This invention defines novel research methodology for use in (a) monitoring the ongoing status of the physiological expression of Charcot-Marie-Tooth disease and (b) screening candidate therapeutic drug agents for possible effectiveness. The presence of this neurodegenerative disease can be characterized in part by the expression in cultured fibroblasts obtained from the patient of one or more proteins which are not the product of a defective disease-inducing gene, but which are stress proteins, one or more other proteins modified by conditions of oxidative stress or other disease-related proteins. This candidate drug screening technology offers advantages in terms of (a) providing new research opportunities, (b) cost effectiveness, (c) ability to be used readily on a large scale, (d) ability to generate meaningful data in a comparatively short period of time, and (e) providing an opportunity to obtain information based on direct interaction of a candidate drug and a living tissue disease model.

1. Field of the Invention
The present invention relates to new diagnostic procedures or to protocols suitable for use in screening candidate therapeutic drug agents. The present invention provides human, living, dynamic experimental models, and metabolic markers related thereto, for examining some aspects of the pathophysiology of familial or non-familial neuro-degenerative diseases selected from the group hereby limited solely to Charcot-Marie-Tooth disease, familial Alzheimer's disease, familial Parkinson's disease, Huntington's disease, spinal muscular atrophy, Friedreich'a ataxia, giant axon neuropathy, juvenile ceroid-lipofuscinosis, familial motor neuron diseases, juvenile diabetic polyneuropathy and Down's syndrome, including various individual genetic subvarieties thereof.
2. Description of Prior Art
J. T. Coyle and P. Puttfarcken (1993), Science 262:689-695 (1993) noted that                There is an increasing amount of experimental evidence that oxidative stress is a causal, or at least an ancillary, factor in the neuropathology of several adult neurodegenerative disorders, as well as in stroke, trauma, and seizures . . . [pg. 689]The authors proceeded to review the various sources and origins of neuronal oxidative stress and reviewed the known intrinsic metabolic mechanisms for natural protection against such stress. They mentioned the ability of vitamin E to inhibit lipid peroxidation (pg. 690, first column, lines 5-9), and they referred to the neuroprotective effect of other antioxidants (i.e., page 692, column one). Notably, on page 690, second column, lines 1-5 the authors also mentioned that        Furthermore, peroxy radicals can combine with an abstracted hydrogen atom to form lipid hydroperoxides which, in the presence of Fe2+, decompose to alkoxy radicals and aldehydes.On page 692 (column three, lines 7-11) the authors specifically mentioned that they were referring to diseases such as Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD). In another statement of particular relevance (page 693, column three, lines 32-39), the authors commented that        . . . notably, protein carbonyl content, a measure of protein oxidation, was elevated by 85% in patents with sporadic ALS as compared to controls, suggesting that oxidative stress is a common feature of ALS whether the disease is due to loss of CuZnSOD activity or to other causes . . .The authors concluded (page 694, column two, lines 5-11), in part        . . . Nevertheless, the evidence, while still largely circumstantial, is convincing that oxidative stress represents an important pathway, initiated in part by Glu, that leads to neuronal degeneration in a manner consistent with the course and pathology of several degenerative disorders of the brain . . .
One aspect of cellular oxidative stress is the pathological formation of crosslinked proteins. As the H polypeptide chains of neurofilaments have an especially high lysine content (20%), neurofilaments are particularly susceptable to spurious crosslinking reactions which may be induced by lipid peroxidation products [Carden et al., Neurochem. Pathol. 5:25-35 (1986)]. The results of several published research studies suggest that dysfunctional lipid peroxidation may be a contributing factor in the etiology of Parkinson's disease [Fahn, Ann. NY Acad. Sci. 570:186-196 (1989)], multiple sclerosis [Hunter et al., Neurochem. Res. 10:1645-1652 (1985)] and Duchenne muscular dystrophy [Kar and Pearson, Clin. Chim. Acta 94:277-280 (1979); Jackson et al., Med. Biol. 62:135-138 (1984); Hunter and Mohamed, Clin. Chim. Acta 155:123-132 (1986)].
A considerable body of prior art has provided evidence suggesting that the etiologies of certain neurodegenerative diseases include evidence of chemical crosslinking of neurofilaments. Such studies include work on Charcot-Marie-Tooth (CMT) genetic neuropathies [Hughes and Brownell, J. Neurol. Neurosurg. Psych. 35:648-657 (1972); Brimijoin et al., Science 180:1295-1297 (1973); van Weerden et al., Muscle & Nerve 5:185-196 1982; and Goebel et al., Ital. J. Neurol. Sci. 7:325-332 1986)], giant axon neuropathy [Prineas et al., J. Neuropathol. Exp. Neurol. 35:458-470 (1976)], diabetic polyneuropathy [Yamamura et al., in Diabetic Neuropathy, Goto, Y, sr, ed. (Princeton, Excerpta Medica, (1982) pp. 80-85; Sidenius and Jakobsen, Diabetes 31:689-693 (1982); and Tomlinson and Mayer, J. Auton. Pharmac. 4:59-72 (1984)], Alzheimer's disease [Wisniewski et al., J. Neuropath. Exp. Neurol. 29:163-176 (1970); and Wisniewski et al, in Aging and Cell Structure, volume 1, Johnson, Jr., J E, ed. (New York, Plenum Press, 1982) pp. 110-112], Down's syndrome [Goodison et al., Soc. Neurosci. Abstr. 15(pt. 2): 329 (abstract 135.6) (1989)], Pick's disease [Yoshimura, Clin. Neuropath. 8:1-6 (1989)], Parkinson's disease [Oppenheimer, in Greenfield's Neuropathology, Blackwood, W and Corsellis, JAN, eds. (Chicago, Year Book Medical Publishers, 1976) pp. 612-614; and Cohan, in Clinical Aspects of Aging, third edition, Reichel, W, ed. (Baltimore, Williams & Wilkens, 1989) pp. 167)], amyotrophic lateral sclerosis [Carpenter, Neurology 18:841-851 (1968)], infantile spinal muscular atrophy [Lee et al., Neuropediatrics 20:107-111 (1989)], Friedreich's ataxia [Lamarche et al., Can. J. Neurol. Sci. 9:137-139 (1982)], and alcoholic polyneuropathy [Appenzeller and Richardson, Neurology (Minneap) 16:1205-1209 (1966)].
