A cold-rolled flat steel product for packaging materials has a thickness of less than 0.6 mm, which has been cold-rolled from steel along a rolling direction (0°) and which has an excellent isotropy with respect to its mechanical properties.

For reasons of resource efficiency and cost reduction, efforts are underway to reduce the thickness of flat steel products (sheet steel and strip steel) for use in the production of packaging materials (hereinafter also referred to as packaging steel). The thickness of cold-rolled packaging steels is typically in the range of blackplate, i.e., between 0.1 and 0.6 mm. However, since a thickness reduction also entails a decrease of the stiffness of the material, the strength of the packaging steel must be increased so that the material is able to meet the requirements needed to ensure its cold workability in forming operations during the production of packaging materials, e.g., in deep drawing or ironing processes. At the same time, however, the formability of sheet steel in cold working processes must be maintained. Therefore, there is a great need for high-strength sheet steels with a yield strength higher than 550 MPa which, at the same time, have good formability characteristics, e.g., an elongation at break of a minimum of 5% and/or an Erichsen index (according to DIN standard 50101, also designated as Erichsen cupping index, of a minimum of 5 mm as measured according to the cupping test according to Erichsen which is standardized in DIN standard EN ISO 20482).
There are many ways of increasing the strength of sheet steels, e.g., strain hardening, solution hardening (by adding carbon, nitrogen, phosphorus, manganese and/or silicon as alloying elements), precipitation hardening, increasing the strength by causing the formation of a polyphase structure in steel, or grain boundary hardening. However, many of these measures entail undesirable accompanying effects.
As strain hardening increases, an increase in the differences in length and width and, as a result, in the anisotropy occurs during the production of cold-rolled sheet steels, and, at the same time, the ductility decreases disproportionately.
During solution hardening, foreign atoms (for example, N, C, P, Mn, Si) are incorporated into substitutional or interstitial sites of the host lattice of the steel. Many of the potential alloying elements have negative accompanying effects (thus, for example, P is detrimental to steel, Mn and Si impair the surface quality), which explains why the addition of these alloying elements for the purpose of increasing the strength does not lead to the desired results.
When steel is alloyed with carbon, the strength of the steel increases with the carbon content; however, at the same time, during the processing of the sheet steel, a pronounced anisotropy in the form of banding develops, since the carbon, due to the low solubility in the ferrite lattice of steel, is present mainly in the form of cementite. Furthermore, as the carbon content increases, the surface quality deteriorates, and the risk of crack formation in the slab increases as the peritectic point is approached. The carbon content must therefore be reduced to a maximum of 0.1 wt %, since only then will it be possible to effectively prevent the crack formation in the slab and the resultant point oxidation (diffusion of oxygen into cracks).
In the prior art, sheet steels for use as packaging materials and methods of their production are known, in which an amount of carbon and nitrogen sufficient for solution hardening is added to the steel melt in order to achieve strengths higher than 500 MPa. For example, US 2011/0076177 A1 discloses a high-strength sheet steel for the production of cans, having a carbon content of 0.02 wt % to 0.10 wt % and a nitrogen content of 0.012 wt % to 0.0250 wt %, which has ultimate tensile strengths higher than 500 MPa, with the weight percentage of free nitrogen, i.e., the weight percentage interstitially incorporated into the steel, being a minimum of 0.0100%. It was found that an increase in the strength of steel is attributable decisively to the free nitrogen during solution hardening and age hardening. However, the increase in strength obtained by interstitial incorporation of nitrogen is limited by the partial fixation of nitrogen to nitrides, especially to AlN, on the one hand, and by the fact that at a nitrogen content higher than 0.025%, the risk of crack formations in the slab during hot rolling markedly increases, on the other hand.
In precipitation hardening, for example, by adding the alloying elements Ti or Nb, the problem is that because of the high temperature, precipitates form already during hot rolling. Therefore, these precipitates are involved in all of the subsequent production steps, such as cold rolling, annealing and, as appropriate, temper rolling or dressing, and comparable to cementite, they develop a pronounced anisotropy, especially if the precipitation preferentially occurs at grain boundaries. Furthermore, the precipitating agents Ti and Nb contribute to an increase in the recrystallization temperature.
Due to the normative requirements with respect to the alloying components in steel, increasing the strength of packaging steel by causing the formation of a polyphase structure in steel is extremely limited from the outset. The conventional polyphase steels, such as are used in the automobile industry, can therefore not be used for packaging steel since, due to the normative requirements set out in the packaging steel standard (DIN standard EN 10202), the alloying components such as manganese and silicon can be used only up to a maximum percentage by weight. Although it is possible to cause the formation of a polyphase structure in packaging steel by means of a special refrigeration technique, the resultant microstructural status is characterized by considerable instability, and in most cases, the increase in strength goes hand in hand with reduced formability. If the polyphase structure is predominantly based on the alloying element carbon, the additional risk is that the anisotropy of cementite is transferred to the polyphase structure and, as a result, is even further intensified.
In grain boundary hardening, it is possible to increase the strength of steel, while maintaining the formability unchanged, by causing the formation of a fine-grained structure, which fine-grained structure can be technically achieved by means of a low reel temperature (winding temperature after hot rolling), high degrees of deformation during cold rolling, and by means of annealing the cold-rolled sheet steel using continuous annealing. It is further possible to cause the formation of a fine-grained structure by means of microalloying and influencing the precipitation properties in the hot strip. However, the alloying elements needed for this purpose are expensive and increase the annealing temperature required for recrystallization. Furthermore, because of an increased base strength of the hot strip, the cold rollability deteriorates, and the surface of the sheet steel becomes more susceptible to defects.
Consequently, the above-mentioned possibilities of increasing the strength of sheet steels while maintaining the formability lead to problems, particularly with respect to the isotropy, i.e., with respect to the directional dependence of the material properties. Since packaging materials, such as beverage or food cans, e.g., in most cases are (rotationally) symmetrical items, sheet steels used to produce packaging materials frequently are available in the form of round blanks (i.e., in the form of a plane circular sheet metal blank) which are formed into a cylindrical can body or a cylindrical can bottom or lid using deep drawing and ironing operations. Because of the symmetry of the final product, the material properties of the sheet metals should be as isotropic as possible, i.e., the properties of the packaging metals should be as uniform as possible in all directions of the metal plane. For cold-rolled sheet steels, which, by nature of the manufacturing process, are available in the form of strip steel, this is an extremely complex requirement since because of the rolling direction in hot rolling and cold rolling, the material properties, by nature of the manufacturing process, are invariably dependent on the rolling direction. Therefore, cold-rolled sheet steels, by nature of the manufacturing process, always have a pronounced anisotropy. This anisotropy is decisively attributable to the high degree of deformation during cold rolling, which in turn is required to achieve extremely thin metal sheet thicknesses. Since in the production of packaging materials, the cold-rolled sheet steel is always processed independently of the rolling direction, difficulties frequently arise during the forming operation since, e.g., the strength and formability are not uniform across the circumference of the round blank.

Cold-rolled flat steel product for packaging materials


Methods and systems of merging a first document with at least a second document to generate a third document. Each of the first and second documents includes at least one data unit. Each data unit is associated with a unit identifier and an edit identifier. The unit identifiers of each of the documents are compared to the unit identifiers of the other document to determine whether each unit identifier is a matching or non-matching unit identifier. Edit identifiers of the data units associated with the matching unit identifiers are compared to each other. Data units associated with the non-matching unit identifiers are inserted directly into the third document. Data units associated with the matching unit identifiers and the matching edit identifiers are inserted directly into the third document. Data units associated with the matching unit identifiers and the non-matching edit identifiers are merged into the third document.

Merging is an act of reconciling multiple changes made to different copies of a same document. Most often, it is necessary when a document is modified by two people at the same time. Later, these changes need to be merged into a single new document reflecting the intent of both authors.
A conventional merge can be cumbersome and time-consuming. A more efficient merge is desired.


The invention is related to a toothbrush head which comprises a head base, a head frame, and bristles. The head base comprises a front end, a back end, multiple strip-substrates, and multiple junctions. The multiple strip-substrates are aligned between the front end and the back end and each two adjacent strip-substrates link with each other with each of the multiple junctions, and each of the multiple strip-substrates comprises multiple sockets for inserting the bristles. The head frame comprises a bottom surface and multiple accommodating spaces for accommodating the head base. The toothbrush head allows the bristles to be bent into the arc shape when touching the teeth, so as to increase touching areas between the brushes and the teeth for enhancing cleaning effect and decreasing risks of causing caries.

1. Field of the Invention
The present invention relates to a toothbrush head, especially to a toothbrush head comprising a head base made of a rigid material and a head frame made of a soft material.
2. Description of the Prior Art
The conventional toothbrush head comprises a rigid substrate with multiple sockets and bristles, wherein the bristles are inserted in the sockets of the rigid substrate. As a user brushes his teeth with the conventional toothbrush head, the bristles are inflexible when touching the teeth. Crevices between the teeth therefore cannot be cleaned by the bristles of the conventional toothbrush head, which results into growth of bacteria and lesions on the teeth.
To overcome the shortcomings, the present invention provides a toothbrush head to mitigate or obviate the aforementioned problems.


Methods of reforming degenerated intervertebral discs are provided in accordance with methods of the invention. Hybrid materials useful in methods of the present invention are also provided.

