assays that can identify compounds that alter the level of expression of proteins, particularly integral membrane proteins, as well as the mechanism by which that level is altered.

High throughput assay systems and methods for identifying agents that alter expression of cellular proteins


The present invention relates to compositions and methods for modulating conception in animals. More particularly, the composition modulates mRNA degradation during gametogenesis and early development. Yet further, the present invention relates to pharmaceutical compositions and methods for modulating diseases of the reproductive organs, such as hyperproliferative diseases.

Viral infection and interferons can induce the expression of 2′, 5′-oligoadenylate synthetases (OAS) (Rebouillat et al., 1999). These OAS proteins are expressed "ubiquitously" in humans and mice. In humans, there are three reported OAS genes (small, OAS1; medium, OAS2; and large, OAS3) and one OAS-like gene (OASL) which are linked on human chromosome 12. There are two mouse OAS genes (Oas1A and Oas1B) that arose from a gene duplication and encode "small" OAS proteins, as well as an OAS-like gene (Oasl5). OASL5 protein is 60% identical to mouse OAS1A and 1B (Shibata et al., 2001) but distinct from human OASL. The three human OAS proteins and the mouse OAS proteins, except OASL or OASL5, share the ability to convert ATP into 2′, 5′-linked oligomers of adenosine (2–5A) in the presence of double stranded (ds) RNA. GTP can also act as a substrate for OAS, though the in vivo significance of this is not understood. 2–5A oligomers bind and activate RNAse L leading to degradation of viral and cellular RNA and thereby downregulating protein production. However, it is not known if OAS or OAS-like proteins have RNAse L-independent antiviral activities or function in cellular processes unrelated to viral infection (i.e., degradation of oocyte mRNA species after fertilization).
Thus, the inventors of the present invention have identified an OAS related family member and provide the first indication that oligoadenylate synthetase-like proteins function in gametogenesis and early embryonic development. It is envisioned that modulation of this protein play a role in contraception, fertility, cell proliferative disease, i.e., cancer, or other reproductive diseases.

Identification of oligoadenylate synthetase-like genes


One embodiment of the invention provides a process and related apparatus for obtaining quantitative data about a 2-dimensional, 3-dimensional image, or other dimensional image. For example, the invention is capable of classifying and counting the number of entities an image contains. Each entity comprises an entity, structure, or some other type of identifiable portion of the image having definable characteristics. The entities located within an image may have a different shape, color, texture, or other definable characteristic, but still belong to the same classification. In other instances, entities comprising a similar color, and texture may be classified as one type while entities comprising a different color, and texture may be classified as another type. An image may contain multiple entities and each entity may belong to a different class. Thus, the system embodying the invention may quantify image data according to a set of changing criteria and derive one or more classifications for the entities in the image. Once the image data is classified, the total number of entities in the image is calculated and presented to the user. Put simply, embodiments of the invention provides a way for a computer to determine what kind of entities (e.g., entities) are in an image and counts the total number of entities that can be visually identified in the image. Another aspect of the invention is that the information utilized during a training process may be stored and applied across different images.

The ability to differentiate between a series of one or more objects comes naturally to human beings. A 5-year old with a set of building blocks can separate the blocks according to size, color, texture, and many other discernible characteristics. Most children can even add more categories to the classification scheme as new qualities appear. For example, as the building blocks age, the surface of the building blocks may fade. If new blocks are introduced to the child, the child can easily tell the difference between the new blocks and the old blocks. Current computer systems, however, find such tasks enormously difficult. Existing systems for classifying objects contained within an image are inherently limited and cannot, for example, effectively identify how many objects of a particular type exist in an image. The limitations of existing technologies become increasingly evident when complex images are to be processed. For example, when the characteristics that distinguish one entity from another are subtle and vary from entity to entity, existing computer systems become unable to accurately classify entities in an image as belonging to a certain type.
There are many uses for an improved system that can reliably quantify entities across multiple sets of image data. For instance, scientists, laboratory technicians, doctors, and other professionals have a need for a technology that enables the extraction of quantitative information from an image. Accurately counting the number of entities in an image requires that the person performing the count understand the various forms and nuances associated with the types of entity being counted. A pathologist may be able to look at a particular red blood cell sample and approximate how many red blood cells are in that sample. A research biologist may need to quantify the number of entities present in a histological brain section for purposes of an experiment, but be prevented from doing so by the lack of time or expertise required to manually perform such an analysis. Similarly, a materials scientist may want to count the number of carbon fibers within a cross section of a structural support but be prevented from doing so due to the large number of carbon fibers in the structural support.
Current systems do not have a mechanism for incorporating the expertise of people skilled at identifying a certain entity type. As a result, there is a need for an image classification system that can incorporate such expertise and give others the opportunity to benefit from it. For instance, while a histologist may have the patience to count a few given entities, he or she will usually do so only to a limited degree due to time and cost. Thus the scientific field has been dominated by illustrating findings with a few select captured images resulting in overly qualitative conclusions. When image classification is utilized to support a particular finding, it is typically done so in areas where the fields are not particularly crowded or where the entities of interest in an image are rarely represented. Counting the number of entities in a crowded image has been impractical. Similarly the counting of entities requiring searching over many fields is impractical. There is another key issue however in terms of consistency of entity assignment among viewers, whether they be inexperienced or professional. Entities often have different features and diverse forms despite the fact they belong to the same entity class. In many cases even the professional has their own distinct classification criteria that are not clearly defined, giving rise to inconsistent results across studies. The labor, monotony, and expertise required for the task often precludes investigation into avenues that may have significant merit, but that are exceedingly difficult to perform.
Due to the problems associated with quantifying image data, there is a need for an improved technology that aids the process of obtaining quantitative data from images such as scientific samples. Such a technology has the potential to provide scientists and other users with important insights into the progression of many different diseases as well as the identification of distinguishing features among diseases. Likewise, chemists or materials scientists may discover new processes or improve compounds when aided in the classification and quantification of their unique images.
Some examples of current image quantification techniques and the problems associated with these techniques will now be discussed so as to provide the reader with an understanding of the need for an improved solution. Image Pro Plus, a software package for processing biological images, nicely exemplifies the standard approach to classification. Image Pro Plus™, is an example of a current system that provides a mechanism for counting, measuring, and/or classifying entities in digital images. Image Pro Plus provides the user with several methods for classifying pixels in terms of their colors. Image Pro Plus provides a mechanism for classifying entities in an image based on their morphology, but the system is difficult to use and does not "learn" how to improve its analytical skill over time. To classify the pixels in an image, the Image Pro Plus user must first interact with the application to define different pixel classes. For example, in the "color cube based dialog" Image Pro Plus divides the set of possible pixel colors into a cube, where a color corresponds to a point (r, g, b) in the cube with red, green and blue intensities r, g and b. The user defines as many distinct pixel classes as he/she wishes. For each class, the user uses an eyedropper tool to select the colors he/she wants to include in the class. When all classes have been defined, Image Pro Plus displays an image in which pixels are partitioned into the appropriate pixel classes. If a given color has been included in two different classes, pixels of that color get assigned to whichever class was defined first.
What Image Pro Plus and other current systems lack is the ability to embody the knowledge of the trained histologist within a general tool that can be used to automate the classification of pixels and/or entities across a broad range of images. The importance of such a general tool lies in its potential to standardize the classification of histological structures across an entire biomedical field or subfield (e.g., the subfield focusing on Alzheimer's Disease). In addition, these same issues also hinder classification of image data in other scientific disciplines as well (e.g. materials science, chemistry, etc. . . . ).
Thus, there is a need for a system that improves upon the existing methodologies and systems for classifying image data. Such an improved system will now be described in detail.

Method and apparatus for generating special-purpose image analysis algorithms


Various embodiments relate to opthalmoscopic devices, systems and methods for viewing the anterior chamber, trabecular meshwork, iris root, scleral spur, and/or related nearby structures in the eye. In some embodiments, devices, systems and/or methods may employ a plurality of gonioscopic optical elements that form a virtual image that can be imaged by a microscope directly in front of a patient (e.g., without tilting the patient's head). Various embodiments described herein may be useful for ophthalmologic diagnoses, treatments, monitoring and/or surgical procedures. Some embodiments include a gonioscopic attachment configured to attach to a conventional gonioscope and redirect light emitted by the gonioscope. Various embodiments described herein can be incorporated into disposable, single-use gonioscopes.

1. Field of the Invention
Various embodiments relate to opthalmoscopic devices, systems and methods useful for viewing structures including but not limited to the anterior chamber; trabecular meshwork, iris root, scleral spur, and/or related nearby anatomical structures in the eye. In some embodiments, devices, systems and/or methods may employ a plurality of gonioscopic optical elements that form a virtual image that can be imaged by a microscope directly in front of a patient. Various embodiments described herein may be useful for opthalmologic diagnoses, treatments, monitoring and/or surgical procedures.
2. Description of the Related Art
Gonioscopy is a technique used for viewing the inner parts of the eye, such as the retina and the anterior chamber angle of the eye for evaluation, management, and classification of normal and abnormal structures. Devices used for gonioscopy are known as gonioscopes. Observation of the anterior chamber and especially its angle areas, which are difficult or impossible to see with the use of simple microscopes, is commonly used for diagnosis of eye diseases. For example, the classification of glaucoma relies heavily upon knowledge of the anterior segment anatomy, particularly that of the anterior chamber angle. Additionally, some surgical procedures used to treat glaucoma involve placing a small tubular stent into the trabecular meshwork in the anterior chamber angle formed by the iris and the cornea. Proper placement of the stent may depend on visualization of the Trabeculum and the angle.
The anterior chamber of a human eye is commonly evaluated with an illuminated microscope (e.g., slit lamp stereromicroscopy), but the chamber angle is typically hidden from ordinary view because of total internal reflection of light rays emanating from the angle structures. A small optical device known to ophthalmologists as a gonioscope is used to enhance visibility of the Trabeculum and the angle. During surgical applications, it may be hand held by the surgeon in place over the patient's cornea while he/she is performing the surgical procedure.


A medicine inhaler has a main body, to which a source of pressurized gas and a source of medicine are attached. By depressing a valve, compressed air enters an ejector through a main channel and atomizes medicine that is drawn into an atomization region by the compressed air. When a piston is in a lower position, into which it is biased by a spring, medicine is free to run into a dosage chamber but is sealed off from an ejection channel and the environment. When the piston is forced upward by compressed air tapped from the main channel, the dosage chamber is sealed off from the medicine source before the dosage chamber is raised to a position in which it communicates with the ejection chamber. When the piston returns to the lower position it generates a secondary puff of air, which enters the main channel to atomize and force residual medicine to the patient. A return channel is also provided to return post-atomized and condensed or improperly atomized medicine to the dosage chamber. Both a portable and a stationary embodiment is provided.

1. Field of the Invention
This invention relates to an inhaler for delivering medicine to a patient.
2. Description of Related Art
A widespread way to administer medicine to a patient is by using a device that atomizes the drug, which the patient then inhales via a mouthpiece, mask, or hood. Such "inhalers" or "nebulizers" are disclosed in the following texts:
U.S. Pat. No. 3,658,059 (Steil), Apr. 25, 1972;
U.S. Pat. No. 4,007,238 (Glenn), Feb. 8, 1977;
U.S. Pat. No. 4,116,387 (Kremer) Sep. 26, 1978;
U.S. Pat. No. 4,674,491 (Brugger) Jun. 23, 1987; and
U.S. Pat. No. 4,746,067 (Svoboda), May 24, 1988.
In order for an inhaler to be usable and effective for a wide variety of applications, patients, and locations, an inhaler should ideally have the following characteristics:
1. The degree of atomization should be high. In other words, as much of a dose as possible should consist of particles as small as possible.
2. The medicine that is stored in the device should never come in contact with the surrounding air or this contact should at least be kept to a minimum. Such a feature would insure that the medicine would not evaporate or become contaminated or diluted and it would also guarantee that medicine, which is often very expensive or in very limited supply (such as certain known drugs used to treat AIDS patients), is not wasted. Moreover, proper containment also avoids exposing others to the medicine. The medicine should be effectively shielded against contamination up until the moment at which it is atomized.
3. It should be possible to administer medicine in both liquid and powder form.
4. The device should protect the patient from an overdose. In many conventional systems, medicine is atomized when the patient or operator presses some form of "trigger", which then causes compress air to be channeled to an atomization chamber or region within the device. In many known inhalers of this type, medicine is administered to the patient as long as the trigger is depressed. This means that the patient or operator must know when to release the trigger in order to stop the flow of air and end the "dose".
5. Atomized medicine that remains in or has just left the mouthpiece, mask, or hood, or which is still trapped in some cavity of the device, should not be wasted. Such a feature would be of particular importance for patients with breathing difficulties such as those with severe asthma, or unconscious patients.
6. It should be possible to use the inhaler with little or no modification for different types of medicine in order to reduce the cost of using such inhalers, and also for it to have the widest possible area of use.
7. The patient should not need different systems when she is stationary (for example, in a hospital bed) and when she is moving around. The ability to mount an inhaler in a stationary configuration benefits not only individual patients who must remain in the home or hospital, such as AIDS patients, but it is also particularly useful for implementing mass vaccination schemes. A portable inhaler that is also designed to allow easy adaptation to efficient stationary mounting and operation could then be transported to remote or underdeveloped areas.
8. The inhaler should provide effective treatment but should not be cumbersome, and it should be as quite as possible in operation so as not to inconvenience or embarrass the user or disturb others.
9. An inhaler should function simply and it should be easy to take apart and put together. This increases reliability and also promotes and facilitates and easy cleaning.
10. In order to ensure maximum hygiene, it should be possible to clean or sterilize the inhaler in, for example, an autoclave.
Existing inhalers or "nebulizers", such as those described in the patents listed above, fail to meet one or more of the preceding design goals. It is accordingly an object of this invention to provide an inhaler that meets these goals.

Inhaler having ejector structure that provides primary and secondary atomization of an actuated dose of medicament


Transgenes encoding exogenous antibodies are stably integrated into donor cells and are present in the somatic tissue of chimeric birds. The transgenes encode exogenous antibodies and are preferably expressed in the oviduct for collection in the egg. Tissue specificity is provided by selecting the content of the transgene accordingly. Birds whose genome is comprised of transgene-derived exogenous antibody-encoding DNA express exogenous antibodies having desirable chemical properties with increased therapeutic utility compared to antibodies derived from bacterial expression systems.

Genetically modified animals offer the potential for tremendous advances in the sustainable production of valuable pharmaceutical products, such as antibodies. However, the production of genetically modified animals involves significant technical hurdles that have only been overcome for a few species. The ability to incorporate genetic modifications encoding proteins into the DNA of a species for a specific expression requires several distinct technologies that must be developed for each genetic modification. One approach to alter the genetic and physical characteristics of an animal is to introduce cells into recipient embryos of the animal. These cells have the ability to contribute to the tissue of an animal born from the recipient embryo and to contribute to the genome of the offspring of a resulting genetically modified animal.
Significant expenditure of time and resources has been committed to the study and development of cell lines, the manipulation of the genome of the cells, and cell culture techniques that permit such engineered cells to be maintained in culture. Although many attempts have been made, the ability to sustain the pluripotency of engineered cells in culture has been achieved for only a few species, notably mice.
If sustainable cultures were readily available and susceptible to genetic engineering while maintaining pluripotency, a broad application of new technologies would be available. Because cultured cells can contribute to the tissues of a chimeric animal, the physiological characteristics of the animal from which an embryonic stem cell was derived can be transferred to a recipient embryo by incorporating these cells into the recipient animal in an embryonic state. This offers two principal advantages: first, the phenotype of an animal from which embryonic stem cells are derived can be selectively transferred to a recipient embryo. Second, as noted above, when the cell cultures are particularly stable, the genome of the cells can be modified genetically to introduce genetic modifications into a recipient embryo in which the cells are introduced.
In certain cases, the cells can be engineered with a transgene that encodes an antibody. The transgene is a genetic construct that contains DNA that acts as the blueprint for the production of the antibody and contains sufficient coding and regulatory elements to enable the expression of the antibody in the tissue of the animal that is created from the insertion of the cells into a recipient embryo. However, the collection of a valuable antibody from the tissues of an animal typically requires that the expression be limited to certain specific tissue types that facilitate collection of the expressed protein and convey desirable chemical properties. For example, in cows, the expression of a protein in the milk enables the ready collection of the protein by simply collecting the milk of the cow and separating the exogenous protein. In chickens, the robust production of antibodies in the white of the egg also provides an attractive vehicle for the expression and collection of the antibodies. Furthermore, where the tissue specific expression is specific to the oviduct of a chicken, the expression yields antibodies having certain specific desirable chemical properties that increase the therapeutic utility of the antibodies when used in the treatment of a human patient. Thus, one particularly attractive field of research and commercial development is genetically engineered chickens that selectively express antibodies in the egg to facilitate isolation and collection of proteins with desirable chemical properties. The ability to selectively produce exogenous antibodies in specifically selected cells of an animal is particularly valuable because the absence of tissue specificity simply results in the antibody being expressed in all of the tissues of an animal. Under such circumstances, it is unlikely that a meaningful quantity of the antibody could be separated from the animal, the ubiquitous expression of an exogenous antibody is usually very damaging to the overall health and well being of the animal, and the desirable chemical properties exhibited in the chicken oviduct are not present.
If cell culture is sufficiently stable to allow a transgene to become integrated into the genome of the cell, a transgene encoding tissue specific expression of an antibody can be passed to a new chimeric or transgenic organism by several different techniques depending on the target cell and the specific construct used as the transgene. Whole genomes can be transferred by cell hybridization, intact chromosomes by microcells, subchromosomal segments by chromosome mediated gene transfer, and DNA fragments in the kilobase range by DNA mediated gene transfer (Klobutcher, L. A. and F. H. Ruddle, Annu. Rev. Biochem., 50: 533-554, 1981). Intact chromosomes may be transferred by microcell-mediated chromosome transfer (MMCT) (Fournier, R. E. and F. H. Ruddle, Proc. Natl. Acad. Sci. U.S.A., 74: 319-323, 1977). The specific design of the transgene also must consider the content of the DNA sequences encoding the antibody, the target cell line, the specific tissue in which expression is targeted, the host organism in which expression occurs, and the antibody to be expressed. The transgene designed for tissue specific expression must satisfy several parameters to enable successful integration into the genome of a cell and to insure successful expression in the selected tissue of the host organism.
As noted above, the introduction of genetic modifications to produce transgenic animals has been demonstrated in only a very few species. For mice, the separate use of homologous recombination followed by chromosome transfer to embryonic stem (ES) cells for the production of chimeric and transgenic offspring is well known. Powerful techniques of site-specific homologous recombination or gene targeting have been developed (see Thomas, K. R. and M. R. Capecchi, Cell 51: 503-512, 1987; review by Waldman, A. S., Crit. Rev. Oncol. Hematol. 12: 49-64, 1992). Insertion of cloned DNA (Jakobovits, A., Curr. Biol. 4: 761-763, 1994), and manipulation and selection of chromosome fragments by the Cre-loxP system techniques (see Smith, A. J. et al., Nat. Genet. 9: 376-385, 1995; Ramirez-Solis, R. et al., Nature 378: 720-724, 1995; U.S. Pat. Nos. 4,959,317; 6,130,364; 6,091,001; 5,985,614) are available for the manipulation and transfer of genes into murine ES cells to produce stable genetic chimeras. Many such techniques that have proved useful in mammalian systems would be available to be applied to non-mammalian systems if the necessary long term cell cultures were available and if transgenes could be designed that yielded tissue specific expression in specific tissues that facilitate isolation and collection of the exogenous protein.
The transgenes that enable tissue specific expression are complex and the genetic manipulations that are necessary to incorporate the transgenes into a recipient cell line require extensive manipulation that can threaten the pluripotency of the cells unless the culture conditions are optimized. Thus, cell lines suitable for use in transgenesis must be both stable in culture and must maintain pluripotency when the cell is transfected with a genetic construct that is large and complex enough to contain all of the elements necessary for tissue specific expression. In the resulting animal, the transgene must be effectively expressed in specific individual tissue types in which the transgene is designed to be expressed, and should not be expressed in other tissues such that the viability of the animal or the advantageous chemistry of the resulting protein is compromised.
For the production of exogenous antibodies, avian biological systems offer many advantages including efficient farm cultivation, rapid growth, and economical production. Further, the avian egg offers an ideal biological design, both for massive synthesis of antibodies and ease of isolation and collection of product. Furthermore, as described below in the context of the present invention, advantages of the chicken-based expression system compared to vertebrate, plant, or bacterial cell systems can be obtained for large quantities of antibody product.

This patent is subject to a terminal disclaimer.

Tissue specific expression of antibodies in chickens


A solid-state imaging device includes a pixel array section which includes a plurality of pixels arranged in a two-dimensional manner, and a vertical scanning circuit which successively performs selection and scanning for a plurality of rows of the pixel array section. Each of the pixels includes a photoelectric conversion element, a transfer transistor which transfers a signal charge of the photoelectric conversion element to a detecting section, a reset transistor which sets a voltage of the detecting section to a voltage of a power supply terminal, and an amplifying transistor which amplifies and reads a signal charge of the detecting section. A first voltage which is lower than a power supply voltage is applied to the detecting section, in a charge-storage period of the photoelectric conversion element.

1. Field of the Invention
The present invention relates to a solid-state imaging device and a method of driving the same, for example, an MOS solid-state imaging device used for complementary metal oxide semiconductor (CMOS) sensor cameras ready for low-voltage drive and moving images and a method of driving the same.
2. Description of the Related Art
In recent years, MOS solid-state imaging devices using a CMOS sensor have become commercially practical. MOS solid-state imaging devices amplify a signal, which is detected by a photodiode, by a MOS transistor for each cell, and feature high sensitivity.
Each cell (pixel) of the solid-state imaging devices is formed of a photodiode for photoelectric conversion, a read transistor for signal reading, an amplifying transistor for signal amplification, and a reset transistor to reset a signal charge, etc. A source of the amplifying transistor is connected to a vertical signal line, and a signal output to the vertical signal line is output to a horizontal signal line through a horizontal selection transistor.
The pixel size of the solid-state imaging devices has been reduced year after year, due to increase in the number of pixels and demand for reduction in the optical size. For example, the pixel size of CMOS sensors used for digital cameras and the like in recent years is about 2 to 3 μm. Since the number of photons which can receive light is reduced in such fine pixels, the signal-to-noise ratio cannot be maintained unless noise is reduced to compensate it. When the signal-to-noise ratio cannot be maintained, the image quality in playback images degrades, and the quality of playback images degrades. Dark current noise which flows into photodiodes during charge storage is one of the main forms of noise. Reducing dark current noise is indispensable for maintaining the signal-to-noise ratio in fine pixels.
In the meantime, in operation of reading a signal from a photodiode, it is necessary to read all charges to prevent leaving of any charges in the photodiode, to suppress an afterimage phenomenon which is caused by reading charges, which were stored in the previous frame, in the following frame. Therefore, it is impossible to increase the threshold of the transfer transistor. The dopant concentration of the channel dope layer of the transfer transistor is low, and generally about 1.0×1015 cm−2 to 1.0×1017 cm−2.
When the channel dope layer has such a dopant concentration, the semiconductor substrate interface directly under the transfer transistor becomes depleted during a charge storage period of the photodiode (during the read transistor turning off). Therefore, electrons being minor carriers are generated to form a dark current, and the dark current flows into the photodiode. The value of the flowing dark current varies pixel to pixel, and thus the dark current becomes a fixed pattern noise on the playback image, and the signal-to-noise ratio in the playback image degrades.
To deal with the above problem, a patent document (Jpn. Pat. Appln. KOKAI Pub. No. 2002-217397) takes the following measure. Specifically, a negative voltage is applied to the gate of the transfer transistor during a charge-storage period, and thereby a sufficient number of positive holes being major carriers are stored in the channel dope layer of the transfer transistor. Thereby, the speed of generating electrons in the interface of the semiconductor substrate remarkably decreases. Thus, the dark current flowing into the photodiode is reduced, and thereby the fixed pattern noise is reduced.
However, the patent document has the following problem. Specifically, when a negative voltage of, for example, −2 V is applied to the gate of the transfer transistor during a charge-storage period, a difference in potential of about 5.5 V occurs between a floating diffusion layer (detecting section) which is biased to, for example, 2.5 V during the charge-storage period and the gate of the transfer transistor. Most of the difference in potential is applied to an end portion on the detection section side in the gate insulating film of the transfer transistor. However, when the electric field applied to the gate insulating film exceeds 5×106 V/cm, generally the voltage-withstand reliability of the gate insulating film degrades, and the insulating property of the gate insulating film badly decreases during operation of the device. Thereby, the gate of the transfer transistor and the floating diffusion layer are short-circuited, and it is impossible to perform signal reading operation of pixels.
Since the thickness of the gate insulating film is about 50 Å in the general CMOS device manufacturing process in recent years, when the above difference in potential is applied to the gate insulating film, the electric field applied to the gate insulating film is about 9×106 V/cm at the maximum. Therefore, according to the device driving method of the above patent document, the reliability of the gate insulating film may degrade, and the device operation may become impossible.

Solid-state imaging device and method of driving the same


A substrate-mounting connector includes a housing, a contact mounted to the housing, and a shield shell. The shield shell includes a first plate and a second plate disposed adjacently. A part of the first plate serves as a first contact portion. A first extension piece is formed in the second plate. A part of the first extension piece serves as a second contact portion. A part of the housing serves as a pressing portion facing the first plate, in a covering state in which the shield shell is mounted to the housing. A part of the first plate, different from the first contact portion, or a part of the first extension piece, different from the second contact portion, serves as a pressed portion pressed by the pressing portion in the covering state. The pressing portion presses the pressed portion to make the first contact portion contact the second contact portion.

FIGS. 1A and 1B show the structure of a receptacle connector described in Patent Literature 1 as a prior art example of this type of a substrate-mounting connector. A receptacle connector 10 includes an insulating housing 11, a shield-shell metal fitting 12, contacts 13, and a shield cover 14. The shield-shell metal fitting 12 and the contacts 13 are integrally mounted to the insulating housing 11. The shield cover 14 is mounted to the insulating housing 11 along a rear flat surface and both side surfaces of the insulating housing 11.
The shield-shell metal fitting 12 has a joining sheath 12a. The joining sheath 12a joins a mating plug to be inserted into the receptacle connector 10. The insulating housing 11, to which the shield-shell metal fitting 12 is mounted, covers an outer peripheral surface and a rear opening of the joining sheath 12a, the mating plug being to be inserted into a front opening of the joining sheath 12a. The insulating housing 11 has a support plate (hidden in FIGS. 1A and 1B) protruding forward in the joining sheath 12a. Contact parts (hidden in FIGS. 1A and 1B) located at the front tips of the contacts 13, which are mounted to the insulating housing 11, are located along the support plate of the insulating housing 11 and are exposed. The legs 13a of the contacts 13 protrude backward from the insulating housing 11. The legs 13a of the contacts 13 are enclosed by the shield cover 14.
Two contact pieces 14a formed in the shield cover 14 are press fitted into two insertion holes 11a formed in the insulating housing 11. Each of the contact pieces 14a is in contact with an exposed portion of the joining sheath 12a, the exposed portion being exposed via a corresponding insertion hole 11a. In FIGS. 1A and 1B, two grounding legs 12b are formed in the shield-shell metal fitting 12, and the shield-shell metal fitting 12 is exposed externally at outside exposure portions 12c via two insertion holes 11b formed in the insulating housing 11.
In the receptacle connector 10, the contacts 13 are electromagnetically shielded by two external shields, namely, the shield-shell metal fitting 12 and the shield cover 14. Therefore, high-frequency signals flowing through the contacts 13 are prevented from radiating externally, and external noise is also prevented from being superimposed on the high-frequency signals.

JAPAN AVIATION ELECTRONICS INDUSTRY, LIMITED


To provide a mask blank for EUVL wherein the incident angle dependence of EUV reflectivity and the film stress in a Mo/Si multilayer reflective film are improved, and a reflective layer-equipped substrate for such a mask blank. The reflective layer-equipped substrate for EUV lithography (EUVL), comprises a substrate, and a reflective layer for reflecting EUV light, formed on the substrate, wherein the reflective layer comprises a second multilayer reflective film having a Mo layer and a Si layer alternately stacked plural times on the substrate, an adjustment layer stacked on the second multilayer reflective film, and a first multilayer reflective film having a Mo layer and a Si layer alternately stacked plural times on the adjustment layer.

1. Field of Invention
The present invention relates to a reflective mask blank for EUV (Extreme Ultraviolet) lithography (hereinafter referred to also as "EUV mask blank" in this specification) to be used for e.g. production of semiconductors.
Further, the present invention relates to a reflective layer-coated substrate for EUV lithography (EUVL). The reflective layer-coated substrate for EUVL is useful as a precursor for a mask blank for EUVL.
2. Discussion of Background
Heretofore, in the semiconductor industry, a photolithography method employing visible light or ultraviolet light has been used as a technique to transfer a fine pattern required to form an integrated circuit with a fine pattern on e.g. a silicon substrate. However, the conventional photolithography method has come close to its limit, while miniaturization of semiconductor devices is being accelerated. In the case of the photolithography method, the resolution limit of a pattern is about ½ of the exposure wavelength. Even if an immersion method is employed, the resolution limit is said to be about ¼ of the exposure wavelength, and even if an immersion method of ArF laser (wavelength: 193 nm) is employed, about 45 nm is presumed to be the limit. Under the circumstances, as an exposure technique for the next generation employing an exposure wavelength shorter than 45 nm, EUV lithography is expected to be prospective, which is an exposure technique employing EUV light having a wavelength further shorter than ArF laser. In this specification, EUV light is meant for light ray having a wavelength within a soft X-ray region or within a vacuum ultraviolet region, specifically for light ray having a wavelength of from about 10 to 20 nm, particularly about 13.5 nm±0.3 nm.
EUV light is likely to be absorbed by all kinds of substances, and the refractive index of substances at such a wavelength is close to 1, whereby it is not possible to use a conventional refractive optical system like photolithography employing visible light or ultraviolet light. Therefore, in EUV lithography, a reflective optical system, i.e. a reflective photomask and mirror, is employed.
A mask blank is a layered product before pattering, to be used for the production of a photomask. In the case of an EUV mask blank, it has a structure wherein a reflective layer to reflect EUV light and an absorber layer to absorb EUV light, are formed in this order on a substrate made of e.g. glass.
Usually, a protective layer is formed between the above reflective layer and the absorber layer. Such a protective layer is provided for the purpose of protecting the reflective layer, so that the reflective layer will not be damaged by an etching process to be carried out for the purpose of forming a pattern in the absorber layer.
As the reflective layer, it is common to use a Mo/Si multilayer reflective film having a molybdenum (Mo) layer as a layer to show a low refractive index to EUV light and a silicon (Si) layer as a layer to show a high refractive index to EUV light alternately stacked to have the light reflectivity improved when the layer surface is irradiated with EUV light.
For the absorber layer, a material having a high absorption coefficient to EUV light, specifically e.g. a material containing chromium (Cr) or tantalum (Ta) as the main component, is used.
Along with a trend for higher NA (numerical aperture) for an exposure device to be used for EUV lithography, an incident angle dependence of the reflectivity at the mirror surface to be used in a reflective optical system has been problematic (Patent Document 1).
Such an incident angle dependence of the reflectivity becomes problematic also in a reflective photomask and a mask blank as a precursor for such a photomask.
For example, if the specification for NA becomes 0.45 from current 0.33, the incident angle θ of EUV light will be required to satisfy the reflectivity characteristics by expanding its range to ±15° from ±11°. The index for the reflectivity characteristics to be required in such a case has not yet been specified, but at least at one wavelength within a range of from 13.2 nm to 13.8 nm, a reflectivity of EUV light of at least 50% will be required in the entire range of −15°≦θ≦+15°, and it will be required that the fluctuation range of the EUV reflectivity within the above range of θ is small. As a specific example, at least it is required that when the minimum value is represented by Rmin (%), the fluctuation range of the EUV reflectivity in the above range of θ is within Rmin× 1/10.
Further, also in a mirror to be used in a reflective optical system, a Mo/Si multilayer reflective film is used as a reflective layer, and in the case of such a Mo/Si multilayer, a deformation of the substrate caused by an internal stress based on its structure has been problematic (Patent Document 2).
And, in the case of a reflective photomask employing a Mo/Si multilayer reflective film as a reflective layer, and a mask blank to be used for such a photomask, higher flatness than a mirror to be used in a reflective optical system is required, and accordingly, a deformation of the substrate caused by an internal stress of the Mo/Si multilayer reflective film becomes more problematic.

Reflective mask blank for EUV lithography, and reflective layer-coated substrate for EUV lithography


Methods and systems for improving utilization of traffic channels in a mobile communications network. A method for allocating communication channels is provided for allocating communication channels for handoff in a first base station having a communication link with active mobile stations located in a handoff area of the first base station and a second base station. The method includes constructing a channel convertible set including communication channels for active mobile stations moving in a direction away from the first base station; receiving a handoff request from a requesting mobile station having a communication link with the second base station; and determining whether a free channel is available for the handoff request. Furthermore, the method includes allocating one of the communication channels in the channel convertible set to the handoff request if a free channel is not available for the handoff request.

In mobile communication networks, mobile handsets communicate with the fixed network via wireless communication links or channels. The network entity that manages wireless communication channels for a particular geographic area is referred to as a base station. Mobile communication networks typically include many base stations—one for each geographic area or cell.
When a mobile subscriber moves from one location to another location during a call, it may be necessary to hand the call off from one base station to another base station or between antennas within the same base station in order to maintain call quality. Handoff is a process by which a call, or active communication link, is transferred from one communication channel to another. There are three types of handoff that occur in mobile communication systems—hard handoff, soft handoff, and softer handoff. A hard handoff is the transfer of one communication channel to another communication channel that has not been previously established. A soft handoff is a conversion from one communication channel to another previously established communication channel where the two communication channels are with different base stations. A softer handoff refers to a transfer from one communication channel to another previously established communication channel where the two communication channels are with the same base station. A softer handoff may occur when a mobile station moves between areas served by different antennas of a base station.
Although the present invention can be applied to all three types of handoffs, a discussion of soft handoffs illustrates problems common to all three handoff methods. Soft handoff is initiated and ended based on the strength of a pilot signal received by a mobile station. A pilot signal is a signal transmitted from a base station to a mobile station via a control channel. Mobile stations measure the signal strength of the pilot signal to determine whether a handoff is necessary. For example, if the signal strength of a pilot signal from one base station exceeds a threshold value, the base station may determine that handoff of an active communication channel from the current base station to a new base station is required.
The process of soft handoff involves finding an available communication channel on the neighboring base station towards which the mobile station is moving in order to establish an active communication link. The available channels on a base station may be divided into two groups—free channels and soft guard channels. Free channels are communication channels available to mobile stations requesting a communication channel to establish a communication link. Soft guard channels are exclusively reserved for those mobile stations requesting a communication link in the handoff area. The reason for having soft guard channels reserved exclusively for handoffs is to reduce the likelihood of calls being dropped when a mobile station moves from one geographic area to another. In other words, the network designers decided to reserve a portion of base station resources exclusively for handoff calls rather than new calls because they decided it was better to refuse to admit new calls than to drop calls in progress. If a free or soft guard channel is not available on the neighboring base station, the communication link between the mobile station and the communication system may be dropped once the mobile station is out of the coverage area of the base station with which it is actively communicating.
Mobile stations continuously measure pilot signal strength with multiple base stations and classify the base stations in one of three sets based on signal strength: a neighborhood set; a candidate set; and an active set. The neighborhood set contains communication channels that are likely candidates for handoff but not currently in the active set or candidate set. The candidate set contains base stations having at least one available communication channel that could successfully establish a communication link between the base station and mobile station. The active set contains the base stations with which the mobile station has an active communication link on which speech frames or other data frames are transmitted. When the received pilot signal strength exceeds threshold TADD, the detected pilot signal is transferred from the neighborhood set to the candidate set. The threshold TADD is a predefined pilot signal strength value considered acceptable for establishing a communication link. If a base station receives a message indicating handoff completion from the mobile station, the associated base station is transferred from the candidate set to the active set. If the pilot signal strength received by the mobile station from the base station of the current cell is less than a predefined threshold TDROP, the base station is transferred from the active set to the neighborhood set and a message indicating handoff completion is transmitted to the base station.
The coverage area of the overlap of cells in soft handoff is known as the handoff area. The handoff area is primarily controlled by the handoff thresholds, TADD and TDROP. The area of a cell not covered by a handoff area (i.e., does not overlap the geographic area covered by another cell) is known as the normal area. The soft handoff process is defined in the Telecommunications Industry Association (TIA) and Electronic Industries Alliance (EIA) IS-95 publication, "Mobile Station-Base Station Compatibility Standard for Dual-mode Wideband Spread Spectrum Cellular System," which is incorporated herein by reference. In the soft handoff process defined in US IS-95, there can be two or more base stations in the active set. When the signal strength of one of the pilot signals of an active set base station is less than TDROP, the corresponding call will leave the handoff area for the normal area after a short duration of time.
Although the capacity of CDMA systems is interference limited in nature, channel shortages may occur and utilization efficiency of traffic channels decreases because mobile stations may use several channels simultaneously when located in the handoff area. For example, while in the handoff area, a mobile station requests a soft handoff to a neighboring base station whenever the received pilot signal strength from the neighbor base station exceeds the predetermined threshold, although the mobile station is not actually approaching the neighboring base station. In this case, there exists unnecessary soft handoff calls requested by a mobile station moving in a direction away from the neighboring base station or a mobile station that is stationary. Typically, in urban CDMA cellular systems, the handoff area occupies approximately 30–50% of the cell area. Therefore, in a handoff process in which mobile stations in the handoff area unnecessarily occupy two or more communication channels, the number of available communication channels is reduced and the probability that a call will be dropped is increased. Therefore, a need exists for an improved communication channel allocation method that discriminates between calls in the handoff area. Furthermore, a process for allocating channels for handoff is desired which does not significantly increase computation complexity.


A new and improved thermal type bulkhead assembly comprises a pair of new and improved thermal type bulkhead members which are adapted to be adjustably positioned with respect to each other in an overlapped mode in the widthwise direction whereby oppositely disposed side edge portions of the pair of bulkhead members can effectively engage the oppositely disposed interior side walls of the refrigerated cargo container, while upper sections of the bulkhead members can flexibly engage the ceiling portion of the refrigerated cargo container. In this manner, the lateral extent or width dimension x of the thermal type bulkhead assembly, as well as the vertical extent or height dimension y of the thermal type bulkhead assembly, can be adjustably varied whereby the thermal type bulkhead assembly of the present invention is effectively universal in structure so as to be capable of being utilized within different refrigerated cargo containers characterized by different internal width and height dimensions.

Refrigerated cargo containers, such as, for example, those defined or present within refrigerated trucks, refrigerated trailers, refrigerated railroad cars, or the like, are conventionally used, for example, to house or store, and effectively maintain frozen or refrigerated, perishable cargo, while such perishable cargo is being transported in connection with its commercial distribution, in order to preserve such perishable cargo in its freshest possible condition or state. The refrigeration units are conventionally mounted within the forward end portions of the cargo containers, such as, for example, upon the front walls of the cargo containers. In accordance with conventional cooling processes, cycles, or methodology, cooled or conditioned air is discharged or exhausted from the refrigeration unit outlet, which is disposed within the upper region of the cargo container, such that the air is effectively conducted in the rearward direction and through the cargo container within the vicinity of the cargo container ceiling. At the same time, warmer air is drawn in the forward direction, through the lower region of the cargo container within the vicinity of the cargo container floor structure, so as to effectively be conducted or routed back toward, and into, the refrigeration unit inlet. Such return air is then able to be re-cooled or re-conditioned for recirculation back into the cargo container as a result of again being exhausted or discharged from the refrigeration unit outlet.
In order to properly facilitate or establish the aforenoted air flow patterns within the refrigerated cargo containers, one type of bulkhead structure that has been conventionally installed within refrigerated cargo containers comprises air return bulkhead structures which are disposed in spaced relationship with respect to the front walls of the refrigerated cargo containers so as to effectively define plenum chambers or spaces into which the warmer return air can be effectively be conducted back toward the refrigeration unit inlet. More particularly, the air return bulkhead structures, in addition to effectively defining the aforenoted plenum space or chamber, also serve to effectively protect the refrigeration units from being damaged, such as, for example, by means of the cargo loads which may tend to shift in place during the transportation of the same. Conventional air return bulkhead structures, of the aforenoted type, are disclosed, for example, within U.S. Pat. No. 6,203,419 which issued to Onken on Mar. 20, 2001, U.S. Pat. No. 6,116,044 which issued to Gothier on Sep. 12, 2000, U.S. Pat. No. 5,993,310 which issued to Onken on Nov. 30, 1999, U.S. Pat. No. 5,947,812 which issued to Henning et al. on Sep. 7, 1999, U.S. Pat. No. 5,807,046 which issued to Onken on Sep. 15, 1998, and U.S. Pat. No. 5,769,704 which issued to Henning et al. on Jun. 23, 1998. While all of the aforenoted air return bulkhead structures are constructed so as to achieve or perform their predetermined objectives in a substantially satisfactory or adequate manner, it is noted that such air return bulkhead structures do not comprise, in effect, thermal barriers which are required for defining separate freezer, refrigerated, and dry compartments within the refrigerated cargo container.
Accordingly, a second type of bulkhead structure that has conventionally been incorporated within refrigerated cargo containers is a thermal barrier type bulkhead structure, however, it is known that such conventional PRIOR ART thermal barrier type bulkhead structures have inherent operational, installation, and manufacturing drawbacks or disadvantages. For example, it is known in the art or industry that different cargo containers, as defined within differently sized trucks, trailers, railroad cars, or the like, are characterized by different internal width and height dimensions. It can therefore be readily appreciated that when a thermal barrier type bulkhead structure is to be internally incorporated within a particular refrigerated cargo container, it must obviously be manufactured or fabricated in accordance with predeterminedly precise dimensional specifications. It can be further readily appreciated, however, that such manufacturing or fabrication processing is very costly, such manufacturing or fabrication processing requires a substantial lead-time in order to achieve the manufacture or fabrication of the thermal bulkhead structure, and lastly, such manufacturing or fabrication processing results in a correspondingly long delivery time of the bulkhead structure to the end customer. While it is noted that the various air return bulkhead structures, as disclosed, for example, within the aforenoted patents which issued to Onken, do comprise upper support panels which are provided with ridges or other discontinuities along which a cutting tool may be guided so as to effectively form different spaces for accommodating differently sized refrigeration units, and while, still further, other structural components or parts of the air return bulkhead structures may likewise be removed so as to alter the return airflow patterns leading back to the refrigeration unit inlet, the provision and use of such severable structural components or parts nevertheless do not address the aforenoted problem concerning the requirement or need for providing individual, precisely sized thermal bulkhead structures which are to be internally incorporated within the differently sized refrigerated cargo containers. More particularly, it is noted that the air return bulkhead structures, as disclosed, for example, within the aforenoted patents which issued to Onken, are not capable of having their dimensional sizes expanded or contracted so as to effectively be used in a properly sealed manner with respect to the internal wall members of the differently sized refrigerated cargo containers which define the internal cargo container space within the refrigerated cargo containers.
A need therefore exists in the art for a new and improved thermal type bulkhead structure for incorporation within differently sized refrigerated cargo containers, such as, for example, those defined or present within refrigerated trucks, refrigerated trailers, refrigerated railroad cars, and the like, wherein the new and improved thermal type bulkhead structure can be readily and easily expanded and contracted so as to effectively alter the height and width dimensions of the thermal type bulkhead structure in order to permit the thermal type bulkhead structure to be utilized within differently sized refrigerated cargo containers in a properly sealed manner with respect to the internal wall members of the differently sized refrigerated cargo containers which define the internal cargo container space within the refrigerated cargo container. In this manner, the thermal type bulkhead structure can effectively comprise a single, universal thermal type bulkhead structure which could effectively be mass-produced and subsequently installed in an onsite manner within any particularly sized or dimensioned refrigerated cargo container so as to respectively define freezer, refrigerated, and dry compartments within the refrigerated cargo container. As a result of the provision of such a universal thermal type bulkhead structure, the need to manufacture or fabricate a multitude of differently sized or dimensioned thermal type bulkhead structures, in accordance with predetermined size dimensions characteristic of different, predetermined or specific refrigerated cargo containers, would be obviated, rendered unnecessary, and eliminated.

Expandable/contractible universal thermal bulkhead structure for use within refrigerated cargo containers


A system for industrial radiography is disclosed comprised of (1) an industrial radiographic element comprised of a support covered on each of its major faces with a tabular grain emulsion layer in which at least 50 percent of total grain projected area is accounted for by silver bromide tabular grains having an average aspect ratio of at least 2 and a volume greater than 0.03 .mu.m.sup.3 and (2) disposed on opposite sides of the radiographic element, two intensifying screens designed to emit electrons when exposed to X or gamma rays with an energy greater than or equal to 10 kV. A speed improvement is realized upon exposure and processing.

Industrial radiography is a non-destructive technique for testing and analyzing defects in components such as glass, paper, wood or metal parts. This technique is widely used in aeronautics, the nuclear industry or the petroleum industry since it makes it possible to detect welding defects or defects in the texture of materials in aircraft components, nuclear reactors or pipelines.
This technique consists of exposing a component to be analyzed to an ionizing radiation, in general X or gamma radiations having an energy between 10,000 and 15,000 kV, either directly or by means of an intensifying screen. It is therefore necessary with this technique to use specific radiographic elements which are sensitive to this ionizing radiation.
The sensitivity of the radiographic emulsions to X or gamma radiations is due to the absorption of a part of these radiations by the silver halide grains, which causes a secondary emission of electrons, which form an internal latent image. Consequently the ionization radiations have an action on the silver halide grains solely when they are absorbed by these grains.
However, it is known that the major part of the ionizing radiation passes through the silver halide grains without being absorbed. Only a very small part of the incident radiation (less than 1%) is absorbed and contributes to the formation of developable latent image nuclei.
It is for this reason that the elements for industrial radiography generally consist of silver halide emulsion comprising mainly thick grains (three dimensional or cubic) in order to be able to absorb the maximum amount of ionizing radiations passing through the emulsion layer.
In addition, in order to assist the absorption of the ionizing radiations, it is known that the silver content or the thickness of the emulsion layers can be increased, or that the radiographic support can be covered on each of its faces with a silver halide emulsion layer.
For example, the patent FR 2 367 300 describes a radiographic emulsion comprising silver halide grains having mean diameter of at least 0.25 .mu.m and a substantially regular crystalline structure. In the examples illustrating this patent, the silver halide emulsions consist of regular cubo-octahedral grains of at least 0.7 1 .mu.m.
For several years, there have appeared silver halide photographic elements consisting of tabular grains which offer sensitometric advantages such as, for example, an improved sensitivity/granularity ratio.
In more recent patents, attempts have therefore been made to introduce these tabular silver halide grains into industrial radiography elements.
For example, U.S. Pat. No. 5,230,993 describes a product for medical or industrial radiography which may contain tabular silver halide grains. However, as the examples show, this patent describes spectrally sensitized radiographic elements which are intended to be used with fluorescent intensifying screens which re-emit visible light when they are exposed to X-rays. In this case, the silver halide emulsions are conventional emulsions sensitive to visible light.
U.S. Pat. No. 4,883,748 describes a film for industrial radiography in which the silver halide emulsion comprises silver halide grains having an aspect ratio (the ratio between diameter and thickness) less than or equal to 5 (preferably between 1 and 3) and whose surface region contains a larger proportion of iodide than the internal region. In the examples illustrating the invention, the majority of the emulsions consist of tetradecahedral grains with an aspect ratio of 1. Example 2 shows clearly that by increasing the aspect ratio the contrast of the radiographic element exposed to X-rays is degraded.


A method for through-plating field effect transistors with a self-assembled monolayer of an organic compound as gate dielectric includes through-plating by patterning a gate electrode material, and bringing an organic compound having dielectric properties into contact with the contact hole material and the gate electrode material. A contact hole material and the gate electrode material are at least partially uncovered. The contact hole is material not identical to the gate electrode material. A self-assembled monolayer of the organic compound is formed above the gate electrode material. The method also includes depositing and patterning the source and drain contacts without removing the self-assembled monolayer of the organic compound, and depositing a semiconductor material.

Field effect transistors based on organic semiconductors are of interest for electronic applications that require extremely low production costs, flexible, or unbreakable substrates, or fabrication of transistors and integrated circuits over large areas. For example, organic field transistors are used as pixel control elements in active matrix screens. Such screens are usually produced with field effect transistors based on amorphous or polycrystalline silicon layers. Temperatures of more than 250° C. are usually necessary for fabricating high-quality transistors based on amorphous or polycrystalline silicon layers require the use of rigid unbreakable glass or quartz substrates. Due to the relatively low temperatures at which transistors based on organic semiconductors are fabricated, e.g., usually less than 200° C., organic transistors permit production of active matrix screens using inexpensive, flexible, transparent, unbreakable polymer films with considerable advantages over glass or quartz substrates.
Another application for organic field effect transistors is fabrication of very inexpensive integrated circuits used, for example, for active labeling and identification of merchandise and goods. These transponders are usually produced using integrated circuits based on monocrystalline silicon, which leads to considerable costs in the construction and connection technology. Producing transponders based on organic transistors leads to enormous cost reductions and assists in increasing transponder technology en route to a worldwide breakthrough.
The fabrication of thin-film transistors usually requires a large number of steps in which the different layers of the transistor are deposited. In a first step, the gate electrode is deposited on a substrate, then the gate dielectric is deposited on the gate electrode, and the source and drain contacts are deposited and then patterned. Finally, the semiconductor is deposited between the source and drain electrodes on the gate dielectric.
Efforts to simplify the fabrication process for field effect transistors and to fabricate the field effect transistors with smaller dimensions have been made. Fabrication of organic field effect transistors requires a targeted patterning of the gate dielectric layer since the targeted access necessary for operation of the transistors to the electrodes or contacts in the metallization plane or the metallization planes below an insulating layer of a substrate (i.e., the substrate in which the transistors are formed) are produced by through-plating (also referred to as contact hole or "via") in the insulating layer. An access to the metallization planes situated below the insulating layer is necessary, if the input of one transistor is to be linked to the output of another transistor, as is necessary in many cases in almost every integrated circuit.
In recent years, a plurality of microelectronics elements have been described which have a size of a few nanometers and require no lithographic methods or fewer lithographic steps to be fabricated. These elements are nanoelements fabricated by nanotechnology. The elements have a self-assembled molecular layer (self-assembled monolayer).
When using conventional gate dielectrics, such as silicon oxide and aluminum oxide, for example, the contact holes are opened after deposition of the initially closed dielectric layer. For patterning the gate dielectric, a photoresist is applied, exposed, and developed. Then, the gate dielectric is removed by an etching process in regions of the envisaged contact holes. The photoresist protects the regions that are not to be etched. Finally, the photoresist mask is again removed.
This method is unsuitable for patterning molecular self-assembled monolayers. Photoresists are generally developed in a basic solution, which leads to destruction of the monolayer. Coating monolayers with resist is difficult due to strongly hydrophobic nature of many self-assembled monolayers.

Method for through-plating field effect transistors with a self-assembled monolayer of an organic compound as gate dielectric


When to a memory cell array 21 a read/write operation is performed of the 7-bit data in which parity bits of 3 bits are added to data of 4 bits, an error correction is carried out in concern to each of the 7-bit data. The memory cell array is divided into memory units 31 to 37 each of which has four bits which are arranged along a direction of a word line. On writing the 7-bit data in the memory cell array, bits of the 7-bit data that are different from one another are written as written bit data along the direction of the word line in the memory units 31 to 37, respectively. In the 7-bit data, the written bit data has an interval of four bits. Error correcting circuits performs an error correction of the 7-bit data in each of the 7-bit data.

1. Field of the Invention
This invention relates to a memory circuit having an error correcting function, and more particularly, to a memory circuit which is tough to a multi-bit error in which a plurality of bit errors generates locally.
2. Description of the Prior Art
FIG. 7 is a circuit configuration for illustrating a conventional memory circuit having an error correcting function (hereinafter, simply called memory circuit). In FIG. 7, a reference numeral 11 represents a memory cell array. A reference numeral 12 represents a memory cell. A reference numeral 13 represents a sense amplifier circuit. A reference numeral 14 represents an ECC (Error Check and Correction) circuit. In such a memory circuit, parity bits of n bits are added to data of m bits, where n represents a positive integer which is not less than one, and m represents a positive integer which is not less than two. When an error occurs in at least one bit on carrying out a read/write operation for the memory cell array 11, the ECC circuit 14 carries out a correction of the error bit.
Next, the description will be given of an operation of the memory circuit illustrated in FIG. 7.
In the example being illustrated, the memory circuit illustrated in FIG. 7 has m=4 and n=3. BCH codes are used as error correcting codes. The parity bits of three bits are added to the data of four bits. The read/write operation is carried out for the memory cell array 11 in unit of the data of seven bits in sum. When a specific one of word lines is selected as a selected word line and the read/write operation is carried out for the memory cell array 11, the data of 7 bits are read from and written to seven memory cells 12 which are adjacent to one another. In FIG. 7, the adjacent seven memory cells will be collectively called a memory block.
On a read operation, the data of 7 bits are read out of each of a plurality of memory blocks which correspond to the selected word line. The data of 7 bits are supplied to the ECC circuits 14 through the sense amplifier circuits 13, respectively. In other words, the data of 7 bits are supplied to each of the ECC circuits 14. When an error bit or error bits exist in the data of 7 bits, each of the ECC circuits 14 corrects the data in accordance with the parity bits to output the data of 4 bits as read data.
On the other hand, writing data of 4 bits are supplied to each of the ECC circuits 14 on a write operation. Each of the ECC circuits 14 adds the parity bits of three bits to the writing data to output writing data of 7 bits. Through the sense amplifier circuits 13, the writing data of 7 bits are written to the memory blocks which correspond to the selected word line, respectively.
FIG. 8 shows a view for illustrating a memory block of an SRAM. The memory block has seven memory cells 12a to 12g. The memory cells 12a to 12g are connected to the sense amplifiers 13a to 13g through bit lines, respectively. Through the sense amplifiers 13a to 13d, datum bits are read from and written to the memory cells 12a to 12d, respectively. Furthermore, parity bits are read from and written to the memory cells 12e to 12g, respectively, through the sense amplifiers 13e to 13g.
The description will be given of a read/write operation for the SRAM illustrated in FIG. 8. At first, the data of 7 bits are read out of the SRAM. At that time, the data of 7 bits are supplied to the ECC circuits, respectively, in order to carry out the error check and correction, as described above. When the data of 7 bits have error bits whose number is not less than two, errors may be included in the corrected datum bits and the corrected parity bits. Under the circumstances, each of the ECC circuits outputs 2 bits error detection flag. Responsive to the 2 bits error detection flag, the SRAM is reset.
On the other hand, each of the ECC circuits does not output the 2 bits error detection flag when 1 bit error occurs. Each of the ECC circuits corrects the datum bits or the parity bits to produce corrected datum bits or corrected parity bits. Thereafter, that processing continues with using the corrected datum bits. The corrected datum bits and the corrected parity bits (corrected data of 7 bits) are written in the SRAM. Furthermore, the data of 7 bits are again read out of the SRAM to be processed in a similar manner described above, when it is necessary to read the data out of the SRAM.
FIG. 9 shows a view for illustrating a memory block of a DRAM. The memory block has seven memory cells 121 to 127. The memory cells 121 to 127 are connected to the sense amplifiers 131 to 137 through bit lines, respectively. Through the sense amplifiers 131 to 134, datum bits are read from and written to the memory cells 121 to 124, respectively. Furthermore, parity bits are read from and written to the memory cells 125 to 127, respectively, through the sense amplifiers 135 to 137.
In the DRAM illustrated in FIG. 9, the error check and correction is carried out in a manner similar to the SRAM illustrated in FIG. 8.
By the way, the above-mentioned data error (bit error) may locally occur. Such a data error may be called a soft error. More particularly, a pair of electron and hole generates when alpha ray or neutron ray is plunged into the semiconductor substrate. The alpha ray may be released from a semiconductor material of the semiconductor substrate. The neutron ray occurs in nature. When the electron is absorbed into a latch node of the memory cell, the datum is destroyed in the memory cell so that the soft error occurs. In the other words, the soft error is an error in which the data are locally destroyed in only parts into which the alpha ray or the neutron ray is plunged. On the basis of the cause of error, the soft error will be called an alpha ray soft error or a neutron ray soft error.
A plurality of soft errors may occur locally and simultaneously by one plunge of the alpha ray or the neutron ray. The above-mentioned errors will be called a multi-bit soft error.
Recently, the amount of the accumulated charge becomes low in a memory node of the memory cell in the SRAM, as a semiconductor integrated circuit becomes fine. For example, the amount of the accumulated charge is reduced to a level of 5f-coulombs in 0.18 μm-generation. In as much as electrons, which are generated in the semiconductor substrate by each particle of the alpha ray and the neutron ray, have charges of 20 f-coulombs to 200 f-coulombs, there is a growing possibility that errors simultaneously occur in adjacent memory cells by the plunge of one particle.
Inasmuch as the data of (m+n) bits are read out of the memory cells of (m+n) that are adjacent to one another, in the conventional memory circuit, there is a drawback in which makes it impossible to correct the errors when the multi-bit soft error occurs in which a plurality of bit errors generates locally and simultaneously, as described above. In other words, there is a drawback in which makes it impossible to correct the errors when bit errors having a bit number greater than a correctable one occur simultaneously due to the multi-bit soft error.
For example, there is a drawback in which it is impossible to correct the errors when the errors simultaneously occur in two bits due to the multi-bit soft error in the adjacent data of 7 bits as described above.


A method and system for multi-bridge LAN aggregation is disclosed. The method includes aggregating a plurality of LANs coupling a host to a first and a second intermediate network device. The system includes an intermediate network device. The intermediate network device includes a multi-bridge engine. The multi-bridge engine includes a tunnel engine coupled to a bridge interconnect port and a first physical port.

1. Field of the Invention
The present invention relates generally to computer networks and, more specifically, to a multi-bridge LAN aggregated method and system for use in a computer network.
2. Description of the Related Art
Computer Networks
Generally, a computer network is a group of computers (or hosts) coupled to each other in a way that allows information to be exchanged between the computers. A local area network is a common example of a computer network. As its name implies, a LAN is a computer network which is organized within a given geographic area or locale, such as a college campus, a site of a corporation, a single building, etc. Various types of LANs include Ethernet, FDDI, and Token Ring. The LAN type refers to the physical medium and connections over which traffic (i.e., data) is carried using hardware specific to the LAN type. Data on LANs are carried in frames. As used herein, a frame refers to information which is transferred between a host and a bridge and/or between multiple bridges. Each frame includes, at least, a destination link layer address, a source link layer address, a frame type indication, and data. Each frame transmitted to a given LAN can be observed and/or received by every other computer or intermediate network device attached to that LAN.
A number of individual LANs may be coupled together with bridges to create a Bridged LAN. Bridges are intermediate network devices which can be used to interconnect LANs at the link layer to enable computers on one LAN to communicate with the computers of another LAN. Bridges forward frames, as necessary, from one LAN to another, using the destination link layer address of the frames. Bridges learn which LAN Segments to forward the frames on based on the source link layer addresses of the frames. In general, a Bridged LAN can connect many more computers together, and cover a much wider geographical range, than a single LAN. The term "LAN Segment" is often used to refer to a non-bridged LAN (a LAN that includes no bridges). Although a LAN may refer to a computer network organized in a given locale, as used herein, the term "LAN" is used to refer to a physical connection between one or more hosts (e.g., a LAN Segment). Also, as used herein, the term "host" refers to an end-station which is the source of, or destination of, frames transmitted over a network.
A router is an intermediate network device which also interconnects a number of LANs and/or other types of transmission media. For example, a router may be used to connect one Ethernet LAN (or Bridged LAN) to another, or to connect a FDDI LAN to a digital satellite link. Routers generally forward packets, which are essentially data coupled with header information which describes properties of the packet such as a source network layer address, a destination network layer address, and a packet length. The router forwards packets from one LAN to another, adding or removing frame information such as link layer addresses, as needed. A router knows which LAN to send the packets on based on information within the packet itself and a configuration table accessible by the router which correlates address information to LAN information. The term "switch" is sometimes used for an intermediate network device that combines some or all of the functions of both a router and a bridge.
Often, it is desirable to have redundant physical connections to a computer network (e.g., redundant physical connections to multiple intermediate network devices) to improve availability. Unfortunately, some current methods of providing redundancy are inefficient, limited in use, and create undesirable consequences.
Link Aggregation
FIG. 1 illustrates a host 102 coupled to a LAN 104 via a bridge 106 and LANs 108 and 109. Host 102 includes network interfaces 110 (e.g., S0 and S1), both of the same medium (e.g., Ethernet). Bridge 106 includes ports 114 (e.g., ports A0-A2). As seen in FIG. 1, two LANs are provided from host 102 to bridge 106, LAN 108 from network interface S0 to port A0, and LAN 109 from network interface S1 to port A1. In configuring host 102 and budge 106 in this manner, should one of the LANs 108-109 fail, another LAN is available to transport data.
Unfortunately, a consequence of utilizing multiple network interfaces 110 of host 102 to connect to LAN 104 is an increase in the number of IP addresses which host 102 is associated. This increase results from an internet protocol (IP) address being associated with each network interface of a host. Having multiple IP addresses associated with a single host is disadvantageous for a number of reasons. Initially, confusion results as to which IP addresses should be used to communicate with the host and management of the host is made more difficult. Further, use of multiple IP addresses for a host creates inefficiency due to the time it takes to determine the IP addresses associated with the host, and the space consumed in storing the multiple IP addresses.
Link aggregation (also known as trunking) alleviates some of the problems associated with multiple IP addresses by grouping LANs of the same medium type and speed together to form a link aggregation group, which is treated as a single link with the capacity of all the links combined. Commonly known protocols and software may be used to enable link aggregation on bridge 106 and host 102. For example, Link Aggregation Control Protocol (LACP) is a common link aggregation protocol defined in IEEE Std.802.3-2000, clause 43. Similarly, Port Aggregation Protocol (PAgP) is a well known protocol developed by Cisco Systems, Inc. and useful for dynamically aggregating redundant links connecting two or more devices.
With bridge 106 and host 102 configured for link aggregation, the multiple links between them are seen as one link, and consequently host 102 may be seen from a network as having one IP address, even though multiple interfaces of host 102 may be connected to the network. Additionally, aggregating the multiple links through link aggregation has the advantage of increasing the bandwidth between host 102 and bridge 106 to twice that of what the bandwidth would be without link aggregation. Further if one of the links between host 102 and bridge 106 were to fail, communication would resume on the remaining links. Unfortunately, although link aggregation provides a redundant coupling to bridge 106, no redundancy is provided between LAN 104 and bridge 106. Thus, if bridge 106 were to fail, host 102 would lose communication with LAN 104.
Another method of providing redundant connections between a host and a LAN is to couple a host to multiple bridges with multiple wires. FIG. 2 includes a host 202 coupled to LAN 204 via bridges 206-208 and LANs 210-212. Host 202 includes network interfaces 214 (e.g., S0 and S1). Bridges 206 and 208 includes ports 218 (e.g., ports A0-A1 and B0-B1, respectively). As can be seen from FIG. 2, redundancy is provided from host 202 to LAN 204, accomplished in part by bridges 206 and 208.
The advantages provided by the configuration illustrated in FIG. 2 include the utilization of redundant bridges. If bridge 206 where to fail, host 202 would still be able to communicate with LAN 204, and vice versa if bridge 208 were to fail. However, two IP addresses are associated with host 202, one for each network interface S0 and S1, which introduces the aforementioned disadvantages associated with managing hosts with multiple IP addresses. Link aggregation is not available in such a scenario because link aggregation does not support multi-bridge configurations with a single host. Link aggregation is traditionally only available between two devices (e.g., one bridge and one host). In addition, although two LANs are shown coupled to host 202, the bandwidth of host 202 is not automatically doubled. The use of LANs 210-212 is determined by the host IP address chosen, and thus may be under the control of neither host 102 nor bridges 206-208.
Another traditional implementation of providing redundant physical connections to a network involves stacking multiple bridges together and configuring the multiple bridges to appear as one bridge. In order to accomplish this, however, the bridges must be configured to communicate with each other for sharing and learning network and frame information. Although this configuration may be a reasonable solution for providing redundancy if the bridges are in close proximity to each other (e.g., stacked on top of or next to each other) and the necessary cabling and configuration is provided, it has many pitfalls. If one of the bridges and or cables connecting the bridges were to fail, the network connection would be lost, since the bridges could no longer "learn" from each other (e.g., learning link layer addresses from each other). Additionally, such a configuration is not desirable if the bridges are to be at arms length from each other and independent of each other (i.e., not have to depend on other bridges for learning network and address information).