A method for treating uterine disorders, including hyperplasic, hypertonic, cystic and/or neoplastic uterine gland tissue by local administration of a botulinum toxin to or to the vicinity of the afflicted uterine tissue.

The present invention relates to methods for treating uterine disorders. In particular, the present invention relates to methods for treating uterine glandular disorders with a botulinum toxin.
An object of the present invention is to treat uterine tissues, including atypical uterine tissues, such as hyperplasic tissues, fibroids and uterine neoplasms (including tumors and cancers). A further object of the present invention is to prevent the development of, or to cause the regression or remission of, atypical uterine tissues, fibroids and neoplasms. An additional object of the present invention is to treat uterine disorders, both benign and cancerous, as well as for treating hyperplasic and/or hypertonic uterine gland cells by local administration of a Clostridial toxin to or to the vicinity of the afflicted uterine tissue.
Uterine Disorders
The uterus is a hollow muscular organ with significant glandular tissue. Upon release from the ovaries an egg travels through the Fallopian tubes to the uterus and if fertilized, the ovum embeds in the endometrium, a glandular lining of the uterus. The cervical canal extends from the vagina through the cervix (the lower portion of the uterus) to the body of the uterus. The fundus is the top of the uterus (the area between the fallopian tubes). The myometrium is the muscular wall of the uterus.
It is known that hyperplasic uterine tissues can, if not treated, develop into cancerous tissue. See e.g. Sivridis E. et al., Prognostic aspects on endometrial hyperplasia and neoplasia,
Virchows Arch 2001 August; 439(2):118-26. Additionally it is known that: different hyperplasia, metaplasic or atypical breast tissues can develop into cancers (see e.g. Ellis I. O., et al, Tumors of the Breast, chapter 16 (pages 865-930) of "Diagnostic Histopathology of Tumors", volume 1, edited by Fletcher C. D. M., second edition, Churchill Livingstone (2000), discussed further infra, as well as Fabian C. J. et al Beyond tamoxifen new endpoints for breast cancer chemoprevention, new drugs for breast cancer prevention. Ann NY Acad Sci 2001 December; 952:44-59); hyperplasic intestinal tissues, such as polyps can transform into carcinomas (see e.g. Der, R. et al Gastric Neoplasms, chapter 5 (pages 105-144) of Chandraspma, P., "Gastrointestinal Pathology", Appleton & Lange (1999), in particular pages 106-107; oral and oropharyngeal epithelial hyperplasia indicates a precancerous lesion. Sunaga H., et al. Expression of granulocyte colony-stimulating factor receptor and platelet-derived endothelial cell growth factor in oral and oropharyngeal precancerous lesions. Anticancer Res 2001 July-August; 21 (4B):2901-6, and; kidney and prostate cell hyperplasia has been documented as a factor leading to development of cancerous cells. Van Poppel, H., et al., Precancerous lesions in the kidney Scand J Urol Nephrol Suppl 2000; (205): 136-65.
Common cancers of the uterus include cervical and endometrial cancer. Endometrial cancer occurs most often in woman between the ages of 50 and 70 and it more common in women who have not had children. The usual symptom of endometrial cancer is vaginal bleeding after menopause. Diagnosis can be by biopsy or endometrial scraping.
Cervical cancer can take many years to develop. Before it does, early changes can occur in the cells of the cervix. The abnormal, non-cancerous cells (but which may become cancerous) are called cervical intra-epithelial neoplasia (CIN) or dyskaryosis.
Smooth muscle tumors of the uterus can be submucosal, intramural, and subserosal leiomyomata (fibroids). Uterine leiomyomas (fibroids) of the uterus are one of the most common pathologic abnormalities of the female genital tract. Fibroids are typically mostly in the muscle of the uterus (intramural) and by virtue of their size or position can impinge upon the endometrium and cause bleeding. Fibroids of the uterus are present in about 25% of women and require treatment: (a) if due to position or size they cause irregular uterine bleeding that cannot be controlled with hormonal therapy or removal of a polyp-like fibroid (submucosal) from the inside of the uterus at time of hysteroscopy & D&C; (b) they are so big (usually softball size or larger) that they give either pelvic pressure, bladder or rectal pressure or pelvic fullness symptoms; (c) they are in a position (usually near the ovaries or they have grown so rapidly that there is a question they might be malignant; (d) they cause recurrent pain due to the blood supply being compromised; (e) the fibroids cause distortion of the endometrial cavity and women have problems either during pregnancy or then they have frequent miscarriages.
The location of fibroids is variable. Most commonly, they are intramural and are noted by an irregular enlargement of the uterine corpus. The tumors can enlarge from the surface of the uterus late or early in their course and become subserous. Alternatively, they can protrude into the endometrial cavity and distort it. The submucous fibroid is one that has penetrated the endometrial cavity and has enlarged so as to stretch the mucosa over the tumor to the point that the submucosa is absent and ulceration of the overlapping endometrium may occur. Although not all submucous fibroids cause clinical bleeding or interfere with conception and normal pregnancy, they certainly are associated with significant symptomatic disturbances of this type, exhibiting menorrhagia, anemia, pelvic cramping, infection, infertility, and abortion among the more commonly seen problems.
Myomectomy removes the fibroid without removing the uterus. Laparoscopic Myomectomy involves removing pedunculated subserosal fibroids through the navel and abdomen with the use of a laparoscope. Hysteroscopic Myomectomy involves the vaginal removal of submucosal fibroids through the use of a hysteroscope. Laparotomy (abdominal myomectomy) involves an abdominal incision that allows for the removal of all fibroids no matter their location, size, or number. Laparoscopic myomectomy with allows for the removal of slightly larger subserosal fibroids than what the laparoscope alone can handle and generally includes a relatively small incision of 3 inches or less in the abdomen.
Laparoscopic assisted vaginal myomectomy (LAVM) allows for the laparoscopic removal of subserosal fibroids from the uterus with the total removal of fibroid material through a vaginal incision. Uterine fibroid embolization (UFE, also known as uterine artery embolization UAE) is a minimally-invasive, non-surgical procedure performed by an interventional radiologist (IR). This procedure involves placing a catheter into the artery and guiding it to the uterus. Small particles are then injected into the artery. The particles block the blood supply feeding the fibroids.
Myolysis involves surgical instruments that are inserted through a laparoscopic incision in the abdomen and a high frequency electrical current that is sent to the fibroid. The electrical current causes the blood vessels to vaso-constrict (become very small or close down) and this basically cuts off the blood flow to the fibroids. The fibroids remain in place and are not surgically removed. Without a blood supply, the fibroids eventually die and shrink.
There are three primary forms of hysterectomy. Subtotal, total and radical hysterectomy. Subtotal Hysterectomy involves only the removal of the uterus. The pelvic structural ligaments are not cut and the cervix is left in place. Fallopian tubes and ovaries may or may not be removed. This procedure is always done through the abdomen.
Total Hysterectomy involves removing both the body of the uterus and the cervix, which is the lower part of the uterus. It can sometimes be done through the vagina (vaginal hysterectomy); at other times, a surgical incision in the abdomen is preferable. In a total hysterectomy and bilateral salpingo-oophorectomy, the ovaries and fallopian tubes are removed, along with the uterus and cervix.
In radical hysterectomy the entire uterus and usually both tubes and ovaries as well as the pelvic lymph nodes are removed through the abdomen.
In addition to the direct surgical risks, there may be longer-term physical and psychological effects, potentially including depression and loss of sexual pleasure. If the ovaries are removed along with the uterus prior to menopause, there is an increased risk of osteoporosis and heart disease as well.
The surgical risks of hysterectomy and myomectomy include fever, bladder infection and wound infection. A blood transfusion before surgery may be necessary because of anemia or during surgery for blood loss. Complications related to anesthesia may occur. Other complications can include blood clots, postoperative hemorrhage, bowel obstruction, injury to the urinary tract and death (eleven women die for every 10,000 hysterectomies performed).
Since clinically undetectable uterine cancer cells may be left following local excision of the cancer, typically radiation therapy is given for local tumor control. Radiation therapy can also be used preoperatively to shrink large uterine tumors and make them more easily resectable. Palliative radiation therapy is commonly used to relieve the pain of bone metastasis and for the symptomatic management of metastases to other sites, such as the brain. Fatigue, skin reactions, changes in sensation, color and texture of the skin, and uterine swelling are common during and immediately following a course of radiation therapy to the uterus.
Chemotherapy, hormone therapy, or a combination of the two can be used to palliate the effects of metastatic uterine disease. Recommendations for adjuvant chemotherapy and/or adjuvant hormone therapy are usually based on the number of positive axillary nodes, menopausal status, size of the primary tumor, and the estrogen receptor assay. The chemotherapeutic drugs most commonly used are alkylating agents, antimetabolites, antitumor antibiotics (Herceptin) and vinca alkaloids. Hormone manipulation is achieved primarily through hormone blockers and infrequently by surgical removal of sex hormone-producing glands (oophorectomy, adrenalectomy, or hypophysectomy). Tamoxifen, an anti-estrogen, is the most widely used hormonal agent. The second-line hormonal agents, such as Femara, and Arimidex, are now available for ER/PR negative patients and/or patients who failed tamoxifen. Unfortunately, chemotherapy for uterine cancer can have numerous deleterious side effects including fatigue, weight gain, nausea, vomiting, alopecia, disturbances in appetite and taste, neuropathies, diarrhea, bone marrow suppression, menopausal symptoms, hair loss and weight gain. Additionally, the first line drug of choice, tamoxifen, can increase the risk of uterine cancer and blood clots.
Botulinum Toxin
The anaerobic, gram positive bacterium Clostridium botulinum produces a potent polypeptide neurotoxin, botulinum toxin, which causes a neuroparalytic illness in humans and animals referred to as botulism. The spores of Clostridium botulinum are found in soil and can grow in improperly sterilized and sealed food containers of home based canneries, which are the cause of many of the cases of botulism. The effects of botulism typically appear 18 to 36 hours after eating the foodstuffs infected with a Clostridium botulinum culture or spores. The botulinum toxin can apparently pass unattenuated through the lining of the gut and attack peripheral motor neurons. Symptoms of botulinum toxin intoxication can progress from difficulty walking, swallowing, and speaking to paralysis of the respiratory muscles and death.
Botulinum toxin type A is the most lethal natural biological agent known to man. About 50 picograms of botulinum toxin (purified neurotoxin complex) type A1 is a LD50 in mice. One unit (U) of botulinum toxin is defined as the LD50 upon intraperitoneal injection into female Swiss Webster mice weighing 18-20 grams each. Seven immunologically distinct botulinum neurotoxins have been characterized, these being respectively botulinum neurotoxin serotypes A, B, C1, D, E, F and G each of which is distinguished by neutralization with type-specific antibodies. The different serotypes of botulinum toxin vary in the animal species that they affect and in the severity and duration of the paralysis they evoke. For example, it has been determined that botulinum toxin type A is 500 times more potent, as measured by the rate of paralysis produced in the rat, than is botulinum toxin type B. Additionally, botulinum toxin type B has been determined to be non-toxic in primates at a dose of 480 U/kg which is about 12 times the primate LD50 for botulinum toxin type A. Botulinum toxin apparently binds with high affinity to cholinergic motor neurons, is translocated into the neuron and blocks the release of acetylcholine. 1Available from Allergan, Inc., of Irvine, Calif. under the tradename BOTOX®.