Considerable biomedical literature indicates that certain sites on normal proteins and lipids are specific targets for spurious chemical crosslinking, most notably the ε-amino groups of lysine residues in proteins and the amine groups of phosphatidyl-ethanolamine molecules in cell lipid membrane bilayers. These primary amine groups are especially prone to attack by small molecular weight carbonyl-containing hydrocarbons. Such carbonyl-containing molecules may originate by many pathological mechanisms still only partly defined, but, in general, they originate from peroxidation of fatty acids or as by-products of sugar metabolism. A mono-carbonyl specie can bind to a protein or amino-lipid, alter its three dimensional structure and possibly affect its chemical activity. A dicarbonyl hydrocarbon can react with two amine groups, thus making a covalent chemical crosslink. The specific primary pathological changes that underlie this type of deterioration remain largely undefined, but their structural products have been characterized in many respects.
For example, the senile plaques and neurofibrillary tangles typical of Alzheimer's disease consist largely of networks of intermediate size protein filaments helically wound in pairs having a periodicity of 80 nm [Selkoe et al. Science 215:1243-1245 (1982)]. Isolated paired helical filament (PHF) has proven to have remarkable properties of chemical stability. PHF chemical crosslinking bonds are not broken by sodium dodecyl sulfate, β-mercaptoethanol, 9.5 M urea, two percent Triton X-100, one percent NP-40, 6 M guanidine hydrochloride, 0.2 N HCl or 0.2 N NaOH. As heating of PHF in the presence of either reducing agents such as β-mercaptoethanol or detergents such as Triton X-100 or NP-40 did not solubilize PHF, bonds other than disulfide are implicated in amino acid crosslinking of this type of rigid intracellular polymer. This unusual chemical stability has seriously impeded PHF analysis by gel electrophoresis [Selkoe et al. (1982)]. As a postulated mechanism for such unusual crosslinking Selkoe et al. noted that "different protein polymers in senile cataracts, terminally differentiated epidermal cells, and red blood cells are covalently cross-linked by γ-glutamyl-ε-lysine sidechain bridges." Like PHF, these other protein complexes are insoluble in sodium dodecyl sulfate and not solubilized by reducing agents. Selkoe et al. speculated that such γ-glutamyl-ε-lysine crosslinks may also form pathologically in nerve cells, as human brain contains a transglutaminase capable of acting on normal neurofilament to form an insoluble high molecular weight filamentous polymer.
Kikugawa and Beppu [Chem. Phys. Lipids 44:277-296 (1987)] noted that lipid radicals, hydroperoxides and their secondary products (including various aldehydes and ketones) react with neighboring protein molecules, damaging protein structure and function. Such damage includes formation of fluorescent chromophores, lipid-protein adducts, and protein-protein crosslinks. Using sodium dodecyl sulfate-polyacryl-amide gel electrophoresis, these investigators demonstrated that malonaldehyde (also known as malondialdehyde), a bifunctional molecule having two aldehyde groups, can covalently crosslink proteins. This reaction primarily involves Schiff base formation with protein ε-amino groups on the sidechains of lysine residues. Kikugawa and Beppu (1987) also reported that monofunctional aldehydes such as acetaldehyde, 1-hexanal, 1-heptanal and 2,4-decadienal can also crosslink proteins, generating fluorescent products. This biochemical curiosity still not well understood. Some form of self-condensation may be involved.
A report by Piersanti et al. [Neurobiol. Aging 13:S111 (abstract 437) (1992)] documented an increased susceptibility of Alzheimer's disease patient skin fibroblasts to free radical damage. The Piersanti report, taken together with CMT research findings discussed below, lends credence to the concept that skin fibroblast samples from patients having other neurodegenerative disorders will also show evidence of oxidative stress.
Evidence of increased deposition of lipofuscin in various neurodegenerative diseases has been presented. This observation has been documented in studies on amyotrophic lateral sclerosis [Carpenter (1968)], Guam Parkinsonism-dementia [Tan et al., Clin. Exp. Neurol. 17:227-234 (1981)], Alzheimer's disease [Tsuchida et al., Chem. Phys. Lipids 44:297-325 (1987); Moran and Gomez-Ramos, Soc. Neurosci. Abstr. 15(pt. 2):1039 (abstract 414.8) (1989)], Huntington's disease [Tellez-Nagel et al., J. Neuropathol. Exp. Neurol. 33:308-332 (1974)], Meniere's disease [Ylikoski et al. Arch. Otolaryngol. 106:477-483 (1980)], and juvenile ceroid-lipofuscinosis [Schwendemann, in Ceroid-Lipofuscinosis (Batten Disease), Armstrong, D, sr. ed. (New York, Elsevier Biomedical Press, 1982) pp. 117-136]. Heart lipofuscin has been shown to have the following general composition: lipids, 20-50%; protein, 30-60%; and strongly pigmented resin-like hydrolysis-resistant material, 9-20%. Although the exact nature of the hydrolysis-resistant chemical bonds remains to be unequivically defined, the similarity between lipofuscin fluorescence and that of Schiff bases formed between malonaldehyde and primary amines suggests that similar chemical crosslinks may be part of lipofuscin structure [Tsuchida et al. (1987)].