Back pain is one of the most frequently reported musculoskeletal problems in the United States. 80% of the adults will miss work at least three times in their career due to back pain. The most common factor causing low back pain is the degeneration of the disc. At the ages between 35 to 37, approximately a third of the U.S. population will have suffered from a herniated disc.
The main functions of the spine are to allow motion, transmit load and protect the neural elements. The vertebrae of the spine articulate with each other to allow motion in the frontal, sagittal and transverse planes. As the weight of the upper body increases, the vertebral bodies which are designed to sustain mainly compressive loads increase in size caudally. The intervertebral disc is a major link between the adjacent vertebrae of the spine. The intervertebral disc, the surrounding ligaments and muscles provide stability to the spine.
The intervertebral discs make up about 20-33% of the lumbar spine length. They are capable of sustaining weight and transferring the load from one vertebral body to the next, as well as maintaining a deformable space to accommodate normal spine movement. Each disc consists of a gelatinous nucleus pulposus surrounded by a laminated, fibrous annulus fibrosus, situated between the end plates of the vertebrae above and below.
The nucleus pulposus contains collagen fibrils and water-binding glycosaminoglycans. At birth, the nucleus pulposus contains 88% water, however, this percentage decreases with age. This water loss decreases its ability to withstand stress. The annulus fibrosus consists of fibrocartilaginous tissue and fibrous protein. The collagen fibers are arranged in between 10 to 20 lamellae which form concentric rings around the nucleus pulposus. The collagen fibers within each lamella are parallel to each other and runs at an angle of approximately 60 degrees from vertical. The direction of the inclination alternates with each lamellae. This crisscross arrangement enables the annulus fibrosus to withstand torsional and bending loads. The end-plates are composed of hyaline cartilage, and are directly connected to the lamellae which form the inner one-third of the annulus.
When under compressive loads, the nucleus pulposus flattens and bulges out radially. The annulus fibrosus stretches, resisting the stress. The end-plates of the vertebral body also resist the ability of the nucleus pulposus to deform. Thus, pressure is applied against the annulus and end-plate, transmitting the compressive loads to the vertebral body. When tensile forces are applied, the disc is raised to a certain height straining the collagen fibers in the annulus. At bending, one side of the disc is in tension while the other side is in compression. The annulus of the compressed side bulges out.
When the disc is subjected to torsion, there are shear stresses which vary proportionally to the distance from the axis of rotation, in the horizontal and axial plane. The layer of fibers oriented in the angle of motion is in tension while the fibers in the preceding or succeeding layer are relaxed. Similarly in sliding, the fibers oriented in the sliding direction are in tension while the fibers in the other layers relax.
Repeated rotational loading initiates circumferential tears in the annulus fibrosus, which gradually form radial tears into the nucleus pulposus until the nucleus degrades within the disc. In addition to the water loss which occurs with age, more water is also lost due to nucleus rupture, thereby reducing its ability to resist compressive loads. As such, the annulus bulges. As the severity of the tear increases, much of the contents of the disc is lost, leaving a thin space of fibrous tissue. This condition is called disc resorption.
Increasing disc collapse can cause facet subluxation and stenosis of the intervertebral foramen. Subsequently, the degenerative process involves the facet joints equally. As the annulus bulges out posteriorly into the spinal canal, the nerve root may be compressed causing sciatica. Pain is felt from the lower back to the buttocks and the leg. Following the rupture of the disc, excessive motions such as excessive extension or flexion can occur, resulting in spine segmental instability. The spine is thus more vulnerable to trauma. Herniation can occur due to disc degeneration or excessive load factors, especially compression. Pain may result due to nerve root compression caused by protrusions.
The unstable phase of the degeneration progress allowing excessive movement may result in degenerative spondylolisthesis, which is a breakdown of posterior joints. The nerve is trapped between the inferior articular facet of the vertebrae above and the body of that below. Thus, sliding of a vertebral body on one another damages the posterior joints due to fatigue and applies traction on the nerve root causing pain.
Surgical treatments for herniated disc include laminectomy, spinal fusion and disc replacement with protheses.
At this time, 150,000 spinal fusion procedures are performed per year in the U.S. alone, and the numbers are growing exponentially. However, the results of spinal fusions are very varied. Some of the effects include non-unions, slow rate of fusion even with autografts, and significant frequency of morbidity at the graft donor site. In addition, even if the fusion is successful, joint motion is totally eliminated. Adverse effects of spinal fusions have also been reported on adjacent unfused segments such as disc degeneration, herniation, instability spondylolysis and facet joint arthritis. A long-term follow-up of lower lumbar fusions in patients from 21 to 52 years of age found that 44% of patients with spinal fusions were currently still experiencing low-back pain and 57% had back pain within the previous year. 53% of the patients tracked were on medication, 5% had late sequela secondary surgery, 15% had a repeat lumbar surgery, 42% had symptoms of spinal stenosis, and 45% had instability proximal to their fusion. This clinical data shows that significant long-term limitations are associated with spinal fusion.
An alternative to spinal fusion is the use of an intervertebral disc prosthesis. Ideally, a successful disc prosthesis will simulate the function of a normal disc. The disc replacement must be capable of sustaining weight and transferring load from one vertebral body to the next. It should be robust enough not to be injured during movement and should maintain a deformable space between the vertebral body to accommodate movement.
Disc protheses should last for the lifetime of the patient, should be able to be contained in the normal intervertebral disc space, should have sufficient mechanical properties for normal body function, should be able to be fixed to the vertebrae adjacent to the disc, should be possible to implant, should not cause any damage should the disc fail, and should be biocompatible.
There are at least 56 artificial disc designs which have been patented or identified as being investigated, McMillin C. R. and Steffee A. D., 20th Annual Meeting of the Society for Biomaterials (abstract) (1994), although not all these devices have actually been made or tested. They can be divided into two main categories. Lee et al., Spine, Vol. 16, 253-255 (1991). A first class includes devices for nucleus pulposus replacements which includes metal ball bearing, a silicone rubber nucleus, and a silicone fluid filled plastic tube. Devices for total or subtotal replacement of the disc have also been proposed such as a spring system, low-friction sliding surfaces, a fluid filled chamber, elastic disc prosthesis and elastic disc encased in a rigid column.
An example of total disc replacement is described by Urbaniak et al., Bio. J. Med. Mater. Res. Sym., Vol. 4, 165-186 (1973) who developed and tested, using chimpanzees, an intervertebral disc device made of a central silicone layer sandwiched between two layers of Dacron embedded in the silicone. The open-mesh Dacron was chosen to allow tissue ingrowth for fixation to the adjacent vertebrae. While spinal mobility was restored and the device tolerated by the host, due to inexact fit of the device, bone resorption and reactive bone formation were observable. Loose fibrous tissue also indicated possible movement of the device.
Hou et al., Chinese Medical Journal, Vol. 104(5), 381-386 (1991), developed a disc implant made of silicone rubber which restored normal disc function. However, the presence of fibrous tissue surrounding the implant indicated possible movement of the device.
The SB Charite intervertebral disc endoprosthesis, White and Panjabi, Clinical biomechanics of the lumbar spine, Churchill Livingstone, London (1989), which has been tested clinically, is fabricated from a biconvex polyethylene core sandwiched between two concave-molded titanium end-plates. However, the endoprosthesis shows insufficient mechanical performance and unlikely long-term bone fixation to the device.
Two types of disc prostheses were developed and evaluated by Lee et al., 35th Annual Meeting of the Orthopaedic Research Society, Las Vegas, Nev., February 6-9 (1989): Dacron fiber-reinforced polyurethane elastomer (reinforcement located for the annulus section), and a prosthesis made from thermoplastic polymer which is increasingly rigid moving from the nucleus out to the end-plates. Yet another design is made of cobalt-chromium-molybdenum (Co--Cr--Mo) alloy by Hedman et al., Spine, Vol. 16, 256-60 (1991).
U.S. Pat. No. 4,911,718 (Lee et al.), U.S. Pat. No. 5,002,576 (Fuhrmann et al.), U.S. Pat. No. 4,911,718 (Lee et al.) and U.S. Pat. No. 5,458,642 (Beer et al.) also teach permanent intervertebral disc endoprostheses for total disc replacement.
All of the foregoing intervertebral disc prostheses, however, merely replace all or a part of the disc with synthetic materials which must remain in place ad infinitum. These prostheses are generally permanent implants which require observation of long term biologic responses throughout the life of the prothesis. Furthermore, discs that are not comprised of biocompatible material may be rejected by the patient.
Procedures by which the tissues of the intervertebral disc are made to reform or replace the degenerated tissue of the intervertebral disc would be highly desirable and a significant improvement over the current state of the art which presently use such permanent implants. Although efforts in tissue-engineering have been reported, no one has, until now, accomplished reformation of intervertebral disc tissue.
Repair of skin tissue has been achieved. For instance, skin deficiencies which arise in severely burnt patients or in decubitus wounds of diabetic patients have been so treated. Sabolinski, Biomaterials, Vol. 17, 311-320 (1996). Cells are seeded onto templates of either resorbable or non-resorbable material. Once tissue begins to form the templates are dressed onto the site in need of treatment. Tissue engineering of the skin, however, is significantly different from tissue engineering of the intervertebral disc because tissue compositions differ significantly. In addition, the mechanical requirements of engineered skin tissue are significantly different from those of intervertebral disc tissue.
Some intervertebral disc prostheses provide for regrowth of the intervertebral disc and concurrent resorption of the prothesis. For example, U.S. Pat. Nos. 4,772,287 and 4,904,260 (Ray et al.) teach prosthetic discs having an outer layer of strong, inert fibers intermingled with bioresorbable materials which attract tissue ingrowth. However, this prosthesis is purely a synthetic material at the time of implantation and does not include any cells or developing tissue. In addition, it provides only partial resorption and the problems associated with permanent implants remain.
U.S. Pat. Nos. 5,108,438 and 5,258,043 (Stone) teach a porous matrix of biocompatible and bioresorbable fibers which may be interspersed with glycosaminoglycan molecules. The matrix serves as a scaffold for regenerating disc tissue and replaces both the annulus fibrosus and nucleus pulposus. However, replacement of this much tissue is a relatively invasive procedure which requires lengthy recovery time. Furthermore, these matrices do not use any cells to stimulate tissue recovery nor is there any incipient tissue formation in this device at the time of implantation.
Various materials have been seeded with cells in order to facilitate cell function including proliferation and extracellular matrix synthesis. For instance, El-Ghannam, et al., Journal of Biomedical Materials Research, Vol. 29, 359-370 (1974), teaches in vitro synthesis of bone-like tissue using bioactive glass templates. Schepers, et al., J. Oral Rehab., Vol. 18, 439-452 (1991), analyzed the use of bioactive glass as fillers for bone lesions. Also, porous polymeric matrices have been used. The polymers include poly(lactic acid), poly(glycolic acid) and their co-polymers. However, these polymers have not been taught to be appropriate substrates for intervertebral disc cells which until now have not been used to seed implants of any sort.
Ideally, intervertebral disc treatment would guide and possibly stimulate the reformation of the tissue of affected intervertebral disc, especially nucleus pulposus and annulus fibrosus tissue. It could also biodegrade while allowing concurrent nucleus pulposus and annulus fibrosus tissue ingrowth, thereby providing for disc regeneration. Such an intervertebral disc material which is biodegradable while still satisfying the mechanical requirements of an intervertebral disc, has not been available until now.

Compositions and methods for intervertebral disc reformation

Trustees of the University of Pennsylvania


Provided are therapeutic and/or preventive agents for migraine which comprise, as an active ingredient, a compound having a selective adenosine A2A receptor antagonistic activity or a pharmaceutically acceptable salt thereof; therapeutic and/or preventive agents for migraine which comprise, as an active ingredient, a compound having a selective adenosine A2A receptor antagonistic activity, which has an affinity for the adenosine A2A receptor 10 times or higher than that for the adenosine A1 receptor, or a pharmaceutically acceptable salt thereof; and the like.

Migraine is a paroxysmal headache that lasts 4 to 72 hours, accompanied by nausea, vomiting, sensitivity to light, sensitivity to sound, or the like [The Merck Manual, Seventeenth Edition, Chapter 168; Therapeutic Guideline of The Japanese Society of Neurology; International Classification of Headache Disorders-II: ICHD-II, 2004]. Vasodilation in the extra- and/or intra-cranial vessels including the superficial temporal artery has been proposed as one of the pathophysiology of migraine and its pathogenesis [Arch. Neurol. Psychiatr., Vol. 39, p. 737-763 (1938); Cephalagia, Vol. 1, p. 143-147 (1981); Internal medicine, Vol. 81, p. 601-609 (1998); Internal Medicine, Vol. 81, p. 639 (1998)]. It has also been known that ergot alkaloid and sumatriptan, hydrophilic agonists of serotonin receptor 5-HT1 (5-hydroxytryptamine 1), that do not cross the blood-brain barrier are effective for the treatment of migraine, because these agonists act on the serotonin receptor 5-HT1 in the cerebral vascular smooth muscle to constrict the dilated blood vessels [Ann. N.Y. Acad. Sci., Vol. 600, p. 587-600 (1990); Neurology, Vol. 43, p. S43-S47 (1993)].
It is thus believed that migraine can be treated by suppressing vasodilation in the extra- and/or intra-cranial vessels. Concerning the cause of migraine onset, there have also been reports presenting theories based on neurogenic inflammation around the trigeminal nerve and cerebral blood vessel, or around the dura mater blood vessel, or based on activation of the central nerve such as in cortical spreading depression [Lancet, Vol. 363, p. 381-391 (2004)].
There are further reports concerning migraine (see Non-Patent Documents 1 to 3).
Some of the examples of therapeutic agents for migraine currently in use in the clinic include non-steroidal antiphlogistic analgetics such as triptans (for example, sumatriptan), and ibuprophens. As for the preventive agents, for example, antiepileptic agents such as topiramate, and calcium antagonist agents such as flunarizine are currently used in the clinic.
It is known that the adenosine concentration in the blood plasma of migraine patients an hour after a migraine attack increases by an average of 68% from that during the normal period, and that the activation of the adenosine A2 receptor by adenosine suppresses the serotonin uptake by platelets in a manner that depends on adenosine concentration, and causes vasodilation as a result of a rapid serotonin release [Can. J, Neurol. Sci., Vol. 2, p. 55-58 (1998)]. Further, intravenous administration of an adenosine enhancer to a migraine patient is known to induce a migraine attack [Med. J. Aust., Vol. 162, p. 389-390 (1995)]. It is also known that adenosine possesses a strong vasodilating action, and that the adenosine A2A receptor and the adenosine A2B receptor are involved in vasodilation during migraine and in adenosine-induced vasodilation [Am. J. Physiol. Heart Circ. Physiol., Vol. 280, p. 2329-2335 (2001)]. It is thus believed that migraine can be treated by suppressing adenosine-induced vasodilation.
Caffeine, which has a non-selective adenosine antagonistic activity, is known to relieve migraine; however, caffeine has side-effects, namely, psychiatrical dependence, and causes caffeine withdrawal headache [see Pain, 1991, Vol. 44, p. 151-155; Drugs, 1995, Vol. 49, p. 37-50]. Further, xanthine derivatives are known to be useful as therapeutic drugs for migraine (see Patent Document 1).
It is known that adenosine is distributed abundantly in the whole body, and exhibits a variety of physiological activities on the central nervous system, the cardiac muscle, the kidneys, the smooth muscle, and the like through its receptors (see Non-Patent Document 4).
For example, adenosine A1 antagonists are known to facilitate defecation (Jpn. J. Pharmacol., 1995, Vol. 68, p. 119). Further, involvement of the adenosine A2A receptor, particularly in the central nervous system is known. The antagonists of the adenosine A2A receptor are known to be useful as, for example, therapeutic drugs for Parkinson's disease (see Non-Patent Document 5), or therapeutic drugs for sleep disorder (see Nature Neuroscience, 2005, p. 1; Patent Document 2).
There are some reports concerning the relationship between adenosine receptors and migraine (see Non-Patent Documents 6 to 13).
For example, compounds represented by the following formulae (I), (II), (III), (IV), (V), (VI), and (VII) are known as compounds having a selective adenosine A2A receptor antagonistic activity (see Patent Documents 3 to 9, and Non-Patent Documents 14 and 15).

(wherein R1 represents methyl, ethyl, propyl, butyl, or 3-methylbutyl, or any of these groups substituted with hydroxy; R2 represents phenyl, pyridyl, pyrimidinyl, 5,6-dihydro-2H-pyridylmethyl, or tetrahydropyranyloxy, or any of these groups substituted with 1 to 3 substituents selected from a fluorine atom, a chlorine atom, a bromine atom, methyl, ethyl, methoxy, and ethoxy; R3 represents pyridyl or tetrahydropyranyl; R4 and R5 may be the same or different, and each represent a hydrogen atom, a fluorine atom, or 2-methoxyethoxy; and R6 represents methyl, ethyl, propyl, or butyl)


A piezo-electric actuator comprising: piezo-electric element 1a having piezo-electric body 3a which is provided with at least two opposing surfaces, wherein the surfaces perform an expanding and contracting motion in accordance with the state of an electric field; a constraint member 21a for constraining piezo-electric element 1a on at least one of the two surfaces, a supporting member disposed around constraint member 21a, and a plurality of beam members 22a each having both ends fixed to constraint member 21a and supporting member 4a, respectively, wherein each beam member has a neutral axis for bending in a direction substantially parallel with the constrained surface, wherein the constraint member vibrates by vibration which is generated by the constraining effect between the constraint member and the piezo-electric element, and is amplified by the beam members.

Electromagnetic actuators have been generally utilized as driver components for acoustic elements such as speakers, due to their easy handling. An electromagnetic actuator comprises a permanent magnet, a voice coil, and a diaphragm, and causes a low-stiffness diaphragm that is made of an organic film and is fixed to the coil to vibrate, through the operation of a magnetic circuit in a stator which uses the magnet. Therefore, they present a reciprocal vibration mode and can provide large vibration amplitude.
By the way, the demand for power-saving actuators has been increasing, together with an increased demand for cellular phones and personal computers in recent years. However, electromagnetic actuators have the problem that the reduction in power consumption is difficult due to the large amount of current which flows in the voice coil to generate magnetic force. Further, despite the need for a reduction in size of actuators for mounting in a cellular phone or a personal computer, it is difficult to reduce the thickness due to its configuration, because, if a permanent magnet in an electromagnetic actuator, which is one of the components of the actuator, is reduced in thickness, orientation of the magnetic poles will not align, causing failure in ensuring stable a magnetic field, and thus resulting in difficulties in controlling the synchronization of the vibrating film and the voice coil. Further, magnetic flux may leak from the voice coil and may induce malfunctions in other electronic components which constitute the electronic device. Thus, an electromagnetic shield is required when applying the actuator to an electronic device. However, this shield requires a large space. For this reason as well, an electromagnetic actuator is not suitable for use in small devices such as a cellular phone. Additionally, there is the problem that if a voice coil is made of thinner wire, and has increased resistance, the voice coil may be burnt due to the large amount of current, which features the electromagnetic acoustic element, to drive the coil.
Thus, a piezo-electric actuator which employs a piezo-electric element as a driver component, having such features as small size, light weight, low power consumption, no leakage of magnetic flux, and so on, is desired as a thin vibration element, instead of an electromagnetic type vibration element. A piezo-electric actuator generates vibration through the expanding and contracting motion or the bending motion of a piezo-electric element that is in the shape of a thin plate. A piezo-electric actuator is fabricated by bonding a piezo-electric ceramic element to a base, as disclosed in the specification of Japanese Patent Laid-open Publication No. 168971/86.
An example of a conventional piezo-electric actuator is illustrated in FIGS. 1A, 1B. FIG. 1A illustrates an exploded perspective view of a piezo-electric actuator. Piezo-electric body 203 made of piezo-electric ceramics is fixed to the central region of circular base 202 to form piezo-electric element 201. The outer periphery of base 202 is supported by circular supporting member 204. As a predetermined AC voltage is applied to piezo-electric body 203, piezo-electric body 203 performs an expanding and contracting motion. A bending motion is induced in base 202 in an out-of-plane direction to generate vibration through the constraining effect of the fixed portion between piezo-electric body 203 and base 202. As illustrated in FIG. 1B, base 202 vibrates in an out-of-plane direction, with supporting member 204 fixed (as node) and the central portion moving as an antinode.
By the way, because a piezo-electric ceramic has high stiffness, a piezo-electric actuator has the problem that it vibrates only in small average amplitude as compared with an electromagnetic actuator. In particular, a piezo-electric actuator, which is fixed along its periphery and which has an arc-shaped vibration mode in which the central portion deforms dominantly, deforms only in small amplitude on average, making it even more difficult to achieve sufficient amplitude of vibration. Further, due to the high stiffness of the piezo-electric ceramic, the amplitude of vibration varies significantly around the resonance frequency, so that it is difficult to achieve vibration amplitude having flat frequency characteristic.
Further, the resonance frequency of the piezo-electric actuator largely depends on its shape. When a piezo-electric actuator is applied to low frequency acoustic components such as a loud speaker, the piezo-electric ceramic element must be either enlarged in area or extremely reduced in thickness in order to lower the resonance frequency. However, due to the brittleness of the ceramic material, enlargement in area or reduction in thickness may causes deterioration in reliability such as cracking during handling, breakage due to dropping, and the like. This makes the piezo-electric actuator unsuitable for practical use in many cases.
Additionally, when the actuator is applied to an electronic device, due to the large vibration reaction force of a piezo-electric ceramic, vibration tends to propagate to a housing, which contains the piezo-electric actuator, through support members. This leakage of vibration may cause the disadvantage that the housing generates abnormal sound.
Thus, to address the foregoing problems, the specification of Japanese Patent Laid-open Publication No. 2000-140759 discloses a technique in which a vibrator having a piezo-electric ceramic and a base is supported by springs along the periphery of the housing. The resonance frequency of the spring structure is set at near the resonance frequency of the vibrator. Since a large amount of energy is carried in the spring structure, large amplitude of vibration can be obtained.
For similar purposes, the specification of Japanese Patent Laid-open Publication No. 2001-17917 discloses a technique in which slits are provided in the peripheral region of a base along its circumference to form leaf springs in order to provide a similar function.


The invention provides a photothermographic material including, on a same surface of a substrate, photosensitive silver halide grains, a non-photosensitive organic silver salt, a reducing agent and a binder, in which the photosensitive silver halide grains include iridium and a metal of groups 3 to 10 of the periodic table other than iridium, and 90% or more of the total iridium amount within the grain are contained in a core of 50% or less of the grain.

1. Field of the Invention
The present invention relates to a photothermographic material and a method for producing silver halide to be employed therein.
2. Description of the Related Art
In recent years, it is strongly desired in the medical field to reduce the amount of waste processing liquids in view of environmental preservation and space saving. For this reason, there is desired a technology for a photothermographic material for medical diagnosis and for photographic applications, capable of efficient exposure with a laser image setter or a laser imager and of forming a sharp black image with a high resolution and a high sharpness. Such photosensitive thermal-development photographic material can eliminate use of processing chemicals in solutions and can provide users with a thermal development system which is simpler and does not contaminate the environment.
An image for medical use requires a particularly high image quality excellent in sharpness and graininess because a delicate image presentation is required. Also there is preferred an image of cold black tone in consideration of ease of diagnosis. Currently various hard copy systems utilizing pigments or dyes, such as an ink jet system and an electrophotographic system, are available as ordinary image forming systems, but no such system yet is satisfactory as an output system for the image for medical use.
On the other hand, a thermal image forming system utilizing an organic silver salt is disclosed in U.S. Pat. Nos. 3,152,904 and 3,457,075 and in "Thermally Processed Silver Systems", B. Shely, Imaging Processes and Materials, Neblette 8th edition, edited by Sturge, V. Walworth and A. Shepp, p.2 (1996). More specifically, a photothermographic material has a photosensitive layer in which a catalytic active amount of a photocatalyst (for example silver halide), a reducing agent, a reducible silver salt (for example organic silver salt) and a toning agent for regulating the color of silver if necessary, are generally dispersed in a matrix binder. The photothermographic material is heated, after an exposure to an image, to a high temperature (for example 80° C. or higher) whereby a black silver image is formed by a redox reaction between the silver halide or reducible silver salt (acting as an oxidizing agent) and the reducing agent. The redox reaction is accelerated by a catalytic effect of a latent image in silver halide, generated by the exposure to light. Therefore, the black silver image is formed in an exposed area. Such system is described in various references including U.S. Pat. No. 2,910,377 and Japanese Patent Publication (JP-B) No. 43-4924, and a Fuji Medical Dry Imager FM-DPL has been commercialized as a medical image forming system utilizing a photothermographic material.
In the image forming system utilizing such organic silver salt, since the photosensitive silver halide or the reducing agent remains even after the development process because of the absence of a fixing step, an image preservability, particularly a gradual blacking of an unblackened area when exposed for example to an indoor light for a prolonged period (such phenomenon being called "print-out" in the present invention) has been a major issue. For alleviating such print-out, there has been proposed to use a halogen precursor compound or another development terminating agent, but such compound also has a drawback of inhibiting the image formation itself and cannot therefore be sufficiently effective. Also U.S. Pat. No. 6,143,488 and EP 0922995 disclose a method of utilizing AgI formed by converting the organic silver salt. However, such method cannot provide a sufficient sensitivity, and it is difficult to formulate a practically acceptable system. Also photosensitive materials utilizing AgI are disclosed in WO 97-48014 and 97-48015, U.S. Pat. No. 6,165,705, Japanese Patent Application Laid-Open (JP-A) No. 8-297345, Japanese Patent No. 2785129 etc., but none of these has attained a sufficient sensitivity and a sufficient fog level and has been practically usable.
In a photosensitive silver halide emulsion employed in a photothermographic material, it is well known a heavy metal doping can increase the sensitivity. For example JP-A No. 2001-42471 describes a doping of a transition metal of groups 6 to 10 of the periodic table in silver halide grains. It is also described that such doped metal is preferably distributed either at higher content at the surface or in the vicinity thereof of the grain than in the interior thereof, or uniformly throughout the grain, thereby contributing to an increase of the sensitivity.
JP-A No. 2001-042473 discloses a photosensitive silver halide emulsion having a high content phase of an iridium metal complex at a surface phase of silver halide grains. As an effect, there is obtained a high sensitivity.
Such heavy metal doping methods describe a heavy metal doping on the surface of silver halide grains, thereby obtaining a high sensitivity under an exposure with a high illumination intensity. However there has not been mentioned the issue of print-out which is specific to a photothermographic material, and it is estimated that the influence of the distribution of the doped heavy metal within the grain has not been recognized at all.
On the other hand, JP-A No. 2000-66325 discloses a method of doping an iridium-based dopant and a dopant based on a transition metal other than iridium in different areas of a silver halide grain respectively, and describes an effect of obtaining a higher sensitivity, particularly a sensitivity under an exposure of a high illumination intensity. There is described that the iridium-based dopant is doped in an area of 50 to 55% from the center of the silver halide grain, in an amount of 6×10−6 mol/mol.Ag, while the metal other than iridium is doped in an area of 65 to 70% from the center, in an amount of 4×10−5 mol/mol.Ag. It is also described that such method is applicable to a multi-color photosensitive material having two or more silver halide emulsion layers but a photothermographic material has not been mentioned. Consequently, it is considered that the issue of print-out, which is specific to the photothermographic material, has never been recognized.

This patent is subject to a terminal disclaimer.

Photothermographic material and method for producing silver halide used for it


A golf putter has a head and a shaft connected to the head at a toe end. The head has an L-shaped cross section and a lower edge of a putting surface is smoothly curved with a lowermost point at an approximate midpoint between the toe and a heel of the head. The head has a hosel thereon that is integral with the head for receiving the shaft at a fixed angle. The shaft is straight.

1. Field of the Invention
This invention relates to a golf putter having a head with a heel and a toe and a shaft attached to the head at or near the toe. The head has a putting surface that is smoothly curved from heel to toe with a lowermost point located at or near a midpoint.
2. Description of the Prior Art
Golf putters are one of the most common and necessary golf clubs and putting is an extremely important part of the game of golf. Golf putters have various shapes and sizes and there is a continuous quest to create an improved putter that enables a user to putt a golf ball more accurately. Most putters have a shaft that is connected at or near a heel of the head. Golfers using existing putters often have difficulty lining up the putter with the ball and the cup, or the putters do not provide a smooth stroke to the golf ball, or the putters tend to move out of alignment when the golf ball is struck, or the golf ball tends to bounce on the putting surface after it is struck, thereby resulting in a missed putt, or the putter does not provide a high degree of comfort and confidence to the user.
A putter that has a shaft connected to the head at a toe of the head is described in U.S. Pat. No. 6,723,002 issued on Apr. 20, 2004 and naming Barlow as an inventor. The head is divided into three solid bodies with the middle solid body being much larger than the two outer solid bodies. The shaft is inserted perpendicularly into a bore in the outer solid body at the toe and is bent at an angle of ten to twenty degrees at one to four inches above the top surface of the head toward the user. The head has a flat ball-striking surface. The main body has a top surface and a bottom surface that both have a straight front edge at the ball-striking surface. Putters with bent shafts can be more difficult to line up with the cup when putting a golf ball. Putters with a straight lower edge are more difficult to use by persons of different heights as the angle of the straight edge to the putting surface varies with the height of the user.


Simple and robust methods and apparatus for switching between different types of combining in a receiver in a communication system are disclosed that minimize Layer 1 processing overhead and power consumption. A method of selecting among a plurality of types of combining for received replicas of an information bitstream in a communication system includes the steps of determining a time offset between received replicas; determining a selection threshold; comparing the time offset with the selection threshold; and selecting one of the plurality of combining types based on the comparing step. The system may be a wideband code division multiple access system and the replicas may be included in a multimedia broadcast/multicast service.

This invention relates to communication devices and more particularly to communication devices that receive multiple replicas, sent from different transmitters, of the same information.
Digital communication systems include time-division multiple access (TDMA) systems, such as cellular radio telephone systems that comply with the GSM telecommunication standard and its enhancements like GSM/EDGE, and code-division multiple access (CDMA) systems, such as cellular radio telephone systems that comply with the IS-95, cdma2000, and wideband CDMA (WCDMA) telecommunication standards. Digital communication systems also include "blended" TDMA and CDMA systems, such as cellular radio telephone systems that comply with the universal mobile telecommunications system (UMTS) standard, which specifies a third generation (3G) mobile system being developed by the European Telecommunications Standards Institute (ETSI) within the International Telecommunication Union's (ITU's) IMT-2000 framework. The Third Generation Partnership Project (3GPP) promulgates the UMTS standard. This application focusses on WCDMA systems for economy of explanation, but it will be understood that the principles described in this application can be implemented in other digital communication systems.
WCDMA is based on direct-sequence spread-spectrum techniques, with pseudo-noise scrambling codes and orthogonal channelization codes separating base stations and physical channels (terminals or users), respectively, in the downlink (base-to-terminal) direction. User terminals communicate with the system through, for example, respective dedicated physical channels (DPCHs). WCDMA terminology is used here, but it will be appreciated that other systems have corresponding terminology. Scrambling and channelization codes and transmit power control are well known in the art.
FIG. 1 depicts a mobile radio cellular telecommunication system 10, which may be, for example, a CDMA or a WCDMA communication system. Radio network controllers (RNCS) 12, 14 control various radio network functions including for example radio access bearer setup, diversity handover, etc. More generally, each RNC directs mobile station (MS), or remote terminal, calls via the appropriate base station(s) (BSs), which communicate with each other through downlink (i.e., base-to-mobile or forward) and uplink (i.e., mobile-to-base or reverse) channels. RNC 12 is shown coupled to BSs 16, 18, 20, and RNC 14 is shown coupled to BSs 22, 24, 26. Each BS serves a geographical area that can be divided into one or more cell(s). BS 26 is shown as having five antenna sectors S1-S5, which can be said to make up the cell of the BS 26. The BSs are coupled to their corresponding RNCs by dedicated telephone lines, optical fiber links, microwave links, etc. Both RNCs 12, 14 are connected with external networks such as the public switched telephone network (PSTN), the Internet, etc. through one or more core network nodes like a mobile switching center (not shown) and/or a packet radio service node (not shown). In FIG. 1, MSs 28, 30 are shown communicating with plural base stations: MS 28 communicates with BSs 16, 18, 20, and MS 30 communicates with BSs 20, 22. A control link between RNCs 12, 14 permits diversity communications to/from MS 30 via BSs 20, 22.
At the UE, the modulated carrier signal (Layer 1) is processed to produce an estimate of the original information data stream intended for the receiver. The composite received baseband spread signal is commonly provided to a rake processor that includes a number of "fingers", or de-spreaders, that are each assigned to respective ones of selected components, such as multipath echoes or streams from different base stations, in the received signal. Each finger combines a received component with the scrambling sequence and the appropriate channelization code so as to de-spread the received composite signal. The rake processor typically de-spreads both sent information data and pilot or training symbols that are included in the composite signal.
FIG. 2 is a block diagram of a receiver 200, such as a mobile terminal in a WCDMA communication system, that receives radio signals through an antenna 202 and down-converts and samples the received signals in a front-end receiver (Fe RX) 204. The output samples are fed from Fe RX 204 to a rake combiner and channel estimator 206 that de-spreads the pilot channel, estimates the impulse response of the radio channel, and de-spreads and combines received echoes of the received data and control symbols. An output of the combiner/estimator 206 is provided to a symbol detector 208 that produces information that is further processed as appropriate for the particular communication system. Rake combining and channel estimation are well known in the art.
In order to accommodate the increasing demand for higher data rates in wireless user equipment (UE), such as cellular telephones, combination cellular telephones-personal digital assistants, and wireless-enabled personal computers, a high-speed downlink shared channel (HS-DSCH) was introduced in WCDMA. The HS-DSCH has a spreading factor of sixteen and can use several channelization codes simultaneously, with modulation being either quadrature phase shift keying (QPSK) or 16-ary quadrature amplitude modulation (16QAM). Each transmission time interval (TTI) includes one transport block, and the length of a TTI is three slots. After encoding, interleaving, and rate matching, the bits to be transmitted are distributed over one or more channelization codes. This is described in "Multiplexing and channel coding (FDD)", 3GPP Technical Specification (TS) 25.212 ver. 5.6.0 (September 2003), for example. Since the chip rate in a direct-sequence CDMA system is typically constant, a higher spreading factor generally corresponds to a lower information bit-rate.
A multimedia broadcast and multicast service (MBMS) for the frequency division duplex (FDD) aspect of the WCDMA system is being standardized by 3GPP. MBMS is described in 3GPP Technical Specification TS 23.246 ver. 6.2.0 Technical Specification Group Services and System Aspects; Multimedia Broadcast/Multicast Service (MBMS); Architecture and functional description (Release 6) (April 2003) and Technical Report TR 23.846 ver. 6.1.0 Technical Specification Group Services and System Aspects; Multimedia Broadcast/Multicast Service (MBMS); Architecture and functional description (Release 6) (December 2002), among other places.
MBMS is intended to offer high-speed and high-quality broadcast, or multicast, transmission to mobile stations (UEs). To enhance the quality and bit rate of the MBMS transmission, it has been agreed in 3GPP to use large interleaving depths, i.e., large TTIs, to obtain interleaving gain, and to use multicast on Layer 1, i.e., the UE should be able to receive multiple replicas of the same bitstream from different base stations, each of which is a Node B in 3GPP vocabulary. It has also been agreed that UEs must be able to receive 128-kilobits-per-second (kbps) and 256-kbps bitstreams. The combination of long TTI, multicast on Layer 1, and bit rates as high as 128 kbps and 256 kbps results in very large buffer memory sizes for Layer 1 processing in the UE.
Further, it has been agreed that the UE should be able to do selective combining on the radio link control (RLC) level (Layer 2). This means that different bitstreams are separately processed on Layer 1, and the RLC entity selects transport blocks, called RLC protocol data units (PDUs), from the different streams based on whether they pass a cyclic redundancy check (CRC) or not. Instead of using RLC PDUs, selective combining can also be carried out between multiple antennas, polarization angles, etc. This kind of separate processing of bitstreams on Layer 1 also results in very large buffer sizes since all received bitstreams must be separately buffered. Selective combining is well known in the art.
Besides selective combining, another well-known combining technique is soft combining or maximum ratio combining. Soft combining, which UEs already perform on Layer 1, can save both buffer space and processing time since the bitstreams are combined early in the receiver chain and since the soft-combined bitstream is processed as one stream, not several. Soft combining is well known in the art, and is used by some kinds of turbo decoders and by hybrid automatic repeat request (HARQ) in high-speed downlink packet access (HSDPA) in 3G radio communication systems.
Generally, the buffer size required for soft combining increases linearly with the timing difference between the transmission links involved in a broadcast or multicast. On the other hand, the Layer 1 buffer size required for selective combining is substantially constant with timing differences. This and other differences between selective and soft combining have caused problems for UE designers, who have not been able to optimize their designs for both types of combining simultaneously.

Methods and apparatus for selectively processing information replicas


A backlight structure comprises a frame, a circuit board, and a connector. The frame has an opening. The circuit board is located below the frame and has a through hole, wherein the through hole aligns with the opening. The connector passes through the opening and the through hole, protrudes from a surface of the frame, and is electrically connected to the circuit board.

1. Field of the Invention
The invention relates to a backlight structure, and more particularly, to a backlight structure having an assembly of a connector and an electrically conductive element, or an assembly of a first electrically conductive element and a second electrically conductive element.
2. Description of the Related Art
Referring to FIG. 1, a schematic view of a conventional backlight structure, FIG. 2, an A-A sectional view of FIG. 1, and FIG. 3, an exploded view of a tubular lamp and a fixture of the conventional backlight structure, the conventional backlight structure 20 comprises a frame 201, a circuit board 202, a fixture 203, a supporting seat 204 and a male connector 205, described in detail in the following.
The frame 201 has a through hole 210. The circuit board 202 is disposed below the frame 201 and has a female connector 206. The fixture 203 has a passageway 211 for a power wire, a cavity 212 and at least a notch 213, wherein the passageway 211 for a power wire connects with the cavity 212 and the notch 213 is disposed on an edge of the fixture 203. The male connector 205 has a power wire 208 and is connected to the female connector 206 of the circuit board 202. A tubular lamp 207 is disposed in the cavity 202 of the fixture 203.
An assembly process of the conventional backlight structure is described in detail in the following.
The fixture 203 is squeezed into the through hole 210 of the frame 201 and fixed to the frame 201 via the notch 213. The power wire 208 of the male connector 205 of the circuit board 202 is passed through the passageway 211 of the fixture 203 and protrudes from the cavity 212. The power wire 208 is welded to the tubular lamp 207 to electrically connect to the tubular lamp 207. Then, the tubular lamp 207 is put in the cavity 212.
Then the male connector 205 is electrically connected to the female connector 206 to thereby finish the electrical connection between the tubular lamp 207 and the circuit board 202.
Then, the circuit board 202 is fixed to the frame 201 by a screw 209 which is passed through the supporting seat 204 disposed between the circuit board 202 and the frame 201 to finish the assembly process of the conventional backlight structure.
For the conventional backlight structure, however, assembly and disassembly of the circuit board, frame, and the tubular lamp are complicated and requires manual welding. Thus, problems associated with costs, labor and assembly are prevalent and efficiency of the assembly and manufacturing process is hampered.

Backlight structure including clipping connectors


A photon source comprising a quantum dot comprising a confined conduction band energy level capable of being populated with at least one carrier and a confined valence band energy level capable of being populated by at least one carrier is provided, the source further comprises supply means for intermittently supplying at least one carrier to the energy levels to create an exciton in the quantum dot, wherein the supply means are configured to regulate the supply of carriers such that as the exciton decays either a single photon or a plurality of single photons each having different distinct energies are emitted during a predetermined time interval. The source is configured to be able to enhance the production of a desired type of exciton and can also be configured to exploit the use of higher order excitons such as biexcitons.

There is a need for so-called "single photon sources" for use in optical quantum cryptography where, for example, the security key for an encryption algorithm is formed by sending a stream of single photons which are regularly spaced in time. It is essential for the security of this technique that each bit is encoded on just a single photon. This is because an eavesdropper trying to intercept the communication will be forced to measure and thereby alter the state of some photons. Therefore, the sender and the intended recipient can determine if their communication has been intercepted.
Such a source is also useful as a low-noise source for optical imaging, spectroscopy, laser ranging and metrology. Normal light sources suffer from random fluctuations in the photon emission rate at low intensities due to shot noise. This noise limits the sensitivity of many optical techniques where single photons are detected. A single photon source which produces photons at regular time intervals has a reduced shot noise.
Recently, advances have been made in making such single photon sources from semiconductor quantum dot structures. Michler et al in "A Quantum Dot Single-Photon Turnstile Device" Science 290 p 2282 to 2284 (2000) and Santori et al "Triggered Single Photons from a Quantum Dot" Physics Review Letters 86 p 1502 to 1505 (2001) also describe single photon sources which operate by optically pumping a single quantum dot.
The above devices all concentrate on the production of a photon from the decay of a single neutral exciton (simple exciton) where prior to emission of the single photon there is a single electron in the ground state of the conduction band of the quantum dot and a single hole in the valence band of the quantum dot.
However, photons can also arise from the decay of more exotic excitons such as charged excitons or higher order excitons such as bi-excitons, triexcitons, quad excitons etc. Warburton et al, Nature 405 p926 to 929 describes photons arising from neutral and single, double, triple, quadruple and quintuple negatively charged single excitons in a quantum ring.
Findeis et al, Phys Rev B 63 p 121309-1 to 121309-4 (2001) and Finley et al, Phys Rev B 63 073307-1 to 073307-4 (2001) report observations of charged excitons from quantum dots.
Finally, Hartmann et al, Phys Rev Lett 84 p 5648 to 5651 describes experiments where they observe the presence of bi-excitons and higher order excitons in quantum dots.
In every single photon source where a photon is emitted due to recombination of an electron and a hole, there is always some uncertainty in the actual time when the photon will be emitted. This is usually referred to as the "jitter". The applicants have surprisingly found that by using photons resulting from the decay of higher order excitons or charged excitons, the jitter of the photon source can be reduced.

Photon source and a method of operating a photon source


In one aspect, the invention includes a method of forming a gated semiconductor assembly, comprising: a) forming a silicon nitride layer over and against a floating gate; and b) forming a control gate over the silicon nitride layer. In another aspect, the invention includes a method of forming a gated semiconductor assembly, comprising: a) forming a floating gate layer over a substrate; b) forming a silicon nitride layer over the floating gate layer, the silicon nitride layer comprising a first portion and a second portion elevationally displaced from the first portion, the first portion having a greater stoichiometric amount of silicon than the second portion; and c) forming a control gate over the silicon nitride layer. In yet another aspect, the invention includes a gated semiconductor assembly comprising: a) a substrate; b) a floating gate over the substrate; c) a control gate over the floating gate; and d) an electron barrier layer between the floating gate and the control gate, the electron barrier layer comprising a silicon nitride layer, the silicon nitride layer comprising a first portion and a second portion elevationally displaced from the first portion, the first portion having a greater stoichiometric amount of silicon than the second portion.

Read-only-memories (ROMs) are memories into which information is permanently stored during fabrication. Such memories are considered "non-volatile" as only read operations can be performed.
Each bit of information in a ROM is stored by the presence or absence of a data path from the word (access) line to a bit (sense) line. The data path is eliminated simply by insuring no circuit element joins a word and bit line. Thus, when the word line of a ROM is activated, the presence of a signal on the bit line will mean that a 1 is stored, whereas the absence of a signal indicates that a 0 is stored.
If only a small number of ROM circuits are needed for a specific application, custom mask fabrication might be too expensive or time consuming. In such cases, it would be faster and cheaper for users to program each ROM chip individually. ROMs with such capabilities are referred to as programmable read-only-memories (PROMs). In the first PROMs which were developed, information could only be programmed once into the construction and then could not be erased. In such PROMs, a data path exists between every word and bit line at the completion of the chip manufacture. This corresponds to a stored 1 in every data position. Storage cells during fabrication were selectively altered to store a 0 following manufacture by electrically severing the word-to-bit connection paths. Since the write operation was destructive, once the 0 had been programmed into a bit location it could not be erased back to a 1. PROMs were initially implemented in bipolar technology, although MOS PROMs became available.
Later work with PROMs led to development of erasable PROMs. Erasable PROMs depend on the long-term retention of electric charge as the means for information storage. Such charge is stored on a MOS device referred to as a floating polysilicon gate. Such a construction differs slightly from a conventional MOS transistor gate. The conventional MOS transistor gate of a memory cell employs a continuous polysilicon word line connected among several MOS transistors which functions as the respective transistor gates. The floating polysilicon gate of an erasable PROM interposes a localized secondary polysilicon gate in between the continuous word line and silicon substrate into which the active areas of the MOS transistors are formed. The floating gate is localized in that the floating gates for respective MOS transistors are electrically isolated from the floating gates of other MOS transistors.
Various mechanisms have been implemented to transfer and remove charge from a floating gate. One type of erasable programmable memory is the so-called electrically programmable ROM (EPROM). The charge-transfer mechanism occurs by the injection of electrons into the floating polysilicon gate of selected transistors. If a sufficiently high reverse-bias voltage is applied to the transistor drain being programmed, the drain-substrate "pn" junction will experience "avalanche" breakdown, causing hot electrons to be generated. Some of these will have enough energy to pass over the insulating oxide material surrounding each floating gate and thereby charge the floating gate. These EPROM devices are thus called floating-gate, avalanche-injection MOS transistors (FAMOS). Once these electrons are transferred to the floating gate, they are trapped there. The potential-barrier at the oxide-silicon interface of the gate is greater than 3 eV, making the rate of spontaneous emission of the electrons from the oxide over the barrier negligibly small. Accordingly, the electronic charge stored on the floating gate can be retained for many years.
When the floating gate is charged with a sufficient number of electrons, channel function is inhibited. The presence of a 1 or 0 in each bit location is therefore determined by the presence or absence of a conducting floating channel gate in each program device.
Such a construction also enables means for removing the stored electrons from the floating gate, thereby making the PROM erasable. This is accomplished by flood exposure of the EPROM with strong ultraviolet light for approximately 20 minutes. The ultraviolet light creates electron-hole pairs in the silicon dioxide, providing a discharge path for the charge (electrons) from the floating gates.
In some applications, it is desirable to erase the contents of a ROM electrically, rather than to use an ultraviolet light source. In other circumstances, it would be desirable to be able to change one bit at a time, without having to erase the entire integrated circuit. Such led to the development of electrically erasable PROMs (EEPROMs). Such technologies include MNOS transistors, floating-gate tunnel oxide MOS transistors (FLOTOX), textured high-polysilicon floating-gate MOS transistors, and flash EEPROMs. Such technologies can include a combination of floating gate transistor memory cells within an array of such cells, and a peripheral area to the array which comprises CMOS transistors.
A prior art EPROM device is described with reference to semiconductor wafer fragment 10 of FIGS. 1–3. FIG. 1 is a top view of wafer fragment 10, and FIGS. 2 and 3 are cross-sectional side views along the lines labelled X—X and Y—Y, respectively, in FIG. 1. Wafer fragment 10 comprises a substrate 12, having field oxide regions 14 formed thereover. Substrate 12 can comprise, for example, lightly doped monocrystalline silicon. To aid in interpretation of the claims that follow, the term "semiconductive substrate" is defined to mean any construction comprising semiconductive material, including, but not limited to, bulk semiconductive materials such as a semiconductive wafer (either alone or in assemblies comprising other materials thereon), and semiconductive material layers (either alone or in assemblies comprising other materials). The term "substrate" refers to any supporting structure, including, but not limited to, the semiconductive substrates described above.
Field oxide regions 14 can comprise, for example, silicon dioxide. An active region 15 extends over and within substrate 12 between field oxide regions 14. A floating gate 16 and a control gate 18 are formed over the active region. Gates 16 and 18 can comprise, for example, conductively doped polysilicon.
Floating gate 16 is separated from substrate 12 by a tunnel oxide 11 layer 20. Gates 16 and 18 are separated from one another by an insulative layer 22 which can comprise, for example, a combination of silicon dioxide and silicon nitride, such as the shown ONO construction wherein a silicon nitride layer 17 is sandwiched between a pair of silicon dioxide layers 19. The silicon nitride comprises Si3N4, although other forms of silicon nitride are known. Such other forms include silicon enriched silicon nitride layers (i.e., silicon nitride layers having a greater concentration of silicon than Si3N4, such as, for example, Si4N4). An advantage of silicon-enriched silicon nitride layers relative to Si3N4 is that the silicon-enriched silicon nitride layers frequently do not require separate, discrete antireflective coatings formed between them and a photoresist. However, silicon enriched silicon nitride is difficult to pattern due to a resistance of the material to etching. Silicon enriched silicon nitride layers are formed to have a substantially homogenous composition throughout their thicknesses, although occasionally a small portion of a layer (1% or less of a thickness of the layer) is less enriched with silicon than the remainder of the layer due to inherent deposition problems.
Wafer fragment 10 further comprises silicon dioxide layers 24 and 26 extending along sidewalls of gates 16 and 18, and comprises a silicon dioxide layer 28 over control gate 18. Layers 24, 26 and 28 can electrically insulate gates 16 and 18 from other circuitry (not shown) that may be present on substrate 12.
The gate assembly shown in FIGS. 1–3 can be formed as follows. Initially, a portion of substrate 12 within the active region is oxidized to form an oxide layer which will ultimately be patterned into tunnel oxide 20. Next, a polysilicon layer is formed over the silicon dioxide layer, with the polysilicon layer ultimately being patterned to form floating gate 16. An antireflective coating is formed over the polysilicon layer, and a layer of photoresist formed over the antireflective coating.
After the photoresist is formed, it is patterned by selectively exposing portions of the photoresist to light to render the portions either more soluble or less soluble in a solvent than portions which are not exposed to the light. The antireflective coating absorbs light that penetrates the photoresist to prevent such light from reflecting back to either constructively or destructively interfere with other light passing through the photoresist. The photoresist is then exposed to the solvent to remove the more soluble portions of the photoresist and leave a patterned photoresist block over a portion of the polysilicon layer that is to become floating gate 16.
The patterned photoresist block protects the portion of the polysilicon layer it covers, while uncovered portions of the antireflective coating, polysilicon layer, and silicon oxide layers are removed with an etch. The portions of the polysilicon layer and oxide layer which remain are in the shape of floating gate 16 and tunnel oxide 20.
After the etch of the antireflective coating, polysilicon and oxide, the photoresist and antireflective coating are removed from over floating gate 16. The polysilicon of floating gate 16 is then exposed to oxygen under conditions which form a silicon dioxide layer over exposed surfaces of the polysilicon to create oxidized sidewalls 24 and 26, and a portion of insulative layer 22. Subsequently, layers of silicon nitride and silicon dioxide are provided to complete formation of insulative layer 22. Next, a second polysilicon layer is provided and patterned to form control gate 18. The second polysilicon layer is then exposed to oxygen to form silicon dioxide layers 24 and 26 at the sidewalls of control gate 18, and to form silicon dioxide layer 28 over a top of control gate 18.
Source and drain regions can be provided within active area 15 and operatively adjacent floating gate 16. The source and drain regions can be provided by implanting a conductivity enhancing dopant into substrate 12 after forming floating gate 16 and before oxidizing sidewalls of floating gate 16.
A continuing goal in semiconductor device fabrication is to minimize the number of fabrication steps required to form a semiconductor device. Accordingly, it would be desired to eliminate one or more of the above-discussed steps in forming a gated semiconductor assembly.

Gated semiconductor assemblies and methods of forming gated semiconductor assemblies


One exemplary method for configuring multi-thread status in a system having a core with multi-thread capability which comprises the steps of selecting a desired multi-thread status from either enabled status or disabled status and configuring the core to the desired multi-thread status.

Computing architectures that operate efficiently and that can process large volumes of data quickly are often preferred over their counterparts. Additionally, it is often desired to operate a variety of tasks, using a variety of computer resources, simultaneously within a computer system. Accordingly, developing complex multiprocessor systems has been the subject of significant research.
One recent development is the advent of processor chips that contain multiple processors on a single chip. Each individual processor is known as a core. Each core on a silicon chip operates as an individual processor.
Additionally, the concept of threads has been developed in order to increase the efficiency of individual processors or processor cores. The term thread is used to define the number of execution strings that can be processed simultaneously within a processor or processor core. In a traditional core, instructions are executed sequentially, with the execution of one instruction completed before execution of a subsequent instruction begins. Often, however, a particular instruction may interact with various other components in the system (e.g., data must be read from a fixed drive, etc.). This can cause the core to reside in a waiting state for several clock cycles until the desired data is retrieved. By enabling a core to run more than one string of execution instructions simultaneously, the time lost waiting for actions such as data retrieval can be reduced. When one string of instructions, or thread, reaches a state where a wait cycle would occur, the core can switch to another thread and continues to process instructions. In this manner, core processing capabilities are increased.
Threads are beneficial in increasing the speed at which certain applications run on the core. Other applications, however, can theoretically be slowed by a core that runs multiple threads. Applications such as some database programs are designed to operate on multiple cores at the same time. These applications view each thread in a multi-thread core as another available core that can process a string of executable instruction. Because, however, a thread does not have the same processing capabilities as a complete core processor (i.e., a thread must share the core with one or more other threads), these applications are slowed by using multi-thread cores instead of employing additional cores. As a result, multiple threads can be undesirable for particular applications.
In systems that run applications where multiple threads are not advantageous, it is often desired to disable the multi-thread capability of a processor core. Core manufactures currently offer cores that can have their multi-thread capabilities disabled before shipping to the customer. This is usually done using a fuse within the chip. A voltage is used to "blow" the fuse to disable the multi-thread capability. This, however, is a permanent configuration. Once the multi-thread capability has been disabled in this manner, it cannot readily be enabled at a later time.
Because it is rarely possible to know which application will be run on a system at system installation time, and many systems will run numerous types of applications, system efficiency is reduced by choosing an enabled/disabled multi-thread state when a system is installed.

Hewlett-Packard Development Company, L.P.


A method for controlling access to a restricted resource is provided. The method may include receiving, by a cloud server, an identifier from a user device over a long range wireless channel. Further, the method may include comparing the identifier with a plurality of identifiers registered with an access control device. Further, the method may include authenticating the user device based on the comparing and subsequently transmitting a code to the user device upon successful authenticating. Thereafter, the user device may transmit the code to the access control device over a short range wireless channel. Further, the access control device may be configured to provide access to the restricted resource based on receiving of the code. Further, the method may include transmitting the code to the access control device over a long range wireless channel so that the access control device may authenticate the user device.

Existing techniques for controlling access to an access control location are deficient with regard to several aspects. For instance, current technologies do not eliminate the need for the wire networking infrastructure that may be needed in a multi-point access control system. Furthermore, current technologies do not provide multiple ways of accessing the access control location.
Therefore, there is a need for improved methods, systems, apparatuses, and devices for controlling access to an access control location that may overcome one or more of the above-mentioned problems and/or limitations. Any modern access control system users can be grouped in two—RFID key card holders and mobile device carriers. The wifi connection is only needed for adding and removing RFID key card numbers to and from the readers which can store more than ten thousand card numbers locally at each reader. When a user places a RFID card next to the access control device, the device functions just like the traditional one—comparing the card number with those already stored in the device and if one matches then the device grants the access. The card numbers are updated in each reader via the wifi connection with an encryption protocol. The security manager sends the update from the cloud server to all the readers simultaneously and the update can either be done instantly or queued for a certain time when wifi connection is available, say 1 am in the morning. The process for RFID users ensures that the users can open door anytime with or without wifi since their numbers are stored in each reader locally and their identity information is protected because its kept in the cloud server which simply matches the card numbers with individual identity. It should be noted wifi connection is not needed for opening the doors and gates and its reliability will not affect the experience of RFID users. The wifi is only used for updating the card numbers in the readers and for uploading the entry records of RFID users.
For mobile device users the system authenticates their identity in the cloud server and then the server sends a bluetooth key to the access control device via the phone to unlock. In this mode no wifi connection is necessary for the users to unlock because it can rely on cellular connection to authenticate and send the key. The specific detail of the process is that the app detects bluetooth signal from the access control devices (if there are multiple ones nearby) and pick one closest in front of the user to authenticate and unlock. Since no user info is stored in the readers only multiple bluetooth keys the number of cell phone credentials for the readers is limitless. Preferably, the invention is capable of storing at least 10,000 card numbers in each reader and the system requires less than one foot of wiring at each control location.

Methods, systems, apparatuses, and devices for controlling access to an access control location


Method for performing acoustic model estimation to optimize classification accuracy on speaker derived feature vectors with respect to a plurality of classes corresponding to phones to which a plurality of acoustic models respectively correspond comprises: (a) initializing an acoustic model for each phone; (b) evaluating the merit of the acoustic model initialized for each phone utilizing an objective function having a two component discriminant measure capable of characterizing each phone whereby a first component is defined as a probability that the model for the phone assigns to feature vectors from the phone and a second component is defined as a probability that the model for the phone assigns to feature vectors from other phones; (c) adapting the model for selected phones so as to increase the first component for the phone or decrease the second component for the phone, the adapting step yielding a new model for each selected phone; (d) evaluating the merit of the new models for each phone adapted in step (c) utilizing the two component measure; (e) comparing results of the evaluation of step (b) with results of the evaluation of step (d) for each phone, and if the first component has increased or the second component has decreased, the new model is kept for that phone, else the model originally initialized is kept; (f) estimating parameters associated with each model kept for each phone in order to optimize the function; and (g) evaluating termination criterion to determine if the parameters of the models are optimized.

The present invention relates to model estimation and, more particularly, to apparatus and methods for performing model estimation utilizing a discriminant measure which enables the design of classifiers to optimize classification accuracy.
In a general classification problem with N classes, the training procedure involves constructing models for each of the N classes using samples of data points from each of these classes. Subsequently, these models are used to classify an incoming test data point by evaluating its "closeness" to each of the N models. There are several possible categories of models that are often used, for instance, linear discriminants (as disclosed by P. O. Duda and P. E. Hart in "Pattern Classification and Scene Analysis", Wiley, New York, 1973), neural networks (as disclosed by R. Lippman in "Pattern Classification Using Neural Networks", IEEE Communications Magazine, pp. 11:47-64, 1989) and gaussian mixtures. The training procedure usually involves selecting a category of model (including its size), and then adjusting the parameters of the model to optimize some objective function on the training data samples. The first step of the training procedure, which involves choosing the type and size of the model, is generally done in an ad-hoc fashion, but more recently, some objective criteria have been introduced as an alternative (e.g., as disclosed by Y. Normandin in "Optimal Splitting of HMM Gaussian Mixture Components with MMIE Training", Proceedings of the ICASSP, pp. 449-452, 1995). The second step of the training procedure involves training the parameters of the model. Several objective functions have been developed in the past to do this, the most commonly used ones being (i) maximizing the likelihood of the data points given the correct class (as disclosed by A. P. Dempster, N. M. Laird, D. B. Rubin in "Maximum Likelihood Estimation from Incomplete Data", Journal of the Royal Statistical Society (B), vol. 39, no. 1, pp. 1-38, 1979) or (ii) maximizing the likelihood of the correct class given the data points (as disclosed by L. R. Bahl, P. F. Brown, P. V. de Souza, R. L. Mercer in "Maximum Mutual Information Estimation of Hidden Markov Model Parameters for Speech Recognition", Proceedings of the ICASSP, pp. 49-52, 1986 and as disclosed by B. H. Juang, W. Chou, C. H. Lee in "Minimum Classification Error Rate Methods for Speech Recognition", IEEE Trans. Speech and Audio Processing, vol. 5, pp. 257-265, May 1997).
When modelling data samples corresponding to a class with, for example, a mixture of gaussians, the parameters of the model are the number of mixture components and the means, variances and priors distributions of these components. In general, the number of mixture components is chosen using some simple ad-hoc rule subject to very loose constraints; for instance the number of components has to be sufficient to model the data reasonably well but not so many as to overmodel the data. A typical example of the choice of the number is to make it proportional to the number of data samples. However, such methods may result in models that are sub-optimal as far as classification accuracy is concerned. For instance, if the number of gaussians modelling a class is inadequate, it may result in the class being mis-classified often, and if too many gaussians are chosen to model a class, it may result in the model encroaching upon the space of other classes as well. These two conditions will be referred to as "non-aggressive" and "invasive" models, respectively.
Once the number of mixture components has been decided, the next step is to estimate the means and variances of the components. This is often done so as to maximize the likelihood of the training data samples. Though this necessarily gives the parameters that best fit the model to the data, it may result in a model that encroaches on the sample space of a different class, and hence lead to misclassifications. An alternative to maximum likelihood is maximum mutual information or MMI (as disclosed in the L. R. Bahl article cited above) or minimum classification error or MCE (as disclosed in the B. H. Juang article cited above), where the model parameters are directly estimated to minimize misclassification error. Methods that use such objective functions are called discriminant methods because they try to maximize the discrimination power of the models.
However, it would be advantageous to provide an objective function that can be used to both select an optimum size for the model and to train the parameters of the model which, further, may be applied to any category of classifier with one example being gaussian classifiers. It would also be advantageous to provide a measure that can be used to determine the number of mixture components in order to avoid classes of models characterized as "non-aggressive" and "invasive". It would still further be advantageous to provide an objective function that falls into the category of discriminant objective functions, but differs from MMI and MCE, and that can be used to tune the size of the models as well as estimate the parameters of, for example, the gaussians in the models.

Apparatus and method for performing model estimation utilizing a discriminant measure

International Business Machines Corporation


The invention is directed to a system for automatically adjusting the gear ratio of a continuously variable transmission mounted next to the motor of a vehicle. The gear ratio is adjusted with a specific speed. The essence of the invention is that a mechanism is provided which facilitates a determination of the speed of the adjustment of the gear ratio of the transmission in dependence upon detected operating parameters. With the system of the invention, an adjustment characteristic of the transmission is obtained which is comfortable for the driver of the vehicle.

Continuously variable transmissions are known, for example, from European patent publication 0,451,887 as well as from U.S. Pat. No. 5,514,050. In such systems, the change of gear ratio of the vehicle transmission is effected with a specific adjusting speed. In U.S. Pat. 5,514,050, a manual actuation for such a continuously variable transmission is disclosed. In this so-called lever-positioning operation, the driver is afforded the possibility to adjust the continuously variable transmission by actuating an actuating device. Especially, it is here provided that the adjustment of the gear ratio takes place at a constant rate of change.
The speed at which the gear ratio is changed should be adapted optimally to the driver command in order that the driving performance of a vehicle having a continuously adjustable transmission is realized so as to be more attractive for the driver of the vehicle. For a normal acceleration operation of the vehicle, the driver expects an increase of the engine rpm to be a function of the vehicle speed as the driver is already accustomed to from a manual transmission or from a conventional step automatic. When the accelerator pedal is pressed down rapidly such as for a kickdown in a step automatic, a higher motor capacity should be made available immediately, that is, the motor rpm should increase in a relatively short time span. In addition, the driver would like to utilize the braking action of the motor during overrun operation and during braking operation.
Furthermore, the influence of a driver evaluation characteristic variable should be considered.

System for automatically adjusting the gear ratio of a continuously variable transmission


An object of the present invention is to develop and provide a method for efficiently producing a nucleic acid aptamer, particularly, a DNA aptamer, having higher specificity and binding activity against a target substance than those of nucleic acid aptamers obtained by conventional methods. The present invention provides a transcribable or replicable nucleic acid aptamer comprising a natural nucleotide and a non-natural nucleotide having an artificial base-pairable artificial base. The present invention also provides a method for sequencing a non-natural nucleotide-containing single-stranded nucleic acid molecule selected from a single-stranded nucleic acid library.

In recent years, nucleic acid aptamers, as with other functional nucleic acids such as siRNAs, have received attention as novel active ingredients for pharmaceutical drugs or diagnostic drugs in place of low-molecular-weight compounds and are under research and development in various ways around the world with the aim of medically applying the aptamers.
These nucleic acid aptamers are functional nucleic acids capable of strongly and specifically binding, through their own conformations, to target substances such as proteins to inhibit or suppress the functions of the target substances. A vascular endothelial growth factor (VEGF)-targeting modified RNA aptamer for treatment of age-related macular degeneration (Macugen) approved by FDA in 2004 is known as a typical example of the nucleic acid aptamer pharmaceutically used.
Such nucleic acid aptamers are constituted by only 4 kinds of bases in comparison with antibodies which are proteins composed of 20 kinds of amino acids. In addition, these 4 kines of bases are very similar in chemical or physical properties. For these reasons, the nucleic acid aptamers are disadvantageously limited by variations and performance.
In order to solve this problem, previously reported methods employ one or two types of modified natural bases composed of natural bases bound with substituents via linkers in a nucleic acid library for nucleic acid aptamer separation (Patent Literatures 1 and 2 and Non Patent Literatures 1 to 3). DNA aptamers that are intended for application to nucleic acid chips capable of detecting proteins and may be used in the diagnostic field are also known as modified nucleic acid aptamers comprising such modified natural bases (Non Patent Literature 3). However, one or two types of modified natural bases introduced in the modified nucleic acid aptamers result in the replacement of approximately 25% or more of bases in the whole nucleic acid aptamer with the modified natural bases. This raises another issue of reduced selectivity or cytotoxicity of the aptamers, though enhancing the production efficiency of the aptamers. Hence, use of the modified nucleic acid aptamers having the modified natural bases is currently limited to diagnosis, and none of such aptamers have been approved as therapeutic drugs (Non Patent Literature 3).

Nucleic acid fragment binding to target protein