Botulinum toxins have been used in clinical settings for the treatment of neuromuscular disorders characterized by hyperactive skeletal muscles. Botulinum toxin type A has been approved by the U.S. Food and Drug Administration for the treatment of blepharospasm, strabismus, hemifacial spasm and cervical dystonia. Non-type A botulinum toxin serotypes apparently have a lower potency and/or a shorter duration of activity as compared to botulinum toxin type A Clinical effects of peripheral intramuscular botulinum toxin type A are usually seen within one week of injection. The typical duration of symptomatic relief from a single intramuscular injection of botulinum toxin type A averages about three months.
Although all the botulinum toxins serotypes apparently inhibit release of the neurotransmitter acetylcholine at the neuromuscular junction, they do so by affecting different neurosecretory proteins and/or cleaving these proteins at different sites. For example, botulinum types A and E both cleave the 25 kiloDalton (kD) synaptosomal associated protein (SNAP-25), but they target different amino acid sequences within this protein. Botulinum toxin types B, D, F and G act on vesicle-associated protein (VAMP, also called synaptobrevin), with each serotype cleaving the protein at a different site. Finally, botulinum toxin type C1 has been shown to cleave both syntaxin and SNAP-25. These differences in mechanism of action may affect the relative potency and/or duration of action of the various botulinum toxin serotypes.
The molecular weight of the botulinum toxin protein molecule, for all seven of the known botulinum toxin serotypes, is about 150 kD. Interestingly, the botulinum toxins are released by Clostridial bacterium as complexes comprising the 150 kD botulinum toxin protein molecule along with associated non-toxin proteins. Thus, the botulinum toxin type A complex can be produced by Clostridial bacterium as 900 kD, 500 kD and 300 kD forms. Botulinum toxin types B and C1 is apparently produced as only a 500 kD complex. Botulinum toxin type D is produced as both 300 kD and 500 kD complexes. Finally, botulinum toxin types E and F are produced as only approximately 300 kD complexes. The complexes (i.e. molecular weight greater than about 150 kD) are believed to contain a non-toxin hemaglutinin protein and a non-toxin and non-toxic nonhemaglutinin protein. These two non-toxin proteins (which along with the botulinum toxin molecule comprise the relevant neurotoxin complex) may act to provide stability against denaturation to the botulinum toxin molecule and protection against digestive acids when toxin is ingested. Additionally, it is possible that the larger (greater than about 150 kD molecular weight) botulinum toxin complexes may result in a slower rate of diffusion of the botulinum toxin away from a site of intramuscular injection of a botulinum toxin complex.
In vitro studies have indicated that botulinum toxin inhibits potassium cation induced release of both acetylcholine and norepinephrine from primary cell cultures of brainstem tissue. Additionally, it has been reported that botulinum toxin inhibits the evoked release of both glycine and glutamate in primary cultures of spinal cord neurons and that in brain synaptosome preparations botulinum toxin inhibits the release of each of the neurotransmitters acetylcholine, dopamine, norepinephrine, CGRP and glutamate.
Botulinum toxin type A can be obtained by establishing and growing cultures of Clostridium botulinum in a fermenter and then harvesting and purifying the fermented mixture in accordance with known procedures. All the botulinum toxin serotypes are initially synthesized as inactive single chain proteins which must be cleaved or nicked by proteases to become neuroactive. The bacterial strains that make botulinum toxin serotypes A and G possess endogenous proteases and serotypes A and G can therefore be recovered from bacterial cultures in predominantly their active form. In contrast, botulinum toxin serotypes C1, D and E are synthesized by nonproteolytic strains and are therefore typically unactivated when recovered from culture. Serotypes B and F are produced by both proteolytic and nonproteolytic strains and therefore can be recovered in either the active or inactive form. However, even the proteolytic strains that produce, for example, the botulinum toxin type B serotype only cleave a portion of the toxin produced. The exact proportion of nicked to unnicked molecules depends on the length of incubation and the temperature of the culture. Therefore, a certain percentage of any preparation of, for example, the botulinum toxin type B toxin is likely to be inactive, possibly accounting for the known significantly lower potency of botulinum toxin type B as compared to botulinum toxin type A. The presence of inactive botulinum toxin molecules in a clinical preparation will contribute to the overall protein load of the preparation, which has been linked to increased antigenicity, without contributing to its clinical efficacy. Additionally, it is known that botulinum toxin type B has, upon intramuscular injection, a shorter duration of activity and is also less potent than botulinum toxin type A at the same dose level.
It has been reported that botulinum toxin type A has been used in clinical settings as follows:                (1) about 75-250 units of BOTOX® per intramuscular injection (multiple muscles) to treat cervical dystonia;        (2) 5-10 units of BOTOX® per intramuscular injection to treat glabellar lines (brow furrows) (5 units injected intramuscularly into the procerus muscle and 10 units injected intramuscularly into each corrugator supercilii muscle);        (3) about 30-80 units of BOTOX® to treat constipation by intrasphincter injection of the puborectalis muscle;        (4) about 1-5 units per muscle of intramuscularly injected BOTOX® to treat blepharospasm by injecting the lateral pre-tarsal orbicularis oculi muscle of the upper lid and the lateral pre-tarsal orbicularis oculi of the lower lid.        (5) to treat strabismus, extraocular muscles have been injected intramuscularly with between about 1-5 units of BOTOX®, the amount injected varying based upon both the size of the muscle to be injected and the extent of muscle paralysis desired (i.e. amount of diopter correction desired).        (6) to treat upper limb spasticity following stroke by intramuscular injections of BOTOX® into five different upper limb flexor muscles, as follows:                    (a) flexor digitorum profundus: 7.5 U to 30 U            (b) flexor digitorum sublimus: 7.5 U to 30 U            (c) flexor carpi ulnaris: 10 U to 40 U            (d) flexor carpi radialis: 15 U to 60 U            (e) biceps brachii: 50 U to 200 U. Each of the five indicated muscles has been injected at the same treatment session, so that the patient receives from 90 U to 360 U of upper limb flexor muscle BOTOX® by intramuscular injection at each treatment session.
The success of botulinum toxin type A to treat a variety of clinical conditions has led to interest in other botulinum toxin serotypes. A study of two commercially available botulinum type A preparations (BOTOX® and Dysport®) and preparations of botulinum toxins type B and F (both obtained from Wako Chemicals, Japan) has been carried out to determine local muscle weakening efficacy, safety and antigenic potential. Botulinum toxin preparations were injected into the head of the right gastrocnemius muscle (0.5 to 200.0 units/kg) and muscle weakness was assessed using the mouse digit abduction scoring assay (DAS). ED50 values were calculated from dose response curves. Additional mice were given intramuscular injections to determine LD50 doses. The therapeutic index was calculated as LD50/ED50. Separate groups of mice received hind limb injections of BOTOX® (5.0 to 10.0 units/kg) or botulinum toxin type B (50.0 to 400.0 units/kg), and were tested for muscle weakness and increased water consumption, the later being a putative model for dry mouth. Antigenic potential was assessed by monthly intramuscular injections in rabbits (1.5 or 6.5 ng/kg for botulinum toxin type B or 0.15 ng/kg for BOTOX®). Peak muscle weakness and duration were dose related for all serotypes. Water consumption was greater in mice injected with botulinum toxin type B than with BOTOX®, although botulinum toxin type B was less effective at weakening muscles. After four months of injections 2 of 4 (where treated with 1.5 ng/kg) and 4 of 4 (where treated with 6.5 ng/kg) rabbits developed antibodies against botulinum toxin type B. In a separate study, 0 of 9 BOTOX® treated rabbits demonstrated antibodies against botulinum toxin type A. DAS results indicate relative peak potencies of botulinum toxin type A being equal to botulinum toxin type F, and botulinum toxin type F being greater than botulinum toxin type B. With regard to duration of effect, botulinum toxin type A was greater than botulinum toxin type B, and botulinum toxin type B duration of effect was greater than botulinum toxin type F. As shown by the therapeutic index values, the two commercial preparations of botulinum toxin type A (BOTOX® and Dysport®) are different. The increased water consumption behavior observed following hind limb injection of botulinum toxin type B indicates that clinically significant amounts of this serotype entered the murine systemic circulation. The results also indicate that in order to achieve efficacy comparable to botulinum toxin type A, it is necessary to increase doses of the other serotypes examined. Increased dosage can comprise safety. Furthermore, in rabbits, type B was more antigenic than as BOTOX®, possibly because of the higher protein load injected to achieve an effective dose of botulinum toxin type B.
It is known to use a botulinum toxin to treat: intrathecal pain (see e.g. U.S. Pat. No. 6,113,915); paragangliomas (see e.g. U.S. Pat. No. 6,139,845); otic disorders (see e.g. U.S. Pat. No. 6,265,379); pancreatic disorders (see e.g. U.S. Pat. Nos. 6,143,306 and 6,261,572); migraine (see e.g. U.S. Pat. No. 5,714,468); smooth muscle disorders (see e.g. U.S. Pat. No. 5,437,291); prostate disorders, including prostatic hyperplasia (see e.g. WO 99/03483 and Doggweiler R., et al Botulinum toxin type A causes diffuse and highly selective atrophy of rat prostate, Neurourol Urodyn 1998; 17(4):363); autonomic nerve disorders, including hyperplasic sweat glands (see e.g. U.S. Pat. No. 5,766,606); wound healing (see e.g. WO 00/24419); reduced hair loss (see e.g. WO 00/62746); skin lesions (see e.g. U.S. Pat. No. 5,670,484), and; neurogenic inflammatory disorders (see e.g. U.S. Pat. No. 6,063,768). U.S. Pat. No. 6,063,768 cursorily discloses at column 6 lines 39-42 treatment of the inflammatory joint condition pigmented villonodular synovitis and a particular type of joint cancer, synovial cell sarcoma. Column 6, line 53 of U.S. Pat. No. 6,063,768 also discloses, without further explanation, that "tumors" can be treated.
Additionally it has been disclosed that targeted botulinum toxins (i.e. with a non-native binding moiety) can be used to treat various conditions (see e.g. U.S. Pat. No 5,989,545, as well as WO 96/33273; WO 99/17806; WO 98/07864; WO 00/57897; WO 01/21213; WO 00/10598.
A botulinum toxin has been injected into the pectoral muscle to control pectoral spasm. See e.g. Senior M., Botox and the management of pectoral spasm after subpectoral implant insertion, Plastic and Recon Surg, July 2000, 224-225.
Both liquid stable formulations and pure botulinum toxin formulations have been disclosed (see e.g. WO 00/15245 and WO 74703) as well as topical application of a botulinum toxin (see e.g. DE 198 52 981).
Acetylcholine
Typically or in general, only a single type of small molecule neurotransmitter is released by each type of neuron in the mammalian nervous system. The neurotransmitter acetylcholine is secreted by neurons in many areas of the brain, but specifically by the large pyramidal cells of the motor cortex, by several different neurons in the basal ganglia, by the motor neurons that innervate the skeletal muscles, by the preganglionic neurons of the autonomic nervous system (both sympathetic and parasympathetic), by the postganglionic neurons of the parasympathetic nervous system, and by some of the postganglionic neurons of the sympathetic nervous system. Essentially, only the postganglionic sympathetic nerve fibers to the sweat glands, the piloerector muscles and a few blood vessels are cholinergic and most of the postganglionic neurons of the sympathetic nervous system secrete the neurotransmitter norepinephine. In most instances acetylcholine has an excitatory effect. However, acetylcholine is known to have inhibitory effects at some of the peripheral parasympathetic nerve endings, such as inhibition of the heart by the vagus nerves.
The efferent signals of the autonomic nervous system are transmitted to the body through either the sympathetic nervous system or the parasympathetic nervous system. The preganglionic neurons of the sympathetic nervous system extend from preganglionic sympathetic neuron cell bodies located in the intermediolateral horn of the spinal cord. The preganglionic sympathetic nerve fibers, extending from the cell body, synapse with postganglionic neurons located in either a paravertebral sympathetic ganglion or in a prevertebral ganglion. Since, the preganglionic neurons of both the sympathetic and parasympathetic nervous system are cholinergic, application of acetylcholine to the ganglia will excite both sympathetic and parasympathetic postganglionic neurons.
Acetylcholine activates two types of receptors, muscarinic and nicotinic receptors. The muscarinic receptors are found in all effector cells stimulated by the postganglionic neurons of the parasympathetic nervous system, as well as in those stimulated by the postganglionic cholinergic neurons of the sympathetic nervous system. The nicotinic receptors are found in the synapses between the preganglionic and postganglionic neurons of both the sympathetic and parasympathetic. The nicotinic receptors are also present in many membranes of skeletal muscle fibers at the neuromuscular junction.
Acetylcholine is released from cholinergic neurons when small, clear, intracellular vesicles fuse with the presynaptic neuronal cell membrane. A wide variety of non-neuronal secretory cells, such as, adrenal medulla (as well as the PC12 cell line) and pancreatic islet cells release catecholamines and insulin, respectively, from large dense-core vesicles. The PC12 cell line is a clone of rat pheochromocytoma cells extensively used as a tissue culture model for studies of sympathoadrenal development. Botulinum toxin inhibits the release of both types of compounds from both types of cells in vitro, permeabilized (as by electroporation) or by direct injection of the toxin into the denervated cell. Botulinum toxin is also known to block release of the neurotransmitter glutamate from cortical synaptosomes cell cultures.
Wide Distribution of the Botulinum Toxin Substrate
It is known that a botulinum toxin can denervate muscle cells resulting in a flaccid paralysis due to a presynaptic inhibition of acetylcholine release from neurons at a neuromuscular junction. The proteolytic domain of a botulinum toxins acts upon a particular substrate in the cytosol of target cells, cleavage of the substrate preventing membrane docking and exocytosis of acetylcholine containing secretory vesicles. The absence of acetylcholine in the synaptic cleft between innervating neuron and muscle cell prevents stimulation of the muscle cells and paralysis thereby results.
The botulinum toxins are intracellular proteases that act specifically on one or more of three different proteins which control the docking of acetylcholine to containing secretory vesicles. These specific substrates for the botulinum toxins are synaptobrevin, syntaxin and/or SNAP-25. See e.g. Duggan M. J., et al., A survey of botulinum neurotoxin substrate expression in cells, Mov Disorder 10(3); 376:1995, and Blasi J., et al., Botulinum neurotoxin A selectively cleaves the synaptic protein SNAP-25. Nature 365; 160-163:1993. For botulinum toxin types B, D, F and G the particular intracellular substrate is synaptobrevin. SNAP-25, synaptobrevin and syntaxin are known as SNAREs (soluble N-ethylmaleimide sensitive factor attachment protein receptors).
Significantly, it is not only the nerves which innervate muscles which contain the substrate for the botulinum toxins: "The presence of SNAP-25 in presynaptic regions of numerous neuronal subsets and in neural crest cell lines suggests that this protein subserves an important function in neuronal tissues." Oyler G. A. et al., Distribution and expression of SNAP-25 immunoreactivity in rat brain, rat PC-12 cells and human SMS-KCNR neuroblastoma cells, Brain Res Dev Brain Res 1992 Feb. 21; 65(2):133-146, 1992.
Additionally, "[T]he wide occurrence of the SNARE proteins in endocrine cells suggests that they may also serve as general diagnostic markers for endocrine tumors . . . ", Graff, L., et al. Expression of vesicular monoamine transporters, synaptosomal-associated protein 25 and syntaxin1: a signature of human small cell lung carcinoma, Cancer Research 61, 2138-2144, Mar. 1, 2001, at page 2138. For example, it is known that SNAP-25 is widely distributed in neuroendocrine cells (including in chromaffin cells, PC12, GH3, and insulinomas). Furthermore, the botulinum toxin substrate synaptobrevin has been found in fibroblasts and myeloid cells (e.g. mast cells). Duggan M., et al., supra.
Indeed, SNAREs apparently influence or control the membrane fusion of secretory vesicles in most if not all secretory cells. Andersson J., et al, Differential sorting of SNAP-25a and SNAP-25b proteins in neuroblastoma cells, Eur J. Cell Bio 79, 781-789:November 2000.
Thus, the substrate for a botulinum toxin are not restricted to neuronal cells which release the neurotransmitter acetylcholine. The botulinum toxin substrates are therefore "ubiquitously involved in membrane-membrane fusion events" and the evidence points to "a universal mechanism for membrane fusion events" (i.e. for the docking of secretory vesicles with the cell wall) (Duggan 1995, supra).
Thus, the intracellular substrate for botulinum toxin has a ubiquitous distribution in both neuronal and non-neuronal secretory cells. This is clearly illustrated by discovery of the presence of SNAP-25 (a 25 kiloDalton synaptosomal-associated protein and substrate for at least botulinum toxin type A) in at least:    (1) the pancreas (Sadoul K., et al., SNAP-25 is expressed in islets of Langerhans and is involved in insulin release, J. Cell Biology 128; 1019-1029:1995;    (2) the hypophysis (Dayanithi G., et al. Release of vasopressin from isolated permeabilized neurosecretory nerve terminals is blocked by the light chain of botulinum A toxin, Neuroscience 1990; 39(3):711-5);    (3) the adrenal medulla (Lawrence G., et al. Distinct exocytotic responses of intact and permeabilised chromaffin cells after cleavage of the 25-kDa synaptosomal associated protein (SNAP-25) or synaptobrevin by botulinum toxin A or B, Eur J. Biochem 236; 877-886:1996);    (4) gastric cells (Hohne-Zell B., et al., Functional importance of synaptobrevin and SNAP-25 during exocytosis of histamine by rat gastric enterochromaffin-like cells, Endocrinology 138; 5518-5526:1997;    (5) lung tumors (Graff, L., et al. Expression of vesicular monoamine transporters, synaptosomal-associated protein 25 and syntaxin 1: a signature of human small cell lung carcinoma, Cancer Research 61, 2138-2144, Mar. 1, 2001 (small cell lung carcinomas (SCLCs) contain SNAP-25);    (6) intestinal tumors, Maksymowych A., et al., Binding and transcytosis of botulinum neurotoxin by polarized human colon carcinoma cells, J of Bio. Chem, 273 (34); 21950-21957: 1998 (botulinum toxin is internalized by human colon cancer cells);    (7) pancreatic tumors, Huang, X., et al., Truncated SNAP-25 (1-197), like botulinum neurotoxin A, can inhibit insulin secretion from HIT-T15 insulinoma cells, Mol. Endo. 12(7); 1060-1070:1998 (" . . . functional SNAP-25 proteins are required for insulin secretion . . . ", ibid. at page 1060). See also Boyd R., et al., The effect of botulinum neurotoxins on the release of insulin from the insulinoma cell lines HIT-15 and RINm5F, J. Bio Chem. 270(31); 18216-18218:1995, and; Cukan M., et al., Expression of SNAP-23 and SNAP-25 in the pancreatic acinar tumor cell line AR42J, Molec Biol Cell 20 (suppl); 398a, no. 2305:1999 ("SNAP-25 is a SNARE protein that mediates exocytotic events in neuronal and endocrine systems.");    (8) pituitary tumors as well as in normal pituitary cells, Majo G., et al., Immunocytochemical analysis of the synaptic proteins SNAP-25 and Rab3A in human pituitary adenomas. Overexpression of SNAP-25 in the mammososmatotroph lineages, J. Pathol 1997 December; 183(4):440-446;    (9) neuroblastomas, Goodall, A., et al., Occurrence of two types of secretory vesicles in the human neuroblastoma SH-SY5Y, J. of Neurochem 68; 1542-1552:1997. See also Oyler, G. A, Distribution and expression of SNAP-25 immunoreactivity in rat brain, rat PC-12 cells and human SMS—KCNR neuroblastoma cells, Dev. Brain Res. 65 (1992); 133-146. Note that Goodall (1992) discusses only in vitro identification of certain vesicle docking proteins in a single neuroblastoma cell line;    (10) kidney cells (Shukla A., et al., SNAP-25 associated Hrs-2 protein colocalizes with AQP2 in rat kidney collecting duct principal cells, Am J Physiol Renal Physiol 2001 September; 281 (3):F546-56 (SNAP-25 is involved in kidney cell "regulated exocytosis"), and;    (11) normal lung cells (Zimmerman U. J., et al., Proteolysis of synaptobrevin, syntaxin, and SNAP-25 in alveolar epithelial type II cells, IUBMB Life 1999 October; 48(4): 453-8), and; (12) all ovarian cells (Grosse J., et al., Synaptosome associated protein of 25 kilodaltons in oocytes and steroid producing cells of rat and human ovary: molecular analysis and regulation by gonadotropins, Biol Reprod 2000 August; 63(2): 643-50 (SNAP-25 found "in all oocytes and in steroidogenic cells, including granulosa cells (GC) of large antral follicles and luteal cells".
Cholinergic Mammary Gland Tissues
Diverse hyperplasic and neoplastic mammary gland cells are influenced by cholinergic mechanisms. Thus, it has been discovered that there is a "cholinergic mechanism in the alveolar cells activity". Balakina G. B., et al., Localization of choline acetyltransferase in the alveolar portion of the mammary gland of the white mouse, Arkh Anat Gistol Embriol 1986 April; 90(4):73-7. Additionally, there is cholinergic influence upon both mammary dysplasia (fibrocysts) and mammary carcinoma tissues (Dorosevichi A. E., et al., Autonomic nerve endings and their cell microenvironment as one of the integral parts of the stromal component in breast dysplasia and cancer, Arkh Patol 1994 November-December; 56(6):49-53), as well as "a direct cholinergic stimulation of smooth muscle cells" in mammary arteries (Pesic S., et al., Acetylcholine-induced contractions in the porcine internal mammary artery; possible role of muscarinic receptors, Zentralbl Veterinarmed A 1999 October; 46(8): 509-15).
Significantly, an increase in acetylcholine due to inhibition of cholinesterase has been implicated in increase mammary cell proliferation followed by the development of mammary carcinomas. Cabello G., et al, A rat mammary tumor model induced by the organophosphorous pesticides parathion and malathion, possibly through acetylcholinesterase inhibition, Environ Health Perspect 2001 May; 109(5):471-9. Thus, a decrease in breast cancer cell proliferation appears to be mediated by a cholinergic mechanism. Panagiotou S., "Opioid agonists modify breast cancer cell proliferation by blocking cells to the G2/M phase of the cycle: involvement of cytoskeletal elements, J Cell Biochem 1999 May 1; 73(2):204-11.
Adrenal Medulla
The adrenal or suprarenal glands are small, triangular-shaped structures located on top of the kidneys. Each adrenal gland comprises an adrenal cortex or outer portion and an adrenal medulla or inner portion. The cortex surrounds and encloses the medulla.
The adrenal cortex secretes the hormones cortisol and aldosterone. Cortisol is produced during times of stress, regulates sugar usage, and is essential for maintenance of normal blood pressure. Aldosterone is one of the main regulators of salt, potassium and water balance. If both adrenal glands are removed cortisol and aldosterone replacement therapy is mandatory.
The adrenal medulla secretes the catecholamines adrenalin (synonymously epinephrine) and noradrenalin (synonymously norepinephrine). These hormones are important for the normal regulation of a variety of bodily functions, including stress reaction, when they cause an increase in blood pressure, the pumping ability of the heart, and the level of blood sugar. Removal of the adrenal medulla results in little or no hormonal deficiency because other glands in the body can compensate. Contrarily, excessive catecholamine production can be life threatening.
In the normal adult male about 85% of total catecholamine made by the adrenal medulla is adrenaline, with the remaining 15% being noradrenalin. There is about 1.6 mg of catecholamine present per gram of medulla tissue. Most of the noradrenalin found in blood and urine comes not from the adrenal medulla but from postganglionic sympathetic nerve endings. If the freshly sectioned adrenal gland is placed in fixatives that contain potassium dichromate, the medulla turns brown and this is referred to as the chromaffin reaction, so named to suggest the affinity of adrenal medulla tissue for chromium salts. Hence, cells of the adrenal medulla are often called chromaffin cells. Chromaffin cells also exists outside the adrenal medulla, but usually secrete only noradrenalin, not adrenaline.
The adrenal medulla can be viewed as a sympathetic ganglion innervated by preganglionic cholinergic nerve fibers. These nerve fibers release acetylcholine which causes secretion of catecholamines (primarily adrenaline) by a process of exocytosis from the chromaffin cells of the adrenal medulla. The normal adrenal medulla is innervated by the splanchnic nerve, a preganglionic, cholinergic branch of the sympathetic nervous system. The activity of the adrenal medulla is almost entirely under such cholinergic nervous control.
Chromaffin Cell Tumors
Chromaffin cells (including the chromaffin cells of the adrenal medulla) and sympathetic ganglion cells have much in common as they are both derived from a common embryonic ancestor, the sympathagonium of the neural crest, as shown diagrammatically below. Examples of the types of neoplasms which can arise from each these cell types is shown in brackets. Each of the cell types shown can potentially secrete catecholamines.

While most chromaffin cell neoplasms occur in the adrenal medulla, ectopic and multiple location chromaffin cell tumors are known, occurring most commonly in children.
1. Paragangliomas
A paraganglia (synonymously, chromaffin body) can be found in the heart, near the aorta, in the kidney, liver, gonads, and other places and is comprised of chromaffin cells which apparently originate from neural crest cells and which have migrated to a close association with autonomic nervous system ganglion cells. A paraganglioma is a neoplasm comprised of chromaffin cells derived from a paraganglia. A carotid body paraganglioma is referred to as a carotid paraganglioma, while an adrenal medulla paraganglioma is called a pheochromocytoma or a chromaffinoma.
The carotid body is often observed as a round, reddish-brown to tan structure found in the adventitia of the common carotid artery. It can be located on the posteromedial wall of the vessel at its bifurcation and is attached by ayer's ligament through which the feeding vessels run primarily from the external carotid. A normal carotid body measures 3-5 mm in diameter. Afferent innervation appears to be provided through the glossopharyngeal nerve (the ninth cranial nerve). The glossopharyngeal nerve supplies motor fibers to the stylopharyngeus, parasympathetic secretomotor fibers to the parotid gland and sensory fibers to inter alia the tympanic cavity, interior surface of the soft palate and tonsils). Histologically, the carotid body includes Type I (chief) cells with copious cytoplasm and large round or oval nuclei. The cytoplasm contains dense core granules that apparently store and release catecholamines. The normal carotid body is responsible for detecting changes in the composition of arterial blood.
Carotid paragangliomas are rare tumors overall but are the most common form of head and neck paraganglioma. The treatment of choice for most carotid body paragangliomas is surgical excision. However, because of their location in close approximation to important vessels and nerves, there is a very real risk of morbidity (mainly cranial nerve X-XII deficits and vascular injuries) and mortality which is estimated as 3-9%. Tumor size is important because those greater than 5 cm in diameter have a markedly higher incidence of complications. Perioperative alpha and beta adrenergic blockers are given (if the carotid paraganglioma is secreting catecholamines) or less preferably angiographic embolization preoperatively. Radiotherapy, either alone or in conjunction with surgery, is a second consideration and an area of some controversy. Unfortunately, due to location and/or size, paragangliomas, including carotid paragangliomas can be inoperable.
2. Pheochromocytomas
Pheochromocytomas occur in the adrenal medulla and cause clinical symptoms related to excess catecholamine production, including sudden high blood pressure (hypertension), headache, tachycardia, excessive sweating while at rest, the development of symptoms after suddenly rising from a bent-over position, and anxiety attacks. Abdominal imaging and 24 hour urine collection for catecholamines are usually sufficient for diagnosis. Catecholamine blockade with phenoxybenzamine and metyrosine generally ameliorates symptoms and is necessary to prevent hypertensive crisis during surgery, the current therapy of choice. Standard treatment is laparoscopic adrenalectomy, although partial adrenalectomy is often used for familial forms of pheochromocytoma. Malignant (cancerous) pheochromocytomas are rare tumors.
Pheochromocytomas have been estimated to be present in approximately 0.3% of patients undergoing evaluation for secondary causes of hypertension. Pheochromocytomas can be fatal if not diagnosed or if managed inappropriately. Autopsy series suggest that many pheochromocytomas are not clinically suspected and that the undiagnosed tumor is clearly associated with morbid consequences.
The progression of changes in the adrenal medulla can be from normal adrenal medulla to adrenal medullary hyperplasia (a generalized increase in the number of cells and size of the adrenal medulla without the specific development of a tumor) to a tumor of the adrenal medulla (pheochromocytoma).
Treatment of a pheochromocytoma is surgical removal of one or both adrenal glands. Whether it is necessary to remove both adrenal glands will depend upon the extent of the disease. Patients who have had both adrenal glands removed must take daily cortisol and aldosterone replacement. Cortisol is replaced by either hydrocortisone, cortisone or prednisone and must be taken daily. Aldosterone is replaced by oral daily fludrocortisone (FLORINEF™). Increased amounts of replacement hydrocortisone or prednisone are required by such patients during periods of stress, including fever, cold, influenza, surgical procedure or anesthesia.
3. Glomus Tumors
Glomus tumors (a type of paraganglioma) are generally benign neoplasms, also arising from neuroectodermal tissues, found in various parts of the body. Glomus tumors are the most common benign tumors that arise within the temporal bone and fewer than five per cent of them become malignant and metastasize. Glomus tumors arise from glomus bodies distributed along parasympathetic nerves in the skull base, thorax and neck. There are typically three glomus bodies in each ear. The glomus bodies are usually found accompanying Jacobsen's (CN IX) or Arnold's (CN X) nerve or in the adventitia of the jugular bulb. However, the physical location is usually the mucosa of the promontory (glomus tympanicums), or the jugular bulb (glomus jugulare).
The incidence of glomus jugulare tumors is about 1:1,300,000 population and the most striking bit of epidemiology is the predominant incidence in females with the female:male incidence ratio being at least 4:1. Catecholamine secreting (i.e. functional) tumors occur in about 1% to 3% of cases.
Glomus tumors have the potential to secrete catecholamines, similar to the adrenal medulla which also arises from neural crest tissue and can also secrete catecholamines. The neoplastic counterpart of a glomus tumor in the adrenal gland is the pheochromocytoma, and glomus tumors have been referred to as extra-adrenal pheochromocytoma. Catecholamine secreting glomus tumors can cause arrhythmia, excessive perspiration, headache, nausea and pallor.
Glomus tumors can arise in different regions of the skull base. When confined to the middle ear space, they are termed glomus tympanicum. When arising in the region of the jugular foramen, regardless of their extent, they are termed glomus jugulare. When they arise high in the neck, extending towards the jugular foramen, they are termed glomus vagale. When they arise in the area of the carotid bifurcation, they are called carotid body tumors. Other known sites of glomus tumors include the larynx, orbit, nose, and the aortic arch.
Glomus Jugulare tumors are the most common tumors of the middle ear. These tumors tend to be very vascular and are fed by branches of the external carotid artery. The symptoms of a glomus jugulare tumor include hearing loss with pulsatile ringing in the ear, dizziness, and sometimes ear pain. The patient can have a hearing loss due possibly to blockage of the middle ear, but also there can be a loss of hearing due to nerve injury from the tumor mass. Cranial nerve palsies of the nerves which control swallowing, gagging, shoulder shrugging and tongue movement can all be part of the presentation of glomus jugulare tumors. When the tympanic membrane is examined a red/blue pulsatile mass can often be seen. Symptoms are insidious in onset. Because of the location and the vascular nature of the tumors, a most common complaint is pulsatile tinnitus. It is believed that the tinnitus is secondary to mechanical impingement on the umbo is most cases. Other common symptoms are aural fullness, and (conductive) hearing loss.
Current therapy for a catecholamine secreting glomus tumor is irradiation and/or surgical ablation, preceded by administration of alpha and beta blockers. Treatment for glomus jugulare tumors includes administration of alpha and beta blockers. X-ray therapy can be used to improve symptoms even if the mass persists. It is also possible to embolize the tumor with materials which block its blood supply, however this procedure has associated problems with causing swelling of the tumor which can compress the brain stem and cerebellum as well as releasing the catecholamines from the cells which die when they lose their blood supply. Surgery can be carried out upon small tumors appropriately located. The complications of surgery for a glomus jugulare tumor are persistent leakage of cerebrospinal fluid from the ear and also palsy of one of the cranial nerves controlling face movement, sensation or hearing.
Even though the surgery may be successful glomus jugulare tumors are somewhat problematic because they have a high recurrence rate and may require multiple operations. Surgical ablation carries the risk of morbidity due mainly to iatrogenic cranial nerve deficits and CSF leaks. Lack of cranial nerve preservation is probably the most significant objection to surgical intervention because of the associated morbidity of lower cranial nerve deficits. Radiotherapy also has serious complications, including osteoradionecrosis of the temporal bone, brain necrosis, pituitary-hypothalamic insufficiency, and secondary malignancy. Other postoperative complications include CSF leaks, aspiration syndromes, meningitis, pneumonia and wound infections.
Thus, there are many deficiencies and drawbacks of the current therapies for benign uterine glandular afflictions and uterus cancers and hyperplasic tissues.
What is needed therefore is an effective, non-surgical ablation, non-radiotherapy therapeutic method for treating uterine glandular neoplasms and precancerous hyperplasic uterine tissues.


A touch panel and a manufacturing method thereof, and a touch display device are provided. The touch panel includes a first substrate and a second substrate disposed opposite to each other, and the first substrate and the second substrate have an interval therebetween. The first substrate includes a first base substrate and a force touch electrode layer disposed on the first base substrate, the force touch electrode layer includes a plurality of independent force touch electrodes. The second substrate includes a second base substrate and a capacitance reference layer disposed on the second base substrate.

Force touch is a hot research topic and a cutting-edge technology in the current electronic touch field, which has a broad application prospect and huge market potential.
A usual force touch has a difficult technological process, a complex structure, and high costs, and the usual force touch process is only used in a few high-end flagship electronic devices. It is extremely unfavorable for the promotion of force touch technology.

Touch panel and manufacturing method thereof, and touch display device

Hefei Xinsheng Optoelectronics Technology Co., Ltd.


The present disclosure describes a semiconductor structure and a method for forming the same. The semiconductor structure can include a substrate, a fin structure over the substrate, a gate structure over the fin structure, an epitaxial region formed in the fin structure and adjacent to the gate structure. The epitaxial region can embed a plurality of clusters of dopants.

Advances in semiconductor technology has increased the demand for transistors with higher performance for faster processing systems. To meet this demand, it is important to reduce the transistor's contact resistance to minimize the transistor delay (e.g., RC delay). Heavily doped source/drain terminals can reduce the transistor's contact resistance, thus increasing transistor speed.
Illustrative embodiments will now be described with reference to the accompanying drawings. In the drawings, like reference numerals generally indicate identical, functionally similar, and/or structurally similar elements.

Source/drain structure for semiconductor device

Taiwan Semiconductor Manufacturing Co., Ltd.


A voting system provides for a computer-prepared and computer-printed election ballot generated by input from the voter, and provides for auto-verification whereby the voter has the opportunity and the responsibility to inspect the computer-printed ballot with his or her votes. The voting system also provides for correction of the votes of the voter in the computer station and correction of the votes of the voter shown on the printed ballot if such votes are not shown on the printed ballot as intended by the voter. Ultimately, the voter is presented with a printed ballot prepared by the voting station and its connected printer which accurately presents the votes of the voter for submission by the voter for final tabulation.

Current mechanical and electronic voting systems that do not involve physical alteration of ballot material by the voter do not provide for voter verification of the correctness of his or her own vote. Current voting systems that do involve physical alteration of ballot material by the voter to effect voting are subject to erroneous or incompetent handling by the voter. When such erroneous or incompetent handling by the voter occurs, the mechanical or electronic means for counting the votes on the ballot are affected, and the ballot may be rejected or the counting otherwise rendered inaccurate or suspect. The circumstance of ballot rejection or inconsistent mechanical tabulation in the case of erroneous or incompetent handling by the voter often requires manual examination of ballots, which is not only laborious and subject to its own inaccuracies, but is also inherently fraught with difficulty in maintaining the integrity of the election process. The principal object of the present invention is to provide a voter with a printed ballot prepared by a computer station and printer from input by the voter which completely and accurately presents the votes of the voter, and which is in a familiar form for easy review of his or her vote by the voter, so that machine and human error may be detected and corrected before the ballot is finally submitted by the voter for tabulation with the votes of other voters.
There is no prior art that this invention builds upon except its generic relationship to the well-known concept of electronic and mechanical voting machines, including those which produce a permanent paper record in addition to direct electronic and mechanical tabulation. However, there does not appear to be any prior art which combines accurate electronic or mechanical preparation of a printed ballot with an opportunity for review of the ballot by the voter and mechanical or electronic comparison of the printed ballot with the data stored from the voter input.
The present invention has elements that may be considered to be covered generally by class 235, particularly subclass 51 covering machines employed for casting and counting votes.

Auto-verifying voting system and voting method


The invention relates to an injector for injecting fuel, which is under extremely high pressure, into the combustion chambers of an internal combustion engine. A valve body is provided, which opens and closes a valve chamber received in the injector housing, and an inlet leads from the valve body to the injection nozzle. For actuating the valve body, a control chamber of the injector housing is pressure-relieved by means of a control element. The inlet originating at the high-pressure collection chamber (common rail), extends centrally through the valve body, which is received movably in the injector housing.

1. Field of the Invention
In direct-injection internal combustion engines, injectors are known and used to inject the fuel, which is at very high pressure, into the combustion chambers of internal combustion engines. In injection systems with high-pressure collection chambers (common rails), the inlet lines usually discharge laterally in the housing of the injector body, where they take up space, since the inlets originating at the high-pressure collection chamber leading to the individual injectors for the cylinders of a direct-injection engine must be embodied with enough strength to permanently withstand the high pressures that occur.
2. Description of the Prior Art
German Patent Disclosure DE 198 35 494 A1 relates to a unit fuel injector. The unit fuel injector serves to supply fuel to a combustion chamber of direct-injection internal combustion engines, with a pump unit for building up an injection pressure and for injecting the fuel into the combustion chamber via an injection nozzle. A control unit is also provided, which acts on a control valve embodied as an outward-opening A valve, and a valve actuation unit is also provided, for controlling the pressure buildup in the pump unit. To create a unit fuel injector with a control unit that has a simple design, is small in size, and in particular has a fast response time, the disclosure proposes that the valve actuation unit be embodied as a piezoelectric actuator.
German Patent DE 37 28 817 C2 relates to a fuel injection pump for an internal combustion engine. In a fuel injection pump, the control valve member is embodied of a valve shaft, which forms a guide sleeve and slides in a conduit, and a valve head connected to the valve shaft and oriented toward the actuation device. The sealing face of the valve head cooperates with the face of the control bore that forms the valve seat. The valve shaft, on its circumference, has a recess whose axial length extends from the inlet orifice of the fuel supply line to the beginning of the sealing face, cooperating with the valve seat, at the valve head. A face exposed to the pressure of the fuel supply line is formed in the recess and is equal in area to a face of the valve head that in the closed state of the control valve is exposed to the pressure of the fuel supply line, and as a result, in the closed state the valve is pressure-balanced. A spring that urges the control valve to its opening position is disposed in the guide sleeve.
The available space in the cylinder head region of motor vehicle internal combustion engines is extremely scarce. When the injector proposed by the invention is used to inject fuel that is at high pressure into the combustion chambers of an internal combustion engine, the injector can be designed in a more space-saving way, so that less installation space is needed in the cylinder head region of an internal combustion engine. Moreover, the injector body or in other words the housing of the injector can now be designed and produced much more economically, since the inlet, to be provided laterally on the housing and integrated with the housing, for the inlet line to the high-pressure collection chamber can now be omitted. The connection of the inlet line, originating at the high-pressure collection chamber, can be made substantially more economical by means of a screw fastening element that permanently withstands the incident high pressures.
The accessibility of the injector housing from above exists without requiring that the entire injector body housing be removed in the cylinder head region of an internal combustion engine. Once the inlet line from the high-pressure collection chamber has been unscrewed, a lock nut can very easily be unscrewed from the injector housing, so that the control part can be removed without problems from the injector housing, should that be necessary in an individual case.
Integrating the control chamber between the control part and a central high-pressure connection, provided with a male thread, for connecting the inlet from the high-pressure collection chamber makes it possible to embody the control slide substantially more compactly, resulting in a lower structural height of the injector body housing proposed according to the invention. The spring element that acts on the valve body is let into the control chamber, and the control volume can be reduced by integrating this spring element with the control chamber. A throttle elementxe2x80x94embodied as a simple through borexe2x80x94is provided in the wall of the male-threaded central connection element for the inlet from the high-pressure collection chamber, and with this through bore the high-pressure collection chamber can be acted upon by the fuel supply that forms the control volume. The male-threaded connection piece, acting as a central connection to the high-pressure collection chamber, serves with its extension embodied below the inlet throttle as a guide for the valve body. Upon pressure relief of the control chamber by triggering of a piezoelectric actuator or electromagnet, the valve body, upon pressure relief of the control chamber by the actuator-actuated control element, is guided and centered at the extension of the central high-pressure collection chamber connection piece.

Injector with central high-pressure connection


A plurality of portable tokens are issued e.g. for authenticating instructions within an electronic banking network. Each token requires entry of a respective password in order to operate and becomes locked if a number of incorrect password entries are made. Each token also stores a respective cryptographic key and a random number generator. In order to unlock a locked token it outputs a random number and also encrypts that number under its respective key but does not output the result of the encryption. The random number is transmitted by the user to a central authority which stores the keys for all tokens. The authority encrypts that number under the respective key and returns the result of the encryption to the user of the token. The returned number is entered into the token and if it agrees with the result of the internal encryption the token is unlocked.

The present invention relates generally to the field of electronic access control and more particularly to systems in which respective users are equipped with portable code-generating tokens into which a personal identification number (PIN) or other password corresponding to a respective user account must be entered in order for the token to perform an operation for that account. That operation may in turn be, for example, the generation of a "dynamic password" for use in gaining access to a data network or the generation of a "digital signature" for use in the authorisation of a financial transaction, (as known e.g. in the case of the tokens marketed by the present applicant under the trade mark WATCHWORD). The purpose of the initial password entry is of course to ensure that any such token can be used only by a person authorised to do so. It is also necessary to ensure that the correct password cannot be discovered by an unauthorised person through repeated trial and error. For this reason it is conventional to programme such tokens to become inoperative (or "locked") in response to a predetermined number of consecutive incorrect password entries and once a token has become locked in this way it will remain so even if the correct user account password is subsequently entered. While this is of great value for the prevention of fraud in the event that a token falls into unauthorised hands it is equally of great inconvenience should a token become locked in the hands of an authorised user through the inadvertent repeated entry of an incorrect password, and some means must be provided for unlocking the token in such circumstances.
The conventional technique for unlocking an inadvertently locked token is to enter a separate "master" password which the token (and others used by the same organisation) has been programmed to recognise as overriding its locking function. Since knowledge of this "master" password would prejudice the security afforded by the locking function it is imperative that it is itself kept secret. In practice, therefore, it is usual for this "master" password to be known only to the central authority from whom the locked token was issued and to whom the token must therefore be returned to be unlocked. This is inconvenient to the user whose token will remain out of action until reissued and can represent an expensive administrative overhead to the issuing authority.
The present invention accordingly seeks to provide a means for the unlocking of locked tokens which can avoid the need to return such tokens to their issuing authority while at the same time avoiding the possible dissemination of information useful for subverting their locking function.


A collapsible fixator system comprising a first frame member and a second frame member and at least one strut. Each frame member comprises an upper surface, a lower surface, and a plurality of apertures extending from the upper surface to the lower surface. Each of the at least one struts comprises first and second strut connectors, such that the first and the second strut connectors are operable to releasably connect the strut to the first frame member and the second frame member. When the first and second strut connectors are in a first, collapsed position, the strut is releasably positioned substantially parallel to the upper and lower surfaces of the first and second frame members. When the first and second strut connectors are in a second, erect position, the strut may be fixedly positioned such that the first and second frame members are spaced apart from one another.

External orthopedic fixation devices are commonly used in the treatment of limb injuries and deformations including skeletal fractures, soft tissue injuries, delayed union of skeletal bones resulting from slow healing, non-union of skeletal bones involving unhealed bones, mal-union of bones resulting from the improper healing of broken or fractured bones, congenital deformities resulting from bones developing in a mal-position, and bone widening or twisting. Medical procedures involving external orthopedic fixation devices include limb lengthening, deformity correction, and the treatment of fractures, mal-unions, non-unions, and bone defects. Typically, external fixator systems may be placed on a subject's (e.g., a human or another vertebrate animal) affected limb by a medical professional to set the impacted bones or bone fragments in a desired position. The fixator systems may be adjusted throughout the treatment process in order to set and maintain the bones in a desired position. However, the known fixator systems are often large and unwieldy, making it difficult to transport, store, and then affix to a subject.
Therefore, it is desirable to have an external fixator system that may be readily collapsed or erected to allow the system to be more easily fitted to a patient's limb and for adjustment of the fixator system without the need to remove the system from the patient's limb.

TEXAS SCOTTISH RITE HOSPITAL FOR CHILDREN


A plastic basket of a nestable shopping cart is integrally formed with support projections at upper inner edge portions of the side panels thereof at a position spaced rearward of a front panel. The support projections are adapted to support a pivoting rear gate member of a similarly constructed cart such that, when the two carts are nested, the rear gate panel abuts and is supported by the support projections in order to prevent the rear gate panel from dropping down into the plastic basket during cart nesting.

1. Field of the Invention
The present invention pertains to nestable carts for use at supermarkets or the like and, more particularly, to a rear gate panel support arrangement for blocking a pivoting rear gate panel of one cart from dropping down into a plastic basket of another cart during cart nesting.
2. Discussion of the Prior Art
Nestable carts for use at supermarkets or the like are widely known in the art. In general, such carts each include a basket supported upon a metal frame wherein the basket is formed with a rear panel that is adapted to pivot upon being engaged by a front portion of another cart. With this arrangement, the front portion of one cart can become nested within the basket of the other cart. This enables numerous carts to be stored in a compact manner.
The baskets for such carts are either formed from metal wires or plastic. Forming the baskets from plastic has numerous advantages since, for example, the baskets can be made lighter for ease of maneuverability, the plastic will not rust or corrode, and the baskets are less likely to cause damage to vehicles in the parking lot of a store using such baskets. Unfortunately, as with other types of cart, carts made with plastic baskets suffer from the drawback that, when similarly constructed carts are nested, the pivoting rear panel of a forward cart can drop within the basket portion of a nested cart which makes unnesting the carts extremely difficult.
In the prior art, this problem has been solved in the plastic shopping cart art by providing stop brackets that are welded to a reinforcing ring that supports the plastic basket. These stop brackets extend about an upper edge of the plastic basket and project into the basket itself. Such a known arrangement is exemplified in FIG. 7 of the present application.
Although the presence of the stop brackets can function well to prevent the pivoting rear gate panel of the forward cart from dropping within the basket of a cart nested therewith, the connections between the stop brackets and the reinforcing ring have been known to fail over time mainly due to the fatigue loading placed thereon. In addition, assembly of the stop brackets to the reinforcing ring requires an additional manufacturing step, as well as the production of additional components. Obviously, these factors result in increased repair and manufacturing costs. Furthermore, these stop brackets can catch on articles and the like placed within the basket which is undesirable. Finally, these stop brackets are not aesthetically appealing.
Therefore, there exists a need in the art for a rear gate panel support arrangement for use on plastic, nestable carts which will not only function to prevent a pivoting rear gate of a forward cart from dropping into the plastic basket of a nested cart but which will be more economical to manufacture, more reliable and aesthetically appealing.

Integrally molded gate support arrangement for plastic shopping cart baskets


A method is described that involves referring to first information from a directory table in system memory. The first information includes location information and size information of a first slice of system memory where first tracing data is to be stored. The method also includes tracking the amount of tracing data stored in the first slice of system memory and comparing the amount against the size information. The method also includes, before the first slice of system memory is filled, referring to second information from the directory table in system memory, where, the second information includes location information and size information of a second slice of system memory where second tracing data is to be stored. The first slice is not contiguous with the second slice of system memory.

Software developers often desire to "trace" the execution of their code. Tracing involves keeping a record of the specific sequence of instructions actually executed by software during its runtime. By logging the sequence of instructions, developers can study the instruction sequence to, e.g., identify flaws in the structure and/or flow of the code.
Tracing is typically supported by the underlying processor hardware which contains special logic circuitry to identify instructions as they execute and store them (or respective identifiers of them) in system memory in the order that they execute. For simplicity the remainder of the document may refer to the content of the tracing data as "tracing data", "tracing information", and the like. The reader will understand that tracing data corresponds to actual copies of instructions, portions thereof or some other identifier of the individual instructions or sequence thereof.

Processor that records tracing data in non contiguous system memory slices


A method for coding view-dependent texture attributes of points in a 3D point cloud prior to transmission and decoding includes creating a supplemental enhancement information (SIE) message for the 3D point cloud prior to transmission and decoding. The SEI message includes parameters related to texture attributes of individual points in the 3D point cloud for a plurality of viewing states at an initial time, such that when the SIE message is received at a decoder, the decoder is enabled to use the message to classify the texture attributes and apply one or more texture attributes to individual points such that the texture of each individual point in the decoded 3D point cloud is a correct representation of texture of that individual point in the 3D point cloud prior to transmission and decoding for each of the viewing states.

Point clouds are used for transmission of 3D data, either captured by cameras, scanners, LIDAR sensors etc, or generated by computer graphics for popular applications such as VR/AR. A point cloud is a set of points representing the target object in 3D space. 3D point clouds can carry several attributes associated to one single point. For example, each point may be characterized by texture (meaning color, often defined in terms of R, G, B values), a surface normal (with respect to a frame of reference for the point cloud), and a surface reflectance. So there may be 3 or more different attribute types "attached" to the same single point in the cloud.
An important observation inspiring the present invention is that texture attributes may depend significantly on viewing state. For example, a point may be perceived to be of a certain texture (color) if viewed from one positional point in space and one rotational angle under one particular level and type of illumination, and of a different texture if viewed from a different position and/or rotational angle and/or illumination.
In cases where the initial point cloud data are generated based on views of an object captured by cameras or other image sensors, it may be envisaged that different textures are perceived for one point, related to the different capturing directions from which each texture is "registered" by the camera(s). At the decoder side, if the directions of the capturing cameras are known, the decoder would ideally be able to select the "right" texture according to whatever viewing position the decoded point cloud data is viewed from. To achieve this, however, the decoder would have to receive some extra information associated to the texture attributes, to indicate whether and when to use which value. Moreover, the capturing conditions might change after the initial data are transmitted, so updated information on camera positions etc., would also need to be sent to the decoder for appropriate adjustments to be made in decoding correspondingly updated versions of the cloud point data.
In cases where the initial point cloud data, including texture attributes, are generated by a computer graphics system rather than captured image data, it would similarly be advantageous to generate extra (view-dependent) information associated with those attributes, such that transmitting this information as well as the initial point cloud data to a decoder would enable the decoder to adjust the texture attributes as appropriate for post-decoding viewing position. The texture quality achievable in the decoding will depend in part on the computing resources available, and decisions on the most efficient use of those resources for that viewing position.
Current video coding syntax used in point cloud coding (V-PCC) does not have a mechanism to provide view-dependence information associated with the attributes, or to update the current initial definitions of camera position (which will correspondingly affect attribute values) if the positions or viewpoints change over time definitions. It would therefore be desirable to develop a method of coding point cloud data to include additional information relative to each viewing state for which data is available. This would enable a decoder receiving the point cloud data to use that viewing state information to present each point with the appropriate texture value for each viewing state of interest at the decoder side of the system. Ideally the method would also include information that would allow for changes in viewing state over time to be tracked, and the corresponding textures to be updated as necessary.
It should be noted that in computer graphics applications, where attribute values are generated rather than captured, system resource availability may change over time, affecting the amount of view dependent information than can be generated, and possibly even limiting the information to a view-independent data set. An improved coding syntax would ideally be able to signal such changes to the decoder.

Method and apparatus for coding view-dependent texture attributes of points in a 3D point cloud


A vehicle lamp assembly includes a body having a reflector, a lens, and a bulb. The assembly further includes a bezel, at least one adjuster arm attached to the body and to the bezel, and at least one biasing arm attached to the body and to the bezel. The biasing arm is configured to aim the reflector in accordance with movement of the adjuster arm while minimizing a gap between the bezel and the lens.

Some vehicle lamp assemblies are installed directly to the vehicle fascia. Later, near the end of the manufacturing process or sometimes in an aftermarket setting, the lamp assembly needs to be adjusted. Adjusting the lamp assembly can include changing an angle of the lamp assembly relative to the fascia. Doing so, however, creates gaps between the lamp assembly and the fascia since the margins between the lamp and fascia must be large enough to account for all possible aim conditions. The gaps can negatively affect the aesthetics of the vehicle.


An apparatus to remove periodic disturbances in a recording medium having large eccentricity and deflection mass includes an actuator to change a position of a pickup in response to a combination of first and second compensation signals, an error detector to detect an error between positions actuator and the recording medium, a first compensator to receive the detected error and to output the first compensation signal that the actuator uses to actuate the pickup along the recording medium in upper and lower directions, and right and left directions; and a second compensator to output the second compensation signal from which the disturbance has been removed, to combine the compensated error and previous first and second compensation signals, and to filter the combined result at a predetermined bandwidth.

1. Field of the Invention
The present invention relates to an apparatus and method of operating a recording medium, and more particularly, to an apparatus and method of removing a disturbance in a recording medium having a large eccentricity and deflection.
2. Description of the Related Art
The eccentric mass of a disc in an optical recording medium drive system is caused by a discrepancy between a spindle rotation axis for rotating a disc, the center of a track of the disc and different curvature characteristics of the optical recording medium. Further, the distance between a pickup and an optical recording medium may change according to the shape of the recording medium, or because its surface shakes as the recording medium rotates. In particular, such a change occurs when the surface of the optical recording medium vibrates in the vertical direction of the optical recording medium, which is referred to as "deflection".
The eccentricity and deflection of the optical recording medium are major factors causing a disturbance in an optical recording medium drive system, and clearly affect the recording and reproducing capability of the optical recording medium drive system at a high playback speed. Therefore, the eccentricity and deflection must be compensated in order to precisely follow a track. In the past, the eccentricity of an optical recording medium has been compensated using a learning control algorithm.
FIG. 1 is a block diagram of a tracking control system including a conventional repetition learning control structure. This tracking control system includes a sensor K(S) 10, a controller C(S) 11, a driver V(S) 12, an actuator P(S) 13, and a repetition learning controller 14. The sensor K(S) 10 outputs a tracking error signal e(t) containing information on the center of a track and the position of a pickup. The sensor K(S) 10 includes a photo diode (not shown) that detects the extent to which a pickup (not shown) deviates from a pre-focus position or the center of a track, and a radio-frequency (RF) amplifier (not shown) that amplifies a signal output from the photo diode and outputs the tracking error signal e(t). The controller C(S) 11 receives the tracking error signal e(t) output from the sensor K(S), and outputs a compensation signal instructing the pickup to be positioned at the center of a track even if a disturbance of the track occurs. The compensation signal output from the controller C(S) 11 is applied to the actuator P(S) 13 via the driver V(S) 12.
In an optical recording medium drive system, disturbances occur for many reasons. For example, noise causes a disturbance. However, a main factor in causing disturbances is the eccentricity of a disc. The disturbance due to the eccentricity of a disc is caused by the rotation of the disc, and occurs periodically in accordance with the disc rotation frequency. The disturbance due to eccentricity contributes to the tracking error. In general, an increase in the eccentricity mass of a disc results in an increase in the size of a periodic disturbance component of the tracking error. Thus it is difficult to compensate for such a periodic disturbance with only the controller C(S) 11. For this reason, a repetition learning control is performed by the repetition learning controller 14 so as to cancel the periodic disturbance.
The repetition learning controller 14 reads an output Ufb(t) of the controller C(S) 11 in response to an FG signal, which is a synchronization signal used to judge a period, and stores data Uff(t), which is to be compensated in a memory 14-2 according to a learning control algorithm 14-1. Once the compensation of the data Uff(t) is completed according to the learning control algorithm 14-1, the data Uff(t) is combined with the output Ufb(t) to produce a signal U(t) which is applied to the actuator P(S) 13. As a result, the periodic disturbance due to the eccentricity of the disc is canceled. The performance of the repetition learning controller 14 depends on how much data is stored in the memory 14-2 during a rotation period of a disc.
There are two main methods of learning data using the repetition learning controller 14. One method is to store an output of the controller C(S) 11 in the memory 14-2 during one period of the FG signal, and output the data stored in the memory 14-2 in synchronization with the FG signal during the next period. An advantage of this method is that learning time is short, but the method can only be used on the assumption that the controller C(S) 11 is operating normally.
The other method is to repeatedly learn data for several periods until the size of a tracking error is reduced by a certain degree. In detail, the data Uff(t) output from the learning control algorithm 14-1 is repeatedly learned in consideration of an output of repetition learning performed during the previous period, and a tracking error. Here, the data is continuously learned over several periods. Therefore, the more periods over which the learning is repeated, the more the periodic disturbance contained in a tracking error can be reduced. That is, continuously learning a periodic disturbance makes it possible to cancel as much of the periodic disturbance as possible. However, this method requires a lot of time for repetition learning.
Meanwhile, a repetition learning algorithm uses an FG signal so as to synchronize period. Here, the FG signal has a three or six period according to the phase of a spindle motor during which a disc is rotated for one period. During one rotation period of a disc, the less the number of FG signals, the less the number of FG edges through which synchronization of a period is checked. Thus, the performance of the repetition learning algorithm 14-1 is lowered. In general, the performance of the repetition learning algorithm 14-1 depends on how much data can be stored and output during one rotation period of a disc. However, if the amount of data to be stored is increased, the sampling frequency increases and the capacity of the memory 14-2 in which the data is stored must be increased. On the other hand, if the amount of data to be stored is small, the resolution of the repetition learning controller 14 becomes poor and the performance of the repetition learning algorithm 14-1 deteriorates.
Further, a high performance microcontroller (not shown) or a programmable digital signal processor (DSP) (not shown) is required to apply a repetition learning algorithm 14-1 to a conventional tracking control system. However, in fact, most optical recording medium drive systems use a hard-wired DSP and an inexpensive 8-bit microcontroller. Therefore, a repetition learning algorithm 14-1, which places a burden on the system, is not available.

Apparatus and method of removing disturbances during optical recording and/or reproducing


The present invention relates to cellulose fiber containing 500 to 2000 of filaments and having homogeneous physical properties and the multi-filaments according to the present invention is characterized in that the strength and the breaking elongation of the multi-filaments are 4 to 9 g/d and 4 to 15%, respectively. In particular, the present invention is characterized in that each mono-filament selected 100 strands from every three part divided from multi-filaments has properties as following: (a) 3 to 9 g/d in average strength, 7 to 15% in average breaking elongation and 0.035 to 0.055 in by birefringence, (b) the differences of the above three parts are below 1.0 g/d in average strength, 1.5% in breaking elongation and 0.7 denier in denier, (c) the CV (%) (coefficient of variation) of the above three parts are below 10%, and (d) the birefringence differences of the above three parts are below 0.004.

A cellulose fiber manufactured with a cellulose and NMMO is utilized in various fields needing the cellulose fiber in the process of manufacturing, because all the solvent used in the process of manufacture of the cellulose fiber is recycled and therefore the manufacture of the cellulose fiber corresponds to a non-pollution process, and the produced fiber has high mechanical strength, and referring to EPO no. 0356419, a cellulose solution produced using amine oxide together with NMMO is described, and U.S. Pat. No. 4,246,221 discloses a method for producing a cellulose solution with a tertiary amine oxide, and according to the above U.S. Pat. No. 4,246,221 the cellulose solution is spun using a device for forming such as a spinneret into filaments and then the filaments are precipitated in a bath to pass a coagulating bath and finally the swollen cellulose containing water is produced. But the above method takes a long time from dissolving to spinning process, and the degradation of physical properties results from heat-decomposition owing the long time process. And also the expense of energy is so much that the large costs for manufacturing are non-avoidable.
On the other hand, H. Chanzy et al. (Polymer Vol 31 pp 400˜405, 1990) produced a cellulose fiber with 56.7 cN/tex of strength and 4% of breaking elongation in a manner that DP 5,000 cellulose was dissolved into NMMO to prepare a cellulose solution, and ammonium chloride or calcium chloride was added to the cellulose solution, and then the resultant was spun through an air gap, but the method for producing the cellulose fiber has difficulty with being available commercially because the number of filaments is only 1 strand and the fibril orientated in direction of axis is exfoliated.
Referring to other prior invention, U.S. Pat. No. 5,942,327 describes a cellulose fiber having 50 to 80 cN/tex (5.7 to 9.1 g/d) strength, 6 to 25% elongation and 1.5 dtex mono strand fineness and produced in a manner that an aqueous NMMO solution into which DP 1,360 cellulose is dissolved is spun through an air gap, but the number of filaments is only 50 strands. The cellulose fiber produced in the above manner has difficulty with being available commercially, considering that generally the number of filaments for using as industrial materials should be about 1000 strands (1,500 denier) because (a) the efficient removal of solvent is necessary in view of process and (b) the capacity of inner skin is enough maximized to resist the repeated fatigue in view of physical property.
In general when a spinning process is performed, in view of technology, spinning with 500 to 2,000 orifices per spinning nozzle is more difficult than spinning with 50 orifices per spinning nozzle. The reason is that the uniform adjustment of spinning pressure is more difficult in proportion to the increase of the number of orifices and thus it is difficult to design a spinning nozzle and a distributing plate, in particular to adjust the condition for cooling evenly in an air gap and for washing and drying homogeneously all the filaments of 500 to 2,000, and as result it is very difficult to make all the filaments posses physical properties above a certain level and the homogeneous physical properties, and therefore the physical properties of 50 strands according to U.S. Pat. No. 5,942,327 is not sufficient for reference to the application of industrial materials.
In particular, because the increase of the number of filaments affects the stability of process relating to adhesion to the filaments spun from the nozzle and the efficiency when a spinning is performed through an air gap, the number of holes in a distributing plate for dispersing evenly the cellulose solution on the nozzle, the space of the holes and the diameter of the holes as well as the outer diameter of the nozzle and the diameter and space of orifices are very important.
As described in the above, as the number of filaments increases a new design for spinning is necessary considering the length of air gap, the blowing condition of cooling air, the direction of the coagulating solution and the spinning speed, and the physical properties may be different according to the design.
U.S. Pat. No. 5,252,284 describes a cellulose fiber having 800 to 1,900 of filaments, however, it was found that when the filaments was spun under the condition of short air gap less than 10 mm and winding speed of 45 m/min the resultant had 15.4% elongation, sufficiently high, and the 47.8 cN/tex (5.3 g/d) strength, not sufficient for use of a industrial material, in particular tire-cord. And the cellulose has disadvantage that the physical properties of each filament are not homogeneous.

This patent is subject to a terminal disclaimer.


The general inventive concepts provide a lighting system, a light device and a receiving device. The lighting device applies a liquid crystal display panel as a luminaire, the liquid crystal display panel has a first polarizer only on a light input side. The receiving device comprises a second polarizer and a magnifying component. The second polarizer is used for polarization-analyzing an emitted light, which is emitted from the liquid crystal display panel and carries confidential information. Light passes through the first polarizer and becomes linearly polarized light, which linearly polarized light is emitted after passing through the liquid crystal display panel. The confidential information carried therein cannot be identified by the naked eye. Therefore, the human eye regards it as white light, the lighting device can thus be used as a lighting luminaire. However, when watching the lighting device through the receiving device, the confidential information displayed by the liquid crystal display panel can be seen clearly.

In general, lighting luminaires are necessary in modern society. For example, the city square, traffic roads, community, home, shopping mall and office building, all need lighting luminaires for lighting or decoration. Due to the abundance of choices of light sources, the evolution of lighting luminaires provides an opportunity for improvement. The emergence of new light sources (such as fluorescent lamps, energy-saving lamps, LED, etc.) plays an important role in the development of lighting luminaires, which cannot be ignored.
Conventionally speaking, lighting luminaires are mainly used for lighting; this limits the development of more functions for the lighting luminaires. Therefore, it is necessary to develop the function of lighting luminaires more extensively, which makes them have a wider application field, thereby making full use of the lighting luminaires.

Lighting system, lighting device and receiving device