Another fundamental physiological aspect of metabolic oxidative stress is the induction of genes that code for stress proteins, originally known as heat shock proteins (hsp's). Highly conserved genes for these proteins are present in bacteria, plants, yeast and higher animals [Welch, Sci. Am. 268(5):56-64 (1993, pgs. 61-62)]. A wide variety of environmental stimuli are known to induce the expression of these genes, including brief exposures to elevated temperatures, exposure to toxic metals, alcohols, various metabolic poisons, protein denaturants and conditions which induce ischemia/reperfusion trauma (i.e., oxidant injury). Welch [Sci. Am. 268(5):56-64 (1993, pgs. 61-62)] noted that                In animal studies, researchers have observed the induction of stress responses in both the heart and brain after brief episodes of ischemia and reperfusion . . .        Cells that produce high levels of stress proteins appear better able to survive the ischemic damage than cells that do not . . .To some limited extent, some hsp's are normally (i.e., constitutively) expressed in plant, microbial and animal cells. They play a role in normal protein post-translational processing and normal metabolic turnover of proteins. Yet even constitutive hsp's are stress inducible. Of the several different classes of hsp's, the hsp70 gene family is the most stress-inducible member.
Heretofore, some thought has been given to the question of what role hsp's might play in the neurodegenerative diseases addressed herein. However, the question has received little previous attention, and only within a quite limited scope. Autosomal dominant familial forms of Parkinson's disease are now well recognized [Gasser et al., Ann. Neurol. 36(3):387-396 (1994)]. However, a Medline database search from 1976 to April 1995 for references addressing familial Parkinson's disease and stress proteins generated no matches. When a Medline database search from 1976 to April 1995 was expanded to include non-familial cases of Parkinson's disease and stress proteins two references were found [Renkawek et al., Acta Neuropath. 87(5):511-519 (1994) and Namba et al. [Japanese] No to shinkei [Brain & Nerve] 43(1):57-60 (1991)]. However, both of these studies were based on analysis of brain tissue and neither disclosed nor anticipated the present invention.
Likewise, numerous publications have reported genetic forms of Alzheimer's disease [Campion et al. Neurology 45(1):80-85 (1995)]. A Medline database search from 1976 to April 1995 for references addressing familial Alzheimer's disease and stress proteins generated only one match [Guillemette et al., J. Neurochem. 47(3):987-997 (1986)], but actually this paper did not mention that any of its Alzheimer patients had a genetic form of the disease. The report by Guillemette et al. described studies on RNA transcripts obtained from post-mortem Alzheimer's brain biopsy samples. They observed elevated levels of hsp mRNA transcripts in brain samples from Alzheimer patients who had fever immediately prior to death. They also studied human brain mRNA translation (i.e., protein) products. Guillemette et al. reported, in part, that                A positive correlation was found between elevated amounts of the 70-kDa protein and an agonal process accompanied by fever. Two-dimensional analysis of the protein products showed two or more polypeptides for each 70-kDa protein band observed in one-dimensional gels . . . The protein patterns resemble those reported for heat-treated HeLa cells (Slater et al., 1981), suggesting the possibility that heat-shock proteins are expressed in human brain during agonal processes accompanied by fever . . . Despite similarities in the fever profile during the agonal process, control (FIGS. 4b and e) and [Huntington's disease] non-Alzheimer dementia-associated brains (FIGS. 4c and f) exhibited higher yields of 70-kDa peptides than those from Alzheimer-afflicted brains . . .        . . . These results indicate that Alzheimer's disease, in the absence of fever, is not associated with heat-shock response. [pg. 993]        . . . To examine the possibility that the primary pathogenic events that initiate Alzheimer's disease may induce heat-shock expression in the absence of fever, we probed total RNA from the neocortex of an otherwise healthy patient with Alzheimer's disease who died quickly from suicide by hypoxia (K513, FIG. 5, lane 3). There was no detectable expression of the [hsp70] heat-shock transcript in this case . . . [pgs. 994-995].
Hence, Guillemette et al. restricted their study to analysis of brain samples and did not consider the possibility that stress proteins might be expressed preferentially in cultured non-neuronal tissue. They additionally investigated postmortem brain samples from several Huntington's disease patients, which may explain why this paper is considered to be a genetic study in the Medline database system. Yet for this familial neurodegenerative disorder also, Guillemette et al. attributed the expression of hsp70 to the presence of agonal fever (pg. 993). These investigators did not consider Huntington's disease fibroblasts in their studies. Hence, the present invention was not anticipated by Guillemette et al.
A Medline database search from 1976 to April 1995 was expanded to include references addressing non-familial Alzheimer's disease and stress proteins, and several additional reports were found. Yet none disclosed or anticipated the present invention. A representative sampling of these is presented below. The findings of Guillemette and coworkers regarding hsp expression in Alzheimer's disease postmortem brain samples have been independently confirmed by Morrison-Bogorad et al. [J. Neurochem. 64(1): 235-246 (1995)], who noted that                . . . approximately 40% of the [Alzheimer's disease] patients had a recorded fever of > or =39.2 degrees at or near death . . . Levels of hsp70 mRNAs were increased three- to 33-fold in cerebellum of febrile patients compared with levels in patients whose recorded temperatures were < or =37.5 degrees C. . . . These results indicate that a specific agonal stress, namely fever, can increase the levels of heat shock 70 mRNAs in AD brain . . .
Renkawek and coworkers (1994) reported immunohistochemical and immunoblotting findings which indicated a "highly induced" expression of hsp27 in Alzheimer brain samples. They also noted that hsp27 expression was also induced, albeit to a lesser extent, in brain samples obtained from patients having other types of dementia, such as Parkinson's dementia, multi-infarct dementia and normal pressure hydrocephalus. Shinohara et al. [J. Neuro. Sci. 119(2):203-208 (1993)] reported that increased levels of two other small heat shock proteins, α-B crystallin and hsp28, were also found in Alzheimer brain samples. Using an antibody specific for α-B crystallin to immunostain nerve samples from patients having several neurodegenerative diseases, Lowe et al. [Neuropath. Appl. Neurobiol. 18(4):341-350 (1992)] studied ballooned neurons having excess phosphorylated neurofilaments. They found that ballooned nerve samples obtained from classical Pick's disease cases, Alzheimer's disease cases and motor neuron disease cases all showed "strong diffuse cytoplasmic immunoreactivity." They concluded that " . . . α-B crystallin may be involved in aggregation and remodelling of neurofilaments in disease."
Using cultured neuronal PC12 cells which had been heat shocked by incubation at 45° C. for 30 minutes, Johnson et al. [Annals NY Acad. Sci. 695:194-197 (1993)] reported evidence of induced expression of hsp72, alterations in the phosphorylation and metabolism of amyloid precursor protein (APP), and formation of a stable complex between hsp72 and tau. Johnson et al. concluded that "these results suggest that heat shock proteins may play either a protective or a promoting role in the formation of A68 and/or the amyloidogenic C-terminal fragment of APP." Speculating along similar conceptual lines, Hoyer [J. Geriatr. Psych. Neurol. 6(1):3-13 (1993)] stated that in the earliest stages of Alzheimer's disease several stress-related physiological abnormalities, such as glycogen accumulation, might induce the expression of hsp's, and that such events might lead to enhanced generation of amyloid precursor protein. Two other reported studies in this general field, the work of Abe et al. [Neurosci. Letters 125(2):169-171 (1991)] which used cultured lymphoblastoid cells and the work of Morandi et al. [Prog. Clin. Biol. Res. 317:819-827 (1989)] which used cultured rat dorsal root ganglial cells, failed to disclose or anticipate the invention embodied herein.
Approximately 10% of patients having amyotrophic lateral sclerosis (ALS), one of the motor neuron diseases, have a familial form of this disease [Marx, Science 259:1393 (1993)]. Familial cases of ALS are now known to result from a defect in the gene which codes for Cu/Zn-binding superoxide dismutase, an enzyme involved in oxidative free radical metabolism. A Medline database search from 1976 to May 1995 for citations regarding ALS and stress proteins generated three matches [i.e., Migheli et al. Neuropathol. Appl. Neurobiol. 20(3):282-289 (1994)]. Yet all three of these reports were based on studies of anterior hom cell neuronal tissue and none disclosed or anticipated the present invention. When an ALS/stress protein Medline database search from 1976 to May 1995 was expanded to include fibroblasts as a main heading three additional studies were listed [Witt et al., J. Neurol. Sci. 126(2):206-212 (1994); Tandan et al., J. Neurol. Sci. 79(1-2):189-203 (1987); and Beach et al., J. Neurol. Sci. 72(1):49-60 (1986)]. However, the Witt paper focused on calcium homeostasis in ALS fibroblasts. The Tandan et al. study focused on DNA repair abilities of ALS fibroblasts. The Beach et al. study focused on collagenase activity in ALS fibroblasts. None of these additional studies included work on stress proteins. Hence none of them disclosed or anticipated the present invention.
The appearance of high molecular weight ubiquitin-protein conjugates under stress protein inducing conditions is a well documented phenomenon [Raboy et al. Acta Biol. Hung. 42(1-3):3-20 (1991), pg. 8]. Ubiquitin-protein conjugates such as ubiquitinated paired helical filaments [Morishima-Kawashima et al. Neuron 10(6): 1151-1160 (1993)] have been described in studies based on analysis of nerve biopsy tissue. Yet a Medline review of ubiquitin prior art has not revealed a previous search for or identification of disease-associated ubiquitin-protein conjugates in fibroblasts obtained from patients having neurodegenerative diseases.
In U.S. Pat. No. 5,348,945 P. A. Berberian et al. described compositions for and methods of treating certain physiological stress-related states by use of an hsp70 protein as a medicinal agent. The invention embodied in U.S. Pat. No. 5,348,945 is beyond the scope of and irrelevant to the practice of the present specification. The methods and compositions of the present invention were neither disclosed nor anticipated by Berberian et al. Indeed, as defined below, the exogenous introduction of an hsp70 protein into any of the methods and compositions of the present invention would only serve to invalidate the findings, thus rendering useless the practice of the present invention.

Methods and compositions for development of drug screening procedures and diagnostic tools


An interface for connecting an actuator and a wide variety of valve types. The presented invention is configured such that any actuator can be manufactured, having only one female splined output shaft as a standard and precision inserts, utilizing powder metallurgy, for example, and be configured to transition the output shaft connection to any output shaft specification, providing the manufacturer the ability to manufacture the main drive component in one standard configuration, and convert it into different configurations as required. Thus, the manufacture gains the ability to mass produce one standard part rather than many special parts requiring design and testing for each change and high costs to produce specials. Particularly, the present invention contemplates a system comprising a rack interface for an actuator linear gear, a pinion member configured to interface said rack, the pinion including an internal shaft configuration configured to interface with the valve coupling component. The present invention provides a compact interface, allowing the actuator to be easily mounted upon the valve unit, without the need for additional mounting apparatus, such as bands, braces, or the like.

This invention relates generally to the method of coupling the output shaft of an actuator to a valve. Actuators are used to open and close a valve. This invention applies in particular to quarter-turn butterfly valves.
A butterfly valve is a flow control device which incorporates a rotational disk to control the flowing media in a pipe. It generally consists of a body, liner, shaft and disk assembly for insertion between a pair of spaced flanges in a fluid passageway more commonly known as a pipe and having the ability to seal off the flow completely at one extreme of its rotation and the ability to allow maximum flow through the pipe at the other extreme of its rotation and to provide some measure of reduced flow capacity at any point in between these two extremities.
An actuator is a control device mounted on a valve which causes the disk of a butterfly valve to rotate. Actuators are either manual or automatic and can be operated by hand, electronics, pneumatics, hydraulics, or springs. The proper actuator for a given valve application must be selected due to torque requirements imposed by the valve application, the means of operation available or practical at the valve location, and cost.
An actuator can be either manual or automatic. An actuator is the device which mechanically causes disk to rotate. As noted above, actuators can be powered by different power sources; however, for illustration purposes of this invention, a pneumatic actuator is used as an example (FIG. 1).
The rack and pinion mechanism simply consists of a length of linear gearing (rack) and pinion gear, which serves as the rotary output shaft. The gear rack is fitted to or machined directly into an arm on the face of the piston. As the piston strokes, the gear rack engages and drives the pinion at a dimension from the center of rotary output, which is the radius of the pinion shaft (FIG. 1). This produces torque. The stroking length of the piston is limited, so that the actuator produces output torque over 90 degrees (1/4 turn) of rotation.
The gear rack contacts the pinion at a point that is a constant dimension from the center of rotation; therefore, the torque output throughout rotation is constant. When the pinion shaft is connected directly to the shaft of a butterfly valve, this provides the most direct connection without the use of brackets and couplings.
To date there are several manufacturers of actuators for direct mount to their own manufacture of butterfly valves. In each case the manufacturer of the actuator must machine an output shaft that is fitted to their own butterfly valve. If a valve manufacturer does not manufacture its own actuator for direct mounting to its own butterfly valve, the valve manufacturer must use an actuator manufactured by another manufacturer and must adapt this actuator to his valve with the use of brackets and couplings.
Quarter turn valves are actuated with either manual or automatic actuators. Automatic quarter turn actuators are commonly pneumatic or electric. When valves are operated by actuators, the actuator usually has to be mounted to the top of the valve using a bracket as a connecting member. The valve shaft is then connected by a coupling to the actuator shaft. The valve is then opened or closed by transferring the torque from the actuator to the valve through the rotary motion of the actuator shaft through the coupling.
In this configuration the actuator shaft has to be of the same general configuration as the valve shaft i.e. if the valve shaft is of a parallel flat configuration the actuator shaft must be of the same female configuration to accept the valve shaft.
To date, each butterfly valve manufacturer presenting a direct mounting capability of its actuator with its valve has to have an actuator of sufficient dimension and output shaft configuration to mount only to and drive only its own manufacture of valves.
The concept of mounting actuators to quarter turn valves has been known in the art for many years. Some of the difficulties encountered with actuators having standard drive dimensions is that a specialty coupling has to be designed and manufactured each time an actuator is mounted or applied to any quarter or half turn valve.
When a special request is made for a connection configuration that is not within the fabricators manufacturing standard, a new shaft for the actuator has to be designed, manufactured, and tested, in order to comply with the requirement This type of request has to be handled as a special project each time, which is costly and time consuming, and often interrupts and delays standard production.


An illumination device including a voltage transformer module, a switching unit, a control module, a sensor module, a first illumination module and a second illumination module. The switching unit is coupled to the rectifier module and the voltage transformer module. The control module is coupled to the switching unit and the voltage transformer module. The sensor module is electrically connected to the control module. The sensor module senses an invading object within an induction area. The first illumination module is electrically connected to the switching unit. The second illumination module is electrically connected to the sensor module. The sensor module supplies electricity to the second illumination module to emit light. The sensor module outputs a sensing signal to the control module when the sensor module senses the invading object. The control module controls the switching unit to be turned on so that the first illumination module emits light.

1. Technical Field
The present invention generally relates to an illumination device and, more particularly, to an illumination device for lighting.
2. Description of Related Art
Since the light-emitting diode (LED) has advantages such as low power consumption, high luminance and long lifetime, it has been widely used in various lighting apparatuses. A lighting apparatus includes rectifier circuits, switches, illumination modules and a current source. The illumination module includes a plurality of light-emitting diodes connected in series. The rectifier circuit, for example, a full-wave rectifier circuit rectifies alternate current (AC) power to provide a pulsating direct current supplied to the light-emitting diode. When the light-emitting diodes connected in series are turned on, the current source supplies steady current to the light-emitting diodes in the illumination module.
Generally, an induction lighting apparatus senses an invading object and outputs light with high luminance. When a passerby or a third party enters or stays in an induction area of the induction lighting apparatus so that the induction lighting apparatus senses an invading object, the induction lighting apparatus suddenly emits light with high luminance. Therefore, the passerby or the third party is shocked by the sudden light to even fall down, crash or get hurt. It is inconvenient to use such an induction lighting apparatus.

PARAGON SEMICONDUCTOR LIGHTING TECHNOLOGY CO., LTD.


The present invention provides transgenic, non-human animals that include a transgene that encodes a fatty acid desaturase, e.g., stearoyl-CoA desaturase, and methods for producing such animals. The invention further provides an expression cassette that includes a coding region for a desaturase such as stearoyl-CoA desaturase, operably linked to a heterologous, tissue-specific animal cell promoter. The invention further provides methods of producing a food product, such as milk, meat, or eggs, using a subject transgenic non-human animal, as well as food products harvested from a subject transgenic non-human animal.

Saturated fatty acids are long-chain aliphatic carboxylic acids with linear hydrocarbon chains having an even number of carbon atoms, usually C12-C20. Unsaturated fatty acids contain one or more double bonds, the first usually at carbon number 9. Fatty acids are stored in the form of triacylglycerols. Triacylglycerols serve three basic functions: (1) they are the storage forms of carbon and energy in adipose tissue; (2) they form lipoprotein particles which transport ingested fatty acids; and (3) they provide physical protection and thermal insulation for body organs.
Many epidemiological, clinical, and animal studies have indicated that high levels of dietary fat, especially saturated fat, lead to an increase in blood cholesterol levels and increased risk for atherosclerosis. The risk for coronary artery disease can be predicted directly from serum cholesterol levels. Saturated fatty acids are directly responsible for increasing serum cholesterol levels. A diet that minimizes cardiovascular risk factors and contributes to an overall reduction of diseases not cardiovascular in nature, such as diabetes, could be achieved by changing the dietary fat or mix of fatty acids in the diet. Plasma cholesterol levels tend to respond more to reducing saturated fatty acids than to reducing total fat intake, and plasma cholesterol reduction can be achieved with saturated fatty substituents such as monounsaturated or polyunsaturated fatty acids. Both mono- and polyunsaturated fatty acids affect cardiac risk by lowering low density lipoprotein cholesterol levels. Likewise, in many non-insulin-dependent diabetes mellitus patients, the reduction of dietary saturated fat helps lower plasma cholesterol levels and reduce the risk for coronary heart disease.
Conjugated linoleic acids (CLAs) are a group of 18 carbon FAs that have two double bonds, with positional and geometric variations around the 9, 10, 11 and 12 carbon positions. Dietarily they are principally derived from ruminant animals in meat and dairy products, as they occur only in trace amounts in plants. Considerable work has been carried out in experimental systems and animal models indicating that CLAs, principally the C 18:2 cis9 trans11 form, play a considerable role in a number of areas affecting human health. CLAs have been shown to be anti-carcinogenic and anti-athersclerosis, as well as helping to reduce severe wasting (cachexia) associated with cancer. Other studies, in a variety of animal species, have shown that CLAs can promote lean body growth, increase feed efficiency and decrease fat accumulation. Furthermore, several studies suggest that CLAs can modulate the immune response and thus reduce the cachetic response, enhance cell-mediated responses, and decrease the inflammatory response.
Approximately one third of saturated fatty acids in American diets comes from the consumption of dairy products, and approximately one quarter of saturated fatty acids in the diet are supplied by the consumption of meat. Problems associated with control of intake of saturated fatty acids include consumer compliance, with consumers generally favoring foods that have a higher content of saturated fatty acids.
There is a need in the art for food products that have lower levels of saturated fatty acids. The present invention addresses this need by providing transgenic animals that make food products (e.g., milk, meat, and eggs) having lower levels of saturated fatty acids.
Literature
U.S. Pat. No. 6,432,684; Maga and Murray (1995) Bio/Technol. 13:1452-1457; Strittmatter et al. (1974) Proc. Natl. Acad. Sci. USA 71:4565-4569; van Berkel et al. (2002) Nat. Biotechnol. 20:484-487; U.S. Pat. Nos. 6,432,469, 6,410,761, and 6,333,353.

Stearoyl CoA desaturase transgenic non-human animals

The Regents of the University of California


Apparatus for eliminating the necessity for manually dialing a local area code as a prefix to a call within the same area code in telephone systems in which such action is a requirement. An automatic dialer is activated and immediately transmits the local area code onto the caller's telephone line when an off-hook condition is sensed; e.g., when a telephone handset is picked up. Thus, the caller can merely then dial an ordinary seven digit telephone number within the local area code. In order to provide for the selective dialing of long distance, when the caller "flashes" his line within a predetermined period (typically, a few seconds) after picking it up, a hang-up followed by a second off-hook is emulated; however, the automatic dialer is inhibited from again transmitting the area code. Consequently, the caller is presented with a dial tone, and a telephone number, including an area code which may be different from the local area code, may be successfully dialed.

Local telephone calls have, for many years, been effected by dialing a seven digit code. At one time, all long distance calls were handled by "long lines" operators who more or less manually established a routing for a given call. However, since the late 1950s, direct dial long distance calling has been widely used. Directly dialed long distance calls involve the dialing of a first prefix, typically "1", to indicate to the telephone company apparatus that a long distance call is contemplated, then dialing a second prefix, the three digit area code, before the local seven digit number of the called party is dialed. In this manner, a long distance call can be carried out without the intervention of an operator. Variations of this process, typically dialing longer strings of numbers, permits international long distance direct dialing.
When this system was established, largely under the auspices of American Telephone and Telegraph Company, it was believed that the allocation of possible telephone numbers (including area codes) was adequate to handle all demand for many years. However, it is becoming evident that such is no longer the case. In particular, the remarkable proliferation in dedicated line demand for fax machines and the like, and, especially, for modems which may be used, inter alia, for connecting a computer to the Internet and other networks, has pushed the allocation of available lines, notwithstanding the application of various technological advances, to near the limit possible with the current system.
One technological advance which promises to alleviate this problem for a number of years is to require a calling party to dial the area code of a called party even when the two parties are within a common area code. Thus, one would be required to dial a ten digit code even if the called party is next door. It will be readily apparent that this change will be highly inconvenient to many persons who wish to continue the use of the traditional seven digit dialing for local calls. Accordingly it will be understood that a method and apparatus which, in such a contemplated modified telephone dialing system, permits the ongoing use of standard seven digit dialing for routine local calls would be highly desirable, and it is to this end that the present invention is directed.


A rolling footrest is provided and a method of using such by a wheelchair occupant. The footrest may optionally include a foot retainer, a platform and freely rolling castors. In some embodiments, replacing a fixed footrest will shorten the length of the wheelchair enabling the wheelchair to traverse sharp curves. In some embodiments, the footrest may include a swivel lock and/or a ratchet. In some embodiments the footrest may be used for therapeutic exercise. In some embodiments, the footrest may be used for propelling a wheelchair.

The present invention, in some embodiments thereof, relates to a device and method to improve mobility of a handicapped individual and, more particularly, but not exclusively, to a rolling footrest adapted for use by a wheelchair occupant.
U.S. Pat. No. 3,833,256 to Dehner discloses an apparatus comprising a folding footrest which may be permanently mounted to a wheelchair. It folds with the chair between an open supportive position and a closed storage position. The footrest is mounted to the wheelchair frame in such a manner that it may be moved longitudinally with respect to the chair to Protrude forwardly of the chair while in use or be retracted within the chair frame for greater maneuverability in close quarters for compactness in storage or for better fitting to the best position of the feet of the invalid The footrest is operative at all times for the patient.
U.S. Pat. No. 5,937,440 discloses a wheeled support for supporting a kneeling person including a pair of knee supports each having a frame, a pad mounted on the frame, and three wheel assemblies mounted on a bottom of the frame. Also included is a pair of wheeled foot supports.
U.S. Pat. No. 740,071 to Allen provides a rest for the foot or a seat which when not supporting the weight of the foot or person will be on casters so as to be readily moved on the floor but when supporting said weight will bear as to the whole or a part directly on the floor without the intervention of casters so that it will not be easily or inconveniently movable on the floor.
U.S. Pat. No. 5,380,021 to Doherty discloses a sheet material sling supported on a horseshoe-shaped device mounted on three casters which forms a vehicle to support a knee of a user. Two such supports are used, unconnected to each other by users who must kneel in their work and must scoot along a support surface. Provisions are made for the supports to be interconnected by a flexible connector or by a rigid table like sheet.
U.S. Pat. No. 4,484,755 discloses a cart having a basket and wheeled metal chassis and adapted for use by handicapped, invalid and frail persons.
U.S. Pat. No. 7,980,572 to Bennett discloses an amputee mobility device includes a wheeled frame, and seat with webbed pocket for receiving an amputated leg.
Additional background art includes U.S. Publication No. 2011/0121535; U.S. Publication No. 2010/0289230; U.S. Publication No. 2010/0164201; U.S. Publication No. 2006/0172862; U.S. Publication No. 2004/0094915; U.S. Pat. No. 7,922,187; U.S. Pat. No. 7,681,248; U.S. Pat. No. 7,611,447; U.S. Pat. No. 7,484,742; U.S. Pat. No. 7,426,970; U.S. Pat. No. 7,197,770; U.S. Pat. No. 6,955,400; U.S. Pat. No. 6,607,246; U.S. Pat. No. 6,219,845; U.S. