Methods of inhibiting the replication of influenza viruses in a biological sample or patient, of reducing the amount of influenza viruses in a biological sample or patient, and of treating influenza in a patient, comprises administering to said biological sample or patient a safe and effective amount of a compound represented by any of Formulas I-III, or a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprises a safe and effective amount of such a compound or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle.

Influenza spreads around the world in seasonal epidemics, resulting in the deaths of hundreds of thousands annually-millions in pandemic years. For example, three influenza pandemics occurred in the 20th century and killed tens of millions of people, with each of these pandemics being caused by the appearance of a new strain of the virus in humans. Often, these new strains result from the spread of an existing influenza virus to humans from other animal species.
Influenza is primarily transmitted from person to person via large virus-laden droplets that are generated when infected persons cough or sneeze; these large droplets can then settle on the mucosal surfaces of the upper respiratory tracts of susceptible individuals who are near (e.g. within about 6 feet) infected persons. Transmission might also occur through direct contact or indirect contact with respiratory secretions, such as touching surfaces contaminated with influenza virus and then touching the eyes, nose or mouth. Adults might be able to spread influenza to others from 1 day before getting symptoms to approximately 5 days after symptoms start. Young children and persons with weakened immune systems might be infectious for 10 or more days after onset of symptoms.
Influenza viruses are RNA viruses of the family Orthomyxoviridae, which comprises five genera: Influenza virus A, Influenza virus B, Influenza virus C, Isavirus and Thogoto virus.
The Influenza virus A genus is responsible for seasonal flu and pandemic flu epidemics. It has one species, influenza A virus, and wild aquatic birds are the natural hosts for a large variety of influenza A. Occasionally, viruses are transmitted to other species and may then cause devastating outbreaks in domestic poultry or give rise to human influenza pandemics. The type A viruses are the most virulent human pathogens among the three influenza types and cause the most severe disease.
The influenza A virus can be subdivided into different serotypes based on the antibody response to these viruses. The serotypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are: H1N1 (which caused Spanish influenza in 1918), H2N2 (which caused Asian Influenza in 1957), H3N2 (which caused Hong Kong Flu in 1968), H5N1 (a pandemic threat in the 2007-08 influenza season), H7N7 (which has unusual zoonotic potential), H1N2 (endemic in humans and pigs), H9N2, H7N2, H7N3 and H10N7.
The Influenza virus B genus is responsible for season flu, and has one species, influenza B virus. Influenza B almost exclusively infects humans and is less common than influenza A. The only other animal known to be susceptible to influenza B infection is the seal. This type of influenza mutates at a rate 2-3 times slower than type A and consequently is less genetically diverse, with only one influenza B serotype. As a result of this lack of antigenic diversity, a degree of immunity to influenza B is usually acquired at an early age. However, influenza B mutates enough that lasting immunity is not possible. This reduced rate of antigenic change, combined with its limited host range (inhibiting cross species antigenic shift), ensures that pandemics of influenza B do not occur.
The Influenza virus C genus has one species, influenza C virus, which infects humans and pigs and can cause severe illness and local epidemics. However, influenza C is less common than the other types and usually seems to cause mild disease in children.
Influenza viruses are very similar in structure. The influenza virus genome consists of eight single-stranded RNAs packed into rod-like structures of varying size, known as the ribonucleoprotein complex (RNP). Each RNP contains a unique viral RNA, multiple copies of the scaffolding nucleoprotein, and a heterotrimeric viral polymerase consisting of the PA, PB1, and PB2 subunits, which catalyzes the transcription and replication of the viral genome. Recent biochemical and structural studies of influenza polymerase complex provide insight into the mechanistic understanding of cap-snatching and RNA synthesis by influenza polymerase. Briefly, the PB2 cap-binding domain first squesters the host pre-mRNAs by binding to their 5′ cap. PA, the endonuclease subunit, then cleaves the captured pre-mRNA 10-13 nucleostides downstream of the cap. The PB2 subunit subsequently rotates about 700 to direct the capped primer into the PB1 polymerase active site. The PB1 subunit directly interacts with both PB2 and PA subunits. These subunits contain highly conserved domains among different influenza strains, and have attracted as an attractive anti-influenza drug target. In addition to the polymerase complex, the influenza genome encodes its own neuraminidase (NA), hemagglutinin (HA), nucleoprotein (NP), matrix proteins, M1 and M2, and non-structural proteins, NS1 and NS2. NA is the target for the antiviral drugs oseltamivir (Tamiflu) and zanamivir (Relenza). These drugs are sialic acid analogues which inhibit the enzymatic activity of NA, thus slowing down the release of progeny virus from infected cells.
Influenza produces direct costs due to lost productivity and associated medical treatment, as well as indirect costs of preventative measures. In the United States, influenza is responsible for a total cost of over $10 billion per year, while it has been estimated that a future pandemic could cause hundreds of billions of dollars in direct and indirect costs. Preventative costs are also high. Governments worldwide have spent billions of U.S. dollars preparing and planning for a potential H5N1 avian influenza pandemic, with costs associated with purchasing drugs and vaccines as well as developing disaster drills and strategies for improved border controls.
Current treatment options for influenza include vaccination, and chemotherapy or chemoprophylaxis with anti-viral medications. Vaccination against influenza with an influenza vaccine is often recommended for high-risk groups, such as children and the elderly, or in people that have asthma, diabetes, or heart disease. However, it is possible to get vaccinated and still get influenza. The vaccine is reformulated each season for a few specific influenza strains but cannot possibly include all the strains actively infecting people in the world for that season. It takes about six months for the manufacturers to formulate and produce the millions of doses required to deal with the seasonal epidemics; occasionally, a new or overlooked strain becomes prominent during that time and infects people although they have been vaccinated (as by the H3N2 Fujian flu in the 2003-2004 influenza season). It is also possible to get infected just before vaccination and get sick with the very strain that the vaccine is supposed to prevent, as the vaccine takes about two weeks to become effective.
Further, the effectiveness of these influenza vaccines is variable. Due to the high mutation rate of the virus, a particular influenza vaccine usually confers protection for no more than a few years. A vaccine formulated for one year may be ineffective in the following year, since the influenza virus changes rapidly over time, and different strains become dominant.
Also, because of the absence of RNA proofreading enzymes, the RNA-dependent RNA polymerase of influenza vRNA makes a single nucleotide insertion error roughly every 10 thousand nucleotides, which is the approximate length of the influenza vRNA. Hence, nearly every newly-manufactured influenza virus is a mutant-antigenic drift. The separation of the genome into eight separate segments of vRNA allows mixing or reassortment of vRNAs if more than one viral line has infected a single cell. The resulting rapid change in viral genetics produces antigenic shifts and allows the virus to infect new host species and quickly overcome protective immunity.
Antiviral drugs can also be used to treat influenza, with NA inhibitors being particularly effective, but viruses can develop resistance to the approved NA antiviral drugs. Also, emergence of a multidrug-resistant pandemic influenza A viruses has been well documented. Drug-resistant pandemic influenza A becomes a substantial public health threat. In addition to the drug resistant influenza A viruses, the NA inhibitors are approved for the treatment early influenza infection (within 48 hours of influenza symptom onset).
Thus, there is still a need for drugs for treating influenza infections, such as for drugs with expanded treatment window, and/or reduced sensitivity to viral titer.

Pyrrolopyrimidine derivatives useful as inhibitors of influenza virus replication


An improved process for preparing carbamic ester derivatives of the general formula (1)

Carbamic ester derivatives of the general formula (1) and especially (2-carboxy-4-methylphenyl)carbamic esters of the general formula (1′)
are suitable intermediates for active pharmaceutical ingredients.
Thus, for example, hexadecyl (2-carboxy-4-methylphenyl)carbamate as compound of the formula (1′) with R═C16H33 is disclosed as an intermediate in the preparation of 2-hexadecyloxy-6-methyl-4H-3,1-benzoxazin-4-one of the formula (3)
from the originally published version of WO-A 00/40569. 2-Hexadecyloxy-6-methyl-4H-3,1-benzoxazin-4-one of the formula (3) is described therein as potential active ingredient for the treatment of obesity and type II diabetes. In this originally published version of WO-A 00/40569, two synthetic routes 1 and 2 are described for preparing 2-hexadecyloxy-6-methyl-4H-3,1-benzoxazin-4-one (3), each of which starts from the 5-methyl-substituted anthranilic acid (4).
In the two-stage synthetic route 1, the 5-methyl-substituted anthranilic acid (4) is reacted with hexadecyl chloroformate (5) and subsequently with methyl chloroformate to give 2-hexadecyloxy-6-methyl-4H-3,1-benzoxazin-4-one (3), although the overall yield obtained is only 31%.
The one-stage synthetic route 2 with an excess of pyridine affords 2-hexadecyl-oxy-6-methyl-4H-3,1-benzoxazin-4-one (3) in an even lower yield of 15%.

The starting compound which is required for both the synthetic routes 1 and 2, the 5-methyl-substituted anthranilic acid (4), is not easily obtainable, however.
It is prepared by the method described in J. Org. Chem. 1952, 17, 141. This starts from p-toluidine, which is reacted with chloral hydrate and hydroxylamine hydrochloride. The resulting oxime is cyclized with acid catalysis, and subsequently the ring is cleaved again by oxidation under basic conditions.

The disadvantages of this synthesis are the low yields and the fact that only very low concentrations can be used. For this reason, this synthetic route is unattractive for an industrial reaction.
Further alternative routes known in principle for obtaining anthranilic acids are as follows:                J. Org. Chem. 1978, 43, 220 and Chem. Ber. 1909, 42, 430 disclose initial nitration of 3-cyanotoluene, then reduction of the nitro group and subsequent hydrolysis of the nitrile to the carboxylic acid.
                                    A disadvantage of this synthesis is that the nitration of 3-cyanotoluene does not proceed selectively and therefore a further purification step is necessary. This requires additional effort and reduces the yield.                        The synthesis which is described in J. Chem. Soc. Perkin I, 1973, 2940 and which starts from 3-toluic acid with subsequent nitration and reduction of the nitro group also has the same disadvantage.        The synthesis which is disclosed in Monatsh. Chem. 1920, 41, 155 and starts from 2,4-dimethyl-1-nitrobenzene is likewise unsuitable because oxidation of the methyl group next to the nitro group does not proceed selectively and therefore an elaborate separation of isomers is necessary.
                EP-A 0 034 292 discloses a process for preparing optionally substituted anthranilic acids which includes a transition metal-catalysed carbonylation reaction with carbon monoxide to give an anthranilic acid derivative. This carbonylation reaction takes place in an aqueous reaction medium containing a trialkylamine and a catalyst formed from palladium and a tertiary phosphine. The anthranilic acid derivatives can be obtained by eliminating the protective group. The precursors employed for the carbonylation are obtained starting from optionally substituted anilines as shown in principle in the reaction scheme below:
                                    EP-A 0 034 292 describes this reaction sequence of acetylation (a), halogenation (b), carbonylation (c) and subsequent elimination of the acetyl group (d) as affording the optionally substituted anthranilic acids in good yields (>80%). However, the introduction of the acetyl group is a disadvantage. This is necessary because the free anilines give only poor yields in transition metal-catalysed carbonylation reactions because of pronounced complexation [J. Org. Chem. 1981, 46, 4614-4617].                        WO-A 97/28118 discloses a comparable process.
Because of the diverse difficulties, described above, associated with the known processes for preparing optionally substituted anthranilic acids and the yields, which are only unsatisfactory and thus limiting for the overall process, of the subsequent synthetic routes 1 and 2, the object of the present invention was to provide an improved process for preparing carbamic ester derivatives of the general formula (1).

Process for preparing carbamic ester derivatives

Abstract: by reaction with carbon monoxide and water in the presence of a palladium catalyst is provided.


The present invention provides a wearable device with wireless transmission. The wearable device includes: a first exterior member configured to operate at a first frequency band; a second exterior member configured to operate at a second frequency; and a connecting member configured to electrically insulate the first exterior member from the second exterior member, so the wearable device is able to operate at the first frequency band and the second frequency band simultaneously. A frame structure of the wearable device is formed by stacking the first exterior member, the connecting member and the second exterior member in sequence from top to bottom. In addition, a method for manufacturing the same is also provided in the present invention.

1. Field of the Invention
The present invention relates to the fields of structure design and wireless transmission, and more particularly, relates to a wearable device with wireless transmission.
2. the Prior Arts
As electronic technology advances, it has become a trend nowadays to use smart phones and tablets instead of personal computers. The popularization of smart phones not only promotes the development of software application (commonly known as APPs), but also creates an enormous market and great business opportunities for related accessories. On the other hand, "wearable devices" have also become popular on the market today, and people are starting to wear such wearable devices instead of common watches. These wearable devices not only provide the functions of common watches, but are also equipped with the function of global positioning system (GPS) or Wi-Fi transmission integrated with the antenna system.
Limited by the structure and size of the wearable device, the wearable devices with antenna that are available on the market nowadays usually utilize a part of its housing to be the antenna, such as a bezel structure. Generally speaking, bezel structures can be divided into two categories. FIG. 1 is a schematic view showing a bezel being a single piece of metal member with a single layered structure. As shown in FIG. 1, the wearable device 1 includes a bezel structure 10, a metal member 11 and a printed circuit board (PCB) 12. Although the bezel structure 10 is a single metal piece that has a high structural strength, the signal quality and efficiency of the antenna is still low due to the electrical connection between the metal member 11 and the PCB 12 necessitated by grounding, and also due to the direct connection between the bezel structure 10 and the metal member 11. FIG. 2 is a schematic view illustrating an exterior bezel structure 21, which is integrated by a metal and a plastic structure 22, having a double layered structure. As shown in FIG. 2, wearable device 2 includes a metal member 24, a plastic structure 22 and a PCB 23. Such wearable device 2 is advantageous in that because of the assembling method of the wearable device 2, to be more specific, because of the separation between the metal member 24 and the exterior bezel structure 21 by the plastic structure 22, the antenna signal strength is not compromised; however, the overall structural strength of such wearable device 2 is relatively low because part of the housing is made of plastic material, and the exterior bezel structure is likely to be separated with the plastic structure 22.
Due to the above reasons, for the sake of the wearable device, it is preferable to inject plastic material at the region between the exterior member (such as bezel structures) and the internal metal member with insert molding technique to separate the two metal members without compromising the overall structural strength of the wearable device. In such a way, not only is the overall structural strength of the wearable device maintained, the interference against the antenna signal by the metal members can also be reduced. Therefore, it is a pressing matter for the industry to develop such a device to maintain a good signal quality and good efficiency of the antenna.
Additionally, in conventional insert molding processes, metal members (such as aluminum ingots) are usually embedded first for the injection molding to form a workpiece. Subsequently, computer numerical control (CNC) machining is utilized to form the outer appearance of the workpiece. Finally, the workpiece undergoes appearance finishing process to become the final product. Nevertheless, the process as described above may cause dust or moist to enter the final product during the manufacturing process, thus lowering the product yield or degrading the performance of the final product.
Hence, there is a need for the industry to develop an insert molding process in which the appearance finishing treatment is performed first before the embedding of the insert molding process. In such a way, once the insert molding process is finished, the exterior members are connected with the internal metal members, thereby forming the final product.

Wearable device with wireless transmission and method for manufacturing the same


Aspects of the disclosed subject matter are directed to a graphical display that efficiently conveys information to a vehicle operator. In accordance with one embodiment, a method is provided that presents scrollable graphical elements on a shared screen area. More specifically, the method includes assigning a priority level to scrollable graphical elements that convey vehicle readings on the graphical display. Then, the one or more scrollable graphical elements are rendered on the graphical display at locations that change locations periodically. When an abnormal vehicle reading is identified, the method dynamically assigns an enhanced priority level to the scrollable graphical element that is configured to convey the abnormal vehicle reading. If the scrollable graphical element is currently assigned an off-screen location, the method causes the scrollable graphical element to be rendered.

Increasingly, electronic components are being relied upon to facilitate the operation of a vehicle. These electronic components aid in the development of sophisticated vehicle systems such as collision detection systems, automated cruise control systems, global positioning navigation, and the like. In this regard, systems have been developed that allow electronic components to communicate in accordance with standard protocols. For example, a sensor, which may have been developed by an engine manufacturer, may encapsulate and transmit data in accordance with a standard protocol. A cab-mounted electronic control unit developed by a different entity may receive and process the received data. Since standard communication protocols exist, components from different manufacturers are able to communicate so that readings may be presented to a vehicle operator.
A graphical display within an interior surface of a vehicle is provided to convey information to a vehicle operator. With the continued development of sophisticated vehicle systems, increasing amounts of information about vehicle conditions should be accessible to a vehicle operator. However, limitations in display area size may preclude the display of some readings that describe all vehicle conditions.

Graphical display with scrollable graphical elements


A method for preparing a slurry target for use in a sputtering apparatus. The target material is ground into a powder form, and mixed with a solvent to form a slurry. The slurry is poured into a target mold and allowed to slow dry by evaporation at or near room temperature. The target is mechanically stable, can be positioned in any orientation without falling out of the mold, and resists failure from thermal stresses during sputtering.

Sputtering is one of several well known techniques for applying or depositing a layer on a substrate. Generally, the substrate is placed in a deposition chamber which is evacuated or pressurized to a desired pressure. A particle flux of the coating material is generated within the chamber and the coating or deposition occurs by condensation of the particle flux onto the substrate surface.
In the ion beam bombardment sputtering technique, a high-energy source beam of ions is directed toward the target. The force of the bombarding ions imparts sufficient energy to the atoms of the target to cause the energized atoms to leave the target and form a particle flux. The resulting deposition upon a substrate forms a thin film.
Sputtering targets may be, for example, solid metallic blocks of a selected element or alloy. For sputtering of ceramic materials, targets may be dry powders made into a unitary porous structure. Other dry powder targets may be prepared by mixing the materials to be deposited into a binder-solvent slurry, casting the slurry into a mold, and applying heat to drive off the solvent and cure the binder. Such targets are prone to impurities (from the binder), frequent cracking from thermally-induced stresses, blistering (from embedded gasses), and difficulty in repairing targets damaged during the sputtering operation.

Sputtering target and method of manufacture

Minnesota Mining and Manufacturing Company


Glass for vehicles comprising from 65 to 80% by weight of SiO.sub.2, from 0 to 5% by weight of Al.sub.2 O.sub.3, from 0 to 5% by weight B.sub.2 O.sub.3, from 0 to 10% by weight of MgO, from 5 to 15% by weight of CaO, from 10 to 18% by weight of Na.sub.2 O, from 0 to 5% by weight of K.sub.2 O, from 5 to 15% by weight in total of MgO and CaO, from 10 to 20% by weight in total of Na.sub.2 O and K.sub.2 O, from 0.1 to 1% by weight of cerium oxide in terms of CeO.sub.2, from 0.2 to 0.6% by weight of iron oxide in terms of Fe.sub.2 O.sub.3, from 0 to 0.005% by weight of CoO, from 0 to 0.01% by weight of NiO, and from 0.0005 to 0.005% by weight of Se, and glass for vehicles comprising from 65 to 80% by weight of SiO.sub.2, from 0 to 5% by weight of Al.sub.2 O.sub.3, from 0 to 5% by weight of B.sub.2 O.sub.3, from to 10% by weight of MgO, from 5 to 15% by weight of CaO, from 10 to 18% by weight of Na.sub.2 O, from 0 to 5% by weight of K.sub.2 O, from 5 to 15% by weight in total of MgO and CaO, from 10 to 18% by weight in total of Na.sub.2 O and K.sub.2 O, from 0.1 to 1% by weight of cerium oxide in terms of CeO.sub.2, from 0 to 1% by weight of TiO.sub.2, from 0.2 to 0.6% by weight of iron oxide in terms of Fe.sub.2 O.sub.3, from 0 to 0.005% by weight of CoO, from 0 to 0.01% by weight of NiO, and from 0.0005 to 0.005% by weight of Se. The glass is gray-tinted while exhibiting excellent ultraviolet and heat absorption.

Colored glass which has been used as window glass of vehicles includes blue-tinted glass containing Fe.sub.2 O.sub.3 doped with CoO, green-tinted glass having a higher Fe.sub.2 O.sub.3 content than blue-tinted glass to have improved heat ray absorption, and gray-tinted or bronzed glass containing Fe.sub.2 O.sub.3, CoO, NiO, and Se as colorants.
While blue-tinted and green-tinted glass having a relatively high Fe.sub.2 O.sub.3 content has relatively high heat and ultraviolet absorbing power, there still is an eagerness to protect interior trim from deterioration due to ultraviolet light with the recent trend to luxurious trim of automobiles. To cope with this demand, glass having high ultraviolet absorbing power while satisfying the requirements for energy saving has recently been developed. Having a higher Fe.sub.2 O.sub.3 content than in conventional glass, this glass is also tinted in green.
On the other hand, gray-tinted or bronzed glass has been desired from considerations of designs of vehicles. However, having a lower Fe.sub.2 O.sub.3 content than in blue-tinted glass, conventional gray-tinted or bronzed glass has insufficient ultraviolet and heat absorption for satisfying the eagerness to protect interior trim from ultraviolet deterioration. It has therefore been demanded to develop grain-tinted or bronzed glass having high ultraviolet and heat ray absorbing power.
The present inventors previously proposed gray heat-absorbing glass containing tin oxide as a reducing agent and thereby having a high heat ray absorption, but this glass is costly because tin oxide is expensive.


In one embodiment, a hands-free user interface device includes a first plate, a second plate spaced from the first plate, a sensor associated with the plates adapted to detect when the first plate pivots relative to the second plate, and a controller adapted to receive signals from the sensor and output control signals to another component based upon the received signals.

Various equipment is designed to be controlled with a human user's hands. One example of such equipment is power wheelchairs. Such wheelchairs often comprise a joystick that is mounted to an armrest of the chair that can be used to control drive motors of the wheelchair. While joysticks and other hand-operated user interface devices can be effective in such applications, they are less effective when the user has difficulty using his or her hands. In such a case, it may not be possible for the user to control the equipment using a hand-operated user interface device. In view of this, it can be appreciated that it would be desirable to have hands-free user interface devices.


A joint disc made of a fiber composite material with a plurality of flexible leaf elements and a plurality of angular fixing elements which are composed of laminations of fiber composite material, with the leaf elements, at each of their ends, having an increasing thickness extending at least over 10% of their length.

The invention relates to a flexible coupling element or joint disc (which latter term is used herein for convenience) made of laminations of a fiber composite material and comprising an even number of angular fixing elements spaced about the disc and a plurality of flexible leaf elements extending circumferentially therebetween.
The leaf elements may be straight so the disc is generally in the form of a polygon. In a basic design of joint discs of the aforesaid type, it is made of superimposed laminations which, in outline, each extend over one leaf element and two adjoining fixing elements. Layering a plurality of said leaf elements in the shape of a polygon thus leads to fixing elements of double thickness relative to the leaf elements because the former contain double the number of superimposed laminations as compared to the latter. The laminations comprising fabric impregnated with resin, each have a main fiber orientation which may vary between the individual laminations. In the central layers of laminations within the leaf elements the main fiber orientation may coincide with the longitudinal direction of the laminations, whereas the outer layers may comprise alternately opposed angles of intersection of the main fibre orientation relative to the longitudinal direction of the leaf element.
Joint discs or shaft coupling elements of this type used for connecting two shafts and suitable for relatively limited angles of articulation between the shafts are known from DE-3725957-C1 and DE-4033596-C1. Flange parts of the two shafts be coupled are circumferentially alternately bolted to the fixing elements of the joint disc, which are provided with bolt holes. Whereas the fixing elements and reinforced eye regions thereof around the bolt holes respectively can be regarded as substantially rigid, the leaf elements or web regions therebetween, in the case of shafts articulated relative to one another, are bent in the form of an S-wave on which are superimposed forces due to torsion. To reduce load peaks the former publication DE-3725957-C1 already proposes to provide the transition between the web regions and eye region with radii; in DE-4033596-C1 it is proposed--again in order to reduce load peaks--to position the fixing holes radially inwardly with reference to the longitudinal center lines of the web region. Furthermore, the previously mentioned shaft coupling elements are limited to relatively small operating angles. An important factor continues to be load peaks in the case of shafts which are angled relative to one another, i.e. load peaks in the regions of transition between leaf elements and fixing elements.
It is therefore the object of the present invention to improve a joint disc of the initially mentioned type in such a way as to permit larger operating angles when using a joint disc of a predetermined size, i.e. of a certain diameter.

Joint disc made of a fiber composite material


An automatic call distribution network (10) with an originating automatic call distributor (ACD) (12A) which transfers a received call to a destination ACD (12B) through an external telephonic network (24), a call overflow system (32) with a central processing unit (16A) at the originating ACD (12A) to compile data relating to an overflow call to be transmitted through the external telephonic network (24) to the destination ACT) (12B) of at least one of the types of information of: identification of a selected gate (26B) of the destination ACD (12B) to which the overflow call is to be routed, identification of the originating ACD (12A), a time information relating to a time the overflow call was in a queue at the originating ACD (12A), an ANI number representation of a telephone number of the call received at the originating ACD (12A) and a priority level of the overflow call, the central processing unit (16A) at the originating ACD (12A) sending the compiled data to the destination ACD (12B) to route the call at the destination ACD (12B).

1. Field of the Invention
This invention relates generally to the field of automatic telephone call distribution networks and, more particularly, to such call distribution networks in which telephonic calls are sent from one automatic call distributor to another automatic call distributor through a regular public external telephonic network.
2. Description of the Related Art Including Information Disclosed Under 37 C.F.R. Section 1.97-1.99
Automatic call distributors employing a multiport switch controlled by a central processing unit for selectively interconnecting a plurality of interior telephonic units with external telephonic units received at the multiport switch through an external telephonic network are well known. Examples of such call distributors are shown in patent application U.S. Ser. No. 07/770,197 of Jones et al. entitled "Multichannel Telephonic Switching Network With Different Signaling Formats and Connect/PBX Treatment Selectable For Each Channel", filed Oct. 2, 1991, U.S. Pat. No. 5,268,903; U.S. Pat. No. 5,140,611 of Jones et al. entitled "Pulse Modulated Self-Clocking and Self-Synchronizing Data Transmission and Method for a Telephonic Communication Switching System", issued Aug. 18, 1992; U.S. Pat. No. 5,127,004 of Lenihan et al. entitled "Tone and Announcement Message Code Generator for a Telephonic Switching System and Method", issued Jun. 30, 1992 and U.S. Pat. No. 4,627,047 of Pitroda et al. entitled "Integrated Voice and Data Telecommunications Switching System", issued Dec. 2, 1986.
It is also known to send an external telephonic call received at an automatic call distributor to another automatic call distributor in an automatic call distribution network. Examples of such automatic call distribution networks are shown in U.S. patent application Ser. No. 07/960,995 of Blaha entitled "Automatic Call Distributor With Intersubnetwork Customer Information Transfer System and Method" filed Oct. 14, 1992.
In these known systems, a telephonic call made from an external telephonic unit of a regular public telephone network to which the ACD is connected, typically from a customer, is carried through the regular, public external telephonic network to one of the plurality of automatic call distributors (ACDs) in the private automatic call distribution network. Once the call is received, the automatic call distributor logically determines how the call is to be routed. The call is often directed to an agent associated with a gate at the originating ACD to service the call. However, it is desirable in an ACD network having two or more call distributors to route the telephonic call traffic as evenly as possible throughout the network. Therefore, in many situations, a call must be transferred or overflowed to an agent at another ACD in the private automatic call distribution network. The agent receiving the original call may not be able to properly service the customer at the external telephonic unit, thus, the call must be transferred to another agent located at another destination ACD. Moreover, the telephonic traffic flow often exceeds the call capacity of a particular gate at the originating ACD thereby requiring a call to be overflowed to another trunk group or gate at another ACD in the network.
The automatic call distributors in such known systems are placed at various distant locations throughout the network. A call transferred between automatic call distributors is done through dedicated trunks interconnecting the ACDs in the network. Disadvantageously, excessive costs are associated with installing, maintaining and operating these dedicated trunk lines between the ACDs in private automatic call distribution network.
In such known automatic call distribution networks, the transmission of information between automatic call distributor nodes over costly dedicated intertandem trunks or tie lines requires approximately a 1.0 to 1.5 second set-up signalling and verification time between the ACD sending the overflow call and the ACD receiving the overflow call. Thus, there is as much as a two to three second call set up delay when overflowing a call from one ACD to another ACD over dedicated intertandem trunks in known ACD networks. In automatic call distribution networks servicing 1-800 or toll free calls, the user or owner of the network pays for the cost of each call received at a call distributor. Disadvantageously, in such known call distribution networks receiving thousands of calls per hour, a two or three second set-up delay per call costs the user of the network substantial amounts each year.
Furthermore, in such known ACD networks information is sent between ACDs across tie lines as dual tone multiple frequency (DTMF) tones. These tones are transmitted one at a time across tie lines and require a 160 millisecond transmission time for each tone. Unfortunately, when twenty or thirty digits of information transmitted as tones are desired to be sent with a call, the transmission time is too long to efficiently transfer a call between ACDs. Thus, only a few digits of information relating to the overflow call are transmitted across tie lines thereby limiting the routing and application features for the call at the receiving ACD. Therefore, these known ACD networks provide the disadvantage of long call set up and transfer times and further limit the amount of digital information which can be sent with a call.
It is known to transfer a call from one automatic call distributor to another automatic call distributor through the a regular public external telephonic network. The Look-Ahead Interflow feature developed by American Telephone and Telegraph Company establishes a connection via the public external telephonic network from one ACD to a second ACD and transfers a received call at the one ACD to the second ACD. However, the Look-Ahead Interflow feature is limited in the amount and type of data information which is carried with the telephonic call to the second ACD. Look-Ahead Interflow does not provide data to identify which gate the transferred call is to be routed at the receiving ACD. Disadvantageously, the receiving ACD must perform several time consuming processes in attempting to properly route the call. Moreover, since many variable conditions must be met at the receiving ACD to properly route the call, by not having information identifying the gate at which the call is to be routed increases the possibility of a call being routed to a wrong location. Furthermore, the Look-Ahead Interflow does not identify the original sending ACD which transfers the call to the receiving ACD. Thus, there is nothing to prevent the inefficiency of calls being transferred or overflowed from the destination ACD back to the originating ACD which is not able to efficiently route the call.
The Look-Ahead Interflow feature also fails to provide information relating to the number of times a call has been overflowed. Disadvantageously, calls can be continually transferred between numerous ACDs prior to being routed to a gate and serviced by an agent thereby increasing the amount of time to route and service an incoming call to the network.
Furthermore, the Look-Ahead Interflow feature fails to supply the delay time of a call in queue at the originating ACD when transferring the call to another ACD. Consequently, the total delay time for overflow calls cannot be ascertained. In such case, it is not possible to accurately evaluate the overall performance of an automatic call distribution network. For example, a call may have a delay time of fifteen seconds at an originating ACD and an additional five second delay after being overflowed to another or destination ACD. In such known networks, the system administrator at the destination ACD is only aware of the five second delay time and not the twenty second total delay time, and thus calls at the destination ACD are not able to be efficiently routed.
Additionally, the Look-Ahead Interflow feature disadvantageously fails to send Automatic Number Identification (ANI) information with an overflowed call and thus limits the information available for the receiving or destination ACD to effectively route the overflowed call and to trigger various optional features of the system such as announcements, screen displays, etc.
Therefore, these known systems are limited by the limited amount of information transferred with an overflow call, thereby reducing the amount of routing and application features available in such automatic call distribution network with overflow capability.

Automatic call distribution network with call overload system and method


Disclosed herein is a simple, inexpensive linear actuator which is capable of controlling the displacement of the movable body by regulating the amount of electric energy applied without the necessity of detecting the displacement of the movable body with a displacement sensor or controlling the displacement of the movable body by feedback control in response to the detected value.

1. Field of the Invention
The present invention relates to a linear actuator which displaces a movable body linearly with electromagnetic force. More specifically, the present invention relates to a linear actuator capable of driving said movable body at low seeds.
2. Description of the Related Art
There has long been known a linear actuator which drives a load by displacing a movable body linearly with electromagnetic force. The linear actuator of this type usually consists of an exciting coil, a core which generates electromagnetic force when the exciting coil is energized, and a movable body which is displaced by electromagnetic force as thrust force which is supplied from said core.
The linear actuator mentioned above is usually so constructed as to be driven with a large thrust force in order that said movable body is displaced surely and stably against load and sliding resistance. Consequently, said movable body moves at a high speed and produces noise when it collides violently against the stroke end. One way to reduce noise was by using a rubber damper which absorbs shocks to the movable body. However, this poses a problem with durability and dusting.
There have been proposed several techniques to address the above-mentioned problem by controlling the driving speed of said linear actuator. For example, Patent Document 1 discloses a method for controlling the driving speed by detecting how the movable piece of the linear motor changes with time in stroke and speed with the help of a measuring apparatus (displacement sensor), comparing the detected data with a characteristic curve which has previously been established in a control apparatus, and regulating the target of electric energy according to the difference between the detected value and the characteristic curve. However, this method needs a displacement sensor and a complex control circuit, which inevitably makes the actuator larger and the control unit more complex. Patent Document 1: Japanese Patent Laid-open No. 2001-23818

Linear actuator capable of low-speed driving

Abstract: The linear actuator comprises an electromagnetic unit which generates magnetic force in response to the amount of electric energy applied, a movable body which is displaced linearly by magnetic force as thrust force which is supplied from the electromagnetic unit, a spring means which applies a spring force to the movable body in the direction opposite to the direction of said thrust force, and a control apparatus which controls the amount of electric energy to be applied to said electromagnetic unit, wherein said control apparatus is so constructed as to control the rate of displacement of said movable body in response to the amount of electric energy applied, with voltage or current applied to said electromagnetic unit varying from that which generates a thrust force balancing with said spring force.


A surgical instrument for cutting and applying a plurality of surgical fasteners in the same direction to body tissue includes a frame having a proximal end and a distal end, with a handle positioned at the proximal end and an end effector positioned at the distal end. The end effector is shaped and dimensioned for supporting a cartridge housing and an anvil. The cartridge housing and anvil are relatively movable between a first spaced apart position and a second position in close approximation with one another, and the cartridge housing includes a knife structure adapted for cutting tissue by moving between the cartridge housing and the anvil. The instrument also includes a firing mechanism associated with the end effector and the cartridge housing for selective actuation of the knife structure and surgical fasteners for movement in the same direction. The knife structure includes a rearwardly facing coupling member shaped and dimensioned for engaging a distal end of the firing mechanism as the cartridge housing is loaded into the end effector of the surgical instrument.

1. Field of the Invention
The present invention relates to a surgical stapling and cutting instrument adapted for use in the diagnosis and therapy of pathologies treated by stapled resection. More particularly, the invention relates to a firing mechanism for utilization in conjunction with the cartridge module of a surgical stapling and cutting instrument.
2. Description of the Prior Art
Surgical stapling and cutting instruments are commonly utilized in the diagnosis and treatment of pathologies treated by stapled resection. Surgical stapling and cutting instruments provide a mechanism to extend the transluminal exploitation of mechanical suturing devices introduced via the anal canal, mouth, stomach and service accesses. Although surgical stapling and cutting instruments are most commonly utilized with rectal pathologies, surgical stapling and cutting instruments may be used in a variety of environments.
Over time, surgical stapling and cutting instruments have been developed. These instruments generally include a support frame, an anvil attached to the support frame and a cartridge housing carrying a plurality of staples. The instruments also include a driver within the cartridge housing which pushes all of the staples out simultaneously into the anvil to form the staples into a generally B-shape, suturing tissue together. In addition, these instruments include approximation mechanisms for moving the cartridge housing from a spaced position from the anvil to accept tissue therebetween to a closed position where the tissue is clamped between the anvil and the cartridge housing. Finally, the instruments include a firing mechanism for moving the driver forward to form the staples against the anvil.
In order to facilitate reuse of the surgical stapling and cutting instruments, many of these devices are provided with cartridge modules. The cartridge modules provide for the ready replacement of staples and/or blades without disposing of the entire surgical stapling and cutting instrument.
In accordance with prior art instruments, the cartridge housing for surgical stapling and cutting instruments contains a knife for transecting tissue. The knife resides in the cartridge housing and a fresh knife is therefore, provided for use in conjunction with each firing. After completion of the firing stroke, and upon release of the firing trigger, it is desirable to have the knife retract automatically into the housing for the cartridge housing. Furthermore, it is desirable for the knife to be positively connected to the firing mechanism so that if a knife becomes jammed in the tissue or in the cutting washer, the user can free it by rotating the firing trigger (in the direction opposite the firing).
As such, a cartridge housing offering a retracted knife and a knife directly linked to the firing mechanism are desired. The present invention provides such a knife structure.

Knife retraction arm for a curved cutter stapler


An apparatus comprising: a sleeve; and a pocket that is coupled to the sleeve; wherein the sleeve is configured to fit around a seat portion of a collapsible chair; wherein the pocket is configured to secure one or more items to the collapsible chair as the chair moves among a plurality of positions.

Generally, stadium chairs are collapsible chairs. In this example, a collapsible chair includes a chair in which the seat portion of the chair changes positions, e.g., based on whether a person is sitting in the chair or has stood up. For example, as a person stands up, the seat portion of the collapsible chair moves in an upward, vertical direction. As a person sits in the collapsible chair, the seat portion moves in downward, vertical direct. The periodic movement of the seat portion of the chair, e.g., as a person stands up and sits down, prevents an individual from placing items (e.g., a purse, a backpack, and so forth) in a secure position on the collapsible chair. For example, as a person stands up from the collapsible chair, the upward, vertical motion of the seat will displace (e.g., knock off) personal items that were previously placed on the seat portion.

Receptacle with a pocket for a collapsible chair


A shape detection device incorporated as part of a pinch roll assembly in a hot strip reversing mill. The shape detection device replaces one of the rolls in the pinch roll assembly. The shape detection device is used to provide data to an automated shape control and steering system.

1. Field of Invention
The present invention relates to shape detection methods and apparatuses for a hot strip mill, and more particularly, to a shape detection device and method used in conjunction with a pinch roll assembly and a hot strip reversing mill or mills.
2. Background Art
During the hot rolling of metal strip, such as steel, the rolling process can cause undesirable shape defects in the profile and flatness along the width of the metal strip. This generally results from internal stress differentials within the strip which appear during reduction in a hot strip reversing mill having coiler furnaces on opposite sides. As the need for improved shape is ever present from a mill, techniques are required to ensure the desired shape is achieved during the reduction of the metal strip.
These shape defects can be greatly minimized and often avoided by applying shape control techniques in controlling the rolls of the mill. Shape control techniques include adjustments at the reversing stand of roll bending, screw down positions and roll shifting. Also, it is important to control the steering of the metal strip between the rolls at the reversing stand to keep the metal strip tracking on mill center.
In order to apply the shape control techniques, the operator must be able to detect when the process is causing the shape defects or when the metal strip tracks off mill center. Currently, the operator visually checks for defects caused by the process and to ensure that the metal strip is tracking on mill center. The operator then must adjust the mill manually using the shape control techniques to correct for defects and adjust steering of the metal strip if the metal strip is off mill center.
Pressure transducers and load cells have been used on each side of the reversing stands to detect force differentials between the stand sides to indicate the metal strip is tracking off mill center. The use of pressure transducers or load cells can be unreliable because strip geometry, temperature changes in the metal or hardness of the metal can also cause force differentials that can be detected by the pressure transducers or the load cells.
Today, automated shape control systems using computer technology can control shape and steering of the metal strip with the use of shape control sensors. Shape control sensors detect metal strip position and shape defects throughout the metal strip. The shape control system uses the data from the sensor for monitoring and continuously correcting the flatness of the metal strip. The automated shape control system relieves the operator from visually checking for defects and manually making changes to the process. Such systems and shape control sensors are described in U.S. Pat. Nos. 3,459,019; 3,688,571; 4,289,005; 4,356,714; 4,428,244; 4,512,170; 4,700,557; 4,809,527; 4,809,528; 4,860,212; 4,964,289; 5,089,776; 5,231,858; 5,267,170; 5,285,684; and 5,400,258.
The problem that arises is that shape control sensors must be incorporated into the design of a mill. Shape control sensors can be a contact or non-contact shapemetering device as discussed in the above-mentioned patents. Each type of shapemetering device has the sole purpose of detecting shape defects in the metal strip and has been used in cold strip mills. Currently for Steckel and other hot strip reversing mills, an operator still checks for shape defects visually and makes manual adjustments to the mill. Visual detection by an operator is still employed because the mills already in operation are generally restricted to the space available to add a contact or non-contact shapemetering device. Non-contact shapemetering devices are not used because their size does not allow them to be located near the rolls of the reversing stand where the reduction process takes place. Contact shapemetering devices are not used because it could prove to be a complicated and costly process to add a device to current mill designs that can make contact with the metal strip under tension.
Therefore, it is an object of the present invention to integrate a sensor for shape control and steering of the metal strip into existing hot strip reversing mills with minimal modification to the mill design as well as provide new mills with the same advantage.


A system for the distribution of optical fibers is disclosed. The system has a first furcation area, which is associated with a first fiber optic cable, to tap off a subset of the optical fibers of the first fiber optic cable in the form of a tether cable. The first fiber optic cable may be a riser cable. The tether cable is supplied to a spool device to store any excess length of the tether cable while complying with the minimum permissible bending radius of the optical fibers. The system has a second furcation area, which is associated with the spool device, to separate the optical fibers of the tether cable. The separated optical fibers of the tether cable can each be supplied to an individual splice storage device in which, in each case, one spliced joint can be placed between a separated optical fiber of the tether cable and an optical fiber of a second fiber optic cable, which may be a drop cable.

1. Field of the Disclosure
The technology of the disclosure relates to a system for the distribution of optical fibers, specifically optical fibers furcated from a first fiber optic cable, in particular a riser cable, to second fiber optic cables, in particular to drop cables.
2. Technical Background
Particularly in the case of so-called FTTH (fiber to the home) applications, it is necessary to furcate the optical fiber of a first fiber optic cable which has a plurality of optical fibers to connect to a plurality of drop cables, which each have a single optical fiber. Systems such as these must have a simple design and must be scalable as required in order, depending on the requirement, to increase the number of the second fiber optic cables, in particular the drop cables, whose optical fibers are intended to be connected to the optical fibers in the first fiber optic cable, in particular the riser cable. Until now, no systems which meet these requirements have been known for distribution of optical fibers.

System for the distribution of optical fibers


An insulated crawlspace vent to provide airflow in a crawlspace in the summer and insulate it in the winter. An aluminum extrusion built as a picture frame is glued to the opening in the foundation of the crawlspace. An insulated door closes from the outside and is latched shut to keep out the cold.

Crawlspace vents are used to ventilate the space between the house and the ground. The conventional vents used by masons are mortared in place and are usually flush to the outside cinder block.
In the winter, or in preparation for the winter, many homeowners crawl through their spider-infested crawlspaces and place blanket insulation in back of the conventional crawlspace vent to aid in limiting heat loss. Many homeowners also put a piece of foam insulation in front of the conventional vent, and an additional cement or cinder block.
The present invention alleviates the aforementioned inconveniences and problems.
The prior, but not necessarily relevant, art is exemplified by the following United States patents.
Koontz U.S. Pat. No. 3,863,553, entitled "COMBINATION INSULATION STOP AND VENTILATION BAFFLE, discloses a combination ventilation baffle and insulation stop for use in building structures to provide air passage to the space between the roof and the ceiling. When installed, the apparatus defines an air passage between its central section and the structure roof. The passage may be selectively sealed through use of a pivotable tab during application of insulation, and then subsequently reopened thereby insuring proper ventilation.
Koontz U.S. Pat. No. 4,184,416, entitled "COMBINATION THERMAL INSULATION STOP AND VENTILATION BAFFLE ARTICLE", discloses an insulation stop and ventilation baffle for assisting in the installation of loose fiber or particulate thermal insulation in the crawlspace or attic between a ceiling and roof of a building structure. The article is constructed of a rather stiff sheet material having parallel side fold lines formed therein adjacent to and spaced inwardly from parallel side edges. The fold lines define side sections that may be folded upwardly to receive the ends of an elongated flexible rod. The baffle will prevent seepage of insulation into the air passage leading to ventilators in the eaves and allow a maximum buildup of insulation above the exterior wall plates.
Buonaiuto, Sr. et al. U.S. Pat. No. 5,890,845, entitled "METHOD AND MEANS FOR SEALING CRAWLSPACE SURFACES", discloses a method of sealing the entire surfaces of a crawlspace and other areas difficult to access in a structure, by which a uniformly thick layer of a quick drying and moldable lightweight concrete is flowed over the entire surfaces to be covered in a uniform thickness sufficient to seal the surface.
It is a desideratum of the present invention to avoid the animadversions of the conventional vent devices and the above-described prior art techniques and devices.

Insulated crawlspace vent apparatus, and methods of installing same


A device for reading and learning indicia, particularly music notation and other music-related indicia, is disclosed. The device is constructed with at least one sheet and has a main image portion and a hanging portion. The main image portion is foldable about first folds and second folds and the hanging portion is foldable about an edge fold and second folds to form a variety of display, storage and travel configurations, including a poster configuration, self-standing configuration, storage pocket configuration and pocket folder configuration. Fastening devices are employed to releasably maintain contact between the surfaces of the learning device. Indicia may be positioned anywhere on the learning device to facilitate reading and learning.

Music notation is widely used for learning and playing a piece of music. The traditional way of notating music is through the use of a system of notes, letters, marks and other symbols arranged on a group of five parallel lines, called a staff or stave. Pitch is shown by the placement of notes on the staff and duration is shown with different note shapes and additional symbols, such as ties. More recently, and with increasing popularity, music is also being notated using tablature, a form first used in the Renaissance for lute music. Tablature notation uses vertical lines to represent the strings of an instrument, horizontal lines to represent the frets of an instrument and dots selectively placed on the horizontal lines to indicate finger placement. In sum, tablature notation tells a musician where to place his or her fingers on a particular instrument rather than which pitches to play. Tablature is typically used to notate music for fretted string instruments, e.g., guitar, bass, lute, mandolin and banjo and, today, is most commonly used in notating pop music.
Music notation has traditionally been written or printed on sheets of paper approximately 8½″×11″ in size, providing for convenient storage and transport of the music as well as use on a music stand during practice and/or performance. See U.S. Pat. No. 1,354,176to Dobson and U.S. Pat. No. 650,783 to Martin. As a result, however, conventional music notation is small in size and does not facilitate group collaboration, particularly among musicians working on the same piece of music. Sharing a single piece of music detracts from a musician's overall learning experience when studying with others. This is particularly disadvantageous in those settings where two or more musicians are trying to learn a new song or a new part of a song together from the same piece of music. For example, two guitar players may want to strum through the chords of a song in unison or have one guitarist play chords while the other guitarist plays a solo. The inconvenience and frustration of crowding around a single 8½″×11″ sheet of music hinders a musician's ability to learn and causes unneeded expense by requiring musicians to purchase additional copies of the same piece of notation.
Moreover, a single piece of music often requires the use of multiple pages to notate an entire song for a single instrument. In turn, a practicing or performing musician is required to remove at least one hand from his or her instrument to turn to the next page of music. Keeping both hands on the instrument is critical for most instruments and removal thereof marks a significant interruption in the learning process. This is particularly problematic for beginning musicians trying to develop rudimentary finger techniques, proper playing posture, sight-reading skills and an understanding of rhythm. It is well-known in the art that many novice musicians never advance past the first page of music notation in light of the difficulty in turning a page while keeping both hands on the instrument. As a result, many musicians are never able to learn a single song in its entirety.
Furthermore, it is becoming increasingly more common for ensembles, e.g., rock bands, jazz bands and many other musical groups, to learn and play a broad repertoire of popular music comprising songs written and/or performed by a variety of artists. Music notation for these songs is commonly published and sold as part of a bundle or collection of transcriptions within a magazine or as a book of songs from a particular time period by a single artist or music group. Therefore, musicians are often required to purchase an entire magazine or book to obtain the music notation for a single song. In addition, a majority of these magazines and books are not self-standing and require the use of a music stand or some other support device. For many musicians, particularly those traveling from performance to performance, carrying a music stand is inconvenient or often not feasible. This issue of portability is compounded when a group of musicians are collaborating and each needs his or her own stand to display their music. Further still, such magazines and books are typically manufactured with stiff bindings that tend to make reading, learning and playing a piece of music notation a frustrating and unproductive experience, detracting from the musician's ability to learn and play an entire song.

This patent is subject to a terminal disclaimer.


A method is disclosed, as well as systems, performed by one or more processors, for interacting with data in a data repository. The method comprises receiving, in a data catalogue environment, a search request relating to one or more items in the data repository and determining an object type associated with the one or more items. Other operations comprise loading an object template in dependence on the determined object type, populating the template with data from the data repository in dependence on the search request to create an object view, and displaying the object view within the data catalogue environment. The data repository comprises a plurality of joined datasets, and wherein the object view comprises one or more links to items in a joined dataset.

Data is often modelled as tables, and data relating to specific objects/items can be spread across multiple tables, which can then be joined. This type of structured data is difficult for a user to search and interact with. For example, a user often has to learn database querying semantics.
Data catalogues can be used to facilitate a user searching for data. The data must usually be exported to a further program for the user to interact with and explore. This makes joined datasets difficult to handle within a data catalogue, and the user often has to manually determine data joins before exporting the required data.

System and method for querying a data repository


A power conversion apparatus including a three-phase transformer having at least four three-phase windings, and three converter arms each configured by connecting one or plural unit converters each including a switching device and an energy storage element in series. A power source or a load is connected to a first three-phase winding of the transformer, three series circuits which connects second and third three-phase windings of the transformer, and the converter arms in series with each other are connected in parallel, the parallel connection point is a DC terminal, and a magnitude relationship between a coupling coefficient of the first and second three-phase windings, and a coupling coefficient of the first three- and third three-phase windings is equal to a magnitude relationship between a coupling coefficient of the fourth and second three-phase windings, and a coupling coefficient of the fourth and the third three-phase windings.

The present invention relates to a power conversion apparatus for converting an AC electric power into a DC electric power or converting a DC electric power into an AC electric power, and a power conversion system. More particularly, the invention relates to a power conversion apparatus which includes an arm configured by connecting one or plural unit converters in series with one another, and thus is suitable for converting an electric power, and a high-voltage DC transmission system.
In recent years, a technique for converting an AC electric power into a DC electric power or converting a DC electric power into an AC electric power has been used in many cases. As far as this sort of apparatus, an apparatus which utilizes a unit converter is known. This apparatus is such that plural unit converters are connected in series with one another, and a semiconductor switching device is operated for an energy storage element in each of the unit converters, thereby carrying out an electric power converting operation. A power conversion apparatus which can withstand a high voltage is relatively, readily obtained.
As far as this power conversion apparatus, a circuit configuration is known in which plural series circuits each composed of an arm composed of a series circuit of one or plural unit converters, and a transformer winding are connected in parallel with one another. This power conversion apparatus, for example, is described in JP-A-2010-233411.
The circuit configuration described above is a type of multilevel converter. Thus, with the circuit configuration concerned, a voltage equal to or higher than a withstanding voltage of the switching device can be outputted by using an ON/OFF controllable power semiconductor device such as an Insulated-Gate Bipolar Transistor (IGBT), a Gate Turn-Off Thyristor (GTO), or a Gate-Commutated Thyristor (GCT) or the like.
It is noted that in this specification, a circuit system of the power conversion apparatus disclosed in JP-A-2010-233411 is referred to as a Zero-Sequence Cancelling Modular Multilevel Converter (ZC-MMC).

Power conversion apparatus and high-voltage DC transmission system


The present disclosure is directed to improved methods for efficiently producing neuroprogenitor cells and differentiated neural cells such as dopaminergic neurons and serotonergic neurons from pluripotent stem cells, for example human embryonic stem cells. Using the disclosed methods, cell populations containing a high proportion of cells positive for tyrosine hydroxylase, a specific marker for dopaminergic neurons, have been isolated. The neuroprogenitor cells and terminally differentiated cells of the present disclosure can be generated in large quantities, and therefore may serve as an excellent source for cell replacement therapy in neurological disorders such as Parkinson's disease.

1. Field of the Invention
The present disclosure relates to an improved method of producing terminally differentiated neuronal cells such as dopaminergic and serotonergic neurons from pluripotent embryonic stem cells such as human embryonic stem cells. The dopaminergic and serotonergic neurons generated according to the present disclosure may serve as an excellent source for cell replacement therapy in neurodegenerative disorders and neuronal diseases.
2. Description of Related Art
Neurodegenerative disorders and neuronal diseases such as Parkinson's disease, Alzheimer's disease, and schizophrenia are destructive diseases that are becoming ever more prominent in our society. Many of these neurological disorders are associated with dopaminergic or serotonergic neurons. Dopaminergic neurons reside in the ventral and ventro-lateral aspects of the midbrain, and control postural reflexes, movement, and reward-associated behaviors. These neurons innervate multiple structures in the forebrain, and their degeneration or abnormal function is associated with Parkinson's disease, schizophrenia, and drug addiction (Hynes et al., 1995, Cell 80:95-101). Serotonergic neurons are concentrated in the ventral and ventro-lateral aspects of the hindbrain and innervate most parts of the central nervous system including the cerebral cortex, limbic system and spinal cord. These neurons control levels of awareness, arousal, behavioral traits, and food intake, and their abnormal function has been linked to aggression, depression, and schizophrenia (Jacobs and Gelperin, 1981, Serotonin Neurotransmission and Behavior. The MIT Press, Cambridge, Mass.). Serotonergic dysfunction may also play a role in the pathophysiology of various psychiatric, neurologic, and other diseases, for example, mental depression (Asberg et al., 1986, J. Clin. Psychiatry 47:23-35), suicide (Lester, 1995, Pharmocopsychiatry 28(2):45-50), and violent aggressive behavior (Brown et al., J. Clin. Psychiatry, 1990, 54:31-41; Eichelman, 1990, Annu. Rev. Med. 41:149-158).
Parkinson's disease is a progressive neurological disorder caused by the degeneration of nerve cells (neurons) in the region of the brain that controls movements. This degeneration creates a shortage of the brain signaling chemical (neurotransmitter) known as dopamine, causing the movement impairments that characterize the disease. Pathological studies indicate that loss of dopaminergic neurons in the substantia nigra contributes to Parkinson's disease. For example, bilateral lesions of the nigrostriatal pathway produce a syndrome in experimental animals that is quite similar to the observed motor dysfunctions observed in Parkinson's disease: resting tremor, rigidity, akinesia and postural abnormalities. Bilateral lesions of the nigrostriatal pathway caused by 6-hydroxydopamine (OHDA) caused profound akinesia, adipsia, aphagia and sensory neglect in rodents (Ungerstedt, 1971, U. Acta Physiol. Scand. Suppl. 367:95-121; Yirek and Sladek, 1990, Annu. Rev. Neurosci. 13:415-440).
In parkinsonism, changes in the status of dopaminergic receptors may be dependent on the stage of progression of the disease. The hallmark of parkinsonism is a severe reduction of dopamine in all components of the basal ganglia (Hornykiewicz, 1988, Mt. Sinai J. Med. 55:11-20). When dopamine is depleted, various other areas in the brain such as the thalamus, globus pallidus, and the subthalamic nucleus start to malfunction. Since these areas send signals to other parts of the brain, malfunctions in these small areas can lead to widespread brain dysfunction.
The prevalence of Parkinson's disease varies widely from 82 per 100,000 in Japan and 108 per 100,000 in UK, to nearly 1% (approximately 1 million) of the population in North America. In India, the prevalence rate of Parkinson's disease is 14 per 100,000 in North India, 27 per 100,000 in South India, 16 per 100,000 in East India, and 363 per 100,000 for the Parsi community in Western India. While Parkinson's disease is currently considered incurable, a variety of medications are available that provide symptomatic relief from Parkinson's disease, including Levodopa, Bromocriptine, pergolide, selegiline, anticholinergic, and amantadine. Although these drugs may provide relief from the symptoms of Parkinson's disease, they often have significant side effects. Moreover, these drugs neither cure the disease nor slow down the progressive loss of neurons, and only relieve the symptoms, with the beneficial effects often wearing off with time. Some patient become less responsive to medication, while others become hypersensitive and develop dyskinesias.
These unsatisfactory outcomes have led to development of other strategies for treating this disease, such as dopa-receptor agonist therapy and surgical approaches that include pallidotomy, deep brain stimulation (DBS) of the globus pallidus, and attempts to interrupt network abnormalities by destroying overactive brain areas or placing DBS electrodes to quiet these area. Although these and other types of surgery for patients with Parkinson's disease patients have produced some beneficial results, the long-term effects of such surgeries are not yet known. These treatments also have certain limitations and side effects.
Another strategy being pursued for this incurable disease is gene therapy. Discovery of the molecular basis of neurological disease and advances in gene transfer systems have allowed focal and global delivery of therapeutic genes for a wide variety of central nervous system disorders. But gene therapy has certain limitations such as stability and regulation of transgene expression, and safety of both vector and expressed transgenes (Costantini et al., 2000, Gene Therapy 7: 93-109). Vectors shown to be used for gene therapy include but are not limited to Herpes Simplex Virus type-1 (HSV-1) (During et al., 1994, Science 266:1399-1403), adeno-associated virus vector (AAV) (During et al., 1998, Gene Therapy 5:820-827), retrovirus, HSV/Epstein-Barr Virus (HSV/EBV) hybrid vector, and HSV/AAV hybrid vector. One gene therapy approach has been found useful to treat an animal model of Parkinson's disease. An encapsulated, genetically engineered cell line releasing the neuroprotective molecule, glial cell line-derived neurotrophic factor gene (GDNF), and a lentiviral vector encoding the GDNF gene improved graft survival and differentiation, thereby accelerating behavioral recovery in the animal model (Zurn et al., 2001, Brain Res Rev. 36:222-229; Date et al., 2001, Cell Transplant 10:397-401). Gene therapy using neural stem cells has also been found to be effective in expressing therapeutic levels of GDNF in vivo (Akerud et al., 2001. J. Neurosci. 21:8108-8118).
Cell implantation is another therapeutic strategy that offers the hope of replacing nerve cells lost in Parkinson's disease, as well as other neurodegenerative disorders and neuronal diseases. Clinical trials with fetal tissue transplantation, still underway, have developed methods for implanting cells into the brain and demonstrated the viability of this concept, as well as produced promising results for at least some patients. Attempts have also been made to transplant precursors of dopaminergic nerve cells directly into the striatum of patients with Parkinson's disease, and transplantation of human fetal or embryonic dopaminergic neurons have been found to have a beneficial effect on patient with Parkinson's disease (Freed et al., 2001, N. Engl. J. Med. 344:710-719). Data suggests, however, that anatomical repair of the pathway rather than ectopic placement of the graft may be required to obtain complete recovery (Winkler et al., 2000, Prog. Brain Res. 127:233-265). Additionally, fetal nigral transplant therapy requires human fetal tissues from at least 5-10 fetuses in order to have a clinically reliable improvement in the patient, which poses enormous ethical, legal, and safety issues. Thus, there is an urgent need for alternative sources of neuronal cells such as dopaminergic neurons to treat neurodegenerative disorders and neuronal diseases.
Recently, a renewable source of neural stem cells was discovered in the adult human brain. Neural stem cells with the capacity to renew themselves and form all cell types of the brain offer a potentially unlimited supply of dopamine producing brain cells, thus promising an entirely new therapeutic approach to neurodegenerative disorders and neuronal diseases (Eriksson et al., 1998, Nature Medicine 4:1313-1317). It has been reported that cultures of neural stem cells derived from the embryonic human forebrain can be expanded up to ten million fold in vitro. These adult neural stem cells have been transplanted into adult rats that are a well characterized model of Parkinson's disease. The cells in this animal model survived for up to a year after transplantation, differentiated into neurons, and were able to decrease motor disorders in some of the experimental animals (Svendsen et al., 1997, Exp. Neurol. 148:135-146). Unfortunately, adult neural stem cells have a limited life span in tissue culture (Kukekov et al., 1999, Exp. Neurol. 156:333-344).
One viable alternative source of dopamerinergic neurons, and other neurons that may be used to treat various neurodegenerative disorders and neuronal diseases, are pluripotent embryonic stem (ES) cells, in particular human ES cells. ES cells can proliferate indefinitely in an undifferentiated state and are pluripotent, which means they are capable of differentiating into nearly all cell types present in the body. Because ES cells are capable of becoming almost all of the specialized cells of the body, they have the potential to generate replacement cells for a broad array of tissues and organs such as heart, pancreas, nervous tissue, muscle, cartilage, and the like. ES cells can be derived from the inner cell mass (ICM) of a blastocyst, which is a stage of embryo development that occurs prior to implantation. Human ES cells may be derived from a human blastocyst at an early stage of the developing embryo lasting from the 4th to 7th day after fertilization. ES cells derived from the ICM can be cultured in vitro and under the appropriate conditions proliferate indefinitely.
ES cell lines have been successfully established for a number of species, including mouse (Evans et al., 1981, Nature 292:154-156), rat (Iannaccone et al., 1994, Dev. Biol., 163:288-292), porcine (Evans et al., 1990, Theriogenology 33:125-128; Notarianni et al., 1990, J. Reprod. Fertil. Suppl. 41:51-6), sheep and goat (Meinecke-Tillmann and Meinecke, 1996, J. Animal Breeding and Genetics 113:413-426; Notarianni et al., 1991, J. Reprod. Fertil. Suppl. 43:255-60), rabbit (Giles et al., 1993, Mol. Reprod. Dev. 36:130-138; Graves et al., 1993, Mol. Reprod. Dev. 36:424-433), mink (Sukoyan et al., Mol. Reprod. Dev. 1992, 33:418-431), hamster (Doetschman et al., 1988, Dev. Biol. 127:224-227), domestic fowl (Pain et al., 1996, Development 122(8):2339-48), primate (U.S. Pat. No. 5,843,780), and human (Thomson et al., 1998, Science 282:1145-1147; Reubinoff et al., 2000, Nature Biotech. 18:399-403). Like other mammalian ES cells, human ES cells differentiate and form tissues of all three germ layers when injected into immunodeficient mice, proving their pluripotency. Published reports show that human ES cells have been maintained in culture for more than a year during which time they retained their pluripotency, self-renewing capacity, and normal karyotype (Thomson et.al., 1995, PNAS 92:7844-7848).
Studies have shown that ES cells can be differentiated into neural progenitor cells (Zhang et al., 2001, Nature Biotech. 19:1129-33; WO 01/88104; U.S. Ser. Nos. 09/872,183, 09/888,309, 10/157,288; WO 03/000868; each specifically incorporated herein by reference). These cells can then be further differentiated into dopaminergic neurons (Rolletschek et al., 2001, Mech. Dev. 105:93-104). An initial step in the differentiation of ES cells can be the formation of embryoid bodies, for example 1 μM of retinoic acid promotes neural differentiation into embryoid bodies (Bain et al., 1995, Dev. Biol. 168:342-357). While retinoic acid can be used to generate neural cells, retinoic acid is a strong teratogen. Several reports have been published on the differentiation of ES cells into dopaminergic neurons by using stromal cell inducing activity (SIDA) (Kawasaki et al., 2000, Neuron 28:1-20), by expressing nuclear receptor related −1 gene (Nurr-1) (Kim et al., 2002, Nature 418:50-56), or by transplanting undifferentiated ES cells directly into the mouse model (Bjorklund et al., 2002, Proc. Natl Acad. Sci. 99:2344-2349). Lee et al. (2000, Nat. Biotechnol. 18:675-79) reported a method for differentiating ES cells into neural progenitor cells and into dopaminergic and serotonergic neurons in vitro. All of these experiments, however, were carried out using mouse ES cells, and the differentiation protocols yielded dopaminergic neurons ranging from 5-50%. About 20% of the mouse ES cells developed into dopaminergic neurons in the study by Lee et al. (WO 01/83715) and 5-50% in the study by Studer et aL. (WO 02/086073). While dopaminergic neurons have also been differentiated from human ES cells, yields of only 5-7% of dopaminergic neurons, as a percentage of total cells in the population, have been obtained (WO 03/000868).
Parkinson's disease is thought to be a particularly suitable clinical target for a cell transplant strategy since it is characterized by the selective and gradual loss of dopaminergic neurons in the substantia nigra of the midbrain. The loss of dopamine-producing neurons within this specific brain site leads to abnormal firing of nerve cells that results in patients being unable to control or direct their movements. But large numbers of dopaminergic neurons are required for cell replacement therapy. Therefore, alternate protocols are needed for deriving dopaminergic neurons from human ES cells more efficiently, which will both accelerate the availability of this treatment for Parkinson's disease and increase the success rate of treatment. Additionally, these dopaminergic neurons can be utilized in vitro to help identify substances that will prevent or reduce death of dopamine producing brain cells in neurodegenerative disorders and neuronal diseases.

Derivation of terminally differentiated dopaminergic neurons from human embryonic stem cells


A system and method are disclosed for creating and describing a configurable data set, configuring the data set and merging a resulting configured data set into a target data set. One or more configurable data elements are stored in a configurable data set that forms part of a configurable merge module. The configurable merge module also includes metadata concerning the configurable data. The metadata describes the data elements and how they can be configured and how to implement changes to the configurable data. Each configurable data element can be presented to the configurable merge module consumer through a user interface. The configurable merge module consumer can thus make configuration choices. Also provided is a transformation engine for customizing the configurable data based on configurable merge module consumer choices and a merge engine for inserting configured data into a target data set.

Computer programs generally require some customization when installed on a computer. Such computer programs can consist of several software components, each of which may need to be customized individually when incorporated into a particular program. A program into which a software component can be incorporated can be considered to be a data set. Similarly, the software component can be considered to be a data set. Thus, the process of configuring and installing a software component can be generalized as a customization of and merging of two of more data sets. A software component may in turn be incorporated into several different programs, each requiring the component to be customized differently.
Before a component can be incorporated into a data set (e.g. into a computer program) it may require configuration specific to that data set. Customizing the component prior to incorporation into a particular data set has historically been a difficult process because each component is customizable in different ways and each target data set may have different requirements. Also, mechanically changing a component has historically been difficult. Generally, the configuration options for a component are not well known to a component consumer. Also, even if the consumer knows the configuration options, the specific physical changes required to customize the component might not be known or might be difficult to implement.
Schemas and automated tools that enable the consumer to customize a component can simplify the consumer's task and reduce the possibility of customization errors. Conventionally, such an automated tool was of limited value, however, because it needed to be specifically designed for the component it was customizing and such specific redesign of the automated tool was at least as difficult as simply customizing the component by hand. Consequently, there is a need for a system and a process to automate and simplify merging of components into a data set.

Configuring software components(merge) with transformation component using configurable and non-configurable data elements


A position controller sets a variable friction compensation value which varies in accordance with a change in sliding characteristics by providing a variable friction compensation value calculation unit that includes a sliding torque normalization calculation unit that normalizes a sliding torque at a predefined speed; a compensation value amplifying ratio calculation unit that calculates a compensation value amplifying ratio based on the sliding torque at the normalized speed; and multipliers.

FIG. 4 is a block diagram showing one example of a previously-known fully-closed position controller (hereinafter referred to merely as "position controller") that controls a position of a movably-formed target system 112 which comprises a movable member such as a table and is joined by coupling or the like to a servo motor (not shown) used as a drive motor.
The configuration and operation of the position controller are described below. The position controller receives an input of a position command value X from a higher-level device (not shown). A subtractor 101 calculates a positional deviation X−xL by subtracting a position detected value xL from the position command value X. The position detected value xL is a position detection signal which is obtained by directly detecting the position of a control target of the target system 112 by a linear scale or the like (not shown).
Further, a time derivative of the position command value X is obtained by differentiators 104, 109 which respectively output the obtained values as a speed command value V and an acceleration command value A. The acceleration command value A is amplified by an acceleration torque conversion constant Ca by an amplifier 110 to be used as an acceleration torque command value τca that causes the target system 112 to be moved at the rate of acceleration. The speed command value A and the acceleration torque command value τca are respectively added to the speed command and the torque command. Such a series of processes form a well-known feed forward block for reducing a constant positional deviation X−xL down to zero.
An amplifier 102 proportionally amplifies the positional deviation X−xL at an amplification factor of a position loop gain Gp. An output from the amplifier 102 becomes the final speed command value Vc after the speed command value V is added to the output by an adder 103. A subtractor 105 calculates a speed deviation Vc−vm by subtracting a motor speed vm from the speed command value Vc. The motor speed vm is a time derivative value, obtained by a differentiator 107, of a rotational angular position xm of a position detector (not shown) connected to a servo motor, or an output of a speed detector (not shown) connected to the servo motor. An amplifier 106 amplifies the speed deviation Vc−vm at an amplification factor of a speed loop gain Gv.
The output of the amplifier 106 becomes a torque command value τc after addition of an acceleration torque command value τca by an adder 108. The torque command value τc becomes a generated torque τ for the target system 112 after being power amplified by a power amplifying unit 111. The power amplifying unit 111, which consists of a power amplifier and a servo motor, amplifies the torque command value τc to output the generated torque τ. The amplification ratio is represented by a torque conversion constant Ct. The generated torque τ is supplied to the target system 112 and used to drive the target system 112. It should be noted that, a reference symbol "S" of the differentiators in FIG. 4 represents a Laplace transform operator indicating a differential operation.
In previously-known position controllers, a positional follow-up deviation due to a frictional force is minimized by providing a friction compensation calculation unit 113 to respectively add compensation values Vsfc, τsfc calculated by the friction compensation calculation unit 113 to a speed command and a torque command.
However, when sliding characteristics of a target system are changed due to deterioration over time, a temperature change, a lubrication state change of a sliding surface, or the like, desirable friction compensation becomes impossible, causing a positional follow-up error and a decrease in processing accuracy. In order to avoid this, control parameters of the friction compensation calculation unit 113 should be reset (re-adjusted). Because resetting is time-consuming and is required every time the sliding characteristics change, resetting is troublesome.
Further, although changing control parameters of the friction compensation calculation unit 113 in accordance with a change in the sliding characteristics may be considered, because the sliding torque changes according to a traveling speed of the target system, it is necessary to compare sliding torques under the same speed in order to quantitatively handle the sliding torques. Therefore, it becomes necessary to obtain sliding toques by providing a dedicated operation mode, which would result in an increase of non-cutting time.
The present invention is provided to overcome these problems. An object of the present invention is to provide a position controller which can maintain desired friction compensation without a need to provide a dedicated operation mode even when sliding characteristics of a target system change due to deterioration over time, a temperature change, a lubrication state change of a sliding surface, or the like.


An alignment device for aligning guiding apparatus with the main axis of a rolling mill comprising a camera and a video display communicating with the camera. The camera is mounted in the steel mill at the position of the guiding apparatus and the camera is moved until it is on the axis of the mill. The camera is then removed to a bench which duplicates the physical characteristics of the mill. The guiding apparatus is mounted on the bench adjacent the camera. The guiding apparatus is physically moved until it is located on the camera axis, which is the mill axis. The guiding apparatus is then remounted in the mill.

Multi-stand rolling mills require critical alignment of the reducing rolls and the guiding devices which feed the work product to the reducing rolls. If for some reason, misalignment between the guide and reducing rolls occurs during a rolling process, the result is often a damaged or "off-gauge" product which may not be marketable. It is therefore essential to have the guiding device in exact alignment with the reducing rolls during a reduction process. Because of the location of the main reducing rolls and the low light levels existing at this location, the adjustment of the guide rolls to their proper setting can present a challenge to a mill technician.
Rolling mills traditionally present an environment which tends to be hostile for most alignment instruments. Usually alignment of the guides and reduction rolls must be accomplished in the shortest possible time under conditions which are less than ideal. The mill usually operates at an elevated temperature with coolant water being copiously applied to the surface of the guide rolls and the reduction rolls.
In most instances the "throat" of the guide is obscured by auxiliary apparatus and the levels of light existing at the guide throat and the main roller "nip" leaves a lot to be desired.
It is therefore seen that even if one was able to adjust the alignment of the guide and its rollers to the correct position to feed the reduction rolls of the mill, the adjustment procedure places an almost impossible task on the mill technician due to the fact that the critical zones of the mill i.e. the main roller gap and the guide throat are almost inaccessible to the human eye.

Method and apparatus for aligning equipment in a steel mill


An instrument for implanting tissue in an eye or other body member is disclosed. The instrument includes an elongated mandrel and a tubular nozzle arranged over the mandrel. The instrument also includes a piston engaging an end of the nozzle and a vacuum passage arranged in the piston. The instrument also includes a body having a portion of the piston arranged therein with one end of the mandrel being secured to the body. The instrument also includes an actuator integrated with the body wherein the actuator interacts with the piston to control movement of the nozzle relative to the mandrel.

The present invention relates to an instrument for implanting delicate tissue and/or materials in the human body, and more particularly to an instrument for surgically restoring eye sight by implanting fetal or other types of retinal tissue into the subretinal space in the back of the eye.
Most common eye problems, for example, myopia (nearsightedness), hyperopia (farsightedness), astigmatism (asymmetrical cornea) and presbyopia (the inability to focus on an object at close range) are due to errors in the refraction of light by the lens and cornea in the anterior part of the eye. Generally, these problems can be corrected by glasses, contact lenses, or corrective surgery.
However, blindness is most commonly due to damage of the retina in the back of the eye and, more specifically, is caused by abnormal function of cells bordering the subretinal space under the retina.
The transparent, layered retina processes light images projected by the cornea and lens. The photoreceptor layer in the back of the retina transforms the light into electrical impulses. Other retinal layers transfer these impulses through the optic nerve to the brain which interprets the impulses into what we perceive as sight.
The subretinal space is the area between the retinal pigment epithelium (RPE) and the photoreceptors of the retina. Normally, the photoreceptors are in close contact with the RPE. The RPE has many functions. It provides nutrition for the photoreceptors, and also removes waste products from the photoreceptors. In a normal eye, there are no blood vessels in the subretinal space. However, in some retinal diseases, blood vessels and connective tissue can grow in the space and cause blindness. The waste products from the photoreceptors accumulate and create a barrier for the nourishment from the RPE. The photoreceptors will then degenerate, resulting in vision loss or blindness, while the other layers of the retina can remain functional. By replacing the diseased RPE and/or photoreceptors that can hook up to the functional part of the retina, vision may be restored.
The most frequent cause of legal blindness is macular degeneration and retinitis pigmentosa. The macula is located in the back of the eye in the central portion of the retina and is responsible for central vision. In patients with macular degeneration, there is initially a dysfunction of the RPE in the macular region, which later leads to ingrowth of blood vessels and destruction of the light sensitive photoreceptors in the overlying retina. This results in impairment of central vision. Age related macular degeneration is an example of an eye disease that can be helped by using the herein disclosed method and instrument. The vision loss can be delayed and vision can be restored to a degree we now do not know the extent of.
Retinitis pigmentosa is a term for genetically caused photoreceptor degeneration. In these patients, the RPE and the photoreceptors must be replaced. Again, the method and instrument of the present invention can be utilized for such procedures.
It is to be noted that the surgical correction of diseases in the subretinal space between the retina and the RPE is rendered extremely difficult by the environment in which the surgery must take place. Moreover, the surgical procedure disclosed herein to implant fetal retinal tissue into the subretinal space of the eye is complicated by the fact that the fetal retinal tissue is in the nature of a transparent mass and extremely fragile.
Therefore, there is a need in the art for an improved subretinal implantation instrument and methodology for implanting such tissue inside the subretinal space.