A low inductance magnetic write head is provided with first and second pole piece layers that have first ends separated by a write gap layer and second ends connected together at a back gap. An insulation stack is provided which is sandwiched between the first and second pole piece layers. A write coil layer and a second coil layer are provided wherein each coil layer has inner and outer ends. The coil layers wind in the same direction from their inner ends to their outer ends. Each of the coil layers has first and second layer portions. The first layer portion of the write coil layer is embedded in the insulation stack. The second pole piece layer is sandwiched between the first portion of the write coil and a non-magnetic layer and the first non-magnetic layer is sandwiched between the second pole piece layer and the first portion of the second coil layer. The inner ends of the coil layers are electrically connected and the outer ends of the coil layers are electrically connected to a write current source so that when the write current source is introduced write fluxes from the coil layers are in opposition. The first layer portion of the second coil layer has a turn density that is less than a turn density of the first layer portion of the write coil layer.

1. Field of the Invention
The present invention relates to a write head with counter current coil layers, and more particularly to a write head with first and second coil layers where the first coil layer is a write coil layer adjacent one side of a second pole piece layer and the second coil layer opposes the write coil layer on an opposite side of the second pole piece layer.
2. Description of the Related Art
A write head is typically combined with a magnetoresistive (MR) read head to form a merged MR head. A merged MR head may have thin film layers with edges that are exposed at an air bearing surface (ABS) for writing and receiving magnetic fields on a magnetic medium, such as a disk or tape drive. In a merged MR head, the write head comprises first and second pole piece layers connected at a back gap that is recessed from the ABS. Each of the first and second pole piece layers has a pole tip, a yoke and a back gap, with the yoke being located between the pole tip and the back gap. The pole tips, which may be referred to as first and second pole tips, terminate at the ABS. An insulation stack, which comprises a plurality of insulation layers, is sandwiched between the yoke portions of the first and second pole piece layers and a write coil layer is embedded in the insulation stack. A processing circuit is connected to the write coil layer for conducting a write current through the coil layer, which, in turn, induces magnetic flux in the first and second pole piece layers. A non-magnetic gap layer is sandwiched between the first and second pole tips so that magnetic flux in the first and second pole tips fringes across the gap layer at the ABS to create write fields.
In a magnetic disk drive a magnetic disk is rotated adjacent to and a short distance from the ABS so that the write fields magnetize the disk along circular tracks. The written circular tracks then contain magnetized segments with fields detectable by a read head.
An MR read head includes an MR sensor sandwiched between first and second non-magnetic gap layers and having an edge located at the ABS. The first and second gap layers and the MR sensor are sandwiched between first and second shield layers. In a merged MR head, the second shield layer and the first pole piece are a common layer. The MR sensor detects magnetic fields from the circular tracks of the rotating disk by a resistance change that corresponds to the strengths of the fields. A sense current conducted through the MR sensor results in voltage changes received by the processing circuitry as readback signals.
One or more merged MR heads may be employed in a magnetic disk drive for reading and writing information on circular tracks of a rotating disk. A merged MR head is mounted on a slider carried on a suspension. The suspension is mounted to an actuator which rotates the magnetic head to locations corresponding to desired tracks. As the disk rotates an air cushion is generated between the rotating disk and the ABS of the slider. A force of the air cushion against the ABS is opposed by an opposite loading force produced by the suspension, causing the magnetic head to be suspended a slight distance (flying height) from the surface of the disk. Flying heights are typically on the order of about 0.05 .mu.m.
A high data rate is desirable for high performance write heads. Data is written by the write head as field signals into the rotating disk. A high data rate increases the density of information recorded on the rotating disk. In digital recording, the circuit supplying write current to the write head is required to switch at a high rate to produce positive and negative field signals. The quicker the switching, the higher the data rate. Unfortunately the write current circuit's inductance limits the data rate. Furthermore high inductance requires a higher write circuit voltage. This decreases battery life of portable computers, and requires a thick write head coil to dissipate heat. A thicker coil increases the height of the write head in the yoke region, which increases the aspect ratio of a photolithography photoresist step employed for patterning the second pole tip. The aspect ratio is the ratio between the thickness of the photoresist in the pole tip region and the track width of the second pole tip. High aspect ratios result in poorly formed second pole tips.
The write coil layer is designed to have a certain turn density, pitch, spacing between the coil turns, thickness and overall diameter. Turn density is the number of coil turns per width across the coil. Pitch is the distance from the beginning of one coil turn to the beginning of an adjacent coil turn, as measured across the width of the coil and thickness is the thickness of the coil layer. The pole piece layers function as a core with respect to the write coil since they conduct the flux generated by the write coil. Upon energizing the write coil with write current, each coil turn generates flux that encircles the turn. Between first and second adjacent turns, the first turn generates flux in one direction in the space between the turns and the second turn generates flux in an opposite direction in the space between the turns. Consequently, flux from adjacent turns is cancelled in the space between the turns. However, flux from the turns above and below the coil layer combines to travel in one of two directions about the write coil layer, depending upon the polarity of the write current. Accordingly, flux about the coil layer is induced into each of the first and second pole piece layers, thereby providing write fields at the write gap.
It should be understood that the first and second pole pieces contribute to the inductance of the write current circuit. The inductance of this ferromagnetic circuit is proportional to the amount of flux conducted through it. This inductance is necessary because the ferromagnetic circuit will not work without the pole piece layers. However, there is also a certain amount of flux beyond the first and second pole piece layers that returns through the coil. This flux, known as "coil flux", is typically modelled as a parasitic inductance of the ferromagnetic circuit. The magnitude of this parasitic inductance is related to the amount of flux that travels through ferromagnetic material, such as the first pole piece layer beyond the ferromagnetic circuit or the first shield layer of the read head below the first pole piece. The magnitude of this parasitic inductance is also related to the pitch or the diameter of the write coil. However, reduction of the pitch or diameter increases the difficulty of manufacturing the write coil. If this parasitic inductance could be reduced, the frequency response of the write circuit could be increased to increase the data rate, the magnitude of the write current could be decreased to conserve power and reduce heat, the thickness of the write coil could be decreased, while pitch or diameter of the coil could be increased to promote manufacturability, and the first shield layer and the first pole piece layer could be extended beyond the back gap region to promote planarity of the head.

Write head with second coil above pole having coil density less electrically connected first coil below the pole

International Business Machines Corporation


A method of fabricating a dual-oxide STI comprising the following steps. A structure having an STI opening formed therein is provided. An HDP silicon oxide layer portion is formed within the STI opening, partially filling the STI opening. A planarized HDP silicon-rich-oxide cap layer is formed upon the HDP silicon oxide layer portion, filling the STI opening to form the dual-oxide STI, whereby any unlanded contact window formed through an overlying interlevel dielectric layer exposing a portion of the dual-oxide STI only exposes a portion of the HDP silicon-rich-oxide cap layer.

The present invention relates generally to semiconductor fabrication and more specifically to fabrication of shallow trench isolation (STI) structures.
After formation of conventional shallow trench isolation structures (STIs), if the subsequent contact photolithography process is misaligned to the OD (active region) layer, the contact etch may attack the STI profile and induce leakage issues.
U.S. Pat. No. 6,297,128 B1 to Kim et al. describes an STI trench filled with multiple layers including high density plasma (HDP) oxide.
U.S. Pat. No. 6,100,160 to Hames describes an STI process using HDP oxide and a nitration step.
U.S. Pat. No. 5,930,645 to Lyons et al. describes an STI process using HDP oxide.
U.S. Pat. No. 6,306,725 to Nag et al. describes an STI trench filled with two layers including HDP oxide.
Accordingly, it is an object of one or more embodiments of the present invention to provide an STI structure that minimizes the deleterious effects of unlanded contact windows.
Other objects will appear hereinafter.
It has now been discovered that the above and other objects of the present invention may be accomplished in the following manner. Specifically, a structure having an STI opening formed therein is provided. An HDP silicon oxide layer portion is formed within the STI opening, partially filling the STI opening. A planarized HDP silicon-rich-oxide cap layer is formed upon the HDP silicon oxide layer portion, filling the STI opening to form the dual-oxide STI, whereby any unlanded contact window formed through an overlying interlevel dielectric layer exposing a portion of the dual-oxide STI only exposes a portion of the HDP silicon-rich-oxide cap layer.

Shallow trench isolation (STI) module to improve contact etch process window

Taiwan Semiconductor Manufacturing Company


Embodiments of the present invention are directed to porous materials for use in solid phase extractions and chromatography. The materials feature at least one hydrophobic component, at least one hydrophilic component and at least one ion-exchange functional group. The materials exhibit superior wetting and ion-exchange performance.

Solid phase extraction (SPE) is a chromatographic technique that is widely used, e.g., for preconcentration and cleanup of analytical samples, for purification of various chemicals, and for removal of toxic or valuable substances from aqueous solutions. SPE is usually performed using a column or cartridge containing an appropriate material or sorbent. SPE procedures have been developed using sorbents that can interact with analytes by hydrophobic, ion-exchange, chelation, sorption, and other mechanisms, to bind and remove the analytes from fluids.
Because different SPE applications can require different sorbents, there is a need for sorbents with novel properties that have unique selectivities. These include superior wetting characteristics, selective capture of analytes of interest, and non-retention of interfering analytes. Sorbents comprising porous particles having the aforementioned properties are described in WO 99/64480 and in U.S. Pat. No. 6,322,695B1.
However, a problem associated with porous particles is the passage or leaching of particles through the retaining frit of the separation device into the sample of interest. In addition to contamination of the sample, the passed particles can further negatively impact test methods and the HPLC systems that are used to test the samples. For example, the particles may clog or block in line filters or column frits which in turn lead to high system backpressures and ultimately HPLC pump shutdown.
Monolith materials have been developed in an attempt to overcome the problem of particle passage or leaching through frits. These include polymeric monoliths such as polymethacrylate monoliths (U.S. Pat. No. 5,453,185, U.S. Pat. No. 5,728,457); polystyrene-DVB monoliths (U.S. Pat. No. 4,889,632, U.S. Pat. No. 4,923,610, U.S. Pat. No. 4,952,349); charge incorporated polymethacrylate monoliths for the application of reversed-phase ion-pairing chromatography (U.S. Pat. No. 6,238,565); monoliths based on ROMP metathesis (WO 00073782); and (EP 852334) continuous monolith columns made from water-soluble polymerizable monomers, such as vinyl, allyl, acrylic and methacrylic compounds, without porogens but in the presence of high concentration of inorganic salts such as ammonium sulfate.
Polymeric monoliths are chemically stable against strongly alkaline and strongly acidic mobile phases, allowing flexibility in the choice of mobile phase pH. However, the prior art monoliths do not necessarily provide the unique selectivities and advantages that are needed for a variety of chromatographic applications, in particular SPE applications.

Porous materials for solid phase extraction and chromatography and processes for preparation and use thereof


The present invention relates to relay supported wireless communication to enhance communication performance. In the wireless communication system according to the invention neighboring relay stations are arranged with substantially overlapping coverage. In the method according to the invention mobile stations makes soft association to relay stations. The mobile stations feed back the selection of relay stations and channel quality measures to the base station. The base station adapts the transmission to the relay stations based on each mobile stations reported soft associations and channel quality measures. In this way the control signaling to and from the relay stations can be very limited.

A main striving force in the development of wireless/cellular communication networks and systems is to provide, apart from many other aspects, increased coverage or support of higher data rate, or a combination of both. At the same time, the cost aspect of building and maintaining the system is of great importance and is expected to become even more so in the future.
Until recently the main topology of wireless networks has been fairly unchanged, including the three existing generations of cellular networks. The topology characterized by the cellular architecture with the fixed radio base stations and the mobile stations as the transmitting and receiving entities in the networks, wherein a communication typically only involves these two entities. An alternative approach to networks are exemplified by the well-known multihop networks, wherein typically, in a wireless scenario, a communication involves a plurality of transmitting and receiving entities in a relaying configuration. Such systems offer possibilities of significantly reduced path loss between communicating (relay) entities, which may benefit the end-to-end (ETE) users.
Attention has recently been given to another type of topology that has many features and advantages in common with the multihop networks but is limited to relaying in only two (or a few) hop. In contrast to multihop networks, aforementioned topology exploits aspects of parallelism and also adopts themes from advanced antenna systems. These networks, utilizing the new type of topology, have cooperation among multiple stations as a common denominator. In recent research literature, it goes under several names, such as cooperative relaying, cooperative diversity, cooperative coding, virtual antenna arrays, etc. In the present application the terms "cooperative relaying" and "cooperative schemes/methods" is meant to encompass all systems and networks utilizing cooperation among multiple stations and the schemes/methods used in these systems, respectively. A comprehensive overview of cooperative communication schemes is given in [1]. Various formats of a relayed signal may be deployed. A signal may be decoded, re-modulated and forwarded, or alternatively simply amplified and forwarded. The former is known as decode-and-forward or regenerative relaying, whereas the latter is known as amplify-and-forward, or non-regenerative relaying. Both regenerative and non-regenerative relaying is well known, e.g. by traditional multihopping and repeater solutions respectively. Various aspects of the two approaches are addressed in [2]. The relays may forward the signal in essentially two ways; relaying the signal on the same resource or changing to another channel, e.g. in time or frequency. In the first case, a challenge is to overcome the coupling between the relay transmission and reception. This may be handled by using two antennas, and interference cancellation techniques. In the second case, the relay may simply receive the signal, and then forward it in the next slot or alternatively on another frequency band concurrently as receiving the signal.
The general benefits of cooperative relaying in wireless communication includes higher data rates, reduced outage (due to different forms of diversity), increased battery life, and extended coverage.
Various schemes and topologies utilizing cooperative relaying has been suggested, as theoretical models within the area of information theory, as suggestions for actual networks and in a few cases as laboratory test systems, for example. Examples are found in [1] pages 37-39, 41-44. The various cooperation schemes may be divided based on which entities have data to send, to which and which entities that cooperates. In FIGS. 1a-f (prior art) different topologies are schematically illustrated, showing where traffic is generated, which entity being the receiver and the path for radio transmissions.
The classical relay channel, illustrated in FIG. 1a, consists of a source that wishes to communicate with a destination through the use of relays. The relay receives the signal transmitted by the source through a noisy channel, processes it and forwards it to the destination. The destination observes a superposition of the source and the relay transmission. The relay does not have any information to send; hence the goal of the relay is to maximize the total rate of information flow from the source to the destination. The classical relay channel has been studied in [1], [7] and in [3] where receiver diversity was incorporated in the latter. The classical relay channel, in its three-station form, does not exploit multiple relay stations at all, and hence does not provide the advantages stated above.
A more promising approach, parallel relay channel, is schematically illustrated in FIG. 1b, wherein a wireless systems employing repeaters (such as cellular basestation with supporting repeaters) with overlapping coverage, a receiver may benefit of using super-positioned signals received from multiple repeaters. This is something that happens automatically in systems when repeaters are located closely and transmit with sufficiently large power. Recently, information theoretical studies have addressed this case, for example by Schein, [4] and [5], who suggest the use of coherent combining based cooperative relaying between a single sender and a single receiver using two intermediate relays. The study is purely an information theoretical analysis, limited to only two relay stations, and lacks the means and mechanisms to make the method practically feasible.
The concept of Multiple-access Channel with Relaying (a.k.a. as Multiple access channels with generalized feedback), schematically illustrated in FIG. 1c, has recently been investigated. The concept involves that two users cooperate, i.e. exchange the information each wants to transmit, and subsequently each user sends not just its own information but also the other users information to one receiver. The benefit in doing so is that cooperation provides diversity gain. There are essentially two schemes that have been investigated; cooperative diversity and coded cooperative diversity. Studies are reported in [1], for example. With respect to diversity, various forms has bee suggested, such as Alamouti diversity, receiver diversity, coherent combining based diversity. Typically the investigated schemes and topologies rely on decoding data prior to transmission. This further means that stations has to be closely located to cooperate, and therefore exclude cooperation with more distant relays, as well as the large number of potential relays if a large scale group could be formed. An additional shortcoming of those schemes is that is fairly unlikely having closely located and concurrently transmitting stations. These shortcomings indicates that the investigated topology are of less practical interest. The broadcast channel with relaying, illustrated in FIG. 1d, is essentially the reverse of the topology depicted in FIG. 1c, and therefore shares the same severe shortcomings.
A further extension of the topology depicted in FIG. 1c is the so-called interference channel with relaying, which is illustrated in FIG. 1e, wherein two receivers are considered. This has e.g. been studied in [8] and [1] but without cooperation between the receivers, and hence not exploiting the possibilities possibly afforded by cooperative relaying.
Another reported topology, schematically illustrated in FIG. 1f, is sometimes referred to as Virtual Antenna Array Channel, and described in for example [9]. In this concept, significant bandwidth expansion between a communicating station and adjacent relay nodes is assumed, and hence non-interfering signals can be transferred over orthogonal resources that allows for phase and amplitude information to be retained. With this architecture, MIMO (Multiple Input Multiple Output) communication (but also other space-time coding methods) is enabled with a single antenna receiver. The topology may equivalently be used for transmission. A general assumption is that relay stations are close to the receiver (or transmitter). This limits the probability to find a relay as well as the total number of possible relays that may be used. A significant practical limitation is that very large bandwidth expansion is needed to relay signals over non-interfering channels to the receiver for processing.
As realized by the skilled in the art real system implementations utilizing cooperative relaying needs control mechanisms for controlling the involved relay stations. The need of control arises primarily due to the mobility of the mobile stations and resulting topology changes and may for example include relay activation and deactivation. The need for control mechanisms is schematically illustrated in FIG. 2, wherein a moving mobile station 220 is communicating via the relay stations 215:1 and 215:2 at time T1 and the relay stations 215:2, 215:3 and 215:4 at time T2.
The control procedures are not fully described in the prior art mentioned above. However, it is indicated, for example in the case described with reference to FIG. 1f, that control messages are exchanged to and from the relay stations directed both to and from the base station and the users. Similar control structure is also disclosed in [11], wherein at least one control terminal is identified, which instructs the relay stations to receive and relay data.
The proposed control mechanism may cause the amount of control data to be excessive, especially when topology changes frequently due to that the mobile user moves fast and has to control the relays transmit parameters (e.g. power) or change relays frequently. In addition, even if topology does not change, the changes in radio propagation can be considerable and dictate fast control message exchange towards the relays. An excessive control signalling consumes radio resources that preferably could have been used for transmitting data.
A further problem that is not addressed in the prior art is how to employ session or user centric control of the relays when multiple receivers are present as they may have conflicting optimal relay configurations and parameters settings. The optimality may differ with respect to which relay is active, transmit power levels, channel assignments, space time coding options and phase adjustment etcetera used. A situation which may give arise to conflicting relay configurations and parameters settings is schematically illustrated in FIG. 3, wherein two mobile stations 320:1 and 320:2 are both communicating partly via the same relay station 315:2. The relay station 315:2 may in this scenario experience conflicting demands from the mobile stations 320:1 and 320:2. The optimization problem of finding an optimal, or close to optimal, configuration for a set of users, will, even if only a few users with potentially conflicting optimal configuration are considered, soon become very complicated and time consuming, or even in practise unmanageable.
Thus, it is in the art demonstrated that cooperative relaying has great potentials in providing for example high capacity and flexibility. However, the in the prior art proposed control mechanisms do not represent solutions that are possible to implement in realistic large-scale networks and do not take full advantage of the anticipated advantages of a network with cooperative relaying.

Method and system for wireless communication networks using cooperative relaying


A cutting apparatus for sheet material, such as a power transmission belt molding pad, which cutting apparatus has a first structure for supporting a sheet material, a second structure for engaging and advancing the sheet material on the first structure to a predetermined cutting position, and structure for guidingly cutting the sheet material in the cutting position.

1. Field of the Invention
This invention relates to power transmission belts and, more particularly, to an apparatus for quickly, accurately, and automatically cutting a sheet material of the type that can be used to define a mold element, such as a molding pad for producing cogged power transmission belts. The invention further contemplates a method of cutting a rubber sheet material using the inventive apparatus.
2. Background Art
Power transmission belts are known in which cogs are spaced at regular or irregular intervals along the length of the belt. These cogged belts, which are normally "raw edge" belts, may be formed by different processes, among which are the "preform" or "spancog" processes. In the conventional preformed process, a fabric layer and an unvulcanized rubber sheet are applied in turn against a mold that has alternating cogs and notches. The laminated sheet and fabric layers are pressed against the mold to conform thereto and define a cogged mold pad. The preformed cogged pad is then wrapped around a cylindrical core on a molding drum. The ends of the cogged pad are each cut in a straight line and abutted together to define an endless, cylindrical configuration around the core. A belt sleeve can then be formed by sequentially wrapping components around the pad.
To consistently define a high quality cogged pad, it is important to precisely precut the pad so that the ends thereof can be closely matched when butted. Typically, the cogged pad is spread out and marked to be cut to the appropriate length. An experienced operator will count the cogs and make a mark, as with chalk, on the cog to be cut. The operator then manually severs the pad with a cutter along the marked cog to define one butt end of the pad. The other pad end is defined in similar fashion.
Proper pad formation requires that the butt ends of the pad be cut so as not only to be straight in a transverse direction, but so that the end thicknesses precisely match when the ends are joined. If the matching is imprecise in terms of the straightness, thickness or angle of the butt edges, an inferior or incomplete joint may result between the butt ends. For example, if the pad is not cut precisely at the cog top, the edge thicknesses will not match. A gap may also form in a worse case, causing a volume crack and resulting in a failed joint. A belt made with the defective pad may develop a crack at the location of the joint as a result of load fluctuation or heat generation as the belt is running.

Method and apparatus for cutting a rubber sheet material used to form power transmission belts


An apparatus and method for sealing the barrel of an underwater gun between firings is disclosed. The apparatus clears the barrel and/or prevents water from entering the barrel based on pressure variations.

Underwater guns are useful as anti-mine and anti-torpedo devices. Recently, autonomous underwater vehicles (AUVs) have been fitted with underwater guns for torpedo defense and underwater "hunter-killer" CONOPs.
A gun, especially one with a high muzzle velocity, cannot be fired when water is in its barrel. If a firing where to incur in a water-filled barrel, a very high breach pressure would result as the ignited propellant charge forces (or tries to force) the water out of the barrel. The likely result would be material failure of the barrel.
The prior art is replete with approaches for waterproofing the barrel of an underwater gun, or for clearing water from its barrel before firing. U.S. Pat. No. 5,639,982 discloses a means for firing a fully automatic gun underwater using a blank barrel-clearance round. Blank barrel-clearance rounds are alternated with live rounds of ammunition. To begin the process, a blank barrel-clearance round is first detonated. This creates gas and steam within the chamber that forms a bubble at the muzzle end of the barrel, thereby displacing water from the chamber. A live round is then immediately fired. The process is repeated, whereby the subsequent detonation of a blank barrel-clearance round displaces any water that has re-entered the barrel subsequent to the firing of the live round.
U.S. Pat. No. 5,648,631 discloses a spooled tape seal for sealing the barrel of an underwater gun. The system includes a tap that covers the opening of the gun barrel and sprockets for advancing the tape across the opening. Hydrostatic pressure keeps the tape pressed to the end of the barrel to create an effective seal. When a bullet is fired, it perforates the tape. During this brief period of egress, the exhaust gases from combustion of the propellant charge keep water from entering the barrel. Almost immediately, a non-perforated portion of the tape is advanced by the sprockets to cover the barrel opening. External hydrostatic pressure re-seats the tape, thereby preventing water from entering the barrel.
U.S. Pat. No. 5,687,501 discloses a sealing plate for providing a watertight seal for a multi- or single-barreled underwater gun. The sealing plate provides one or more firing apertures in an otherwise solid surface. Between firings, the gun muzzle is sealed by a solid surface of the sealing plate. To fire a bullet, the sealing plate or muzzle rotates to align the gun muzzle with one of the firing apertures. This permits unimpeded egress. After the bullet fires, the plate or muzzle again rotates so that a solid portion of the sealing plate covers the muzzle.
These are but a few of the many patents pertaining to various aspects of underwater gun design in general, and to the water-in-the-barrel problem, in particular. Notwithstanding the many approaches to the problem, no truly satisfactory approach has been developed for keeping water out of the barrel of an underwater gun between and during operation.

Underwater gun comprising a passive fluidic barrel seal


A multi-antenna system includes an antenna part and a cable part. The antenna part includes comprising antenna lines forming antenna elements. The cable part includes a feeding lines for the antenna elements. Both the antenna part and the cable part are implemented using a flexible printed circuit board. The antenna part includes a single conductor layer area. The cable part includes a three conductor layer area.

A multi-antenna system uses multiple antenna elements or antenna patterns that are often placed in an apparatus in an organized way. The antenna elements are sometimes separated from each other by certain distances based on various specifications associated with, for example, gain of an antenna array, beam steering properties, isolation between elements, envelope correlation coefficient, etc. Further, each antenna element usually has its own feeding line.
Micro coaxial cables may be used as feeding lines to connect the antenna elements to radio frequency (RF) electronics. If there are multiple antennas in an apparatus, the number of cables is usually the same as the number of antenna elements. This leads to a complex antenna element and micro coaxial cable arrangement with several interconnections. This would also consume a lot of space, as well as sets challenges to manufacturability and final assembly.


A template-free reverse micelle (RM) based method is used to synthesize pyrochlore nanostructures having photocatalytic activity. In one embodiment, the method includes separately mixing together a first acid stabilized aqueous solution including pyrochlore precursor A and a second acid stabilized aqueous solution including pyrochlore precursor B with an organic solution including a surfactant to form an oil-in-water emulsion. Next, equimolar solutions of the first and second acid stabilized oil-in-water emulsions are mixed together. Then, the mixture of the first and second acid stabilized oil-in-water emulsion is treated with a base to produce a precipitate including pyrochlore precursors A and B. After which, the precipitate is dried to remove volatiles. The precipitate is then calcined in the presence of oxygen to form a pyrochlore nanostructure, such as a bismuth titanate (Bi2Ti2O7) pyrochlore nanorod. The method of synthesizing the pyrochlore nanorod is template-free.

Photocatalytic hydrogen production is a possible answer to the present energy crisis. However, efficient hydrogen production requires the development of materials that demonstrate tunable optical response, have UV-visible activity, and are amenable to synthesis using simple methods. Metal oxides, mainly titanium dioxide (TiO2), have been studied for photocatalytic applications. Fujishima et al., Nature 1972, 238, 37; Hoffmann et al., Chem. Rev. 1995, 95, 69. However, decades of work with TiO2, such as to improve its properties via doping and addition of other photoactive materials, has demonstrated only incremental improvements. Martyanov et al., Chem. Commun., 2004, 2476; Anpo et al., J. Catal., 2003, 216, 505.
Pyrochlores (A2B2O7) are a lesser studied family of compounds that offer the flexibility to tune photocatalytic properties. Bismuth titanate (BTO), Bi2Ti2O7, is a photoactive member of the pyrochlore family that can potentially meet the aforementioned objectives desired of a photocatalyst. However, the full potential of this photocatalyst for hydrogen generation has not yet been fully exploited, which is partially because attempts to synthesize and characterize stoichiometric BTO pyrochlore are far and few. The earlier adopted synthesis methods have not always resulted in a pure pyrochlore phase. Yao et al., Appl. Catal. B Environ. 2004, 52, 109; Yao et al., Appl. Catal. A. Gen. 2003, 243, 185; Yao et al., J. Mol. Catal. A. 2003, 198, 343. For example, Radosavljevic et al. reported a method that resulted in a Bi—Ti—O composition of the form Bi1.74Ti2O6.62. Radosavljevic et al., J. Solid State Chem. 1998, 136, 63. Hector and Wiggin reported the synthesis and structural study of stoichiometric BTO along with some impurities of Bi4Ti3O12 using a co-precipitation method. Hector et al., J. Solid State Chem. 2004, 177, 139.
Recently, attempts to prepare stable crystalline BTO with a nanotube structure using anodized alumina as a template have been reported. Zhou et al., J. Mater. Res. 2006, 21, 2941. A template method, however, requires template removal, which is an additional step. To synthesize these materials economically on a large scale requires the development of a template-free method.
Accordingly, a need exists for new template-free methods of synthesizing pyrochlore nanostructures, such as pyrochlore nanorods.

Synthesis of pyrochlore nanostructures and uses thereof

Board of Regents of the Nevada System of Higher Education, on Behalf of the University of Nevada, Reno


A telescopic hanging rack structure. The structure includes a first bar, a second bar and a coupling unit. The outer faces of the first and second bars are formed with axial locating ribs which are cut with multiple notches at equal intervals. The outer ends of the first and second bars are connected with hanging hooks via circular adapters. The coupling unit includes left and right casings mated and locked with each other by screws. The inner wall faces of the left and right casings are respectively formed with two-stage recesses with different curvatures, such that after the first and second bars are fitted with each other, the first and second bars are firmly inserted and located in the left and right casings.

The present invention is related to a telescopic hanging rack structure which can be easily adjusted in. length for conveniently hanging articles thereon.
A conventional hanging hook or U-shaped rack with fixed length is used to hang a clothes or towel thereon. Also, a conventional telescopic hanging rack composed of two bars is used to hang articles thereon.
However, the articles can be hardly reliably hung on the above hanging hook, U-shaped rack or telescopic hanging rack and are likely to drop therefrom, especially when the hanging rack is placed in a moving object such as a car. The hung articles often drop due to swinging. Moreover, it is hard to mount the conventional telescopic hanging rack on the car.
It is therefore a primary object of the present invention to provide a telescopic hanging rack composed of a first bar, a second bar nested in the first bar and a coupling unit for firmly coupling the first and second bars. A press member is disposed in the coupling member. When adjusting the length of the telescopic hanging rack, the press member can be easily pressed and then resiliently restore. An engaging plate is disposed in the coupling unit for preventing the first and second bars from departing from each other due to over-pulling.
It is a further object of the present invention to provide the above telescopic hanging rack in which the first and second bars are formed with locating ribs cut with notches for adjustably fixing the hanging rack at a certain length. In addition, the notches restrict the articles hung on the hanging rack, whereby the articles can be tidily hung and are prevented from displacing or dropping due to swinging.
The present invention can be best understood through the following description and accompanying drawings wherein:


An adaptive filter suitable for fabrication on an RF integrated circuit and used for transmit (TX) leakage rejection in a wireless full-duplex communication system is described. The adaptive filter includes a summer and an adaptive estimator. The summer receives an input signal having a TX leakage signal and an estimator signal having an estimate of the TX leakage signal, subtracts the estimator signal from the input signal, and provides an output signal having the TX leakage signal attenuated. The adaptive estimator receives the output signal and a reference signal having a version of the transmit signal, estimates the TX leakage signal in the input signal based on the output signal and the reference signal, and provides the estimator signal. The adaptive estimator may utilize an LMS algorithm to minimize a mean square error between the TX leakage signal in the input signal and the TX leakage signal estimate in the estimator signal.

I. Field
The present invention relates generally to electronics, and more specifically to techniques for mitigating the deleterious effects of a transmit (TX) leakage signal in a wireless full-duplex communication system.
II. Background
A wireless device in a wireless full-duplex communication system can simultaneously transmit and receive data for two-way communication. One such full-duplex system is a Code Division Multiple Access (CDMA) system. On the transmit path, a transmitter within the wireless device (1) modulates data onto a radio frequency (RF) carrier signal to generate an RF modulated signal and (2) amplifies the RF modulated signal to obtain a transmit signal having the proper signal level. The transmit signal is routed via a duplexer and transmitted from an antenna to one or more base stations. On the receive path, a receiver within the wireless device (1) obtains a received signal via the antenna and duplexer and (2) amplifies, filters, and frequency downconverts the received signal to obtain baseband signals, which are further processed to recover data transmitted by the base station(s).
For a full-duplex wireless device, the RF circuitry in the receiver is often subjected to interference from the transmitter. For example, a portion of the transmit signal typically leaks from the duplexer to the receiver, and the leaked signal (which is commonly referred to as a "TX leakage" signal or a "TX feed-through" signal) may cause interference to a desired signal within the received signal. Since the transmit signal and the desired signal typically reside in two different frequency bands, the TX leakage signal can normally be filtered out and does not pose a problem in itself. However, the TX leakage signal may interact with a "jammer" (which is a large amplitude undesired signal close in frequency to the desired signal) to generate "cross modulation" distortion components on both sides of the jammer, as described below. Distortion components that fall within the signal band of the desired signal and which are not filtered out act as additional noise that may degrade performance.
A surface acoustic wave (SAW) filter is often used to filter out the TX leakage signal and mitigate its deleterious effects. The use of a SAW filter for TX leakage rejection is undesirable for several reasons. First, the SAW filter is normally a discrete component that is not fabricated on an RF integrated circuit (RFIC) and thus occupies space on a circuit board. Second, the SAW filter typically requires other discrete components for input and output impedance matching. Third, the SAW filter and its impedance matching circuitry increase the cost of the wireless device.
There is therefore a need in the art for techniques to mitigate the deleterious effects of a TX leakage signal without using a SAW filter.

Adaptive filter for transmit leakage signal rejection


A method for treating patients in need of percutaneous transluminal coronary angioplasty which comprises administering nonionic contract media to the patient and treating the patient with a fibrinogen receptor antagonist.

Angioplasty procedures are commonly performed on patients having coronary blockages. An estimated 2 million coronary angiographic procedures are performed annually in the United States alone. The objective of angioplasty procedures is to revascularize the coronary artery where the blockage is located. By inflating a balloon at the point of blockage, blood flow is restored.
Contrast dye is used to initially identify the presence and location of the blockage. It is also used during the procedure to provide an image for proper placement of the guide wire, catheter, and angioplasty balloon.
There are key differences among radiographic contrast media. Ionic contrast media are far less expensive than nonionic contrast media. However, ionic contrast media are associated with several infrequent side effects of modest clinical significance including nausea, vomiting and allergic reactions. Bradycardia, abnormalities in repolarization manifest by ST segment and T wave alterations, depression of ventricular systolic function and lowering of systolic blood pressure occur commonly with ionic contrast media but last only seconds.
The side effects associated with ionic contrast media are rare with nonionic contrast agents. However, reports of thrombotic events occurring during routine angiography with nonionic media suggest that nonionic media may be a procoagulant (Grollman et al., Cathet. Cardiovasc. Diagn. (1988) vol. 14 pp. 159-64 and Hwang et al., Cathet. Cardiovasc. Diagn. (1989) vol. 16 pp. 209-13). Studies of percutaneous coronary interventions (which are inherently associated with a heightened risk of intracoronary thrombus formation) have reported increased thrombus formation with nonionic contrast agent use (Doorey ey al., Clin. Cardiol. (1992) vol. 15 pp. 117-20 and Gasperetti et al., J. Am. Coll. Cardiol. (1991) vol. 18 pp. 443-50). Grines et al., JACC (1996) vol. 27, no. 6 pp. 1381-6 conclude that in patients with unstable ischemic syndromes undergoing coronary angioplasty, the use of ionic low osmolality contrast media reduces the risk of ischemic complications acutely and at 1 month after the procedure. Grines et al. recommend that ionic media be strongly considered when performing interventions in patients with unstable angina or myocardial infarction.
It is known that acute or abrupt closure occurs in 2-8% of patients undergoing percutaneous transluminal coronary angioplasty and accounts for most of the short-term morbidity and mortality associated with the procedure. In about 75% of patients with abrupt closure, it occurs within minutes after percutaneous transluminal coronary angioplasty, when they are still in the catheterization laboratory. In the other 25%, it usually occurs within 24 hours after the procedure (Landau et al. New England Journal of Medicine vol. 330 No. 14 p. 986 (1994)).
Glycoprotein IIb/IIIa Fibrinogen Binding Inhibitors
Fibrinogen receptor antagonists, which inhibit the binding of fibrinogen to the glycoprotein IIb/IIIa (.alpha.II.beta.3) platelet receptor site, may be administered during and following angioplasty procedures to reduce the risk of ischemic events. Because the period of time following angioplasty procedures is associated with a higher level of coronary ischemic events, fibrinogen receptor antagonists are administered following angioplasty to inhibit fibrinogen binding to the glycoprotein IIb/IIIa platelet receptor site, reducing the level of ischemic events.
Integrelin is a cyclic peptide that is based on the KGD sequence in the snake venom protein barbourin. It inhibits ligand binding to glycoprotein IIb/IIIa. Among the non-peptide compounds are Ro 44-9883 and MK-383, which are administered intravenously, and are also selective for glycoprotein IIb/IIIa. Orally active agents include SC54684, which is a prodrug (i.e., it requires biotransformation in vivo to its active form) with high oral bioavailability and RO43-8857, GR144053, and DMP728, which are themselves the active inhibitors. Literally thousands of other compounds have been synthesized in an attempt to obtain optimal potency, metabolic stability, receptor specificity, and favorable intravascular survival. Despite variations in these compounds, virtually of all of them retain the basic charge relations of the RGD sequence with a positive charge separated from a negative charge by approximately 10-20 .ANG.. All of these compounds inhibit fibrinogen binding to the glycoprotein IIb/IIIa platelet receptor site. Monoclonal antibody 7E3 also blocks the glycoprotein IIb/IIIa receptor.
We have now found that angioplasty procedures conducted with nonionic contrast media, in combination with glycoprotein IIb/IIIa receptor antagonist administration, reduce the risk of ischemic complications (follow-up intervention associated with acute coronary ischemic syndrome, e.g. coronary artery bypass grafting, repeat percutaneous intervention for acute ischemia, insertion of a coronary endovascular stent) to a greater degree than procedures involving ionic contrast media with glycoprotein IIb/IIIa receptor antagonists, procedures involving nonionic contract media without glycoprotein IIb/IIIa receptor antagonists, or procedures involving ionic contrast media without glycoprotein IIb/IIIa receptor antagonists.

Angioplasty procedure using nonionic contrast media


The invention relates to a modified electronic amplifier of the push/pull configuration. The difference being that only one signal (as apposed to two signals 180 degrees out of phase) is needed to drive the amplifier, the distortion in the nonlinear region is asymmetrical, and a feedback signal is used which automatically compensates for differences between the two active elements (tubes or transistors) that comprise the push/pull amplifier.

For the past 20 years, people have been analyzing the difference between tubes and transistors, this has been particularly true in the audio world. The primary difference between the two has to do with how they operate in the nonlinear region. Tubes tend to distort in an asymmetrical manner (relative to the Q or operating point), and transistors tend to distort in a more symmetrical manner with respect to the Q point. Herein lies the big difference. If a sine wave is input into a tube amplifier, which is operating in the nonlinear region, the output will not exhibit half wave symmetry due to the asymmetrical distortion. The bottom line of this is that even ordered harmonics will be promoted. If a sine wave is input into a transistor amplifier, operating in the nonlinear region, half wave symmetry will prevail in the output signal, due to the symmetrical distortion properties of the transistor. The bottom line of this is that odd ordered harmonics will be promoted. The even ordered harmonic generation is apparently more pleasant to the human ear, thus resulting in a big resurgence in popularity for tube amplifiers.
However, tubes can act like transistors depending on the circuit they are used in. A perfect example of this is in a classic push/pull circuit. One tube in the circuit distorts the top half of the signal, and the other tube in the circuit (operating 180 degrees out of phase) distorts the lower half of the signal in the same manner. Hence, half wave symmetry is promoted and even ordered harmonics are cancelled. Basically, symmetrical push/pull circuits cancel even ordered harmonics and promote odd ordered harmonics when driven into the nonlinear range.
The system of the present invention (a single input push/pull circuit), does exactly the opposite. It cancels odd ordered harmonics and promotes even ordered harmonics. Furthermore, it has become very desireable to match the tube pairs used in push/pull amplifiers, by performance criteria. The system of the present invention eliminates the need to match the tubes due to the feedback path in the circuit. However, high quality, high performance tubes are still recommended.
It should be known that this circuit can also be applied to transistors, or any other solid-state device that emulates the transfer characteristics of a vacuum tube. FETs (field effect transistors) act in this manner if biased correctly.
Many inventions of past address push/pull circuits but don't address the cancellation of even ordered harmonics, the matching of the active components, or the ability to drive the circuit with one signal which affords the designer the ability to apply filtering in the final (push/pull) stage without dual-ganged components.
U.S. Pat. No. 4,021,684 doesn't employ feedback in the same manner as the present invention, and creates symmetrical distortion. U.S. Pat. No. 4,987,381 is nothing more than a FET push/pull amplifier that keeps the preamp in the linear region while saturating the push/pull stage. U.S. Pat. No. 5,032,796 provides asymmetrical distortion but does not address this feature in a push/pull configuration. U.S. Pat. No. 4,710,727 generates distortion but doesn't address a push/pull configuration. Nor does it allow for feedback to compensate for the difference between components if a push/pull amplifier were used for item #305 in the diagram. U.S. Pat. No. 4,079,332 requires two inputs 180 degrees out of phase and doesn't incorporate feedback. U.S. Pat. No. 4,811,401 again is not a push/pull amplifier. U.S. Pat. No. 5,127,059 is a preamp, not a push/pull amplifier. U.S. Pat. No. 4,415,865 is a control for the quiescent current of an AB push/pull amplifier and doesn't address asymmetrical distortion. U.S. Pat. No. 4,644,289 is very similar to the present invention in that it can generate asymmetrical distortion, however, this distortion is generated in a preamp stage and it doesn't address feedback for the purpose of compensating for the difference in component performance.


A method and apparatus for determining a voltage, such as a bias voltage, supplied by an integrated circuit. A nominal terminating resistor is connected across a first and a second input/output pads from which the voltage is supplied. The voltage is measured across third and fourth pads connected, respectively, to the first and second pads. In an alternative embodiment the functionality of the third and the fourth pads is multiplexed between chip operational circuitry unrelated to the voltage to be measured and a connection to the first and second pads for measuring the voltage.

Disk drives are widely accepted as a cost effective data storage system for a computer, music player or other data processing devices. As shown in FIG. 1, a disk drive system 10 comprises a magnetic recording medium, in the form of a disk or platter 12 having a hub 13 and a magnetic read/write transducer 14, commonly referred to as a read/write head. The read/write head 14 is attached to or formed integrally with a suspension arm 15 suspended over the disk 12 and affixed to a rotary actuator arm 16. A structural arm 18, supported by a platform 20, is pivotably connected to the actuator arm 16 at a pivot joint 22. A voice coil motor 24 drives the actuator arm 16 to position the head 14 over a selected position on the disk 12.
As a spindle motor (not shown) rotates the disk 12, the moving air generated by the rotating disk in conjunction with the physical features of the suspension arm 15 lifts the read/write head 14 away from the platter 12, allowing the head 14 to glide or fly on a cushion of air slightly above an upper surface of the disk 12. The flying height of the read/write head 14 over the disk surface is typically less than a micron.
An arm electronics module 30 may include circuits that switch the head function between read and write operations, a write driver for supplying write current to the head 14 during write operations and an amplifier for amplifying the read signal. The arm electronics module 30 is connected to the head 14 by flexible conductive leads 32
The configuration and components of the electronics module 30 vary according to the disk drive design as will be understood by persons familiar with such technology. Although the module 30 may be mounted anywhere in the disk drive 10, a location proximate the head 14 minimizes signal losses and induced noise in the head signals during a read operation. A preferred mounting location for the module 30 comprises a side surface of the structural arm 18 as shown in FIG. 1.
The disk 12, shown in a partial cross-sectional schematic view in FIG. 2 comprises a substrate 50 and a thin film 52, disposed thereover. The magnetic transducer or head 14 comprises a write head 14A for writing data bits to the disk 12 by altering magnetic domains of ferromagnetic material in the film 52, thereby creating magnetic transitions in the magnetic domains. A read head 14B reads the magnetic transitions to determine the stored data bit.
Data bits and timing information to be written to the disk 12 are supplied by a data processing device 60 (e.g. a computer or music player) in the form of bipolar data pulses in PECL (positive emitter-coupled logic) form. Typically, the PECL bipolar signals representing a logic one and a logic zero differ by about 200 mV or by about 450 mV. The data and timing pulses are supplied to a data write circuit 62 where the data bits are formatted and error detection/correction information appended thereto.
To write data bits, the voice coil motor 18 moves the suspension arm 16 to a desired radial position above the surface of the disk 12 while the spindle motor rotates the disk 12 to move a circumferential region to be written under the write head 14A. A write driver 66A of a preamplifier 66 (in one embodiment the preamplifier 66 is disposed within the electronics module 30) supplies a write current (in certain applications between about 10 mA and 70 mA) to the write head 14A responsive to the signal from the data write circuit 62. The write driver 66A scales up the relatively low voltage levels representing the data bits to a voltage range between about +/−6V and +/−10V. In one embodiment the write driver 66A converts the PECL signals to logic signals having a larger differential voltage, such as about 3.3V. The write driver 66A also shapes the write current signal waveform to optimize the data writing process.
Write current supplied by the write driver 66A to the write head 14A (magnetically coupled to a magnetically permeable core not shown) creates a magnetic field that extends from the core across an air gap between the write head 14A and the disk 12. The magnetic field alters a region of ferromagnetic domains in the thin film 52 to store the data bits as magnetic transitions.
The direction of the magnetic field generated by the write head 14A, and thus the direction of the altered ferromagnetic domains, is responsive to the direction of current flow through the write head 14A. Current supplied in a first direction through the write head 14A aligns the domains in a first direction (representing a date 0 for example) and current supplied in a second direction (representing a data 1 for example) aligns the domains in a second direction.
In the read mode, transitions between adjacent domains are detected to determine the stored data bit. The read head 14B (comprising either a magneto-resistive (MR) sensor or an inductive sensor) senses the magnetic transitions in the thin film 52 to detect the stored data bits. A differential output signal produced by the MR sensor responsive to the magnetic transitions has a higher magnitude and a higher signal-to-noise ratio than an output signal produced by the inductive sensor. The MR sensor is thus preferred, especially when a higher areal data storage density is desired. State-of-the-art MR read heads include giant magnetoresistive (GMR) heads and tunneling magnetoresistive (TMR) heads.
The suspension arm 16 moves the head 14 while the disk 12 rotates to position the read head 14B above a magnetized region to be read. A DC (direct current) bias voltage of between about 0.025V and about 0.3V is supplied to the read head 14B by a read circuit 66B of the preamplifier 66. Magnetic domains in the thin film 52 passing under the read head 14B alter a resistance of the magneto-resistive material, imposing an AC (alternating current) component on the DC bias voltage. The AC component representing the read data bits has a relatively small magnitude (e.g., several millivolts) with respect to the DC bias voltage.
The differential read output signal, having an amplitude in a range of several millivolts, is input to a signal processing stage 102 followed by an output or converter stage 104. Typically, both the signal processing stage 102 and the output stage 104 are elements of the preamplifier 66. The signal processing stage 102 amplifies the signal to increase the signal's signal-to-noise ratio. The output stage 104 scales up the head signal voltage to a peak voltage value in a range of several hundred millivolts, supplying the scaled-up signal to channel circuits of a channel chip 106 through an interconnect 108. The channel chip 106 detects the read data bits from the voltage pulses, while applying error detection and correction processes to the read data bits. The read data bits are returned to the processing device 60 via a user interface 110 (e.g., SATA, SCSI, SAS, PCMCIA interfaces).
In other data storage systems the head 14 operates with different types of storage media (not shown in the Figures) comprising, for example, a rigid magnetic disk, a flexible magnetic disk, magnetic tape and a magneto-optical disk.
To increase storage capacity, a disk drive may comprise a plurality of stacked parallel disks 12. A read/write head is associated with each disk to write data to and read data from a top and bottom surfaces of each disk.
Integrated circuits such as the electronics module 30 described above, typically comprise a silicon semiconductor substrate and semiconductor devices, such as transistors, formed from doped regions within the substrate. Interconnect structures are formed in parallel-like layers overlying the semiconductor substrate to provide electrical connection between devices to form electrical circuits. A conventional interconnect system comprises a plurality of substantially vertical conductive vias or plugs and substantially horizontal conductive interconnect runners or traces, with a dielectric layer disposed between two vertically adjacent interconnect layers. The uppermost interconnect layer comprises a plurality of bond pads for receiving conductive bond wires or solder balls to interconnect the devices of the integrated circuit to off-chip external contacts, such as pins or leads of a package structure.
The integrated circuits are fabricated by forming regions of different materials, such as doped regions, dielectric regions and conductive regions, in a semiconductor wafer and on an upper surface thereof. Hundreds of such integrated circuits or die are formed on a single wafer by performing a plurality of sequential fabrication process steps (e.g., implanting and diffusing dopants, depositing materials on the upper surface of the wafer, patterning conductive regions) to form multiple die in the wafer, each die comprising active devices, passive devices (e.g., capacitors and resistors) and the interconnect structures. The manufacturing process steps are carefully developed to maximize the number of integrated circuits that satisfy desired operational specifications.
After completion of the fabrication steps, each die undergoes electrical testing (referred to as wafer probe testing) so that only those die that satisfy applicable performance specifications are accepted. After the wafer is singulated, the accepted die are packaged to protect the integrated circuit from contamination and damage. Package leads provide electrical connection of the integrated circuit to other electronic components, such as electronic components mounted on a printed circuit board with the packaged integrated circuit.
It is necessary for the preamplifier 66 of the electronics module 30 to provide an accurate read head bias (i.e., a DC voltage bias or a DC current bias) to avoid head degradation and improve data reading accuracy. Each preamplifier is evaluated during the wafer probe test to stage to determine whether the bias is within specifications. During the test, the preamplifier is powered through test probes that supply the necessary externally generated power supply voltages to certain conductive pads of the preamplifier integrated circuit. The bias voltage generated on-chip is then measured by test probes in contact with other conductive pads.
It is known that contact resistance between a wafer probe tip and the associated contact region of a bond pad can cause bias measurement errors. Further, contact resistance can increase as testing progresses among die on a wafer as the probe tips collect dirt from the wafer surface. Increased probe tip resistance can cause substantial errors in the measured value of the bias voltage, possibly resulting in misidentification and rejection of otherwise good preamplifiers—or passing unacceptable preamplifiers as acceptable.
A similar bias test is performed for preamplifiers that supply a bias current. The bias current is determined by causing the bias current to flow through a know resistance connected to the wafer test probes and measuring the voltage across the resistance.
A prior art head bias wafer probe test circuit 199 depicted in FIG. 3 is one such test probe circuit sensitive to the effects of wafer probe contact resistance when the bias voltage (or current) is measured. A preamplifier on-chip circuit, represented by a voltage source 200, generates and supplies a bias voltage to input/output pads HRP and HRN during the wafer probe test. When the preamplifier is operational in the disk drive data storage system 10, the input/output pads HRP and HRN are connected to the read head 14B. In the circuit 199, a load resistor RMR, having a resistance equivalent to a nominal head resistance, is connected across the input/output pads HRP and HRN and a voltage measured across these pads indicates the bias voltage. The wafer probe resistances are modeled in FIG. 3 by resistors RPAR1 and RPAR2. A voltage measured by the voltmeter 202 is:
                              V          MEASURED                =                              V            BIAS                                          (                                          R                MR                                                              R                  MR                                +                                  R                  PAR1                                +                                  R                  PAR2                                                      )                                              (        1        )
When probing many die across the wafer the probe tips become dirty and the contact resistances RPAR1 and RPAR2 increase. As can be seen from equation (1), the increased resistance lower the measured voltage relative to the bias voltage. When the disparity between the measured voltage and the bias voltage is so great as to cause the measured voltage to fall below a minimum acceptable bias voltage value, the preamplifier may be rejected as unacceptable. Thus the probe tip contact resistance can adversely influence yield determinations by identifying as faulty devices that generate a correct bias voltage.
The error in the measured voltage is the difference between the actual bias voltage VBIAS and the measured voltage VMEASURED:
      Error                      [    %    ]    =            (                                    R            MR                                              R              MR                        +                          R              PAR1                        +                          R              PAR2                                      -        1            )        *    100        %
For a nominal value of RMR=40Ω (for a GMR read head) and expected values of 0.50Ω for each of RPAR1 and RPAR2, the error is:
      Error                      [    %    ]    =                    (                                            R              MR                                                      R                MR                            +                              R                PAR1                            +                              R                PAR2                                              -          1                )            *      100            %        =                            (                                    40                              40                +                0.50                +                0.50                                      -            1                    )                *        100                %            =              2.4                %            It is known that as the probes become dirty during testing the contact resistance can typically increase to a few ohms, thereby increasing the percentage measurement error.
Current methods for detecting an unacceptably high probe contact resistance include monitoring the measured bias voltage to identify declining voltage values and monitoring the results of any tests that are sensitive to probe contact resistance, such as the bias measurement test of FIG. 3. After an unusually large number of integrated circuits are identified as faulty the test sequence may be paused while the probe tips are cleaned (to reduce the contact resistance) and devices previously identified as faulty are retested. The retesting process wastes time and adds cost to the wafer probe tests. Furthermore, some integrated circuits that passed the wafer probe test prior to probe cleaning may have been faulty.
The combination of various fabrication and operational anomalies can cause performance parameters of an integrated circuit (such as the bias voltage or current) to vary. These variations may cause the parameter to exceed an acceptable range above or below a nominal value. These variations must be controlled to ensure the performance parameters are within the acceptable range and the testing process must properly identify the devices that are outside the acceptable range.
By way of example, the total allowable variation in the bias voltage measurement of a preamplifier may be limited to 7 percent. Factors contributing to this range include fabrication process limitations and operational anomalies that directly affect the bias voltage or current generated on the integrated circuit, and the aforediscussed wafer test anomalies that affect the measured value. The cumulative fabrication and operational anomalies may introduce considerable measurement variability, leaving little head room to accommodate anomalies of the testing process.
It is not uncommon to encounter a variation of 1–1.5 percent in a bias reference circuit (e.g., a band-gap voltage reference) that supplies the reference voltage (or current) to the circuit elements that generate the head bias voltage (or current). Operating temperature, semiconductor process variations and mismatches between integrated circuit devices may add another 2–4 percent. Adding variations in wafer probe contact resistance causes the cumulative variation to approach and perhaps exceed the 7 percent limit, especially as the contact resistance increases. Most test processes use an error margin or guard band of about 1 percent lowering the acceptable margin from 7 percent to 6 percent, further increasing the probability that the cumulative error specification will not be satisfied.
If the cumulative effect of the several factors contributing to test circuit error exceed a specified limit, e.g., 7 percent, there will be an increase in the number of die that fail the probe test because of error associated with the test circuitry and the measurement process. The number of failed integrated circuits therefore increases. While it is important to reduce the contribution of each anomaly to the cumulative measurement error, such reductions may be costly. For example, reducing the effects of fabrication anomalies may require the development of new process steps or the purchase of new process equipment that permits tighter control over the fabrication process and reduces variations in measurable parameters, such as voltages. Clearly there is a need to reduce the effects of probe contact resistance to minimize error associated with bias voltage measurement.

Apparatus and method for performing a four-point voltage measurement for an integrated circuit


Novel photo-active labeled diagnostic and therapeutic peptides which are conformationally constrained backbone cyclized somatostatin analogs, having improved somatostatin receptor subtype affinity and selectivity are disclosed. The backbone cyclized peptide analogs disclosed possess unique and superior properties over other analogs, such as chemical and metabolic stability, selectivity, increased bioavailability and improved pharmacokinetics. Furthermore, the unique patterns of receptor subtype selectivity provide compounds having improved diagnostic and therapeutic utilities. Pharmaceutical compositions comprising the photo-active backbone cyclized somatostatin analogs, reagents for synthesizing same, and methods of using such compositions for diagnostic and therapeutic purposes including optical imaging and photodynamic therapy are also disclosed.

Somatostatin (SST) is a cyclic tetradecapeptide found in both the central nervous system and peripheral tissues. It was originally isolated from mammalian hypothalamus and identified as an important inhibitor of growth hormone secretion from the anterior pituitary. Its multiple biological activities include inhibition of the secretion of glucagon and insulin from the pancreas, regulation of most gut hormones and regulation of the release of other neurotransmitters involved in motor activity and cognitive processes throughout the central nervous system (for review see Lamberts, Endocrine Rev., 9: 427, 1988). Additionally, SST and its analogs are potentially useful antiproliferative agents for the treatment of various types of tumors. In its natural form, SST has limited use as a therapeutic agent since it exhibits two undesirable properties: poor bioavailability and short duration of action. For these reasons, great efforts have been made to find SST analogs with superior potency, biostability, duration of action and selectivity.
The diverse physiological effects of SST are induced by five selective and high affinity binding to receptors (designated SST-R1 through SST-R5), that are members of the seven transmembrane segment receptor superfamily (reviewed in Reisine T., Bell G I., Endocrinology Rev., 16: 427-442,1995).
Somatostatin in Cancer and Radiolabelled SST Analog
Because SST receptors are present in high density in many endocrine and non-endocrine tumors, diagnosis and treatment were attempted using radiolabelled SST analogs in cancer patients. Most tumors express multiple SST receptor-subtypes, although the SST-R2 subtype is most predominantly expressed. Radiolabelled receptor-specific compounds can detect primary sites, identify occult metastatic lesions, guide surgical intervention, stage tumors, predict efficacy of certain therapeutic agents or, when labelled with suitable radionuclides, be useful radiotherapeutic agents. The abundance of high affinity SST receptors in various tumors enables the use of radiolabelled SST analogs for in vivo identification, visualization and localization of these tumors (Lamberts et al. N. Engl. J. Med. 334:246 1996).
Scintigraphy using radiolabelled SST analog tracers helps to localize tumors and to evaluate the potential for chronic treatment of patients with inoperable SST receptor-positive tumors.
Recently, a number of 99mTc-labeled bioactive peptides have proven to be useful diagnostic imaging agents. Okarvi S. M. (Nuc. Med. Comm., 20:1093, 1999) reviews the recent developments in 99Tc-labeled peptide-based radiopharmaceuticals. Another application of radiolabelled SST analogs is radio-guided surgery. This technique has been successfully utilized in surgery of medullary thyroid cancer, carcinoids and islet cell tumors.
SST receptor radio-imaging has been recently used successfully (Aparici et al. Eur. J. Nuc. Med. 27:1754, 2000), for detection of cardiac allograft rejection. Infiltrated activated lymphocytes express SST receptors thus SST receptor imaging could be used to target them.
Optical Imaging
With the clinical success of radiopeptides as diagnostics and therapeutics, interest in the optical imaging of tumors using fluorescent-labeled peptides has been increasing. In addition, in vivo optical imaging is used to assess specific molecular targets for gene- and cell-based therapies (Allport et al. Exp. Hematol. 29, 1237-1246, 2001). In optical imaging (known also as photodynamic diagnosis or PDD), the patient is neither exposed to externally administered ionizing radiation (e.g., CT) nor injected with radioactive materials (e.g., nuclear medicine radiopharmaceuticals); thus, avoiding both radiation and radioactivity, the technique is more acceptable to the general public. The use of peptide conjugates for optical imaging, demonstrated by in vivo targeting to the somatostatin receptor in rats bearing receptor-expressing tumors have been reported by Licha et al. (Bioconjugate Chem. 12, 44-50, 2001) and Achilefu et al. (Investigative Radiology 35, 479-485, 2000). WO 00/61194 discloses somatostatin peptide-dye conjugates used as contrast agents for optical diagnostics. WO 03/003806 discloses dye-azide compounds, including somatostatin ligands, for dual phototherapy of tumors and other lesions, while WO 03/004466 discloses dye-sulfenate derivatives and their bioconjugates for the same purposes.
U.S. Pat. No. 5,211,938 discloses a method of detection of malignant and non-malignant lesions by photochemotherapy of protoporphyrin IX precursors. JP 2000-342297 discloses cancer cell diagnosis by comparative genomic hybridization with fluorescent labeled probes.
Most of the present methods relating to cancer screening using fluorescence detection systems require the use of interventional devices such as endoscopes which have the special capability of delivering specified light frequencies to a targeted area within a patient. These endoscopes illuminate the targeted part of the body in which cancer is suspected. The light delivered at a specified frequency illuminates an area which has previously been subjected to some type of fluorescent marker, such as a porphyrin which causes malignant cells to illuminate or fluoresce under observation of light at a specified frequency. In these cases, introduction of an endoscope into the body requires some type of sedation or general or local anesthesia. Once a tumor has been located by use of the interventional device, depending upon the type of tumor, photochemotherapy or other treatment means can be used. However, prior to actual treatment, there must be a confirmed test of cancer. Accordingly, the tumor still needs to be sampled by an appropriate biopsy method that also require some type of sedation or anesthesia. Thus, traditional methods of confirming a malignancy may require at least two interventional surgical procedures. U.S. Pat. No. 6,316,215 discloses methods of cancer screening utilizing fluorescence detection techniques and selectable imager charge integration periods. The methods are claimed to allow a safe, reliable, inexpensive and minimally invasive diagnosis.
Photodynamic Therapy
An additional application for optically active receptor-targeted peptide conjugates is in photodynamic therapy (PDT). PDT is a medical technique used mainly for the ablation of cancer. In PDT, a patient is administered a PDT drug, and after the drug has accumulated in the tumor, the tumor is irradiated with light of a specific wavelength using a special light delivery system. Certain photo active molecules (most of them related to porphyrins), when irradiated with light of the proper wavelength in the presence of oxygen, generate reactive oxygen species (ROS) within the cancerous cell which kills the cell, and are therefore useful therapeutically in cancer. In the treatment of cancer, PDT combines light and endogenous oxygen with a photosensitizer localized in or around the tumor. Irradiation of the sensitizer produces a cascade of biochemical events that inactivate cancer cells either directly through attack at specific cellular sites or indirectly through the induction of vascular damage to blood vessels feeding the tumor.
Since many PDT drugs fluoresce at another, distinct wavelength, the same compounds can be used to image cancer using a special spectral imaging device. Spectral imaging can be used to locate a tumor for surgical resection, to locate residual tumor for resection control and to guide subsequent PDT. The therapeutic efficacy of PDT can be monitored in real time by fluorescence imaging during PDT. All of the above procedures are potentially achievable in the operating ward, endoscopically and externally.
An increasing number of regulatory-approved PDT procedures are being put into routine clinical practice. PDT has regulatory approval in the USA, Canada, The Netherlands, France, Germany, and Japan for cancers of the lung, digestive tract, and genitourinary tract. Photofrin® is also being evaluated as a protocol for treating cancers of the head and neck region and for treating pancreatic cancer as well as a possible therapy against Kaposi's sarcoma and cancers of the brain, breast (both primary and metastatic), skin, and abdomen. Although Photofri®n has been shown to be effective against a number of malignancies, it is not the "ideal" photosensitizer. Novel water-soluble porphyrins having improved properties were recently suggested. (Hilmey et al J. Med. Chem. 45, 449-461, 2002).
To date, PDT applications have employed non-receptor-targeted molecules that are taken up in cancer. The mechanisms by which cancer cells take up non-targeted PDT drugs are not well understood, and target to non-target ratios of PDT drug concentrations of only about 2-5 are obtained. There are few reports in the literature of PDT drug receptor targeted biomolecule conjugates demonstrating in vitro efficacy. De Luca et al. (J. Pep. Sci. 7, 386-394, 2001), described synthesis and characterization of a porphyrin-CCK8 conjugate in which the porphyrin is used as an indium chelator, but PDT is not mentioned. Del Govematore et al. (Cancer Res. 60, 4200-4205, 2000), demonstrated in vivo use of a chlorin-antibody construct for targeted PDT of colorectal cancer, but none of the background art publications disclose peptide-receptor-targeted in vivo PDT.
U.S. Pat. Nos. 5,308,608 and 5,149,708 disclose specific types of porphyrin compounds which may be used for detection, photosensitization, or the destruction of a targeted biological material when the targeted tissue is contacted with the specified porphyrin, and irradiated with light that excites the compound. WO 01/15694 and WO 00/41727 disclose methods and compounds for PDT of a target tissue using a light source that preferably transmits light to a treatment site transcutaneously. U.S. Pat. No. 6,054,449 discloses compounds and methods for PDT of intimal hyperplasia and other diseases. U.S. Pat. No. 6,333,319 discloses use of bacteriochlorophyll derivatives in PDT methods, while U.S. Pat. No. 6,147,195, U.S. Pat. No. 5,726,169, U.S. Pat. No. 5,955,585, and U.S. Pat. No. 5,650,292 disclose conjugates of chlorophyll and bacteriochlorophyll derivatives with peptides used as photosensitizers in photodynamic therapy and in diagnostics of tumors. U.S. Pat. No. 6,217,848 discloses cyanine and indocyanine dye-peptide, conjugates for diagnostic imaging and therapy, and specifically discloses somatostatin analogs useful for laser assisted guided surgery for the detection of small micrometastases tumors upon laparoscopy.
Improved Peptide Analogs
As a result of major advances in organic chemistry and in molecular biology, many bioactive peptides can now be prepared in quantities sufficient for pharmacological and clinical use. Thus in the last few years new methods have been established for the treatment and diagnosis of illnesses in which peptides have been implicated. However, the use of peptides as therapeutic and diagnostic agents is limited by the following factors: a) tissue penetration; b) low metabolic stability towards proteolysis in the gastrointestinal tract and in serum; c) poor absorption after oral ingestion, in particular due to their relatively high molecular mass or the lack of specific transport systems or both; d) rapid excretion through the liver and kidneys; and e) undesired side effects in non-target organ systems, since peptide receptors can be widely distributed in an organism.
It would be desirable to achieve peptide analogs with greater specificity thereby achieving enhanced clinical selectivity. It would be most beneficial to produce conformationally constrained peptide analogs overcoming the drawbacks of the native peptide molecules, thereby providing improved therapeutic properties.
A novel conceptual approach to the conformational constraint of peptides was introduced by Gilon et al. (Biopolymers 31:745, 1991) who proposed backbone-to-backbone cyclization of peptides. The advantages of this strategy include the ability to effect cyclization via the carbons or nitrogens of the peptide backbone without interfering with side chains that may be crucial for interaction with the specific receptor of a given peptide. Further disclosures by Gilon and coworkers (WO 95/33765, WO 97/09344, U.S. Pat. Nos 5,723,575, 5,811,392, 5,883,293 and 6,265,375), provided methods for producing building units required in the synthesis of backbone cyclized peptide analogs. The successful use of these methods to produce backbone cyclized peptide analogs of bradykinin (U.S. Pat. No. 5,874,529), and somatostatin (WO 98/04583, WO 99/65508, WO 99/65508, U.S. Pat. Nos. 5,770,687, 6,051,554, and 6,355,613) was also disclosed. WO 02/062819 discloses backbone cyclized radiolabelled SST analogs for radioimaging and therapy. All of these methods are incorporated herein in their entirety, by reference.
There remains a need for synthetic SST analogs having increased in vivo stability, to be used diagnostically and therapeutically, as agents labeled with photo-active moiety, for optical imaging in vivo, in vitro and ex vivo, and for therapeutic agents using photodynamic therapy. It would be desirable to achieve peptide analogs with greater specificity to receptor subtypes thereby achieving enhanced diagnostic selectivity to elucidate the specific SST receptor profile in each individual for planning further therapy and/or surgery. Backbone cyclized SST analogs that specifically fulfill these needs are provided by this invention. None of the background art teaches or suggests the photo-active labeled backbone cyclized somatostatin analogs disclosed herein having improved diagnostic and therapeutic activity and selectivity.

Photo-active backbone cyclized somatostatin analogs for photodynamic therapy and imaging


Disclosed is a method for preparing a photosensitive peptide which is capable of being activated or deactivated in a biological system, including the steps of: (a) providing an amino acid including a photolabile molecule; and (b) incorporating the amino acid into a peptide during synthesis, wherein incorporation of the amino acid into the peptide produces a photosensitive peptide. Also disclosed is a method of introducing a photosensitive cleavage site into a synthetic peptide, including synthesizing a synthetic peptide having at least one photolabile amino acid, wherein the photolabile amino acid is positioned within the synthetic peptide so that upon irradiation the synthetic peptide is cleaved.

This invention relates to photosensitive caged molecules, e.g., photosensitive caged peptides.
The development of therapeutic drugs, in general, involves screening natural products or synthetic compounds for substances that affect or interfere with biological processes associated with disease. This random approach was required, in part, by limited knowledge concerning the molecular aspects of such disease processes. Development of molecular genetic techniques has led to the identification of key molecules, e.g., peptides and other small molecules, that regulate normal biological processes, and, in some situations, has defined the cellular pathways responsible for disease. Accordingly, this information can now be exploited and manipulated for the rational design of therapeutic drugs or diagnostic/research agents that specifically target these pathways.
The activity of such molecules can be further controlled and regulated in a specific manner by designing molecules whose biological activity is controlled by light. Such molecules are generally referred to as being "caged." The term caged is utilized as an indication that a biologically active species is trapped inside a larger framework that would be released upon illumination, thus "uncaging" the contents (Adams et al., Annu. Rev. Physiol. 55: 755-784, 1993).
For example, attempts have been made to control the activity of biologically active macromolecules, e.g., peptides, using caging chemistry. Initial efforts, however, to modify peptides selectively on amino acid side chains with photolabile protecting groups, have met with only limited success (Adams et al., supra). This is due, in part, to a lack of specificity for a photolabile caging group to specific amino acid residues in the peptide.


The present invention discloses a method of producing granulocyte-macrophage colony stimulating factor (GM-CSF) in a plant comprising, transforming the plant with a genetic construct comprising a regulatory region functional in the plant, operably associated with a GM-CSF coding sequence, or a fragment or a derivative thereof, operably associated with a transcriptional terminator, and expressing the GM-CSF. Also disclosed are transgenic plants, seeds and cells comprising GM-CSF coding sequences and plant optimized GM-CSF coding sequences.

At present, the majority of recombinant protein-based medicines are produced in mammalian cells or single cell organisms such as bacteria and yeast. However, the capital investment and operational costs associated with these systems are very high. For example, a mammalian cell-based manufacturing plant can cost upwards of $250 million. To achieve greater cost savings, and to address a capacity deficit in the global demand for recombinant protein-based pharmaceuticals, plants are being explored as alternative protein productions hosts (Giddings et al., 2000; Staub et al., 2000; Daniell et al., 2001; Walmsley et al., 2003). Different plant tissues such as leaves, seeds and tubers have been engineered for producing useful recombinant proteins (Vandekerckhove et al., 1989; Sijmons et al., 1990; Pen et al., 1992; Herbers et al., 1995; Ma et al., 1995; van Rooijen et al., 1995; Arakawa et al., 1998; Y Kusnadi et al., 1998; Zeitlin et al., 1998; Farran et al., 2002; Tackaberry et al., 1999). In a number of studies, tobacco has been used as a host plant but has some major drawbacks, including that tobacco is not a major food substance in a mammalian diet.
Granulocyte-macrophage colony stimulating factor (GM-CSF) is a cytokine of clinical importance. The mature GM-CSF is a polypeptide of 127 amino acid residues (Cantrell et al., 1985; Lee et al., 1985; Wong et al., 1985) and it regulates production and function of white blood cells (granulocytes and monocytes), which are important in fighting infections (Metcalf, 1991). GM-CSF is now an integral part of the clinical management for life-threatening neutropenia, the most common toxicity of cancer chemotherapy (Dale, 2002). Other oncology applications include treatment of febrile neutropenic conditions and support following bone marrow transplantation (Dale, 2002). Potential applications are also under evaluation in patients with pneumonia, Crohn's fistulas, diabetic foot infections and a variety of other infectious conditions including HIV-related opportunistic infections (Dale, 2002). The high cost of human GM-CSF in prior culture systems has placed practical limits on its widespread use (Dale, 2002). Previously, human GM-CSF has been produced by recombinant means in COS (Wong et al., 1985), yeast (Ernst et al., 1987) and Namalwa cells (Okamoto et al., 1990). GM-CSF has also been expressed in tobacco, but at very low levels (James et al., 2000; Sardana et al., 2002).
U.S. Pat. No. 5,677,474 (Rogers) teaches a method of producing foreign polypeptides in the seeds of cereal crops, including rice. Transformation of barley plants with a GUS reporter gene is disclosed. No transgenic plants containing GM-CSF were produced.
U.S. Pat. No. 5,889,189 (Rodriguez et al.) teaches a method of producing heterologous peptides in monocots including rice. Expression of a GUS reporter gene in transgenic rice seed is disclosed. No transgenic plants containing GM-CSF were produced.
James et al. (2000) used transformed tobacco cell suspensions to produce and secrete GM-CSF, which was then isolated from the growth medium. Yields were low (maximum of 250 microgram/L) and a complicated process of adding stabilizing proteins and increasing salt concentration of the growth media was necessary to enhance recovery of secreted GM-CSF. No transgenic cereal crops containing GM-CSF were produced.
Sardana et al. (2002) disclose the production of GM-CSF in transgenic tobacco seed. Yields were low with seed extracts containing recombinant human GM-CSF protein up to a level of 0.03% of total soluble protein. No transgenic cereal crops containing GM-CSF were produced.