The output current of a fixed-frequency DC to DC converter is sensed, creating a voltage representative of the load current. This voltage is then compared to one or more threshold voltages using a plurality of comparators, creating a plurality of logic signals indicative of which of a plurality of ranges the output current falls within. These logic signals are coupled to a multiplexer which decodes the logical inputs to one-of-n and selects one gate drive voltage from a plurality of such voltages, each optimized for its corresponding current range. The selected gate drive voltage is then used as the gate drive in a known art DC to DC converter, thereby increasing efficiency over a wide range of output current.

1. Field of the Invention
This invention relates generally to DC to DC voltage conversion, and more specifically to increasing the efficiency of such conversion by optimizing the MOSFET gate drive signal of a switching DC to DC converter as a function of output voltage load current.
2. Description of the Related Art
Conversion of direct current (DC) voltage from one voltage level to another is a common requirement in many electronic systems. One type of voltage converter is referred to as dissipative, wherein a voltage Vin higher than the desired output voltage Vout is applied to a first input terminal of a pass transistor, while a second output terminal of the pass transistor is connected to the load to be driven at voltage Vout. The output voltage applied to the load is sampled, scaled, and compared to a reference voltage, developing an error signal which then drives a third control terminal of the transistor in such a manner as to cause the scaled output voltage to become very close to the desired reference voltage, even with variation in Vin and/or current Iout drawn by the load. The current through the pass transistor in a dissipative converter is typically constant and substantially equal to the load current. One disadvantage of the dissipative converter is that significant power, approximated by P=Iout*(Vin−Vout), is dissipated in the pass transistor, creating undesired heat and inefficiency.
A preferred type of voltage converter has become the switching converter, wherein the pass transistor is rapidly switched on and off to control the current flow to the load, hence voltage applied to the load. A switching converter having an output voltage lower than its input voltage is commonly referred to as a buck converter, while one having an output voltage higher than the input voltage is referred to as a boost converter. The ability of the switching converter to boost an input voltage to a higher level is another advantage over the dissipative converter. The efficiency of a switching converter is also typically much higher than a dissipative converter, especially in applications having a large difference between input and output voltages.
In operation, a switching converter samples and scales the output voltage and compares this scaled voltage to a reference voltage, developing an error signal. This error signal then modulates the width of a pulse-width-modulated signal which drives the control terminal of the pass transistor, for example the gate if the pass transistor is a MOSFET. The gate drive signal causes the typical enhancement-mode MOSFET to have a very low drain to source resistance during the gate drive high state, and a very high resistance during the gate drive low state. By controlling the relative on/off time of the pulse-width-modulated gate drive, the amount of average current flowing through the pass transistor to the load is adjusted to drive the output (load) voltage to the desired value. As the input voltage decreases, increasing on time of the gate drive keeps the output voltage at the desired level. Conversely, increasing input voltage causes a decrease in on time. The frequency of the gate drive signal is typically in the hundreds of kilohertz to many megahertz range.
Ideally, the pass transistor in a switching converter is either fully on, in which case its ideal resistance is zero, or fully off, in which case its ideal current flow is zero. In both ideal cases, no energy is lost in the pass transistor. Available non-ideal pass transistors, however, have non-zero on resistance Rds(on), where Rds refers to the drain to source resistance of a metal-oxide field-effect transistor (MOSFET). This non-zero Rds(on) leads to conduction loss, increasing with increasing load current. Because Rds(on) is reduced as the gate voltage is increased in an enhancement-mode MOSFET, conduction loss may be reduced by driving the gate at a higher voltage. However, the MOSFET gate capacitance must be charged or discharged at each transition. For a given gate capacitance, gate charge time increases with increasing gate voltage. As the transition times of the pass transistor become a significant fraction of the total switching signal period, the switching losses due to gate charging/discharging increase substantially.
It is desirable therefore to optimize the gate drive voltage dependent on output current, keeping the gate drive voltage as low as practical while still achieving low Rds(on). At heavy load currents, efficiency degradation is dominated by MOSFET conduction losses due to non-zero Rds(on), so it is advantageous to apply a higher gate drive voltage to decrease Rds(on). At lighter load currents, switching losses due to gate capacitance dominate, so it is advantageous to apply a lower gate drive voltage, reducing the charge and discharge times of the gate.

Output load adaptable MOSFET gate drive voltage level in a DC-DC controller


A platen knob includes a first hollow cylinder having one bottom wall, a second hollow cylinder extending from the interior surface of the bottom wall coaxially with the first cylinder. The second cylinder is fitted on a shaft of a cylindrical platen through a hollow boss of a casing housing the platen. A cavity defined between the sidewalls of the cylinders receives a vibration-proof lining and/or an acoustical layer. The lining suppresses a vibration of the platen knob. The acoustical layer seals the boss of the casing and leaks no noise from the interior of an electronic apparatus including a platen.

1. Field of Invention Application
The present invention relates generally to a platen knob and more particularly to a platen knob suitable for use in electronic apparatuses such as an impact dot printer.
2. Description of the Related Art
The proportion of impact dot printers to printers is large and the impact dot printers are popular in offices. However, a printing noise by the impact dot printers has recently given rise to a trouble.
A prior-art impact dot printer will be described hereinafter. FIG. 8 is a perspective view of the prior-art impact dot printer. The printer is generally indicated at 50. An upper cabinet of the printer is indicated at 51. The printer 50 comprises a platen knob 52.
FIG. 9a illustrates a main part of the interior of the printer 50. A cylindrical platen 53 is journalled on a framework (not shown) within the upper cabinet 51. A paper feeder (not shown) feeds a printing paper 54 to the platen 53. The printing paper 54 is fitted on the cylindrical surface of the platen 53. A carriage guiding shaft 60 is supported on the framework and extends in parallel to the platen 53. A carriage 61 carrying an impact dot printer head 55 is slidably mounted on the carriage guiding shaft 60. The printer head 55 has a predetermined distance from the cylindrical surface of the platen 53. The carriage 61 carries an ink ribbon 56 covering the front edge 55a of the printer head 55 and is fastened to a drive belt 62. The drive belt 62 extends between a drive pulley 63 and a driven pulley 64 spaced from each other so that the carriage 61 can reciprocally travel across the length of the platen 53. The drive pulley 63 is mounted on the shaft 65a of a spacing motor 65. The torque of the spacing motor 65 is sequentially transmitted to the drive pulley 63, the drive belt 62 and the carriage 61 to move the carriage 61 in a spacing direction. An interior mechanism (not shown) of the carriage 61 transforms a movement of the carriage 61 along the carriage guiding shaft 60 to a rotation of an ink ribbon take-up shaft (not shown) to take up the ink ribbon 56. One end 53b of a shaft of the platen 53 has a spur gear 68 mounted thereon. The shaft 66a of a line feed motor 66 has a pinion 67 mounted thereon and meshing with the spur gear 68. The torque of the line feed motor 66 is sequentially transmitted to the pinion 67, the spur gear 68 and the platen 53 to rotate the platen 53.
The respective printer head 55, spacing motor 65 and line feed motor 66 are electrically connected to a control board 73 through a lead wire 70 from the printer head 55, a lead wire 71 from the spacing motor 65 and a lead wire 72 from the line feed motor 66. The control board 73 comprises a printer control device 74 performing a printing control of the printer head 55, a spacing control of the carriage 61 and a line feed control of the printing paper 54.
FIG. 9b is a sectional view of the knob 52 taken along the line Y--Y in FIG. 9a. The body of the knob 52 is essentially a bottomed hollow round cylinder. A central part of the interior surface of bottom wall 52c of the knob 52 has a fitting boss 52a extending inward of the printer 50. The fitting boss 52a is a double cylinder comprising a fitting inner cylinder 52d, a reinforcing outer cylinder 52e, and ribs (not shown) extending radially from the inner cylinder 52d to the outer cylinder 52e. The fitting boss 52a is fitted on an external end 53a of the shaft of the platen 53.
In operation, manually rotating the knob 52 rotates the shaft of the platen 53 and the platen 53. The manual rotation of the knob 52 also directly causes the paper feeder to feed the printing paper 54 in the direction of rotation of the platen 53. Thus, the printing paper 54 is positioned in the printer 50.
Then, supplying printing instructions to the printer 50 starts a series of operations of the printer 50. The printer 50 line feeds the printing paper 54 to a line of letters to be printed. The printer control device 74 controls the line feed motor 66 to sequentially transmit a torque to the pinion 67, the spur gear 68 and the platen 53 and finally rotate the platen 53. Thus, the paper feeder rotating together with the platen 53 line feeds the printing paper 54 to the line of letters to be printed.
The printer head 55 is then spacing-moved along the carriage guiding shaft 60 to the position of a column of letter to be printed. The printer control device 74 controls the spacing motor 65 to rotate the drive pulley 63 and move the drive belt 62 and the carriage 61 together along the carriage guiding shaft 60. The carriage 61, the printer head 55 and the ink ribbon 56 together travel along the carriage guiding shaft 60 to follow the spacing-movement.
The printer 50 then starts printing letters or the like. The printer control device 74 processes printing data of printing instructions to dot matrices constituting letters and supplies drive signals required for printing to the printer head 55. Thereby, predetermined dot pins (not shown) of the printer head 55 impact the printing paper 54 fitting on the platen 53 via the ink ribbon 56. The dot pins transfer an ink impregnated in the ink ribbon 56 to the printing paper 54 to print one column of a dot matrix constituting a letter on the printing paper 54.
The printer control device 74 then spacing-controls the printer head 55 and the ink ribbon 56 to move to a next column of the dot matrix. The printer control device 74 controls the printer head 55 to print the next column of the dot matrix on the printing paper 54. The printer 50 repeats the cycle of the above-described operations to print letters and further lines of letters. In this case, the ink ribbon 56 is taken up as the carriage 61 moves along the carriage guiding shaft 60, so that the impacting surfaces of the dot pins always receive a fresh part of the ink ribbon 56. When the printer 50 prints a next line of letters on the printing paper 54, the printer control device 74 controls the line feed motor 66 to rotate the platen 53 by an angle corresponding to one vertical spacing between adjacent lines of letters. The paper feeder feeds the printing paper 54 by the one vertical spacing so that the printer head 55 prints a new line of letters. Thus, the printer control device 74 repeats the cycle of the line feed control, the spacing control and the impact control to print on the overall sight of the printing paper 54.
When the printer having the above-described structure operates, the impacts by the dot pins finely vibrates the platen 53. This fine vibration propagates from the shaft of the platen 53 to the fitting boss 52 of the knob 52a. Since a component of the fine vibration and the natural vibration of the knob 52 depending on the shape of the bottom wall 52c of the knob 52 resonate to each other, the bottom wall 52c of the knob 52 constitutes a source of noise. In addition, a cavity defined between the fitting boss 52a, the outermost sidewall 52b and the bottom wall 52c of the knob 52 resonates to the fine vibration to increase noise. The cavity also serves as a passageway through which the impact sounds of the dot pins from the cylindrical surface of the platen 53 leak out of the upper cabinet 51. Therefore, measures for fitting the knob 52 on the end 53a of the shaft of the platen 53 via an elastic element have been taken. However, these measures cannot achieve a sufficient noise reduction.

Matsushita Electric Industrial Co., Ltd.


The workability of operation to be performed, while preventing chemical or biological contamination, using a biosafety cabinet and gloves attached to the cabinet is improved. A biosafety cabinet includes a workspace formed in a main body cabinet thereof. Air in the workspace is discharged to outside via filters. A vertically movable front shutter is disposed on a front of the workspace. A front opening is formed below the front shutter to be at a front of the workspace. The front shutter includes plural laterally movable small windows which are overlapped like layered sliding doors. One of the plural small windows is provided, on the workspace side thereof, with a pair of glove ports to which a pair of gloves for use in operation in the workspace can be air-tightly attached.

The present invention relates to draft chambers, class II biohazard safety cabinets, and chemical hazard safety cabinets (may hereinafter be referred to collectively as "biosafety cabinets") and, more particularly, to a biosafety cabinet suitable for use in handling contaminants in a workspace formed therein.
Draft chambers, cabinets for use in the nanotechnological field, and chemical hazard safety cabinets (may hereinafter be referred to collectively as "biosafety cabinets") include, in many cases, an internal workspace where operation can be performed. A cabinet having such a workspace includes a front shutter and a front opening formed below the front shutter. An operator can extend his/her arms through the front opening into the cabinet and handle, for example, nanomaterial or chemically contaminated material. To prevent the operator from being contaminated by nanomaterial or chemically contaminated material, a flow of inward air being sucked into the cabinet or an air barrier is formed in the front opening.
To more strictly prevent contaminants from coming into contact with the operator, material to be handled is placed in a glove box making up an air-tight workspace, then the operator inserts his/her arms in hand-shaped gloves attached to the front of the workspace separating the workspace from the outside space and handles the material via the gloves. In the case of a chemical hazard safety cabinet or glove box, a high efficiency particulate air (HEPA) filter is used to remove contaminants generated in the workspace so as to safely discharge only clean air to outside the cabinet or glove box. An example of such an existing type of biosafety cabinet is disclosed in Japanese Patent Laid-Open No. 2007-163053.

Hitachi Industrial Equipment Systems Co., Ltd.


The present invention discloses a nut to be used in a spinal screw and plate assembly to affix the screw and plate assembly to the spinal bone. The nut has a polymer insert that when contacted with a screw allows a bone plate and screw structure to relax over time.

A. Field of the Invention
The present invention relates generally to the field of healing bone fractures. More particularly, it concerns apparatus and methods for healing bone fractures by controlling the load transmitted to the fractures throughout the healing process.
B. Description of the Related Art
Spinal columns are prone to deformation and degeneration. These conditions often require corrective surgery. In some surgical procedures it is necessary to remove the intervertebral discs from the damaged part of the spinal column. Bone grafts may then be placed in the position vacated by the disc and the bone graft and vertebrae to be fused are held in a desired position for healing using a device connected to vertebrae on either side of the bone graft. Such a device maintain the vertebrae in a desired position for healing and further prevents the transmission of load through the bone graft while the graft is healing. Devices for the connection of vertebral bodies are disclosed in U.S. Pat. Nos. 4,611,581 and 4836196.
In other procedures the healing of fractured long bones employs implantable plates for internal fixation. The concept is to place a plate in contact with the fractured bone such that the plate spans the fracture, and to fasten the plate to the bone on both sides of the fracture. Compression plates typically are attached to the bone by screws and nuts that act to transfer the load from the bone to the plate and force the broken ends of the bone together. Typical fracture fixation compression devices are disclosed in U.S. Pat. Nos. 4,943,292, 4,513,744, 3,779,240, and 3,552,389.
In a typical situation, use of a conventional bone fracture compression plate made of high modulus 316L stainless steel (200 GPa; 30.times.10.sup.6 psi), may result in stress-shielding the bone under the plate causing a weakening of the cortical bone (at about 15 GPa) under the plate. Relieving the bone from carrying a load over an extended period of time may thus contribute to the development of this type of bone weakening or osteoporosis, also known as osteopenia. When the plate and screws are removed from the healed bone, a re-fracture may result due to such weakening.
Attempts to solve this problem have included the fabrication of the fracture plates from materials that are less rigid than 316L stainless steel. For example, titanium alloys, composites, and resorbable materials have been utilized. Each of these materials, however, presents additional problems.
Bioresorbable bone plates have been investigated by Christal et al.,(1984). A major problem associated with resorbable bone plates made of polyglycolic acid (PGA) or polylactic acid (PLA) polymers is the release of polymer residues into the body. While it is unclear whether these polymer residues produce any side effects, the precise control of the dissolution rate of these polymers over the entire plate is difficult, if not impossible, to control. Moreover, the screws for securing the bone plate to the bone cannot be made from these materials because these materials lack the requisite torsional strength. Hence, conventional metal screws are used, and a secondary operation is needed to remove the screws even when the plates are made of resorbable materials.
One of these conventional compression plate assemblies (U.S. Pat. No. 5,057,111 to Park) utilizes a spacer placed between the screw and the nut to allow the plate to move slightly, resulting in the load being transmitted differentially between the compression plate assembly and the bone. As the bone fracture heals, a greater load is transmitted to the bone. The spacer is made of a material which plastically deforms as a function of time and load transmitted therethrough to decrease the load transmitted between the structure and the fastener. This movement of the fracture plate relative to the bone is known as creep.
The deposit of polymer residue near the site of the wound may be deleterious to the healing process if the spacer breaks down. Also. there is little control over the rate of creep due to changes in the polymer. Thus, here exists a need for a nut for use in securing a bone plate to a bone that allows creep while controlling the unwanted escape of polymer particles.

The University of Iowa Research Foundation


A prefabricated cribbing column for supporting a mine roof. The column includes a plurality of concrete cribbing elements the majority of which are interleaved with load transfer disks. Two of the cribbing elements are interleaved with a handle element. The column assembly of cribbing elements, load transfer disks, and handle element are secured together in an integral unit by a steel strap. The handle element extends substantially beyond the outer periphery of the cribbing elements enabling access and lifting by a forklift or similar machinery. The handle element enables the integral column to be easily moved from one location to another. The cribbing elements are preferably constructed of steel fiber reinforced concrete. A column consisting of five cribbing elements has shown to be capable of supporting a load of 575 tons with a deflection of 2.5 inches or less.

Underground cribbing is commonly used in mines for supporting a mine roof or the like. The cribbing is formed of cribbing elements such as wooden beams or concrete blocks, which are stacked from the mine floor to the mine roof in order to provide support for the roof.
Although many different types of cribbing elements have been proposed for the support of mine roofs, they are typically assembled in a similar manner in the mine. Typically, the cribbing elements are much smaller in height than the distance between the mine floor and the mine roof, and therefore a great many cribbing elements must be transported to the mines and then assembled at each location in which the roof needs to be supported.
Assembling the separate cribbing elements into a mine support is typically laborious and requires a significant amount of time. When stacked vertically, some common cribbing elements must have their outer perimeters in alignment. Other types include notches or other features that require interlocking of adjacent elements to keep them in alignment. Since the cribbing elements are typically much less in height than the clearance between the floor and roof, a significant amount of time and effort are expended at each separate roof support location.
An additional problem arises with cribbing elements constructed of concrete blocks. Typically, mine floors are not perfectly level. They may have slight slopes or may have uneven surfaces. This typically doesn't present a problem when the cribbing elements are constructed of an easily compressible material such as wood, as the wood elements will deform in the area of the high spot on the uneven surface. However, when using concrete block cribbing elements, the relatively uncompressible blocks may break on a high spot on the uneven surface.
Another problem arises with cribbing elements that are aligned along their outer peripheries. Since a large number of cribbing elements must be aligned laterally while building the vertical support, it is sometimes difficult to obtain a true lateral alignment of the elements. If one or more of the cribbing elements is out of lateral alignment, the entire surface of the misaligned cribbing element is not available to support the load, thereby increasing the specific loading per area on the cribbing element and possibly leading to premature failure of the roof support.
Therefore, as should be obvious by the above description, prior art mine roof supports constructed of separate cribbing elements can be improved.


The front sight comprises an A-shaped support whose top is formed by a cross-member between two raised side plates for protecting the front sight which is adjustably mounted in the cross-member. A knob is housed to rotate freely in the cross-member and is provided with an axial tapped hole. The front sight is constituted by an end in the form of a rod for aiming purposes and by a threaded body received in the tapped hole of the knob, said body being provided with a pin for preventing it from rotating, the pin being slidably received in two slots of the hole in the support that freely receives the body of the front sight. The knob projects sideways a little from the support to be accessible to the fingers, and it includes indexing means.

Such an adjustable front sight for a gun in the M16 series is already known. The front sight is constituted by a part provided with an end constituting the sight proper and with a threaded body screwed into a tapped hole in the top cross-member of the front sight support, between the two side plates. The front sight also includes an intermediate part in the form of a washer with peripheral notches, e.g. four notches. A locking stud is provided on the circle of the peripheral notches, sliding in a hole and bearing against the bottom thereof by means of a spring. The locking slide is formed of a cylindrical body terminated by an end that is also cylindrical, but of smaller diameter so as to form a shoulder.
This smaller end occupies a corresponding notch of the front sight disk, while bearing against the bottom face of the disk via its shoulder.
To adjust the front sight, i.e. to lower it by screwing it in or to raise it, it is possible to use a hook or a point to press down the member that prevents rotation so as to retract it, thereby allowing the front sight to be turned using a special tool in the form of a tube provided with teeth that engage in the notches of the front sight disk. The tooth overlying the locking member pushes away said and allows the front sight to be turned since the other teeth are occupying the other notohes in the front sight disc, thereby preventing the looking member from moving beak out.
Nevertheless, this operation is relatively fiddly since the locking member will move back out whenever the next notch come over the housing for the locking member.
That front sight therefore suffers from the drawback of requiring special tool which is relatively small and easily lost, or which is not easy to handle in order to perform adjustment.


Disclosed is a disk drive apparatus which has a manual search function with improved operability. Upon manual search for information TNO(n+1) recorded on the outer periphery of a information write/read medium to information TNO(n) recorded on the inner periphery, there may be an gap (no sound) portion in the information between the outer and inner peripheries. In this case, the information is searched by the front-end position Pb on the outer periphery. Thereafter, no search is performed on the gap (no sound) portion through skipping from the front-end position Pb to the terminal end position Pc of the information TNO(n). Thus, only necessary information is continuously searched upon the manual search without searching the gap (no sound) portion which is not necessary for the user. Thus, the user is provided with improved operability.

1. Field of the Invention
The present invention relates to a disk drive apparatus for reading information from information read/write media such as CD-R disks.
2. Description of Related Art
In recent years, variations of the CD family based on the CDDA (Compact Disk Digital Audio) system have increased and, among all, the CD-R disk has gained attention.
The CD-R disk has a storage layer formed of organic coloring matter and is adapted such that information can be written thereon once and for all. For this reason, the CD-R disk has been receiving attention as an information read/write medium suitable for writing data, for example, image data, audio data, and data such as computer programs, as desired by a user, for long-term storage.
The CD-R disk is also adapted to be compatible with the CD family. Thus, after finalizing processing has been performed on the data written on CD-R disk with the CD-R recorder, the data can be read from the CD-R disk with a CD player in the same manner as by the CDDA method.
However, as described above, the CD-R has an advantage in that information can be written thereon although once only. Thus, for example, suppose that the user has recorded a plurality of tunes with the CD-R recorder and may not desire to read any particular one of the tunes. Even in this case, the user is not allowed to overwrite the tune.
In this context, as a CD-R recorder that can meet the requirements of such a user, a device has been developed which allows address information, having tune data that is not necessary for being read, to be written onto a TOC (Table of Contents). When the CD-R disk on which finalizing processing has been performed is read with a CD player, this apparatus allows only a tune desired by the user to be read without reading the aforementioned specified tune data by protecting the tune data from being read, thereby providing increased operability.
For example, as schematically shown in FIG. 1, suppose that the user writes three pieces of tune data TNO(n) to TNO(n+2) and then performs the aforementioned finalizing processing designating that the second tune data TNO(n+1) is not to be read. Suppose also that a command for requesting the reading of the next tune (referred to as xe2x80x9ctrack searchxe2x80x9d) is entered in the course of reading the first tune TNO(n) from the CD-R disk on which the finalizing processing has been performed with the CD player. In this case, a jump is made from an address P1 being read to a head address ADRn+2 of the third tune data TNO(n+2) to continue the reading.
Thus, the jump is made to the head address ADRn+2, controlled by TOC, where the tune is actually written (rather than to the start address of the gap (with no sound) area in the figure). This allows the second tune data TNO(n+1) which need not be read to be skipped so as to perform reading continuously, thereby providing improved operability.
Some CD-R recorders are also known which have a function of designating data corresponding to a writing error as read-protected data upon being read with a CD player. This is achieved by writing address information including the data corresponding to the writing error onto the TOC when the writing error has occurred during writing of the information.
For example, suppose the second tune data TNO(n+1) shown in FIG. 1 corresponds to the writing error. In this case, the CD player completely reads the first tune data TNO(n) to continue reading from the head address ADRn+2 of the third tune data TNO(n+2). That is, the second tune data TNO(n+1) is automatically skipped and the head address ADRn+2 where the third tune data TNO(n+1) is actually recorded is subsequently read. This allows continuous reading, thereby providing improved operability.
Incidentally, as described above, in order to improve user operability, the CD player is provided with a function referred to as manual search in addition to the track search.
This manual search is a function allowing a search for a read start position desired by the user while reading tune data on fast forward, unlike a function of the track search which switches targets to be read successively for each of the tunes.
For example, as schematically shown in FIG. 2, suppose that in the course of reading the tune data TNO(n+2), the user instructs the manual search to search for a desired read start position while performing what is called fast-reverse. In this case, the pickup of the CD player reverses from an address Pa being read in the direction indicated by the arrows (toward the lead-in area). At the same time, the pickup moves toward the smaller numbers or the tune data TNO(n+1), TNO(n), and so on while partly reading the tune data, while the instruction of the manual search is in effect.
For this reason, with the manual search, the user can perform fast reverse feeding up to a desired position with an operation that feels like an analog cassette tape, so that the reading can be started from the fast-reversed position.
However, the conventional manual search has a problem that data designated not to be read by the user and read-protected data corresponding to a writing error (e.g. the second tune data TNO(n+1), etc. in FIG. 2) are also read as targets to be searched.
For this reason, the manual search takes a long time to search for a read start position desired by the user and takes even an gap (no sound) area where no tune is actually written as a target to be searched. Consequently, the manual search has a problem of requiring an unnecessary operation by the user.
The present invention was developed to overcome the conventional problems mentioned above, and an object of the present invention is to provide a disk drive apparatus having search functions for improving the operability.
A disk drive apparatus according to a first aspect of the present invention for achieving the aforementioned object is a disk drive apparatus having a manual search function. The apparatus is characterized by comprising a detecting means for detecting a front end position of information subsequent to a terminal end position of an gap portion contained in information upon manual search of said information recorded on an information read/write medium from the outer to inner periphery. The apparatus also comprises a searching means for searching for a terminal end position of information recorded on said inner periphery across said gap portion. The apparatus further comprises a control means for skipping said gap portion to move a pickup to said terminal end position to be searched for by said searching means when said detecting means detects said front end position.
By means of this construction, when a manual search is carried out from the information recorded on the outer periphery of the information read/write medium to the information recorded at the inner periphery of the information read/write medium in the case where gap portion exists in the information between the aforementioned outer periphery and inner periphery, after a search is carried out as far as the front end position of the information at the outer periphery a search of the gap portion is not carried out due the search from this front end position to the information of the inner periphery at the end position being skipped. Thus, only necessary information is continuously searched upon the manual search without searching the gap (no sound) portion which is not necessary for the user. Thus, the user is provided with improved operability.
In addition, the disk drive apparatus according to a second aspect of the present invention has a manual search function. The apparatus is characterized by comprising a detecting means for detecting a front end position of information subsequent to a terminal end position of read-protected information contained in information upon manual search of said information recorded on an information read/write medium from an outer to inner periphery. The apparatus also comprises a searching means for searching for a terminal end position of information recorded on said inner periphery across said read-protected information. The apparatus further comprises a control means for skipping said read-protected information to move a pickup to said terminal end position to be searched for by said searching means when said detecting means detects said front end position.
By means of this construction, when a manual search is carried out from the information recorded on the outer periphery of the information read/write medium to the information recorded at the inner periphery of the information read/write medium in the case where read-protected information exists in the information between the aforementioned outer periphery and inner periphery, after a search is carried out as far as the front end position of the information at the outer periphery a search of the read-protected information is not carried out due the search from this front end position to the information of the inner periphery at the end position being skipped. Thus, only necessary information is continuously searched upon the manual search without searching the read-protected information which is not necessary for the user. Thus, the user is provided with improved operability.


A strainer wall (1) to screen off a suction space (3) and a suction duct (5) connected to it in an emergency cooling system of a nuclear power plant includes at least one strainer wall element (2) which has an inlet side (12) and an outflow side (13), wherein the inlet side is essentially oriented perpendicular. The strainer wall element (2) is built up from a plurality of modular cassette units (11), which respectively contain a plurality of screen elements (17.1′–17.nm) open towards the inlet side (12) and connected to the outflow side (13).

The invention relates to a strainer wall for the screening off of a suction space and of a suction duct connected to it.
A reactor in a nuclear power plant is surrounded by a safety container of concrete and steel, the so-called containment. Furthermore, the reactor is equipped with an emergency cooling system (termed Emergency Core Cooling System or ECCS or Containment Spray System or CSS) in order to cool the reactor core in the event of a malfunction or incident. In such a case the water is sucked in from the lowermost part of the safety container, the so-called sump, by emergency cooling pumps via suction ducts and circulated through the reactor core.
In the design scenario for the emergency cooling system it is assumed that debris which arises in an incident falls down into the sump and/or is washed down into the sump by the downwardly flowing water. In order that this debris does not impair the ability of the emergency cooling system to operate, special screen elements, named protective screens in the following, are provided in front of the inlet openings of the suction ducts which lead to the emergency cooling pumps. These protective screens have the task of keeping back the debris resulting from the incident and simultaneously ensuring an adequate through-flow of water. In this connection it must be ensured that the pressure drop caused by the debris does not exceed the permissible limiting value.
Previously known protective screens used in nuclear power plants with pressure water reactors (PWR) are mainly formed as flat grid segments which have only a small screen surface and which can produce an impermissibly high pressure drop. Protective screen elements of corrugated and perforated sheet metal offer a larger effective screen area. However, deformations occur under pressure loading which restrict the size of such protective screen elements. A cylindrical suction screen is described in EP 0 818 227 A1 which admittedly has a very large effective screen area but can only be used in rare cases in the sump region of a PWR nuclear power plant, because the direct environment of the inlet openings of the suction ducts is constructed in such a way that it is not very suitable for the use of cylindrical suction screens. A suction space for the installation of protective screen elements with a suitable screen area is mainly provided in front of the inlet openings of the suction ducts.

Strainer wall for the screening off of a suction space


This invention relates to antibodies or fragments thereof that can be used as indicators of apoptosis. More specifically, this invention relates to antibodies and fragments thereof that selectively bind GP46, a protein whose levels increase significantly upon induction of apoptosis. This invention also relates to the hybridomas that produce anti-GP46 monoclonal antibodies. This invention also discloses a method of detecting cell death by apoptosis in vitro or in vivo by detecting and quantifying GP46 present in biological samples, comprising contacting the sample with the antibodies or fragments to form GP46 immunocomplexes, which may then be detected by the use of known methods. This detection method is useful for research into apoptosis and research relating to diseases in which apoptosis is involved. This method could also be used to diagnose the extent of damage caused by a particular disease or to evaluate the efficacy of drug treatments. The present invention also relates to a method of using the anti-GP46 antibodies or fragments in nuclear medical imaging. The present invention further relates to therapeutic uses of the anti-GP46 antibodies or fragments. The antibodies or fragments can also be incorporated into kits for the detection of apoptosis.

Apoptosis is programmed cell death, a naturally occurring process involved in both the development and aging of cells. It is the process whereby the body can rid itself of unwanted, old, or damaged cells. Apoptosis is the physiological counterpart of cell proliferation. It is essential for both biological processes such as normal tissue turnover, embryonic development, and maturation of the immune system, including pathological processes, such as hormone deprivation, thermal stress and metabolic stress. (Wyllie, A. H., in Bowen and Lockshin (eds.) Cell Death in Biology and Pathology (Chapman and Hall, 1981), at 9-34).
Apoptosis is characterized by a decrease in cell volume, a condensation of chromatin, cellular budding, and the fragmentation of DNA into a ladder of 180 base pair (bp) oligomers with 3'-OH free ends, a hallmark of apoptosis. Cell membranes maintain their integrity through the process, and lysosomes remain intact. There is no inflammatory response from apoptosis. Affected cells undergo phagocytosis by adjacent normal cells and by some macrophages.
The biochemical effector pathways that underlie the apoptotic mechanisms are as yet unknown. It has been suggested that the apoptotic mechanism involves one or more Ca.sup.2+ /Mg.sup.2+ -dependent endogenous endonucleases (Arends et al., (1990) Am. J. Pathol. 136:593-608); transglutaminase activity (Fesus et al., (1987) FEBS Lett. 224:104-108; Taress et al., (1992) J. Biol. Chem. Cell 75:653-660); and the generation of oxygen radicals (Hockenberry et al., (1993) Cell 75:241-251; Butke and Sandstrom (1994) Immun. Today 15:7-10). It appears that gene expression is required for apoptosis as this process can be stopped by inhibitors of RNA or protein synthesis (Martin et al., J. Cell Biol. 106:829-844 (1988)).
Although the apoptotic mechanism has not been determined, several proto-oncogenes, including c-myo, p53, and bol-2, have been implicated in its control (See Grand et al., (1995) Exp. Cell Res. 218:439-451). The delicate balance between these genes determines whether a cell will underto apoptosis or survive. None of these gene products, however, have been identified as a specific marker for apoptosis because these genes are involved in other biochemical processes.
Apoptosis can be activated by a number of intrinsic or extrinsic signals. These signals include the following: mild physical signals, such as ionization radiation, ultraviolet radiation, or hyperthermia; low to medium doses of toxic compounds, such as azides or hydrogen peroxides; chemotherapeutic drugs, such as etoposides and teniposides, cytokines such as tumour necrosis factors and transforming growth factors; and stimulation of T-cell receptors.
When apoptosis is unregulated, disease results. Unregulated apoptosis is involved in diseases such as cancer, heart disease, neurodegenerative disorders, autoimmune disorders, and viral and bacterial infections. Cancer, for example, not only triggers cells to proliferate but also blocks apoptosis. Cancer is partly a failure of apoptosis: the orders for the cells to kill themselves by apoptosis are blocked. New cancer treatments that involve inducing apoptosis are being researched.
Disease and shock can cause cardiac cells to induce apoptosis. For example, cells deprived of oxygen after a heart attack release signals that induce apoptosis in cells in the heart. New treatments involving apoptosis blockers are being developed.
Apoptosis may also be involved in the destruction of neurons in people afflicted by strokes or neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and ALS (Lou Gehrig's disease). There is evidence suggesting that ischemia can kill neurons by inducing apoptosis. It has been shown that neurons that are resistant to apoptosis are also resistant to ischemic damage, thus, inhibition of apoptosis may be a therapeutic strategy for the treatment of neurodegenerative disorders such as stroke.
A failure of apoptosis in the immune system can lead to autoimmune diseases. T-cells differentiate between self and nonself (foreign) cells in the body. Autoimmune diseases such as rheumatoid arthritis, diabetes, and multiple sclerosis, result when a small percentage of T-cells attack the body's own tissue. Drugs are being developed that induce apoptosis in these T-cells.
Evidence also suggests that AIDs develops when the human immunodeficiency virus (HIV) sets off unregulated and untimely apoptosis in CD-4 and CD-8 cells, the defenders of the immune system.
There is an enormous therapeutic potential in controlling apoptosis in these diseases. Much research is now focussing on developing drugs that can either inhibit or induce apoptosis depending on the targeted disease. A major difficulty with researching apoptosis and drugs to control it is that a reliable marker of apoptosis has not yet been developed.
A marker is also needed in order to determine whether cells are dying or have been killed by apoptosis in the diagnosis of these diseases. For example, a marker for apoptosis could be used to determine the extend of neuronal damage caused by a stroke.
Apoptosis drugs are being used in therapy, and a reliable marker is needed in order to evaluate the progress of the therapy. For example, a major goal of some cancer chemotherapies has become to kill cancer cells by inducing apoptosis in these cells. It is estimated, however, that 45 percent of cancer drug treatments fail. It would be useful to have a method to assess the performance of new treatments in a reliable and effective manner. Currently, oncologists have to rely on manual measurements of tumour size and CAT Scan technologies to provide treatment feedback. The former is labour intensive while the latter is very expensive. In addition, both methods require at least one month of treatment to be effective. Furthermore, these methods do not indicate the nature of biochemical activities in the tumour. As such, there is a need for markers of apoptosis in order to determine whether apoptosis has been induced in tumour cells by the cancer chemotherapy.
Apoptosis is one type of cell death, another is necrosis. Cell death by necrosis often interferes with a determination of whether apoptosis has been induced. There are, however, distinguishing characteristics between the two. In contrast to apoptosis, necrosis is not genetically controlled, rather, it is induced by severe environmental trauma, such as chronic doses of heavy metals, chemicals, or extreme heat. The cells have little or no time to respond to the environmental stress and therefore die. Since RNA and protein synthesis are not required in order for cell death to occur, necrosis cannot be inhibited by drugs.
Necrosis is characterized by the swelling and rupturing of cells, the loss of membrane integrity, a random breakdown of DNA into fragments of variable size, and the phagocytosis of cellular debris by macrophages. The release of lysosomal enzymes damages neighbouring cells, thus, cells die in groups. This produces an inflammatory response in tissue. Cell death by necrosis involves no direct RNA or protein synthesis.
The differences in characteristics between apoptosis and necrosis allow one to differentiate between cell death by apoptosis and cell death by necrosis based on the following combinations of characteristics, apoptosis involves RNA and protein synthesis, the production of laddered DNA fragments, the maintenance of membrane integrity, and the exclusion of vital dyes during the process of dying by apoptosis; necrosis involves no RNA or protein synthesis, the production of random DNA fragments, the absence of membrane integrity, and the retention of vital dyes.
Despite the notable differences between apoptosis and necrosis, many long and tedious procedures are required to determine by which mechanism cell death has occurred. These procedures do not identify whether apoptosis is starting or is ongoing in a cell, this causes uncertainty in research, in the development of drugs that induce or inhibit apoptosis, in diagnosis, and in medical treatment. To date, a reliable marker for the early detection of apoptosis does not exist.
To date, a reliable marker for the early detection of apoptosis does not exist. Currently, the marker most commonly used to detect apoptosis is TUNEL labeling of the 3'-OH free end of DNA fragments produced during apoptosis (Gavrieli, Y. et al. (1992) J. Cell Bio. 119:493). The TUNEL method consists of catalytically adding a nucleotide, which has been conjugated to a chromogen system or a to a fluorescent tag, to the 3'-OH end of the 180-bp oligomer DNA fragments in order to detect the fragments. The presence of a DNA ladder of 180-bp oligomers is indicative of apoptosis.
Procedures to detect cell death based on the TUNEL method are offered by both Boehringer Mannheim (Cell Death Kit) and Oncor (Apoptag Plus). This method involves a number of limitations. Early detection of apoptosis is not possible with this method because the DNA ladder is an end-point in the apoptosis pathway. Also, although the TUNEL method distinguishes live cells from dead, it does not accurately determine whether the cells died by apoptosis or necrosis. False positives are often obtained when using the TUNEL method as a result of DNA fragments from cells that have died by necrosis: random DNA breakdown during necrosis generates DNA fragments that have 3'-OH ends. False negatives can also occur in certain cell types or situations where apoptosis does not lead to DNA laddering. Furthermore, the method is not quantitative since the amount of DNA fragments per cell is dependent upon the stage of apoptosis of the cell. In addition, this method is limited to use in flow cytometry and immunofluorescence, which renders it expensive and time consuming.
Another marker that is currently available is annexin, sold under the trademark APOPTEST.TM.. This marker is used in the "Apoptosis Detection Kit" offered by R&D Systems. During apoptosis, a cell membrane's phospholipid asymmetry changes such that the phospholipids are exposed on the outer membrane. Annexins are a homologous group of proteins that bind phospholipids in the presence of calcium. A second reagent, propidium iodide (PI), is a DNA binding fluorochrome. When a cell population is exposed to both reagents, apoptotic cells stain positive for annexin and negative for PL, necrotic cells stain positive for both, live cells stain negative for both. This marker, however, suffers from a number of problems. Annexin has a strong potential for a lack of specificity due to the fact that it is not antigenic. As well, its use is limited to cells grown in suspension, however, most cells are adherent and are grown on a matrix.
The method also requires the use of live or unpreserved cells. Furthermore, this method requires the use of a flow cytometer, expensive equipment that is not always readily available.
There is therefore a great need for a specific, antigenic, versatile marker for the rapid detection of cell death by apoptosis, which can be used for research, diagnostics, and therapeutics. This marker must be able to distinguish between cell death by apoptosis and cell death by necrosis.
The classical cell model to study apoptosis is the isolated thymocyte, a small lymphocyte in the cortex of the thymus. This model, however, includes a number of limitations as follows: apoptosis occurs too rapidly, making it difficult to delineate the sequence of events, thymocytes are predisposed to apoptosis, and thymocytes are non-adherent, and the role of extracellular matrix proteins (ECM) in apoptosis cannot be studied. For these reasons, an adherent cell model was developed from which cells at four different stages of apoptosis can be isolated and studied (Desjardins and MacManus (1995) Exp. Cell Res. 216:380-387).
Recently, it was reported that human and rodent cells undergoing apoptosis express high levels of a protein, termed apoptosis specific protein (ASP) (Grand et al., (1995) Exp. Cell Res. 218:439-451). Induction of apoptosis coincides with the expression of ASP. ASP is not detected or is detected in very low amounts in viable cells and cells dying passively by necrosis. It was concluded that ASP constitutes a powerful marker for the diagnosis and quantitation of apoptosis.
The protein GP46 is known in the literature as HSP47, HSP46, or colligin. This protein was first discovered by Kurkinen et al., (1984) J. Biol. Chem. 259:5915-5922, who described a 47 kDa glycoprotein from murine parietal endoderm cells that bound specifically to gelatin, collagen I, and collagen IV, hence, the name colligin. Later, similar glycoproteins were described in other cell types, including L6 rat myoblasts, 3T3 fibroblasts, keratinocytes, and chick embryo fibroblasts (Cates et al., (1984) J. Biol. Chem 259:2646-2650; Taylor et al., (1985) Exp. Cell Res. 159:47-54; Hughes et al. (1987) Eur. J. Biochem. 163:57-65; and Nagata et al., (1986) J. Cell. Biol. 103:223-229). The similarity between these proteins was later confirmed by comparing cDNA sequences between some of the cell lines (Clarke and Sanwal (1992) Biochim. Biophys. Acta 1129:246-248).
GP46 is localized in the lumen of the endoplasmic reticuhim (ER) of the cell (Nandan et al., (1988) Exp. Cell Res. 179:289-297; Saga et al., (1987) J. Cell Biol. 105:517-527). It has an RDEL (Arg-Asp-Glu-Leu) sequence at the C-terminus which serves as an ER retention signal (Pelham, (1990) Trends Biochem. Sci. 15:483-486). GP46 is known to bind to denatured collagen, collagen I, collagen IV, and procollagen I. Its role may be to act as a molecular chaperone by assisting in protein folding of collagen during its synthesis (Jain et al. (1994) Biochem. J. 304:61-68; Nakai et al., (1992) J. Cell Biol. 117:903-914). It is a member of the serine-proteinase inhibitor family (serpin) and may protect procollagen I chains from degradation by inhibiting collagenase in the ER (Jain et al., (1994) Biochem. J. 304:61-68; Clarke et al., (1993) J. Cell Biol. 121:193-199).
A number of findings have linked the GP46 protein to apoptosis. It has been observed that GP46 mRNA increases in neuronal cells during apoptosis, and that the GP46 levels remain high for 48 hours (Higashi et al., (1994) Brain Res. 650:239-248). As well, it has been reported that when anti-sense RNA of GP46 is added to cells, apoptosis is induced and the cells die (Nagata et al., (1995) "Regulation and Function of Collagen-Specific Molecular Chaperone-Like Protein HSP47" in J. Cell. Biochem. Suppl. 190:195 and oral presentation at the Keystone Symposia on Sress Proteins in March, 1995).
This background information is provided for the purpose of making known information believed by the applicant to be of possible relevance to the present invention. No admission is necessarily intended, nor should be construed, that any of the preceding information constitutes prior art against the present invention. Moreover, publications referred to in the following discussion are hereby incorporated by reference in their entireties in this application.

Method of detecting apoptosis using an anti-human GP46 monoclonal anti-body


Provided are bispecific antibodies having a full-size antibody portion with two light chains and two heavy chains, wherein the two heavy chains each is fused to a single-chain variable fragment (scFv) portion. In certain embodiments, the full-size antibody has specificity to EGFR and the scFv has specificity to VEGF.

A bispecific antibody (BsAb), or specific monoclonal antibody (BsMAb) is an artificial protein comprised of fragments from two different antibodies. By virtue of the inclusion of two different antigen binding regions, a bispecific antibody is capable of recognizing and binding to two different antigens, or two different epitope on an antigen. In cancer immunotherapy, bispecific antibodies are being developed to simultaneously bind to a cytotoxic cell by targeting a receptor like CD3, and a tumor cell to be destroyed.
Bispecific antibodies present challenges in various aspects. First, they are more difficult to manufacture. Further, the in vitro and in vivo stabilities of these artificial proteins may be questionable. Given the close proximity of the antigen binding regions within a single protein, it also remains to be seen whether the antigen binding regions retain their binding affinities.
In order to overcome manufacturing difficulties, a first-generation BsMAb, called trifunctional antibody, has been developed. It consists of two heavy and two light chains, one each from two different antibodies. The two Fab regions are directed against two antigens. The Fc region (the foot) is made up from the two heavy chains and forms the third binding site; hence the name.
Other types of bispecific antibodies have been designed to overcome certain problems, such as short half-life, immunogenicity and side-effects caused by cytokine liberation. They include chemically linked Fabs, consisting only of the Fab regions, and various types of bivalent and trivalent single-chain variable fragments (scFvs), fusion proteins mimicking the variable domains of two antibodies.
Other types of recombinant antibody formats have also been developed in the recent past, e.g. tetravalent bispecific antibodies by fusion of, e.g., an IgG antibody format and single chain domains (see e.g. Coloma, M. J., et al., Nature Biotech 15 (1997) 159-163; WO 2001/077342; and Morrison, S. L., Nature Biotech 25 (2007) 1233-1234).
Also several other new formats wherein the antibody core structure (IgA, IgD, IgE, IgG or IgM) is no longer retained such as dia-, tria- or tetrabodies, minibodies, several single chain formats (scFv, Bis-scFv), which are capable of binding two or more antigens, have been developed (Holliger, P., et al., Nature Biotech 23 (2005) 1126-1136; Fischer, N., Leger, O., Pathobiology 74 (2007) 3-14; Shen, J., et al., Journal of Immunological Methods 318 (2007) 65-74; Wu, C., et al., Nature Biotech. 25 (2007) 1290-1297).
All such formats use linkers either to fuse the antibody core (IgA, IgD, IgE, IgG or IgM) to a further binding protein (e.g. scFv) or to fuse e.g. two Fab fragments or scFvs (Fischer, N., Leger, O., Pathobiology 74 (2007) 3-14). It is important to retain effector functions, such as e.g. complement-dependent cytotoxicity (CDC) or antibody dependent cellular cytotoxicity (ADCC), which are mediated through the Fc receptor binding, by maintaining a high degree of similarity to naturally occurring antibodies.
WO 2007/024715 reports dual variable domain immunoglobulins as engineered multivalent and multispecific binding proteins. A process for the preparation of biologically active antibody dimers is reported in U.S. Pat. No. 6,897,044. Multivalent Fv antibody construct having at least four variable domains which are linked with each other via peptide linkers are reported in U.S. Pat. No. 7,129,330. Dimeric and multimeric antigen binding structures are reported in US 2005/0079170. Tri- or tetra-valent monospecific antigen-binding protein comprising three or four Fab fragments bound to each other covalently by a connecting structure, which protein is not a natural immunoglobulin are reported in U.S. Pat. No. 6,511,663. In WO 2006/020258 tetravalent bispecific antibodies are reported that can be efficiently expressed in prokaryotic and eukaryotic cells, and are useful in therapeutic and diagnostic methods. A method of separating or preferentially synthesizing dimers which are linked via at least one interchain disulfide linkage or dimers which are not linked via at least one interchain disulfide linkage from a mixture comprising the two types of polypeptide dimers is reported in US 2005/0163782. Bispecific tetravalent receptors are reported in U.S. Pat. No. 5,959,083. Engineered antibodies with three or more functional antigen binding sites are reported in WO 2001/077342.
Multispecific and multivalent antigen-binding polypeptides are reported in WO 1997/001580. WO 1992/004053 reports homoconjugates, typically prepared from monoclonal antibodies of the IgG class which bind to the same antigenic determinant are covalently linked by synthetic cross-linking Oligomeric monoclonal antibodies with high avidity for antigen are reported in WO 1991/06305 whereby the oligomers, typically of the IgG class, are secreted having two or more immunoglobulin monomers associated together to form tetravalent or hexavalent IgG molecules. Sheep-derived antibodies and engineered antibody constructs are reported in U.S. Pat. No. 6,350,860, which can be used to treat diseases wherein interferon gamma activity is pathogenic. In US 2005/0100543 are reported targetable constructs that are multivalent carriers of bi-specific antibodies, i.e., each molecule of a targetable construct can serve as a carrier of two or more bi-specific antibodies. Genetically engineered bispecific tetravalent antibodies are reported in WO 1995/009917. In WO 2007/109254 stabilized binding molecules that consist of or comprise a stabilized scFv are reported.
Epidermal growth factor receptor (EGFR) is a trans-membrane receptor encoded by the c-erbB 1 proto-oncogene with a molecular weight of approximately 170 kDa. EGFR is normally expressed in a wide variety of epithelial tissues as well as in the central nervous system. Accumulating evidence suggests that the level of EGFR overexpression is an important factor that directly correlates with active proliferation of malignant cells and poor prognosis of patients, thus, providing the rationale for the development of EGFR antagonists as potentially useful therapeutic strategies for the treatment of EGFR-expressing cancers.
EGFR inhibitors encompassing both small molecules and antibodies have been developed for the treatment of cancer. The small-molecule EGFR tyrosine kinase inhibitors (TKI) erlotinib (Tarceva®) and gefitinib (Iressa®) have demonstrated activity in multiple epithelial tumor types. These compounds reversibly bind to the adenosine triphosphate binding site of the EGFR TKD and inhibit autophosphorylation. Initial results with these molecules as monotherapy or in combination with chemotherapy in unselected populations were disappointing. It is now known that mutations in the EGFR gene alter the tumur phenotype and predict response to treatment, allowing the molecular selection of a subset of patients in which TKI are highly efficacious. The anti-EGFR monoclonal antibodies (mAbs) cetuximab (Erbitux®) and panitumumab (Vectibix®) are established agents in the treatment of CRC (colon and rectal cancer) and SCCHN (Squamous Cell Carcinoma of the Head and Neck). These agents have demonstrated modest clinical efficacy in combination with chemotherapy in phase III trials. However, patients with CRC with KRAS mutations (30%-40% of patients) are unresponsive to cetuximab or panitumumab, when used as monotherapy or in combination with chemotherapy. mAbs targeting cell surface receptors can exert a therapeutic effect either by inhibiting the oncogenic growth signal (blocking ligand binding and/or receptor dimerisation/activation) or through direct cell killing. Cell killing can be achieved by inducing apoptosis in the target cell or cell killing can be achieved by releasing cytotoxic compounds in the target cell through antibody-drug conjugates (ADCs), which consist of cytotoxic agents or toxins chemically conjugated to a monoclonal antibody. Antibody-drug conjugates potentially represent an advantage over treatment with chemotherapy because they are designed to deliver the cytotoxic agent specifically to tumor cells thereby resulting in an improved safety profile.
Angiogenesis is involved in the pathogenesis of a variety of diseases, including solid tumors, intraocular neovascular syndromes such as proliferative retinopathies or age-related macular degeneration (AMD), rheumatoid arthritis, and psoriasis (Folkman, J., et al., J. Biol. Chem. 267 (1992) 10931-10934; Klagsbrun, M., et al., Annu Rev. Physiol. 53 (1991) 217-239). Angiogenesis allows the tumor cells to acquire a growth advantage and proliferative autonomy compared to the normal cells. Human vascular endothelial growth factor (VEGF/VEGF-A) is involved in the regulation of normal and abnormal angiogenesis and neovascularization associated with tumors and intraocular disorders (Ferrara, N., et al., Endocr. Rev. 18 (1997) 4-25; Berkman, R. A., et al., J. Clin. Invest. 91 (1993) 153-159; Brown, L. F., et al., Human Pathol. 26 (1995) 86-91; Brown, L. F., et al., Cancer Res. 53 (1993) 4727-4735; Mattern, J., et al., Brit. J. Cancer. 73 (1996) 931-934; and Dvorak, H., et al., Am. J. Pathol. 146 (1995) 1029-1039).
VEGF is a homodimeric glycoprotein that has been isolated from several sources. VEGF shows highly specific mitogenic activity for endothelial cells. VEGF has important regulatory functions in the formation of new blood vessels during embryonic vasculogenesis and in angiogenesis during adult life (Carmeliet, P., et al., Nature, 380 (1996) 435-439; Ferrara, N., et al., Nature, 380 (1996) 439-442; reviewed in Ferrara and Davis-Smyth, Endocrine Rev., 18 (1997) 4-25. The significance of the role played by VEGF has been demonstrated in studies showing that inactivation of a single VEGF allele results in embryonic lethality due to failed development of the vasculature (Carmeliet, P., et al., Nature, 380 (1996) 435-439; Ferrara, N., et al., Nature, 380 (1996) 439-442.
In addition VEGF has strong chemoattractant activity towards monocytes, can induce the plasminogen activator and the plasminogen activator inhibitor in endothelial cells, and can also induce microvascular permeability. Because of the latter activity, it is sometimes referred to as vascular permeability factor (VPF). The isolation and properties of VEGF have been reviewed; see Ferrara, N., et al., J. Cellular Biochem., 47 (1991) 211-218 and Connolly, J. Cellular Biochem., 47 (1991) 219-223. Alternative mRNA splicing of a single VEGF gene gives rise to five isoforms of VEGF.
Anti-VEGF neutralizing antibodies suppress the growth of a variety of human tumor cell lines in mice (Kim, I., et al., Nature 362 (1993) 841-844; Warren, S. R., et al., J. Clin. Invest. 95 (1995) 1789-1797; Borgstrom, P., et al., Cancer Res. 56 (1996) 4032-4039; and Melnyk, O., et al., Cancer Res. 56 (1996) 921-924). WO 94/10202, WO 98/45332, WO 2005/00900 and WO 00/35956 refer to antibodies against VEGF. Humanized monoclonal antibody bevacizumab (sold under the trade name Avastin®) is an anti-VEGF antibody used in tumor therapy (WO 98/45331).
Bevacizumab, combined with fluoropyrimidine-based chemotherapy is now the standard first-line treatment for metastatic colorectal cancer. Cetuximab, a chimeric IgG1 monoclonal antibody against epidermal growth factor receptor (EGFR), has efficacy as monotherapy and in combination with irinotecan in irinotecan-resistant patients. It would have been expected that the addition of cetuximab to capecitabine, oxaliplatin, and bevacizumab as first-line treatment in patients with metastatic colorectal cancer (the CAIRO2 trial) would achieve better efficacy by blocking both EGFR and VEGF.
However, overall survival and response rates did not improve in the treatment group of combing the two blocking antibodies, cetuximab and bevacizumab. Patients treated with cetuximab who had tumors bearing a mutated KRAS gene had significantly decreased progression-free survival (PFS) as compared with cetuximab-treated patients with wildtype-KRAS tumors (N Engl J Med 2009; 360:563-72).
Panitumumab, a fully human antibody targeting the epidermal growth factor receptor, approved for treatment for patients with metastatic colorectal cancer (mCRC), was evaluated in another trial by adding to bevacizumab and chemotherapy (oxaliplatin- and irinotecan-based) as first-line treatment for mCRC, similar data were obtained. The addition of panitumumab to bevacizumab and oxaliplatin- or irinotecan-based chemotherapy results in increased toxicity and decreased PFS. These simple drug combinations are not recommended for the treatment of mCRC in clinical practice (J Clin Oncol (2009) 27:672-680). Thus, there is an apparent need to a better approach to the treatment of solid tumors by targeting therapeutic agents to the tumor tissues, while simultaneously blocking the signaling pathway by both VEGF and EGFR.
Human domain antibodies selected against VEGF and EGFR were reported by formatting into a dual-targeting IgG (DT-IgG) to directly target both antigens in a single molecule (Int J Cancer. 2012 Aug. 15; 131(4):956-69). This DT-IgG suppressed EGFR positive cell growth, inhibited EGFR activation and induced apoptosis as effectively as cetuximab, and neutralized VEGF as effectively as bevacizumab. However, DT-IgG format is single domain based, and have a very short half-life, and thus is not suitable as therapeutic treatment for cancers.

Bispecific antibodies which bind EGFR and VEGF


A method and apparatus for estimating bias errors in a time-difference-of-arrival/frequency-difference-of-arrival (TDOA/FDOA) geolocation system using a reference signal transmitter in which position and/or motion information of the reference signal transmitter is encoded into the reference signal. The motion information may include the velocity and/or acceleration of the reference signal transmitter. The reference signal is received by multiple collection platforms operating in conjunction with a geolocation system and a reference correction processing system. The reference correction processing system receives, via the multiple collection platforms, the position and/or motion information, which is immediately and unambiguously associated with specific reference signal transmissions. The geolocation system estimates the position and/or velocity of the reference signal transmitter using conventional TDOA/FDOA techniques. The estimated position and/or velocity of the reference signal transmitter is compared to the information contained in the reference signal to estimate bias errors.

Errors in time-difference-of-arrival (TDOA) and frequency-difference-of-arrival (FDOA) measurements used to perform geolocation of non-cooperative emitters (i.e., signals of unknown format or content, transmitted from an unknown location) can be reduced by use of a reference beacon that transmits a signal from a known position. By performing a reverse geolocation using signals transmitted from a reference beacon with a known position and velocity, it is possible to estimate bias errors in the TDOA/FDOA measurements taken by the collection system. The estimated bias errors can then be subtracted from measurements taken of non-cooperative emitter signals to reduce the bias error in those measurements. Such correction is typically performed by a reference correction processing system that is part of or operates in conjunction with the geolocation system.
In order to correctly compute the bias errors using signal data collected from a reference beacon transmitter, it is necessary to know the position (and/or velocity) of the transmitter at the time of transmission.
A reference beacon signal need not contain any information in order to provide useable bias corrections. A random or pseudorandom waveform with good correlation properties can be used as a reference beacon signal. In fact, it is generally simpler to generate a signal containing a pseudorandom waveform, than one which contains information.
Currently deployed reference beacon systems typically use stationary reference beacon transmitters whose locations are constant and known to geolocation processing systems, which compute the TDOA/FDOA bias error corrections based on the reference beacon signals and the locations of the transmitters. The beacon signals transmitted by these transmitters typically consist of pseudorandom waveforms, which contain no data.
The Boeing Company is currently developing a reference beacon system that can be placed on a moving platform (e.g., an aircraft). In such an arrangement, the position of the reference beacon transmitter is provided to the geolocation processing system over a network connection. This approach, however, requires the geolocation processing system to associate sets of position data received over the network from the reference beacon transmitter with sets of RF signal data independently received from one or more collection platforms. This association is accomplished by having the geolocation processing system command the reference beacon to transmit at a known time. In the aforementioned system, the reference beacon transmits its position data over the network at the time it starts transmission of the reference beacon signal. As with other conventional approaches, the reference beacon signals consist of pseudorandom waveforms.

Reference beacon methods and apparatus for TDOA/FDOA geolocation


A burst control circuit for use in a TDMA communications system comprises a power amplifier having two separate control terminals. A level control signal which is the difference between a reference signal and the level of the output burst signal of the amplifier, feedback-controls the level of the output burst signal through a first control terminal, and a waveform control signal having a predetermined waveform, controls the waveform of the output burst signal through a second control terminal. When the level of the reference signal is decreased, the amplitude of the waveform control signal is decreased as a function of the level of the reference signal.

This invention relates to a burst control circuit for use in a time division multiple access (TDMA) communications system.
One of the prior arts of this invention is disclosed in U.S. Pat. No. 5,101,176 entitled "BURST CONTROL CIRCUIT FOR USE IN TDMA COMMUNICATIONS SYSTEM" which is assigned to the same assignee as the present application, and which will hereafter be called the prior circuit.
In the prior circuit, a power amplifier having two control terminals amplifies an input radio signal to produce an output burst signal. A level control signal representing a difference between a reference signal and the level of the output burst signal, feedback-controls the level of the output burst signal through a first control terminal of the amplifier. A waveform control signal of a fixed amplitude controls the waveform of the output burst signal through a second control terminal of the amplifier.
The waveform control signal has a trapezoidal waveform and the rise and fall times of the waveform control signal are so determined that the spectrum bandwidth of the output burst signal is suppressed within an allowable range.
A non-linear power amplifier having a high power efficiency is used as the power amplifier of the prior circuit. In a small power output range of this non-linear power amplifier, a small increment of the level control signal causes an excessively large increment of the output burst signal.
This characteristic of the power amplifier makes it difficult to carry out a fine level control in a small power output range. And this excessively high gain of the amplifier in a small power range often deteriorates the stability of the feedback-control, resulting in overshoots in the leading and trailing edges of the waveform.

Burst control circuit for use in TDMA communications system


The energization current of an indium phosphide or gallium arsenide double channel semiconductor laser is confined within a laser stripe by near and far current blocking arrangements. The near current blocking arrangements are formed by a blocking junction formed in two lateral channels delimiting the stripe. The far current blocking arrangements are formed by an iron-doped semi-insulative layer grown epitaxially before the lateral channels are etched. A particular application is to the fabrication of pump lasers used in optical amplifiers of optical fiber links.

1. Field of the invention
The present invention concerns the fabrication of a double channel semiconductor laser.
2. Description of the prior art
This type of laser structure is internationally known by the acronym DCPBH which stands for "Double Channel Planar Buried Heterostructure". It may be fabricated from a base material in the form of indium phosphide and an active material further comprising gallium arsenide. It can then be used as a pump laser emitting a wavelength of 1 480 nm that can be used in long-haul fiber optic links including erbium-doped amplifying fibers.
A laser of this kind comprises the following elements which, in terms of their functions as stated hereinafter, are common to prior art lasers and a laser in accordance with the invention and which, in the case of a laser in accordance with the invention, are as shown in transverse cross-section in FIG. 1:
A (usually semiconductor) wafer 2 featuring internal crystal lattice continuity and having a thickness between two main surfaces 4, 8. The wafer defines a vertical direction Z which is that of its thickness and longitudinal X and transverse Y directions which are horizontal and mutually perpendicular. The two main surfaces are a lower surface 4 covered with a lower electrode 6 and an upper surface 8 covered with an upper electrode 10. The wafer is made up of layers in vertical succession from the lower surface to the upper surface. It has diversified areas extending longitudinally and juxtaposed transversely. One such area is a stripe area ZR in which the wafer comprises the following successive layers:
a lower injection layer 25 having a first type of conductivity,
an active layer 14 constituting a laser stripe 14A within the area ZR, and
an upper injection layer 16 having a second type of conductivity.
These layers constitute an active system. They are so fabricated that a polarization current connected via the electrodes 6, 10 injects vertically into the laser stripe 14A from the injection layer charge carriers of opposite types enabling the amplification of laser light within the stripe. The stripe has a refractive index which is higher than that of the surrounding layers 12, 25, 16, 26, 20, 22 to constitute a guide for this light. The injection layers extend transversely beyond the stripe area. The wafer 2 has two transverse sequences of areas each running from a respective side of the stripe area ZR. Each such succession comprises firstly a near lateral area ZC in which a lateral channel CL is substituted for the upper injection layer, the active layer and at least an upper part of the lower injection layer. This channel comprises a lower blocking layer 20 having the second type of conductivity on top of which is an upper blocking layer 22 having the first type of conductivity, so that the two blocking layers form between them a blocking junction JB for the polarization current constituting near current blocking means tending to confine the current within the stripe area ZR.
The transverse sequence of areas secondly comprises a far lateral area ZD in which an electrically resistive layer constitutes far current blocking means cooperating with the near current blocking means to confine the polarization current within the stripe area. The implementation of the far current blocking means is specific to the present invention and will be described in more detail later.
Still referring to features common to prior art lasers and a laser in accordance with the invention, the blocking layers 20, 22 extend into the far lateral area but not into the stripe area, this being achieved by the use of appropriate epitaxial growth techniques to grow layers. The blocking junction that they form blocks the current in the channels because they are thick enough here. On the other hand, the blocking is less than perfect in the far lateral layers beause they are thinner there.
This is why far current blocking means are required.
The upper injection layer 16 and these blocking layers have on top of them a thicker additional layer 26 having the second type of conductivity on top of which is a more strongly doped contact layer 28.
Two mirrors (not shown) are formed by the longitudinally remote surfaces of the semiconductor wafer to constitute a laser emitter.
A first prior art laser comprising these common features and arrangements is described in the JAPANESE JOURNAL OF APPLIED PHYSICS. vol. 25, No 6, June 1986, PART II, TOKYO, JP pages 435-436; S.L. SHI ET AL: "BH INGaAsP lasers with an LPE grown semi-insulating layer".
In this laser the energizing current is blocked in the near lateral area and in the far lateral area by three stacked layers grown epitaxially. Two of these layers form a blocking semiconductor junction. The third comprises modifying impurities (cobalt) imparting sufficient electrical resistivity to it for it to be semi-insulative.
This arrangement has the drawback that pinching of the layer deposited in this way may occur at the outer edges of the channels, that is to say at the boundary between the near and far lateral areas. Any such pinching prevents the required electrical confinement.
A second prior art laser comprising these common features and arrangements is described in European patent EP-A 161 016 (Philips).
In the second prior art laser the far current blocking means are formed, after a wafer is fabricated as previously described, by ionic bombardment localized to the far lateral area which induces therein crystalline defects increasing the resistivity of the base material. Protons are used for the ionic bombardment to achieve an adequate depth of penetration. The electrical resistivity created in the area in this way may initially be sufficiently high to enable correct operation of the laser. However, the crystalline defects which are the reason for this are progressively healed if the temperature of the wafer increases, which reduces the reliability and the range of uses of the laser.
An object of the present invention is to enable simple fabrication of a laser which is reliable even at high temperatures and which is easy to manipulate, even during fabrication.

Double channel semiconductor laser and method of fabricating it


An uninterruptible power supply provides internal connection to an auxiliary power to provide continuous device power without duplicating regulation and switching circuits. The power supply includes an AC to DC converter, a transformer and a switch applying DC power from converter to the transformer. A pulse width modulation control circuit assures a regulated output voltage while application of auxiliary power is controlled by a fixed time interval one-shot that assures a smooth transition to AC utility power upon resumption of such power following a failure. An auxiliary AC power output signal is maintained for a video monitor or other device even while operating on auxiliary power.

Uninterruptible power supplies are required for many computer installations such as network file servers, telecommunications equipment or other applications where a sudden loss of power would create an unacceptable and costly occurrence. For example, there may be situations where data would be lost or corrupted if power were lost during a data transfer or perhaps the cost of a business shutdown simply because of the unavailability of a computer would be sufficient to justify the additional cost for an uninterruptible power supply. Thus, for various reasons there are numerous applications where an uninterruptible power supply is required and the numbers of these applications would each increase substantially if the cost were reduced.
Presently available uninterruptible power supplies are placed between the standard AC utility outlet and the AC utility plug for the computer or other electrical device which must receive continuous electrical power. The power supply includes a battery providing electrical energy in the event of a power failure, an AC to DC converter and an inverter converting electrical energy back from DC to AC. The standard device power supply then receives the AC input from the uninterruptible power supply and in turn converts this to the various required regulated and unregulated voltages required for the system. The AC to DC converter of the conventional uninterruptible power supply converts the AC power to DC power at approximately the battery voltage with a trickle charge being available to assure that the battery remains charged at all times. Typically the battery is a lead acid battery. The inverter then reconverts the DC energy from the DC battery voltage back to an AC power supply approximating standard utility AC power. In the event of a power failure, the internal DC voltage from the AC to DC converter drops below the battery output voltage. This causes the battery to begin supplying the DC power to the inverter in lieu of the AC to DC converter. The system proceeds with the battery supplying power until standard AC utility power is restored or the battery discharges.
While such arrangements work satisfactorily, they are relatively expensive and inefficient. Such systems must work at relatively high power levels of typically two hundred to three hundred watts and are typically only 75 to 80 percent efficient. Consequently, substantial amounts of power must be dissipated within the uninterruptible power supply. Large and expensive components are therefore required to dissipate the resulting heat. In addition, the AC to DC converter, the inverter, and corresponding control circuits must be duplicated within the conventional power supply within the computer or other electrical device. The customer must therefore in effect purchase two power supplies; a standard device power supply plus an uninterruptible power supply.


A pluggable optical transceiver is disclosed. The optical transceiver provides a pull-tab assembled with a body of the transceiver. The pull-tab comprises a pair of arms and a handle. The arms in an end portion thereof each provides a leg set in a guide formed in the body. Sliding the pull-tab to disengage the optical transceiver from the cage, the leg is slid within the guide to push the end portion of the arm outwardly. The handle provides in an end thereof a bar including a slope. The optical fiber pulled out from the optical connector set in the optical receptacle of the transceiver rides on the slope even when the transceiver is set in the cage by the upside-down arrangement.

1. Field of the Invention
The present application relates to a pluggable optical transceiver, in particular, the application relates to an optical transceiver having a pull-pull-tab.
2. Background Arts
One type of optical transceivers has been well known as a pluggable optical transceiver that is used by being temporarily and optionally set in a cage prepared in the host system. The United States Patent Applications, such as US 20030171016A and 20120148198A, have disclosed such a pluggable optical transceiver.
FIG. 12 illustrates a pluggable optical transceiver 100 to be set in a cage 201 prepared in the host system 200. The optical transceiver 100 once set in the cage 201 is unable to extract therefrom unintentionally because a stopper 202 provided in a side of the cage 201 prevents the optical transceiver 100 from slipping out of the cage 201. When the optical transceiver 100 is to be extracted from the cage, a mechanism including a bail 101, a slider 102, and a knob 104 prepared in a side of the optical transceiver 100 releases the engagement between the optical transceiver 100 and the cage 201. Specifically, rotating the bail 101 in front of the optical receptacle 103, the slider 102 operable with the bail 101 slides frontward as pushing the knob 104 outwardly, which expands the stopper 202 of the cage to release the engagement with the optical transceiver 100. Thus, the optical transceiver 100 may be pulled out from the cage 201.
However, the slider 102 and the knob 104 of the conventional optical transceiver 100 have substantially no mechanisms to forbidden the lateral movement thereof. When the bail 101 receives a stress along the lateral direction of the optical transceiver 100, the slider 102 and the knob 104 easily stick out from a pocket provided in the side of the optical transceiver where the slider 102 and the knob 104 are ordinarily set therein. The stuck-out knob 104 has no function to expand the stopper 202 of the cage 201 outwardly; accordingly, when the optical transceiver 100 is set in the cage 201 with the stuck-out knob 104, the optical transceiver 100 becomes unable to be pulled out from the cage 201.

Pluggable optical transceiver having pull-pull-tab


A viewfinder optical system has a relay optical system and an eyepiece optical system. The relay optical system has a first, a second, and a third relay lens. The eyepiece optical system has a first and a second eyepiece lens. The first eyepiece lens, which is disposed closest to a secondary-image plane formed by the relay optical system has an aspherical surface on its secondary-image plane side.

1. Field of the Invention
The present invention relates to a viewfinder optical system, and particularly to a viewfinder optical system provided with a relay optical system for use in a single-lens reflex camera or other.
2. Description of the Prior Art
In the viewfinder optical system of a typical single-lens reflex camera, a pentaprism is used as an inverting optical system. However, with the pentaprism, it is difficult to construct a high-magnification viewfinder having a sufficiently long eyepoint distance. By contrast, if a relay optical system is used as an inverting optical system, it is possible to construct a high-magnification viewfinder having a sufficiently long eyepoint distance.
However, a viewfinder optical system provided with the relay optical system has the disadvantage of being unable to achieve satisfactory matching of the pupils.


A video conferencing system, wherein multiple parties at different locations can view, and modify, a common image on their computer displays. The invention also provides a video camera at each computer, which takes a video picture of each party.. The invention distributes data to all computers involved in the conference from which each computer can generate a display containing the common image, the modifications, and the video pictures.

Modern telephone systems allow multiple parties at different locations to hold a conference. However, telephone conferences do not provide all of the conveniences of a face-to-face conference, where participants all meet at a common table in a meeting room.
For example, in a meeting room, participants can view an object of interest, such as a drawing or a product. Such viewing is not possible in a telephone conference.
The invention concerns systems for collaborative video conferencing, using the telephone system. The invention generates a common visual image which is distributed to several computers. The users of the computers can make annotations on the common image. When they do, the invention replicates the annotations on the displays of all computers.
The common visual image can contain different types of images, such as text, graphics, and video.


A process for refining and producing cellulose, lignin and xylose from biomass material comprises the following steps: pulverizing and screening the biomass material; and then dipping the biomass material in organic acid with lower boiling point and decomposing it into xylose, xylo-oligosaccharide, cellulose and lignin to make the biomass material fluidify; cooling the fluidified biomass material after finishing the reaction, adding organic solvent, and mixing uniformly and standing; separating, washing and drying the precipitation to obtain amorphous cellulose after precipitating; distilling the mother solution of precipitation of cellulose and recovering the organic acid and the resulting volatile organic substance; standing the distilled mother solution after cooling, and then separating, washing and drying the precipitation to obtain xylose and xylo-oligosaccharide after precipitating; distilling and recovering the organic solvent in the mother solution of precipitation of xylose and xylo-oligosaccharide, and separating and drying the precipitation separated out from the distilled mother solution.

Biomass refers to the photosynthesis of various biological material from carbon dioxide and water. It can store solar energy in chemical form, renewably store biosphere carbon, and is an important link of the carbon cycle on earth. Biomass mainly in the form of tree such as twig, agriculture waste such as wheat and rice straw, corn stover, as well as grass such as switch grass. These biomass mainly composed with cellulose, hemicelluloses and lignin entangling to form dense texture, resisting to separation and degradation. Thus the de-polymerization and processing is one of the biggest bottle neck of biomass material utilization. The breakthrough of this barrier would improve the economy of biofuel ethanol, increase the supply of bio-originated bulk chemicals, and increase the competition of environment friendly polylactic acid over mineral oil based plastic.
Reference search showed that a Chinese patent (Chinese patent no. 02145150.8) revealed a process of hydrolysis of biomass with diluted acid under temperature of 100-200° C. for preparation of reduced fermentable mono-sugar. Since the dilute acid used is mineral acid as in other strong acid process, there exist the same disadvantage of different recovery and low recycle of mineral acid, waste discharge polluting environment.

Process for refining and producing cellulose, lignin and xylose from biomass material


A multi-functional device for a computer has a first set of functions when the multi-functional device is inserted into the computer and a second set of functions when removed from the computer.

Storage and entertainment devices include video players, DVD players, VCRs, audio players, MP3 players, CD players, radios, tape players, video recorders, cameras, audio recorders, computers, personal digital assistants and televisions, among many others. Some "stand-alone" devices can be connected to a computer system for uploading and/or downloading of content (e.g. entertainment, software, games, data, images, audio, video, etc.) to be played by the stand-alone devices or by the computer system. A cable makes the physical connection between the stand-alone device and the computer system. The stand-alone device, thus, is kept external to the computer system.
Since the stand-alone device is external to the computer system, the stand-alone device occupies a portion of a user's limited workspace. Furthermore, the length of the cable may limit placement of the stand-alone device with respect to the computer. Additionally, when carried with a notebook computer, the stand-alone device and cable are additional items that the user must carry. Carrying the stand-alone device and the cable may be cumbersome, especially if space is limited in a carrying case.
Some computer systems have a built-in storage or entertainment device, such as a CD/DVD player or TV tuner. Thus, the inconvenience of having to make room for and keep up with a separate item is avoided. However, the size and portability advantages of using a compact, stand-alone, lightweight device are lost.

Hewlett-Packard Development Company, L.P.