Antibodies, antigen-binding proteins and Fc-fusion proteins that comprise recombinant polypeptides containing a chimeric heavy chain constant region sequence are provided that bind to certain Fc receptors however have reduced effector functions. Methods of making constructs for expression of such chimeric Fc-containing antibodies, antigen-binding proteins and Fc-fusion proteins in cell systems, and methods of producing and isolating the chimeric Fc-containing proteins are provided.

Immunoglobulins of the IgG class are attractive as therapeutic agents. IgGs exists as four subclasses in humans, IgG1, IgG2, IgG3, and IgG4. The heavy chain constant (CH) region of IgG comprises three domains, CH1, CH2, CH3, where CH1 and CH2 are linked by a hinge. Although the role of each subclass appears to vary between species, it is known that the heavy chain constant domain is responsible for various biological effector functions. The human IgG subclasses mediate a plethora of cellular immune responses through their interaction with Fcγ receptors (FcγRs), such as cell killing, complement activation, phagocytosis and opsonization. In an attempt to understand and manipulate the effects of IgG subclass binding to FcγRs, researchers have made various mutations to the constant domains of IgGs and studied the resulting IgG/FcγR interaction (see e.g. Canfield and Morrison J Exp Med 73, 1483-1491 (1991); Chappel, M. S., et al. JBC 268(33), 25124-31 (1993); and Armour, K. L., et al. Eur J Immunol 29, 2613-24 (1999)).
Fc dependent cytotoxic activity of human IgG antibodies requires binding of the Fc region of the antibody (which consists of at least a functional CH2 and CH3 domain) to an FcγR on the surface of an effector cell, such as a natural killer cell, an activated macrophage or the like. Complement-mediated lysis can also be triggered by the interaction of the Fc region with various complement components. With regard to FcγR binding, it has been suggested that several amino acid residues in the hinge region and in the CH2 domain of the antibody are important (see Sarmay, G, et al. Mol Immunol 29, 633-9 (1992); Greenwood, J et al., Eur. J. Immunol, 23(5), 1098 (1993), Morgan, A. et al, Immunology, 86, 319 (1995), Stevenson, G T, Chemical Immunology, 65, 57-72 (1997)). Glycosylation of a site (N297) in the CH2 domain and variations in the composition of its carbohydrates also strongly affect the IgG/FcγR interaction (Stevenson, G T, Chemical Immunology, 65, 57-72 (1997); Sibéril et al Immunol Ltrs 106, 111-118 (2006)).
For certain antibody therapies, it may be advantageous to engineer the Fc receptor binding properties so as to activate all, some, or none of the available effector mechanisms, without affecting the antibody's pharmacokinetic properties. The desired combination of therapeutic properties may not be available in the natural antibody repertoire. The design of antibodies with reduced effector function should be efficacious for example when the therapeutic objective is not to kill a target cell, but to block or activate a cell surface molecule on its surface without triggering cytotoxicity. Another setting in which reduced binding to Fc receptors could be desirable is when the antibody is bispecific, and its desired therapeutic properties arise from the different binding specificities. For example, a common usage of bispecific antibodies is to combine a tumor targeting specificity with a T cell activating specificity in order to trigger tumor-specific T cell killing. In this case, if the Fc portion binds to an Fc receptor, then potentially that could trigger undesirable killing of cells bearing Fc receptors by T cells, or killing of T cells by Fc receptor-bearing cells such as natural killer cells or macrophages.
Thus, there exists a need for improved biological therapies, such as antibodies with desirable properties for use in such therapies. Applicants have discovered that recombinant proteins containing substituted or otherwise modified antibody heavy chains, including recombinant antibodies and recombinant receptor-Fc fusion proteins, have altered Fc receptor binding activity, which reduce the risk of unwanted side effects, and thus provide improved therapeutic effect.

Antibodies comprising chimeric constant domains


The present invention relates to a housing of a medical device and to a respective medical device, wherein the housing comprises a body to receive at least one device component and wherein the body is flexibly deformable in response to mechanical impact above a predefined threshold.

There exists a variety of portable medical devices such like injection devices or analysis devices, by way of which a patient may conduct self-treatment, in particular self-administration of a medicament.
Especially with patients suffering diabetes, a blood glucose level has to be regularly determined, e.g. by making use of a blood glucose measurement device (BGM). Depending on the measured data and a determined blood glucose concentration the patient may then individually select a dose of a medicament which is to be administered, e.g. by way of injection.
There exists a large variety of medical devices for analysing and treating patients for diagnostic and/or therapeutic purpose. Such medical devices are sometimes rather fragile and sensitive to mechanical impact.
In general, medical devices may comprise a variety of sensitive components which require sufficient protection against external hazards. Portable or mobile medical devices may also comprise a large variety of electronic components, by way of which various functionalities of the device can be configured, controlled and conducted. Additionally, such devices may comprise various input and/or output means, such like a display, operating buttons and knobs, regulators, dose dials and so on.
Moreover, medical devices may also comprise a storage module by way of which repeated use of the medical device can be monitored and logged. Also, medical devices may comprise a communication module, such like an interface, by way of which treatment-related or device-configuration-related data can be exchanged with additional devices, such like personal computers or smartphones.
The various components of such portable medical devices may be rather susceptible to mechanical impact and may affect the general operability of such devices when exposed to mechanical impact above a certain threshold.
It is therefore an object of the present invention to provide an improved housing for a medical device to enhance robustness and susceptibility of the device and its components against mechanical impact. It is a particular aim to provide an impact- or shock-absorbing functionality and to provide further a well-defined impact- or crash-behaviour of the medical device. These improvements regarding impact protection should be rather simple and cost-efficient to realize.

Medical device with impact resistant housing


The present invention relates to novel tin amino-alkoxide complexes and a method for preparing the same, precisely novel tin amino-alkoxide complexes represented by formula 1 and useful as a precursor for tin and tin oxide thin films and a precursor for the production of nano-sized tin and tin oxide particles and a method for preparing the same. In formula 1, A is linear or branched (C2-C10) alkylene substituted or not substituted with halogen; R1 and R2 are independently linear or branched (C1-C7) alkyl substituted or not substituted with halogen.Sn[O-A-NR1R2]2  [Formula 1]

Tin oxide was first reported in 1976 and is known as a transparent conductive oxide having visible light permeability, infrared reflectance and low resistance. Owing to such characteristics, tin oxide has widely been used for gas sensor, solar cell electrode and low resistant glass coating, etc. Many research groups are studying on tin alkoxide, amide, and chalcogenide compounds in the form of monomer, and having 2-coordinated or 4 coordinated structure. To produce tin, tin oxide, and materials containing tin, precursors such as SnCl4, Sn(CH3)4, (CH3)2SnCl2, Sn(C4H9)2(CHCOO)2, Sn(OAc)2, Sn(acac)2 (acac=acetylacetonate), and Sn(XR)2 (X=O, S, N, R=Me, Et, i-Pr, t-Bu) have been used. All the synthetic compounds are stabilized by using a ligand having huge steric hindrance or by an electron donor substrate. The most common tin compounds are thermolysed in a vacuum chamber by MOCVD (metal organic chemical vapor deposition) process via unstable gas phase reaction at 80-450° C. This process is a method based on the decomposition of those compounds in gas phage which are reactive on a substrate as gas phase. But, the method is limited. Decomposition for the formation of thin film is too slow but if decomposition rate is accelerated, the quality of the thin film is reduced. Thin film can be produced by PCVD (plasma-induced chemical vapor deposition) and sputtering, but these methods have structural problem and quality problem of photoelectron (T. W. F. Russel, B. N. Baron and R. E. Rocheleau, J. Vac. Sci. Technol. B2(4), 1984, 840; Sanjay Mathur, Hao Shen, Vladimir Sivakov, and Ulf Werner, Chem. Mater. 2004, 16, 2449; Henry Gerung, Scott D. Bunge, Timothy J. Boyle, C. Jeffrey Brinkerab and Sang M. Han, Chem. Commun., 2005, 1914; Seigi Suh and David M. Hoffman, Inorg. Chem. 1996, 35, 6164; A. Watanabe, M. Unno, F. Hojo, T. Miwa, J. Mater. Sci. Lett., 2001, 20, 491; S. Veprek, J. Prokop, F. Glatz, and R. Merica, F. R. Klingan and W. A. Herrmann, Chem. Mater. 1996, 8, 825).

Tin amino-alkoxide complexes and process for preparing thereof

Korea Research Institute of Chemical Technology


Transdermal fertility-controlling absorption polymer matrix dosage units have been developed which comprise a backing layer, an adjoining layer of a solid polymer matrix in which minimum effective daily doses of an estrogen and a progestin are microdispersed and released for transdermal absorption. Presently preferred is use of the natural estrogen, 17-beta-estradiol, and of the progestin, levonorgestrel. The units have a biologically acceptable adhesive polymer layer. The polymer matrix as well as the adhesive layer can have dispersed one or more skin permeation enhancers. Dosage units are provided which transdermally deliver at least minimum daily doses of the estrogen and progestin for multiple days, such as for one week. The invention also provides a process of fertility control using the novel polymer matrix dosage units for the first three weeks of consecutive menstrual cycles of the subject desiring fertility control.

Fertility has been controlled by use of a number of orally administered hormone products. The products are ordinarily a combination of an estrogen and a progestin. A synthetic estrogen is ordinarily used as the estrogen component since the natural estrogen, 17-beta-estradiol, is almost completely destroyed, usually over 90 percent, when taken orally. It is destroyed to a degree in the digestive tract before it is absorbed but primarily the destructive metabolism of 17-beta-estradiol occurs during the "first pass" hepatic metabolism. Since such a large amount is destroyed, in order to provide an effective dosage orally, a large excess must be administered with uncertain effectiveness and a large amount of unwanted metabolic products. Therefore, a synthetic estrogen such as ethinyl estradiol normally is administered with less than desired results.
The progestin component generally inhibits, as intended, ovulation. Also, in the case of administered progestin, a substantial amount of metabolic breakdown occurs causing undesired metabolic products with undesired effects.
Therefore, in the oral administration of what is commonly referred to as "the pill" or other orally administered products, considerably overdosing is necessary to obtain a high degree of assurance that the desired fertility control will be obtained.
A number of major side effects have reportedly been associated with the administration of oral fertility control preparations, like thrombophlebitis and thrombosis, pulmonary embolism, coronary thrombosis, myocardial infarction, cerebral thrombosis, cerebral hemorrhage and hypertension. These side effects have been attributed to the estrogen component in the oral preparations. Use of the progestin-only preparations (mini-pill) has been found to eliminate the side effects of estrogen. However, the fertility control is less than that of the combined preparations and the menstrual cycle also becomes more irregular. It has been reported that less incidence of irregular bleeding is observed if the progestin is administered at a more constant rate of delivery. Besides the side effects, the oral fertility control preparations also have the disadvantage of fertility control efficacy depending highly on the degree of patient compliance. The risk of pregnancy is known to increase with each pill missed.
An ideal and patient-acceptable fertility control system should provide the following advantages: minimized side effect, increased ease of administration, rapid termination of treatment, if needed, and improved patient compliance. In recent years, considerable attention has already been directed to the development of implantable, intrauterine, intracervical or intravaginal fertility control delivery systems to provide a prolonged and controlled administration of steroidal hormones to the body for achieving fertility control; however, none of the delivery systems developed so far can be considered as ideal and side effect-free.
Other fertility control means have been used, such as topical creams and intravaginal devices, which deliver combinations of one or more progestins and one or more estrogens, including the naturally-occurring estrogen, 17-beta-estradiol. However, the undesirable aspects of such fertility control systems are evident.
It is, therefore, highly desired that transdermal systems be provided which permit 1) use of the natural estrogen, 17-beta-estradiol, 2) use of a minimum number of dosage units for each menstrual cycle, such as use of three successive weekly dosage units, 3) would adhere to the skin of the subject and provide sufficiently high levels of estrogen and progestin hormones to provide high assurance of fertility control without a high amount of undesired metabolic or chemical degradative products. Development of a rate-control transdermal drug delivery system, which is capable of minimizing any individual variability and regional differences in skin permeability, is a necessity to attain a predictable blood level of a drug. The transdermal rate-control drug administration is known to offer several potential advantages for systemic medication: (i) avoidance of the risk and inconvenience of intravenous therapy and of the variability in absorption and metabolism associated with oral therapy; ii) continuity of drug administration, permitting the use of a pharmacologically-active agent with short biological half-life; (iii) efficacy can be achieved with lower total daily dosage of drug, because of reduced hepatic first-pass metabolism and continuous drug input; (iv) less chance of over- or under-dosing, as a result of prolonged, programmed delivery of drug at required therapeutic rate; (v) provision of a simplified medication regimen; and (vi) ability to rapidly terminate the drug infusion, if needed, by removal of the drug delivery system from skin surface. Therefore, a transdermal contraceptive delivery system, which is capable of providing dual-delivery of an estrogen and a progestin at controlled rates for a specific duration would be an ideal system for achieving fertility regulation in women.

Transdermal fertility control system and process

Rutgers, The State University of New Jersey


Methods and systems are provided for facilitating control of a child's purchasing of products from a merchant using a credit card, debit card, gift card, secure token, mobile device, or the like. A payment provider, such as Paypal, Inc., can authorized the purchase of a product from the merchant if both the child and the parent are checked in with the same merchant via one or more social networks (thereby indicating that the child and the parent are in or near the same store). This requirement for proximity between the child and the parent can provide the parent with an opportunity to more closely monitor purchases made by the child.

Technical Field
The present disclosure generally relates to electronic commerce and, more particularly, relates to a method and system for use by parents to restrict purchases made by children, for example.
Related Art
Electronic payment for products purchased at brick and mortar stores is common. Such electronic payment can be made using cards, such as credit cards, debit cards, and gift cards, for example. Such electronic payment can be made using security tokens, such as software security tokens and hardware security tokens, for example. Whether the electronic payment is made by card, security token, or another means, a payment provider, such as Paypal, Inc., can facilitate the payment.
The payment provider can facilitate authentication of the purchaser, determine if the purchaser is authorized to make the purchase (can determine that the purchaser has not exceeded a deposited amount, e.g., for a debit card or gift card, or has not exceeded a credit limit, for example), and can facilitate the transfer of money from the purchaser to a merchant so as to pay the merchant for the purchased product. The payment provider can pay the merchant with money previously deposited with the payment provider by the purchaser, can transfer money from a bank account of the purchaser, or can bill the purchaser for the amount of the purchase.
Location-aware social networks such as Foursquare and Google Latitude provide apps for mobile devices like cellular telephones. By using such an app, a social network member can check in at a location. Checking in at a location allows other, selected, members of the social network to view the location of the member.


A computing system can include a monitor (150) to estimate a temperature of a storage device (120). The monitor estimates the temperature from an activity indicating signal of the storage device. A cooling device controller (155) can be connected to the monitor. The cooling device controller can control the output of a cooling device (115).

Self-Monitoring, Analysis, and Reporting Technology (S.M.A.R.T.) is a signaling method between an internal disk drive electromechanical sensor and the host computer. A hard drive that implements S.M.A.R.T. may include an electromechanical sensor. A S.M.A.R.T. compliant hard drive communicates with the operating system of the host computer through device drivers. The most basic information that SMART provides is the SMART status. The SMART status is represented as "drive OK" or "drive fail" respectively.

Hewlett-Packard Development Company, L.P.


Aspects of the invention can be an inexpensive biosensor capable of measuring a number of samples in a short time, and suitable for only one-time use (expendable). The biosensor according to the invention can include a light transmissive substrate, a probe fixing region provided on one face of the light transmissive substrate, a light emitting element provided on the other face of the substrate that irradiates the probe fixing region from the back side thereof, and a light receiving element provided on the other face of the substrate that detects the light intensity of the reflected light from the back side of the probe fixing region. Thereby, a biosensor formed in one substrate can be obtained.

1. Field of Invention
Aspects of the invention relate to a biosensor for detecting a biological sample or the like, and in particularly to miniaturization of the biosensor.
2. Description of Related Art
Related biosensors that recognize a detecting object, such as DNA, proteins, and antibody molecules efficiently and correctly in a short time, and extracts information, such as the structure, function, weight, and electric characteristics of the detecting object sample, are important since the human genome analysis has been completed. Related biosensors can include, for example, a method (see, for example, U.S. Pat. No. 5,445,934) of measuring DNA hybridization reaction by the fluorescence intensity, and a method (see, for example, Japanese Unexamined Patent Publication No. 2001-296172) of measuring DNA hybridization reaction by surface plasmon resonance (SPR). When detecting by these optical methods, the measurement result can be obtained relatively promptly. Moreover, related methods (electrophoresis) of measuring differences in the amount of DNA displacement that varies depending on the applied electric-field or the like are used. In this case, the detection can be made with relatively simple equipment.

Biosensor and method of manufacturing biosensor


This invention provides a class of compounds which are useful for specifically inhibiting cyclin-dependent kinases. This class of compounds finds use in treating diseases resulting from inappropriate activity of cyclin-dependent kinases, including cancer, viral infections (e.g., HIV) neurodegenerative disorders (e.g. Alzheimer's disease), and cardiovascular disorders (e.g. atherosclerosis). Moreover, certain members of this class are particularly useful for inhibiting cyclin-dependent kinase 7 and are especially useful for the treatment of breast cancer.

The process of cell growth and division is divided into four stages that make up the cell cycle: G1, S (DNA synthesis), G2 and M (mitosis). Progression through the cell cycle is a tightly regulated process, and critical to the cell cycle progression are cyclin-dependent kinases (CDKs). CDKs are the catalytic subunits of a large family of serine/threonine protein kinases. Activation of specific CDKs is required for the appropriate progression through a given stage of the cell cycle and into the next stage in the cell cycle. Hence, regulation of CDK activity is pivotal for the correct timing of cell cycle progression and CDK activity is tightly regulated at many levels, including complex formation with cyclins and CDK inhibitors (CDKI), in particular CIP/KIP and INK-type CDKIs, as well as phosphorylation and dephosphorylation. Central to the activation of a given CDK is the requirement for association with cyclins and phosphorylation at a threonine residue in the activation loop (T-loop). Cyclins are synthesized and degraded during the cell cycle (hence their name), so that activation of a particular CDK occurs only when its cyclin partner(s) becomes available. Additionally, many CDKs require phosphorylation of a threonine residue in the activation loop (T-loop) for their activation. In the case of CDK1, CDK2, CDK4 and CDK6 T-loop phosphorylation is mediated by the CDK activating kinase (CAK).
Deregulation of CDK activity forms an important part of many disease states, generally through elevated and/or inappropriate activation, as CDKs are infrequently mutated. Important mechanisms of CDK deregulation include cyclin overexpression. For example, the cyclin D1 gene is frequently amplified in cancer (Fu et al. Endocrinology 145: 5439-5447 (2004)). CDKI expression is frequently lost, for example, through mutational or epigenetic alterations in genes encoding INK4, CIP or KIP CDKIs in cancer (Malumbres and Barbacid, Nature Reviews Cancer 1, 223-231 (2001)).
CDKs are important targets for the design of drugs with antimimotic, antineurodegenerative, antiviral and antitumor effects. A few specific and high-affinity inhibitors of some CDKs have been developed using CDK2 as a model system. One of these is flavopiridol (clinical phase I/II), which has modest selectivity for CDKs over other kinases and inhibits many members of the CDK family (M. D. Losiewicz et al., Biochem. Biophys. Res. Commun., 201, 589-595 (1994)). One compound class that has yielded many CDK-selective ATP antagonists is 2,6,9-trisubstituted purines. Within this group, roscovitine shows good biological and pharmacological properties (clinical phase I/II) (S. Wang et al., Tetrahedron: Asymmetry, 12, 2891-2894 (2001); M. Mapelli et al., J. Med. Chem., 48, 671-679 (2005)). Recently, another class of compounds having a pyrazolo[1,5-a]pyrimidine skeleton has been developed. These compounds show a high potency for inhibiting CDK2, and in some cases were shown to inhibit the growth of human colon tumor cells (D. S. Williamson et al., Bioorg. Med. Chem. Lett., 15, 863-867 (2005)). However, most CDK inhibitors that have been described do not specifically inhibit one CDK. For example, most CDK2 inhibitors also inhibit CDK1, CDKS, as well as CDK7 and CDK9 (P. M. Fischer, Cell Cycle 3: 742-746). It has also been noted, however, that some inhibitors of structurally similar kinases CDK1, CDK2 and CDKS do not inhibit CDK4 and CDK6 (M. Knockaert et al., Trends Pharmacol. Sci., 23, 417-425 (2002)).
CDK7
While CDK1, CDK2, CDK4 and CDK6 are primarily involved in cell-division control, other cyclin-dependent kinases, such as CDK8 and CDK9, largely regulate transcription. CDK7 is unusual in that it is important in transcription, but also acts as the CDK-activating kinase (CAK) (Lolli and Johnson Cell Cycle 4: 572-577 (2005)). The CDK7 CAK complex comprises cyclin H and the ring finger protein MAT1 and is unusual in that its phosphorylation in the T-loop is not required for its activity (R. P. Fisher et al. Cell 83: 47-57 (1995); Devault et al. EMBO J. 14: 5027-5036 (1995)). In transcription regulation, CDK7/Cyclin H/MAT1 are components of the general transcription factor TFIIH, which is required for initiation of transcription of RNA polymerase II-directed genes. As part of the TFIIH complex, CDK7 phosphorylates the C-terminal domain of the largest subunit of RNA polymerase II (R. P. Fisher J. Cell Sci. 118: 5171-5180 (2005)). Additionally, TFIIH plays a role in RNA polymerase I-mediated transcription (Iben et al. Cell 109: 297-306 (2002)). Further, CAK or TFIIH-associated CAK phosphorylate several transcription factors to regulate their activities (see, e.g., Chen et al Mol Cell 6: 127-137 (2000); Bour et al PNAS 102: 16608-16613 (2005)). With respect to cell cycle regulation, the CDK7 CAK complex phosphorylates the cell cycle CDKs in the activation segment (T-loop), required for the activation of CDKs involved in cell cycle regulation (Lolli and Johnson Cell Cycle 4: 572-577 (2005)).

Selective inhibitors for cyclin-dependent kinases

Imperial College of Science and Technology


A multiplexed computer system allows memory accessing by a processor, a peripheral equipment or a like apparatus even during execution of memory copying to improve the processing performance during on-line maintenance. To this end, the multiplexed computer system includes a plurality of processing units which carry out the same operation in synchronism with each other. Each of the processing units includes a copy processor register for designating a processor to read out contents of a memory unit, copying circuits which transfer copies of the stored contents of the memory unit and data to be written into the memory unit in the same order as that of accesses to the memory unit to a memory unit of another processing unit, a copy mode flag indicating that memory copying processing for making the stored contents of the memory unit of the self system and stored contents of the memory unit of the other processing unit coincide with each other is proceeding, and a copy task flag indicating that the processor is reading out, during memory copying processing, the stored contents of the memory unit.

A conventional multiplexed computer system wherein a plurality of processing units execute a same calculation in synchronism with each other requires means for putting stored contents of memories of all of the processing units into coincidence with each other in order to allow the processing units to perform a same operation in synchronism with each other, that is, to perform a multiplexed operation again after one of the processing units is disabled because of a failure or a periodic inspection is performed for a particular one of the processing units.
As a method of putting stored contents of memories of all processing units which operate, for example, in a duplicated condition into coincidence with each other, the following two memory copying methods are adopted usually.
In particular, as the first memory copying method, in a computer system which operates in a duplicated condition, an operation of copying a fixed region of stored contents of a memory provided in one of processing units which is operating (hereinafter referred to as normal system processing unit) into another memory provided in another one of the processing units which is not operating (hereinafter referred to as abnormal system processing unit) using data transfer means of the normal system processing unit between a memory and a peripheral equipment, that is, so-called DMA engine, is repetitively executed after each fixed interval of time. Further, where a processor provided in the normal system processing unit is constructed so that it can access only the memory in the same processing unit, data to be written from the processor provided in the normal system processing unit into the memory of the same processing unit are transferred to the memory provided in the abnormal system processing unit. An example which discloses a technique regarding this is Japanese Patent Laid-Open Application No. Hei 3-182958.
As the second memory copying method, in a computer system which includes processing units which operate in a triplicated condition and global memories which operate in a duplicated condition and wherein each of the processing units includes a local memory and data transfer means between the local memory and the global memories, that is, so-called DMA engine, an operation of copying a fixed region of stored contents of one of the global memories which is operating (normal system) into the other global memory which is not operating (abnormal system) via the local memory provided in the processing unit using the DMA engine provided in the processing unit is repetitively executed after each fixed interval of time until all regions of the memory are copied. It is to be noted that, while the stored contents of the memory are being transferred, accessing to the global memories by a peripheral equipment, that is, DMA, is inhibited. A technique regarding this is disclosed in Doug Jewett, "Integrity S2: A Fault-Tolerant Unix Platform", Twenty-First FTCS International symposium, Montreal, 1991.
A multiplexed computer system having an obstacle resisting function has a so-called on-line maintenance function of allowing repair or exchange a failed element while executing ordinary processing in order to allow a multiplexed operation to be performed again, and even while such on-line maintenance is performed, it is required to prevent deterioration of a processing performance. Accordingly, memory copying essentially required for on-line maintenance must be performed without making an obstacle to ordinary processing.
However, in memory copying in on-line maintenance, stored contents of the memory provided in the normal system processing unit which always vary by ordinary processing must be transferred to the memory provided in the abnormal system processing unit while maintaining the consistency, and the following problems which disturb this must be solved.
In particular, if the normal system processing unit reads out, immediately before certain regions of the memories provided in the normal system processing unit and the abnormal system processing unit are rewritten simultaneously by ordinary processing, the region of the memory thereof and transfers the thus read out data to the region of the memory of the abnormal system processing unit in order to perform memory copying, then after the regions of the memories of the normal system processing unit and the abnormal system processing unit are rewritten by ordinary processing, the data prior to such rewriting are copied into the region of the memory of the abnormal system processing unit. Consequently, the consistency between the memories of the normal system processing unit and the abnormal system processing unit is lost.
According to the first conventional method described above, memory coping is executed using the DMA engine provided in the normal system processing unit, and consequently, during execution of memory copying, DMA between the two system memories and a peripheral equipment by the DMA engine is not executed. Accordingly, during execution of memory copying, both of the memories are not rewritten by DMA, thereby solving the problem of the loss of the memory consistency described above.
Meanwhile, according to the second conventional system described above, memory copying is executed using a DMA engine provided in a processing unit, and consequently, during execution of memory copying, DMA between a local memory and the two system global memories by the DMA engine is not executed. Further, since DMA between a peripheral equipment and the two system global memories is inhibited during execution of memory copying, the two global memories are not rewritten by DMA during execution of memory copying, thereby solving the problem of the loss of the memory consistency described above.
However, those conventional methods have a problem in that, during execution of memory copying, DMA between a peripheral equipment and a memory and DMA between a local memory and a global memory cannot be executed. Further, they have another problem in that, since an operation of copying a fixed memory region by means of a DMA engine is executed repetitively after each fixed interval of time until all regions of the memory are copied, overheads by pre-processing for memory copying such as setting of a DMA engine or flushing of a cache memory are increased. It is to be noted that, since flushing of a cache memory is performed such that a region of the cache memory corresponding to a memory region to be copied is flushed before memory copying is executed and then, after copying of all of the memory regions is completed, the all regions of the cache memory are flushed again, cache flushing executed in memory copying is equal to the sum total of the memory capacity and the cache capacity. Those problems make causes of deterioration of the processing performance during on-line maintenance.

Multiplexed computer system with the capability to copy data from one processor memory to another


A golf club head comprises: a hollow main body provided with an upper opening located in a crown portion of the head; and a crown plate fitted in the upper opening and having a specific gravity less than that of the main body, wherein the main body is provided around the upper opening with a crown plate support supporting a peripheral edge part of the inner surface of the crown plate. The crown plate support has a width of not more than 5 mm. The minimum distance between the upper edge of the club face and the crown plate in the back-and-forth direction of the head is not less than 10 mm. The thickness of the crown plate is not more than 0.7 mm.

The present invention relates to a golf club head, more particularly to a structure of the crown portion of a hollow head capable of lowering the center of gravity without deteriorating the durability of the crown portion.
Heretofore, a golf club head comprising a hollow main body having an opening in the crown portion and a lightweight crown plate covering the opening has been proposed as disclosed in JP-P2003-250938A. In this golf club head (a), as shown in FIG. 17, the hollow main body (b) is provided around the opening (O) with a support (f) for the crown plate (c) which support has a width (A) of about 10 mm in order to secure a durable junction between the hollow main body (b) and crown plate (c).
Thus, due to the crown plate support (f) having a relatively large width (A), the weight of the crown portion can not be fully reduced in spite of the lightweight crown plate, and as a result, maximal lowering of the center of gravity is not possible.


Apparatus, method and computer readable medium are provided for data transfer wherein an initiator driver in a computing system performs a first write operation to a target system wherein the write operation transfers a block of data from the computing system to the target, the write operation including sending a plurality of data packets which together form the block of data, wherein some or all of the data packets are sent only after the driver receives a ready to transfer command from the target. The initiator driver receives a request for a second write operation from the computing system before all the data packets for the first write operation have been sent, and sending a write command to the target in-between sending two of the data packets so that the second write command is sent before completion of the first write operation. According to another aspect, the initiator driver receives a request from the computing system to perform two or more write operations prior to initiating the first write operation and while no other write operations are being performed, and wherein the initiator system sends at least two write commands, one for each request for a write operation, to the target system prior to receiving a ready to transfer command from the target system.

In a SCSI interface the data transfer protocol provides that the target storage system controls the data transfer between it and the requesting or initiating system. In a typical data transfer scenario, an initiator driver on the requesting system originates SCSI commands and these commands are sent to the storage system without advanced permission. Generally, however, data transfers from the requesting system to the target are not proper protocol without express or implied permission from the target. Express permission is granted using a "ready to transfer" (known as a "R2T" in SCSI terminology) command sent by the target.
Prior to a data transfer operation, SCSI allows the initiator driver on the requesting system to negotiate with the target to establish the size of permissible data chunks, known as PDU's (physical data units). The smallest PDU is typically 8 Kbytes in length, with 64 Kbytes being a larger PDU size. Once this negotiation is completed, the initiator driver sends data to the target in the agreed upon PDU size. Other than the case of implied R2T's where an actual R2T need not be sent, all other transfers of a PDU from the initiator driver requires the target to first send a R2T command granting express permission for the driver to send the PDU.
The time that an initiator driver waits between sending a PDU and receiving the next R2T command is a function of the latency in the network over which the data is being transferred. If the network has a "high" latency, as may occur in TCP/IP iSCSI protocols, there is a relatively long delay between the last PDU being sent and the next R2T arriving back at the initiator driver. This delay has the effect of lengthening the time that the overall data transfer (that is the entire block of data sought to be transferred) takes to complete. This extra time in turn often prevents the computing or other requesting system that requires the data transfer from starting other work that requires the completed transfer. Accordingly, it is desirable if these delays can be reduced so that work can be more quickly and efficiently performed by the requesting system.

Latency reduction in network data transfer operations


A method and a device for producing holes in the circumference of a hollow shape, with a wall piece being separated as a slug from the hollow shape in an internal high-pressure mold and being jammed without projecting relative to the outer circumference of the hollow shape in a previously produced hole. In order to remove the slug produced during punching in simple fashion from the internal high-pressure mold, the separated slug is jammed at a fluid pressure that is reduced relative to an internal high fluid pressure without loss via a punch and can separate the slug following removal of the finished hollow shape from the internal high-pressure mold, from the hollow shape, finally clearing the hole.

This application claims the priority of German application 196 47 962.2, the disclosure of which is expressly incorporated by reference herein.
The invention relates to a method for making holes at the circumference of a hollow shape and a device for this purpose.
A method and a device for making holes at the circumference of a hollow shape are known from U.S. Pat. No. 4,989,482. Following a shaping process involving internal high-pressure shaping at an internal pressure in the range of approximately 7 to 700 bars, a hole is produced in the circumference of a hollow shape still in the mold by guiding a punch against the wall of the hollow shape from the outside, said wall being pressed into the interior of the hollow shape by the flush application of the punch. The punch has a channel that connects its face adjacent the hollow shape and is provided with a cavity communicated with the atmosphere. As a result, a pressure differential develops between the end of the punch in the vicinity of the cavity and the interior of the hollow shape, said pressure differential pressing the hollow shape against the annular contact surface of the face of the punch that surrounds the cavity. During further indentation of the wall of the hollow shape, the limit of stretchability of the material of which the hollow shape is composed is reached, and when it is exceeded the wall of the hollow shape tears around the point of impact of the punch to form a slug. Because of the uneven wall of the hole that is produced, however, there is inadequate sealing of the space that is formed as the punch is advanced between the outside of the hollow shape and the female die guiding the punch, and there is no guidance of the punch by the female die relative to the interior of the hollow shape that is pressurized by a fluid, so that despite the radial application of the wall of the hole to the circumference of the punch, a pressure drop occurs within the hollow shape.
As a result, the pressure differential between the atmosphere and the interior at the hollow shape is so low that the suction exerted by the punch on the slug is canceled out, or at least is reduced to a significant degree. In the former case, the slug comes loose from the punch and drops into the interior of the hollow shape. In the latter case, the slug remains adhering with a low force to the end of the punch. During the return movement of the punch, the slug falls back into the hole. However, this occurs only partially since the wall of the hole, which is bent toward the interior of the hollow shape as a result of the return movement of the slug caused by the retraction of the punch, offers a resistance, so that because of the abovementioned low suction force, when the pressure equilibrium is established, the punch lifts away from the slug. In most cases, the slug immediately falls into the interior of the hollow shape without adhering to the wall of the hole. On the other hand, the slug can remain hanging in the hole, so that the clamping effect in the latter is small.
Contrary to the assertion made in the above-mentioned document, it is possible for pressure to build up inside the hollow shape following jamming of the slug, so that the bent wall of the hole is flattened, resulting in an additional clamping of the slug in the hole. No pressure can develop under these conditions because there is no match between the shapes of the wall of the hole and of the slug in the jammed position in which the slug projects into the interior of the hollow shape. This rules out a position of the slug against the wall of the hole that can provide an effective seal against high pressure. Because of the vibrations of the hollow shape that occur as the hollow shape is removed from the internal high-pressure mold, the slug comes loose from its unstable jammed position and drops into the hollow shape. Since the interior of the hollow shape still has a wet film on it despite the fact that the high-pressure fluid has been removed, the slug slides out of the hollow shape when the latter is removed and drops into the mold. Separate removal of the slug from the mold is very awkward, and a slug that has been "forgotten" and is left in the mold can cause irreparable damage to the mold during subsequent shaping processes.
A goal of the invention is to improve a method and a device for making holes at the circumference of a hollow shape such that the slug produced during perforation can be removed in simple fashion from the internal high-pressure mold.
This and other goals have been achieved according to the present invention by providing a method for producing holes at the circumference of a hollow shape, with a wall portion being separated as a slug from a hollow shape within a mold that uses internal high pressure and can be jammed in a previously formed hole without projecting with respect to the outer circumference of the hollow shape, characterized in that the jamming of separated slug with a high fluid pressure that is relaxed relative to a high internal fluid pressure and secured against loss takes place by means of a punch and in that slug, following removal of finished hollow shape from internal high pressure mold, is separated from hollow shape when hole is finally cleared.
This and other goals have been achieved according to the present invention by providing a device for making holes at the circumference of a hollow shape, with a punch integrated into an internal high-pressure mold, by means of which a punched portion of the wall can be separated as a slug from the hollow shape with preliminary production of a hole, and with a return means by means of which the separated slug can be jammed in a hole, and is then jammed in a previously prepared hole without projecting relative to the outer circumference of the hollow shape, characterized in that the return means is a punch with which slug, without fear of loss, in a pressure state that is less than an internal high pressure that is used for internal high-pressure shaping, can be forced inside hollow shape into previously produced hole and in that the device incorporates a means for removing slug following removal of finished hollow shape from internal high-pressure mold, by which hole is finally produced.
According to the invention, the slug can be jammed without the aid of internal high pressure produced by a fluid in a previously produced hole in such fashion that the hollow shape can be removed from the internal high-pressure mold without the slug falling out of the hole in the process. This eliminates the expense of cleaning slugs out of the mold. In addition, there is no need to develop a high fluid pressure or to provide the apparatus associated therewith for pushing the slug back into the hole, and high-pressure-resistant seals can be eliminated as well. Because of the lack of any projection of the slug in the hole above the exterior of the hollow shape, the hollow shape can also simply be removed from the mold. In addition, problems with recovering the slug as far as process engineering is concerned, involving a pressure drop after the hole is made, are overcome. The jammed slug is removed in simple fashion after the hollow shape has been removed from the mold, with the slug not causing any damage or cleanup cost because of its external removal. Because the slug is firmly jammed, perforation at the circumference of the hollow shape is possible at all angles relative to the axial position of the hollow shape inside the mold, without there being any danger, after the pressure is released following production of the hole, of the slug dropping into the hollow shape or, upon removal of the hollow shape, falling into the mold from the inside to the outside after the hollow shape has been removed.
Other objects, advantages and novel features of the present invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings.

Method and device for making holes at the circumference of a hollow shape


A receptacle for insulating a container. The receptacle includes a bottom and a sidewall circumscribing the bottom and extending from the bottom to an upper edge. The bottom and the sidewall define a cavity for the receptacle, and the cavity is sized to at least partially receive the container therein such that a gap remains defined between the container and an inner surface of the receptacle. The receptacle facilitates insulating the container.

This invention relates generally to insulating containers and, more particularly, to methods and systems for insulating fluids within a container.
Disposable paper or plastic beverage cups having a generally smooth cylindrical or tapered sidewall are commonly used by recreational vendors, coffee shops, fast food restaurants, convenience stores and the like. Although convenient because such cups are easily stacked, such cups generally do not maintain a temperature of the fluid contained in the cup. Specifically, the paper or plastic material used to make these cups often times does not sufficiently insulate the cup.
At least some known insulated receptacles receive cylindrical containers therein to facilitate insulating the portion of the container contained within the insulated receptacle. More specifically, such receptacles are generally sized to circumscribe the container, such that the insulating material tightly contacts the external and bottom surfaces of the cylindrical container. Accordingly, the size and shape of a container that may be effectively received within such insulated receptacles may be limited. Moreover, because of the tight fit created between the insulated receptacle and the container, it may be difficult to remove or install the container into or from the insulating receptacle.
Other known insulated receptacles are used with containers having tapered sidewalls. However, such insulated receptacles generally extend around only a portion of the container such that a portion of the container, including the bottom surface of the container, remains un-insulated. Such receptacles are commonly used with disposable paper coffee cups to facilitate shielding a user's hand from heat transferred through the cup by the hot fluid contained therein.

Method and apparatus for insulating fluids contained within a container


A flexible conduit fitting system includes a housing that defines at least part of a flexible conduit fitting, and a resilient clip supported by the housing. The flexible conduit fitting may include an aperture for receiving an end of a flexible wiring conduit. The resilient clip may have an engagement portion that extends into the aperture of the flexible conduit fitting to engage the generally corrugated outer structure of the flexible wiring conduit. The housing may be configured to support the resilient clip in a manner that allows the resilient clip to flex in a direction of movement of the flexible wiring conduit when the flexible wiring conduit is being inserted into the aperture and past the engagement portion, but to not substantially flex in the direction of movement of the flexible wiring conduit when attempting to withdraw the flexible wiring conduit from the aperture.

Electrical wiring and other components are frequently protected by flexible conduits. Such conduits are typically secured to housings that contain components such as wiring junctions, switches, light fixtures, sensors, actuators, and/or any other suitable components. Often these conduit-housing connections are secured with a set screw or other mechanical method that may require a tool for installation. This may require a time-consuming manipulation in an environment with limited access, illumination and/or space. What would be desirable are devices and methods for making such connections more simply.


Methods are provided for treating injury to or disease of the central or peripheral nervous system. In one embodiment, treatment is effected by administering activated T cells that recognize an antigen of Cop 1 or a Cop 1-related peptide or polypeptide to promote nerve regeneration or to prevent or inhibit neuronal degeneration within the nervous system. In another embodiment, treatment involves administering Cop 1 or a Cop 1-related peptide or polypeptide to promote nerve regeneration or to prevent or inhibit neuronal degeneration in the nervous system, either the central nervous system or the peripheral nervous system. The activated T cells, which have been activated by the presence of Cop 1 or a Cop 1-related peptide or polypeptide, can be administered alone or in combination with Cop 1 or a Cop 1-related peptide or polypeptide.

The nervous system comprises the central and the peripheral nervous system. The central nervous system (CNS) is composed of the brain and spinal cord; the peripheral nervous system (PNS) consists of all of the other neural elements, namely the nerves and ganglia outside of the brain and spinal cord.
Damage to the nervous system may result from a traumatic injury, such as penetrating trauma or blunt trauma, or a disease or disorder, including but not limited to Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), diabetic neuropathy, senile dementia, and ischemia.
Maintenance of central nervous system integrity is a complex "balancing act" in which compromises are struck with the immune system. In most tissues, the immune system plays an essential part in protection, repair, and healing. In the central nervous system, because of its unique immune privilege, immunological reactions are relatively limited (Streilein, 1993, 1995). A growing body of evidence indicates that the failure of the mammalian central nervous system to achieve functional recovery after injury is a reflection of an ineffective dialog between the damaged tissue and the immune system. For example, the restricted communication between the central nervous system and blood-borne macrophages affects the capacity of axotomized axons to regrow; transplants of activated macrophages can promote central nervous system regrowth (Lazarov-Spiegler et al, 1996; Rapalino et al, 1998).
Activated T cells have been shown to enter the central nervous system parenchyma, irrespective of their antigen specificity, but only T cells capable of reacting with a central nervous system antigen seem to persist there (Hickey et al, 1991; Werkele, 1993; Kramer et al, 1995). T cells reactive to antigens of central nervous system white matter, such as myelin basic protein (MBP), can induce the paralytic disease experimental autoimmune encephalomyelitis (EAE) within several days of their inoculation into naive recipient rats (Ben-Nun, 1981a). Anti-MBP T cells may also be involved in the human disease multiple sclerosis (Ota, K. et al, 1990; Martin, 1997). However, despite their pathogenic potential, anti-MBP T cell clones are present in the immune systems of healthy subjects (Burns, 1983; Pette, M. et al, 1990; Martin et al, 1990; Schluesener et al, 1985). Activated T cells, which normally patrol the intact central nervous system, transiently accumulate at sites of central nervous system white matter lesions (Hirschberg et al, 1998).
A catastrophic consequence of central nervous system injury is that the primary damage is often compounded by the gradual secondary loss of adjacent neurons that apparently were undamaged, or only marginally damaged, by the initial injury (Faden et al, 1992; Faden 1993; McIntosh, 1993). The primary lesion causes changes in extracellular ion concentrations, elevation of amounts of free radicals, release of neurotransmitters, depletion of growth factors, and local inflammation. These changes trigger a cascade of destructive events in the adjacent neurons that initially escaped the primary injury (Lynch et al, 1994; Bazan et al, 1995; Wu et al, 1994). This secondary damage is mediated by activation of voltage-dependent or agonist-gated channels, ion leaks, activation of calcium-dependent enzymes such as proteases, lipases and nucleases, mitochondrial dysfunction and energy depletion, culminating in neuronal cell death (Yoshino et al, 1991; Hovda et al, 1991; Zivin et al, 1991; Yoles et al, 1992). The widespread loss of neurons beyond the loss caused directly by the primary injury has been called "secondary degeneration."
One of the most common mediators which cause self-propagation of the diseases even when the primary risk factor is removed or attenuated is glutamate, an excitatory amino acid capable of displaying dual activity: playing a pivotal role in normal central nervous system (CNS) functioning as an essential neurotransmitter, but becoming toxic when its physiological levels are exceeded. Elevation of glutamate has been reported in many CNS disorders. In its role as an excitotoxic compound, glutamate is one of the most common mediators of toxicity in acute and chronic (including optic nerve degeneration in glaucoma) degenerative disorders (Pitt et al, 2000 and Schoepp et al, 1996). Endogenous glutamate has been attributed to the brain damage occurring acutely after status epilepticus, cerebral ischemia or traumatic brain injury. It may also contribute to chronic neurodegeneration in such disorders as amyotrophic lateral sclerosis and Huntington's chorea.
Intensive research has been devoted to attenuating the cytotoxic effect of glutamate by the use of locally acting drugs, such as NMDA-receptor antagonists (Brauner-Osborne et al, 2000). Conventional therapy of this type is often unsatisfactory, however, as in neutralizing the toxic effect it is likely to interfere with the physiological functioning. In humans, such compounds have psychotropic and other side effects that make them unsuitable as therapeutic agents. They also have the disadvantage of interfering with the essential physiological functioning of glutamate as a ubiquitous CNS neurotransmitter. Because glutamate activity is essential for normal physiological functioning, yet is potentially devastating after acute injury or in chronic CNS disorders, any attempt to neutralize its harmful effect must do so without eliminating its essential activity at other sites in the body.
Another tragic consequence of central nervous system injury is that neurons in the mammalian central nervous system do not undergo spontaneous regeneration following an injury. Thus, a central nervous system injury causes permanent impairment of motor and sensory functions.
Spinal cord lesions, regardless of the severity of the injury, initially result in a complete functional paralysis known as spinal shock. Some spontaneous recovery from spinal shock may be observed, starting a few days after the injury and tapering off within three to four weeks. The less severe the insult, the better the functional outcome. The extent of recovery is a function of the amount of undamaged tissue minus the loss due to secondary degeneration. Recovery from injury would be improved by neuroprotective treatment that could reduce secondary degeneration. For example, alleviation of the effect of glutamate is a frequent target of neuroprotective drug development. Among the drugs which are being developed for this purpose are N-methyl-D-aspartate (NMDA)-receptor or alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA)-receptor antagonists. These drugs will inevitably have severe side effects as they interfere with the functioning of NMDA and AMPA receptors, which are crucial for CNS activity. One of the most intensely studied NMDA-receptor antagonists is MK801, which provides effective neuroprotection but with severe side effects. In animal models of cerebral ischemia and traumatic brain injury, NMDA and AMPA receptor antagonists protect against acute brain damage and delayed behavioral deficits. Such compounds are undergoing testing in humans, but therapeutic efficacy has yet to be established. Other clinical conditions that may respond to drugs acting on glutamatergic transmission include epilepsy, amnesia, anxiety, hyperalgesia and psychosis (Meldrum, 2000).
In the laboratory of the present inventors, it has recently been discovered that activated T cells that recognize an antigen of the nervous system (NS) of the patient promote nerve regeneration or confer neuroprotection. Reference is made to PCT publication WO 99/60021, the entire contents of which is hereby incorporated herein by reference. More specifically, T cells reactive to MBP were shown to be neuroprotective in rat models of partially crushed optic nerve (Moalem et al, 1999) and of spinal cord injury (Hauben et al, 2000). Until recently, it had been thought that the immune system excluded immune cells from participating in nervous system repair. It was quite surprising to discover that NS-specific activated T cells could be used to promote nerve regeneration or to protect nervous system tissue from secondary degeneration which may follow damage caused by injury or disease of the CNS or PNS.
NS-specific activated T cells as described in said WO 99/60021 publication are activated T cells having specificity for an antigen of the NS of a patient. The antigen used to confer the specificity to the T cells may be a self NS-antigen of the patient, a peptide derived therefrom, or an NS-antigen of another individual or even another species, or a peptide derived therefrom, as long as the activated T cell recognizes an antigen in the NS of the patient.
Said NS-specific activated T cells are for use to promote nerve regeneration or to prevent or inhibit the effects of disease. If the disease being treated is an autoimmune disease, in which the autoimmune antigen is an NS antigen, the T cells which are used for the treatment of neural damage or degeneration caused by such disease are not activated against the same autoimmune antigen involved in the disease.
The above-referenced PCT publication WO 99/60021 discloses that therapy for amelioration of effects of injury or disease comprising administration of NS-specific activated T cells may optionally be in combination with an NS-specific antigen or peptide derived therefrom. An NS-specific antigen as defined in said WO 99/60021 refers to an antigen that specifically activates T cells such that following activation, the activated T cells accumulate at a site of injury or disease in the NS of the patient. Furthermore, oral administration of NS-specific antigen or a peptide derived therefrom can be combined with active immunization to build up a critical T cell response immediately after injury.
In this prior invention, the NS-specific antigen used to activate the T cells in vitro or in vivo or to immunize the patient, may be an antigen obtained from NS tissue, preferably from tissue at a site of CNS injury or disease. Natural or synthetic NS-specific antigens or epitopes were disclosed to include MBP, MOG, PLP, MAG, S-100, β-amyloid, Thy-1, P0, P2 and a neurotransmitter receptor. Specific illustrative examples of such useful NS-specific antigens disclosed in WO 99/60021 are human MBP, human proteolipid protein (PLP), and human oligodendrocyte glycoprotein. Also disclosed were peptides derived from NS-specific, self-antigens or derivatives of NS-specific antigens that activate T cells, but do not induce an autoimmune disease, such as a peptide comprising amino acids 51-70 of myelin basic protein (MBP).
The mechanism of action of such NS-specific T cells has yet to be discovered, but the massive accumulation of exogenously administered T cells at the site of CNS injury suggests that the presence of T cells at the site of injury plays a prominent role in neuroprotection. It appears, however, that the accumulation, though a necessary condition, is not sufficient for the purpose, as T cells specific to the non-self antigen ovalbumin also accumulate at the site, but have no neuroprotective effect (Hirschberg et al, 1998).
A high molecular weight synthetic basic random copolymer consisting of L-Ala, L-Glu, L-Lys and L-Tyr residues in the molar ratio of about 6 parts Ala to 2 parts Glu to 4.5 parts Lys to 1 part Tyr, and having a molecular weight of 15,000-25,000, was first described in U.S. Pat. No. 3,849,550 as an agent for treatment or prevention of experimental allergic encephalomyelitis (EAE), a disease resembling multiple sclerosis (MS) that can be induced in susceptible animals. Batches of this copolymer of average molecular weight 23,000, designated Copolymer 1 or Cop 1, were shown to be highly effective in protecting and suppressing EAE in several animal species (Teitelbaum et al, 1971, 1974a, 1974b).
Later, Cop 1 was found to significantly reduce the number of relapses in patients with the exacerbating-remitting form of MS (Bornstein et al, 1990; Sela et al, 1990; Johnson et al, 1994). Copolymer 1, in the form of the acetate salts of synthetic polypeptides containing L-Glu, L-Ala, L-Tyr and L-Lys with an average molar fraction of 0.141, 0.427, 0.095 and 0.338, is the active ingredient of COPAXONE®, a medicament for the treatment of multiple sclerosis.
It is thus apparent that the effect of Copolymer 1 in the treatment of MS is in in the achievement of suppression or deactivation of autoimmune T cell reactivity to myelin antigens in multiple sclerosis patients. For this purpose, Copolymer 1 is administered without adjuvants by daily subcutaneous injection.
Cop 1 was originally designed to mimic MBP and to induce EAE, but was found to be non-encephalitogenic and even to suppress EAE induced by MBP (Teitelbaum et al, 1971) (PLP) (Teitelbaum et al, 1996), or (MOG) (Ben-Nun et al, 1996). The precise mechanisms by which Cop 1 prevents the development of EAE and ameliorates multiple sclerosis (MS) are not yet known. Nevertheless, some important immunological properties of this copolymer have emerged. Studies have demonstrated partial cross-reactivity of Cop 1 with MBP at both the T cell (Webb et al, 1973) and the antibody (Teitelbaum et al, 1988) level. Cop 1 can serve as an antagonist of the T-cell antigen receptor for the MBP immunodominant epitope (Aharoni, 1998). It can also bind to various MHC class II molecules and prevent them from binding to T cells with specific antigen-recognition properties (Fridkis-Hareli et al, 1999a). In rodents, Cop 1 induces regulatory cells that probably act as bystander suppressors (Aharoni, 1998) of encephalitogenic T cells. Adoptive transfer of such T cells was found to prevent the development of EAE induced by MBP (Aharoni et al, 1993), PLP (Aharoni, 1998), or whole spinal cord homogenate (Aharoni et al, 1997).
Furthermore, direct evidence has also been reported both for competitive interaction of Cop 1 and related copolymers and Collagen II (CII) peptide with rheumatoid arthritis (RA)-associated HLA-DR molecules and for inhibition of CII-specific T cell responses, suggesting that these compounds may be effective against rheumatoid arthritis (Fridkis-Hareli, 1998, 1999b).
Oral administration of autoantigen in order to obtain "oral tolerance" has been disclosed for the treatment of various autoimmune diseases. For example, EP 359 783 discloses the oral administration of MBP for the treatment of multiple sclerosis. PCT International Publications WO 91/12816, WO 91/08760 and WO 92/06704 all disclose the treatment of other autoimmune diseases using the oral tolerance method with a variety of autoantigens. Treatment of multiple sclerosis by ingestion or inhalation of Copolymer 1, to achieve suppression of the autoimmune T cell response to myelin antigens, has been disclosed in PCT publication WO 98/30227.
Compounds related to Copolymer 1 have also been studied and found to have properties similar to Copolymer 1. For example, copolymers composed of three of the four amino acids found in Copolymer 1 bind to purified Class II MHC molecules (Fridkis-Hareli et al, 1999a, WO 005250). In addition, binding motifs of Copolymer 1 to multiple sclerosis- and rheumatoid arthritis-associated HLA-DR molecules have recently been elucidated (Fridkis-Hareli et al, 1999b). From these binding motifs, polypeptides of fixed sequence can readily be proposed and tested for binding to the peptide binding groove of the HLA-DR molecules. Such peptides would be expected to act in a way similar to Cop 1 itself. Examples of such synthetic peptides are disclosed in WO 005249.
Citation or identification of any reference in this section or any other part of this application shall not be construed as an admission that such reference is available as prior art to the invention.

This patent is subject to a terminal disclaimer.

Use of copolymer 1 and related peptides and polypeptides and T cells treated herewith for neuroprotective glaucoma therapy


A beverage maker including a hinge shaft, a fermentation tank having a space therein and configured to rotatably support the hinge shaft, a fermentation lid connected to the hinge shaft through a bracket and rotating about the hinge shaft to open and close the space, and at least one tube through which a fluid passes, wherein a hinge shaft accommodating space accommodating the at least one tube is defined inside the hinge shaft, and at least one hinge shaft hole through which the at least one tube extends to the outside of the hinge shaft space is defined in the hinge shaft to minimize damage or contamination of the at least one tube and allow the at least one tube to be minimally visible when the fermentation lid is opened.

The present disclosure relates to a beverage maker apparatus, and more particularly, to a beverage maker apparatus including a fermentation tank and a fermentation lid.
Beverages are collectively referred to as drinkable liquids such as alcohol, juice, water, tea, etc.
Beer, for example, is an alcoholic beverage made by making juice of malt sprouting from barley, filtering the juice, adding hop, and fermenting the juice by using the yeast.
Homemade beer (also referred to as "house beer") is becoming popular—especially because it can be made into a variety of types and tastes.
The ingredients for making beer may include water, malt, hop, yeast, flavor additives, and the like.
The yeast, which is called leaven, may be added to malt to ferment the malt and help to produce alcohol and carbonic acid.
Flavor additives, such as fruit, syrup, vanilla beans, etc., are additives that enhance the taste of beer.
The house beer may be made through three stages, first, a wort production stage, second, a fermentation stage, and third, an aging stage. It may take about two to three weeks from the wort production step to the aging stage.
It is important for the house beer to maintain an optimum temperature during fermentation for the beer making process to be as convenient as possible.
An example of the beverage maker may be an alcoholic drink maker that is disclosed in Korean patent Registration No. 10-0793258 B1 (published on Jan. 10, 2008). The alcoholic drink maker includes a tank body having an inner space, a lid sealing the tank body, a clamp fixing the tank body and the lid, a steamer-combined filter box put into the tank body, and a filtering cloth put into the steamer-combined filter box.
A user using the domestic alcoholic drink maker opens the lid to put a predetermined amount of water and beverage ingredients into the tank body and then manipulates the domestic alcoholic drink maker after closing the lid. The alcoholic drink maker may control a temperature of the tank body by using a cooling device or a heating device to perform the fermentation.
The beverage maker according to the related art has limitations in which the foreign substances such as dust are put into the water or the beverage ingredients because the water and the beverage ingredients are directly put into the tank body when the lid is open. The present invention is directed to improvements in the beverage maker apparatus.


Drive coupling assembly (50) for a high-speed rotating brush, comprising:—a coupling head (100) having a coupling head rotation axis (Lch) and including three drive surfaces (106) which are arranged to be rotationally symmetrical through 120° with respect to said coupling head rotation axis; and—a coupling member (200), having a coupling member rotation axis (Lcm) and including three first drive surfaces (210a) which are arranged to be rotationally symmetrical through 120° with respect to said coupling member rotation axis, wherein said coupling head (100) and said coupling member (200) are detachably couplable, such that, in a coupled condition, their rotational axes (Lch, Lcm) are aligned and the coupling head is rotatable to drive each of its drive surfaces (106) in contact with a respective first drive surface (210a) of the coupling member, to thereby exert both a torque and an axially directed force on the coupling member.

A hard floor cleaning device may include one or more high-speed rotating brushes. Each brush may have an elongate cylindrical core, extending axially between a first end and a second end, whose outer surface is covered with a brush material, e.g. soft microfiber filaments. The first and second ends of the brush may be bearingly mounted in the cleaning device so as to enable rotation of the brush around its axis, in particular when the latter is oriented parallel to and in abutment with a floor to be cleaned. The brush may typically be rotationally driven from one of its bearingly mounted ends, for which purpose the respective end may be detachably coupled to a transmission of an (electro)motor by means of a drive coupling assembly. The manner in which a brush is bearingly mounted in the hard floor cleaning device and coupled to the transmission may significantly effect its operating behavior.
For instance, it is known to mount a low-speed rotating brush, configured to be driven at a rotational speed of about 1,500 rpm, in a hard floor cleaning device by means of a drive coupling that includes an axial spring mechanism. The axial spring mechanism serves to take up axial play between the ends of the brush and brush mounting points of the cleaning device and to fix the brush's axial position between these mounting points (i.e. prevent travel of the brush through its range of axial play). This approach, however, does not appear suitable for mounting high-speed rotating brushes, which may be driven at rotational speeds of at least 2,500 rpm, e.g. at about 7,000 rpm. At such rotational speeds, slight imbalances in the mount of the brush may cause undesirably high levels of audible and sensible vibrations. To suppress these vibrations the clasping force exerted on the brush by the axial spring mechanism may be increased so as to stiffen the construction, but this also increases the risk of creep during the multiple-year life span of the device, and hence to further imbalances.

Drive coupling for high-speed rotating brush


A printing method includes: printing an image to be printed on a medium by repeating alternately a dot forming process for forming dots on the medium by ejecting ink from each nozzle of a plurality of nozzles, and a carrying process for carrying the medium in a carrying direction, and forming a plurality of rows of dots, lined up in the carrying direction, that are configured by a plurality of dots lined up in a movement direction; selecting a printing mode according to the number of the dots to be formed in a predetermined region of the medium, from among a plurality of the printing modes each with a different ratio of the number of dot rows formed using a different number of nozzles to the number of dot rows formed using a certain number of nozzles; and printing on the region to be printed based on the selected printing mode.

1. Technical Field
The present invention relates to printing methods, printing systems, and storage media.
2. Related Art
In printing apparatuses such as an inkjet printer, an image to be printed is printed on a medium by alternately repeating a dot forming process for forming dots by ejecting an ink from a nozzle moving in a movement direction, and a carrying process for carrying a medium such as paper in a carrying direction, and arranging continuously in the carrying direction raster lines that are configured by a plurality of the dots arranged in the movement direction.
As printing modes, there are known "interlace printing", "overlap printing", "non-uniform overlap printing" and the like (refer to JP-A-2002-11859). In the "non-uniform overlap printing", the number of nozzles used varies for each raster line. For example, the number of nozzles used for a certain raster line is two, but the number of nozzles used for a different raster line is three.
There is a case where a position of a dot formed by a nozzle is shifted in the carrying direction due to a manufacturing error of the nozzle. As a result, due to the shifting of the dot, there occurs a spacing in between the raster lines, and a stripe-shaped banding occurs. As a cause of banding in which this kind of variation in density occurs, there are other causes such as a carrying amount error or a curling of the printing medium.
With the non-uniform overlap printing, the banding due to variation in density can be suppressed in the raster line that has a large number of nozzles that are used for it. However, according to the non-uniform overlap printing, since there are mixed raster lines that have a different number of nozzles that are used for it, there is the case where banding caused by gloss occurs.

Printing method, printing system and storage medium


The subject matter described herein includes methods, systems, and computer readable media for automated attention assessment. According to one method, a method for automated attention assessment includes obtaining head and iris positions of a user using a camera while the user watches a display screen displaying a video containing dynamic region-based stimuli designed for identifying a neurodevelopmental and/or psychiatric (neurodevelopmental/psychiatric) disorder; analyzing the head and iris positions of the user to detect attention assessment information associated with the user, wherein the attention assessment information indicates how often and/or how long the user attended to one or more regions of the display screen while watching the video; determining that the attention assessment information is indicative of the neurodevelopmental/psychiatric disorder; and providing, via a communications interface, the attention assessment information, a diagnosis, or related data.

Neurodevelopmental and/or psychiatric (neurodevelopmental/psychiatric) disorders affect many people throughout the world. Current estimates indicate that 1 in 9 children may have or develop a neurodevelopmental and/or psychiatric disorder, such as an autism spectrum disorder (ASD), an anxiety disorder, or attention deficient and hyperactivity disorder (ADHD). For example, ASD is associated with deficits in the processing of social information and difficulties in social interaction, and individuals with ASD exhibit atypical attention and gaze. Such deficits in attention are among the earliest symptoms of neuropsychiatric conditions and persist throughout life, and thus can assist in risk detection, diagnosis, and symptom monitoring throughout the lifespan. Traditionally, gaze studies have relied upon precise and constrained means of monitoring attention using expensive equipment in laboratories. Hence, current attention assessment techniques include barriers that prevent or hinder effective diagnosis and symptom monitoring in various conditions, e.g., natural settings.

Methods, systems, and computer readable media for automated attention assessment


A method of routing a packet in a routing device having a main processor that includes a main cache table and an instant cache table is disclosed. The instant cache stores a recent address and a recent interface associated with the most recent packet transmission process made by the routing device. The method includes the steps of receiving a packet that includes its destination address, checking whether the destination address belongs to the routing device, checking whether the destination address is identical to the recent address if the destination address does not belong to the routing device, and transmitting the packet to the recent interface if the destination address is identical to the recent address. As a result, the core information related to the routing path determination is stored not only in the routing table of the protocol layer but also in the main and instant cache tables included in the main processor. Since the selection of the routing path for a given packet depends on the individual characteristic of the packet, the data processing time of the packet is greatly reduced. Consequently, the routing performance of the routing device is greatly enhanced.

1. Field of the Invention
The present invention relates to method of routing a packet in a routing device, and more particularly, to a routing method being able to reduce the packet-processing time by setting a routing path that depends on the characteristic of each packet.
2. Discussion of the Related Art
In general, a device that connects two or more network systems having a same transmission protocol is often referred to as a routing device. A typical routing device included in a network system sets a node in the system itself or in another network system, and it transmits one or more packets received using a given transmission path.
FIG. 1 illustrates a network system including a typical routing device 10. The main processor 1 checks whether a packet is received through a port 6. When the routing device 10 receives a packet, whose destination address is set to another node or another routing device (e.g., R2), the main processor 1 sends the packet to the protocol layer 2 included in the routing device 10. The protocol layer 2 may be any one of the IP (Internet Protocol) layer 2A, IPX (Internetwork Packet exchange) layer 2B, Bridge layer 2C, and many others.
For example, when the IP layer 2A receives the packet from the main processor 1, it initially determines whether to process the packet. Once it decides to process the packet, the IP layer 2A sends the packets to the top application module 3.
On the other hand, if it decides not to process the packet, it checks the destination address of the packet. For example, the IP layer 2A obtains the interface number corresponding to the destination address of the packet by searching the IP routing table 4A of the routing table 4. And it sends the packets to the interface found. Then the packet gets transmitted to a node or routing device corresponding to the destination address of the packet.
As described above, the packet passes through a routing path that includes the main processor 1 and the IP layer 2A, and this is shown in FIG. 2. Since such routing path is formed regardless of the individual characteristic of the packet, the packet-processing rate of the routing device 10 is low. Therefore, the performance of the routing device may be degraded.
Even though it is highly desirable to provide a method of setting a routing path that depends on the individual characteristic of each packet, such method is currently unavailable for the existing routing device.

Method of routing a packet in a routing device


A stress relieving joint for use with riser pipe in floating systems wherein a vessel is subject to variable motion caused by wind, currents, and wave action. The riser pipe has one end connectable to the sea floor and an upper portion adapted to pass through a constraining opening at the bottom of the vessel. A ball joint and socket assembly is removably attached to the keel at the constraint opening. A sleeve is attached at substantially its midpoint in the ball joint. Riser pipe received in the sleeve is provided with wear strips that reduces the rate of reduction in wear surface diameter.

1. Field of the Invention
The invention is generally related to the support of risers used in offshore structure and more particularly to the support of risers at the keel of floating offshore structures.
2. General Background
In the drilling and production of hydrocarbons offshore, the development of deep water operations from floating vessels has included the use of tendons and risers under tension extending from the vessel to the sea floor. Such floating vessels have included tension buoyant towers, and spar structures in which the floating structures extend well below the surface of the water and are subjected to heave, pitch, and roll motions.
The lower ends of the tendons and risers are connected to the sea floor by means of additional pipes or risers embedded in and grouted to the sea floor. The upper ends of the tendons and risers pass through openings in the keel or bottom portion of the vessels and are supported vertically by tensioning means located near the water surface.
The openings in the keel serve to constrain the pipe forming the tendons or risers when the vessel is moved laterally with respect to the sea floor connection. Such lateral movement produces bending of the pipe at the constraint opening or rotation of the pipe about the contact of the pipe with the edges of the opening. Bending of the pipe which is normally under tension results in fatigue and wear at the constraint opening.
Riser pipe diameters can vary according to the functional requirements for the riser with typical designs varying from three to twenty inches. The opening in the keel guide support frame, for present designs, is sized to pass the connector used to tie the riser to the subsea wellhead. This connector diameter typically varies from twenty-seven to forty-eight inches, depending on the style of tieback connector used. Previous keel sleeves were designed to fill the twenty-nine to fifty inch hole provided in the spar keel riser frame. This resulted in a large diameter and thus very heavy and costly keel sleeve. This large diameter keel sleeve was generally too stiff to efficiently provide the bend limiting function that is desired. In addition, the length of the keel sleeve was required to be quite long (fifty to sixty feet) to insure that the sleeve did not leave the keel guide as a result of relative motion between the floating structure and the riser.
Prior proposed means for controlling stress at such a point or area of rotation of the pipe have included tapered pipe wall sections of very large wall thickness. The thick tapered wall sections are usually machined from heavy forgings and are very expensive.
Pending U.S. application assigned Ser. No. 08/431,147 now U.S. Pat. No. 5,683,205 discloses a stress relieving joint wherein a sleeve member is ensleeved over the pipe portion at the constraint opening and has an inner diameter greater than the outer diameter of the pipe portion. Means at opposite ends of the sleeve centralize the pipe within the sleeve such that the bending stresses at the constraint opening are relieved and distributed to the pipe at the ends of the sleeve member.
The known art does not address the need for a riser support at the keel of a vessel that may be installed with the riser and is more readily removed and replaced if required due to damage, wear, and/or fatigue.


An illumination system configured to light an anatomical location of a patient is provided. The illumination system includes an interior illumination device positionable and movable within a body cavity of a patient. The interior illumination device is configured to provide a light having a wavelength that is visible to a clinician. The illumination system includes an exterior illumination device operatively coupled to the interior illumination device and positionable and movable about an exterior of a patient. The exterior illumination device is configured to provide a light having a wavelength that is visible to a clinician.

1. Technical Field
The present disclosure relates to an apparatus and system for performing surgery and, more particularly, to an apparatus and system that includes an illumination device configured to illuminate various anatomical locations of a patient.
2. Related Art
Without limiting the scope of the present disclosure, its background is described herein with respect to surgical procedures, and in particular, laparoscopy and transluminal and endoluminal surgery, e.g., Natural Orifice Transluminal Endoscopic Surgery (NOTES).
Compared with open surgery, laparoscopy results in significantly less pain, faster convalescence and less morbidity. NOTES, an even less invasive surgical approach, is likely to achieve similar results. However, eye-hand dissociation, a two-dimensional field-of-view and instrumentation with limited degrees of freedom contribute to a steep learning curve and demanding dexterity requirements for many laparoscopic and endoscopic procedures. A limitation of laparoscopic and endoscopic procedures is the fixed working envelope surrounding each trocar, often necessitating placement of multiple ports to accommodate changes in position of the instruments or laparoscope to improve visibility and efficiency. The placement of additional working ports contributes to post-operative pain and carries a small risk of bleeding or adjacent organ damage. Another limitation of laparoscopic and endoscopic procedures is that the images often appear "upside-down" and/or "backward" due to the flexible rather than rigid scope typically employed by a clinician during the laparoscopic and endoscopic procedures, which, may result in a clinician becoming disoriented during the laparoscopic and endoscopic procedures.
Therefore, it may prove advantageous to provide an illumination guidance apparatus and system configured for use with a surgical space in a minimally invasive surgical procedure while avoiding any one or combination of the aforementioned limitations.

Apparatus and system for performing surgery


Solenoid controlled hydraulic valves in sealed hydraulic circuits are provided with backup actuation without compromise of the hydraulic circuit by provision of an auxiliary, quick fitting solenoid coil case which incorporates manual switches and which may be attached directly to a battery for energization.

1. Technical Field
The invention relates in general to solenoid control elements for hydraulic valves and more particularly to a quick fitting replacement solenoid for use as a diagnostic tool or backup actuator for a spool type hydraulic valve in a closed hydraulic circuit.
2. Description of the Problem
Vehicle mounted hydraulic systems have been employed for diverse purposes including positioning snowplows, compacting trash, moving support beds and other functions. Such hydraulic systems are controlled using spool valves and these spool valves in turn have often been manually activated, with handles mechanically linked to the spool valves. The mechanical link must of course be sealed to avoid spillage of pressurized hydraulic fluid. However, these seals are prone to wear and leaks almost invariably develop.
To avoid, or at least postpone, the development of leaks, solenoid controlled hydraulic valves have been developed. A solenoid coil is used to generate magnetic fields to control positioning of the spool valve inside the valve body without the need for a mechanical linkage through the valve body. Without a mechanical linkage, the need for mechanical seals around a linkage is eliminated. Solenoid actuated valves are much less prone to leakage than mechanically actuated valves, but they complicate making provision for fitting an override control mechanism to the valve. Some manufacturer's have retained a mechanical linkage to use as a backup to the electromagnetic system. While the linkages are now used less often, they still represent a compromise of the full sealing of the hydraulic system, and they can still develop leaks over time due to thermal cycling or chemical attack. The use of solenoids also eases integration between a vehicle's hydraulic systems and the vehicle's electronic control systems. This in turn raises questions in some minds as to the reliability of the electronic controls or the ability to diagnose a problem as being electronic or hydraulic, should a problem occur.

Manually controlled replacement solenoid for hydraulic valves

International Truck Intellectual Property Company, LLC


Methods and apparatus are provided for determining traffic characteristics and statistics for storage area network flows. An intelligent line card associated with a fibre channel switch is used to snoop selected flows in a storage area network. Flows are characterized using information that may include initiator target pairs and initiator target logical unit number (LUN) groupings. Selected flows are configured for monitoring and information about the selected flows is maintained. Selected flow information can be analyzed at a line card associated with a fibre channel switch.

1. Field of the Invention
The present invention generally relates to storage area networks. More specifically, the present invention provides mechanisms for analyzing traffic flows in a fibre channel fabric.
2. Description of Related Art
In storage area networks, it is often useful to determine traffic characteristics. Fibre channel analyzers, protocol analyzers, and network analyzers are connected to line card ports to snoop traffic and determine traffic characteristics and statistics. However, physically connecting and reconnecting fibre channel analyzers can be cumbersome.
One technique for more efficiently using fibre channel analyzers involves connecting an analyzer to a fibre channel switch port. The fibre channel switch forwards data to the switch port analyzer (SPAN). If a fibre channel switch determines that it wishes to monitor data from a particular input port. Data from that input port is forwarded and also copied to the switch port analyzer. In some instances, SPAN merely forwards the data to a fibre channel analyzer. In other examples, SPAN forwards data to another fibre channel switch or a separate processing entity altogether.
However, existing mechanisms for determining traffic characteristics using mechanisms such as analyzers and SPAN are limited. Consequently, it is therefore desirable to provide methods and apparatus for improving the ability to analyze storage area network traffic and determine traffic characteristics and statistics.

Determining traffic flow characteristics in a storage area network


A computer speaker assembly 22 is disclosed and includes a tweeter or high-frequency speaker 72 which may be selectively moved in relation to a mid-range-woofer speaker 30. Such movement is accomplished by means of a gear 64 and detent 62 arrangement.

1. Field of the Invention
This invention generally relates to a computer speaker and, more particularly, to a computer speaker assembly having a mid-range-woofer and a high-range speaker and which is adapted to be movable from a first closed and stored position to a number of desired operative open positions.
2. Discussion
Speakers are used in a variety of applications to convert an electrical signal to an audio output. Recent advances in computer technology have created "multi-media" computer systems which allow a user to interact with the computer in a variety of different ways. For instance, many of these multi-media computers allow a user to input data by means of a standard keyboard as well as through the use of written text. Moreover, these computer systems provide information to the user by means of the traditional monitor or cathode ray tube (CRT) as well as through various audio signals.
While such multi-media computer systems have gained wide popularity, the quality of the audio output signal has been quite poor. The poor audio quality has been due to a number of factors including the use of highly compressed data, such as that associated with the reduced instruction set computing (RISC) architectures.
These highly compressed architectures provide an increase in computing speed by reducing the amount of data that needs to be processed by the central processor. While such reduced instruction set architectures have allowed large amounts of data to be efficiently processed, the use of such compressed data in conjunction with a audio speaker has resulted in poor audio quality, since only a relatively small amount of the original audio data has been provided to the speaker for audio reproduction. There is therefore a need to provide a speaker for use with such a multi-media computer system; which will accurately form an audio signal from a minimal amount of input audio data; which is relatively compact in shape so as to be capable of being used in relatively close spaces; and which has selectable and modifiable output energy characteristics which allow the output audio signal to be tailored to a specific audio environment.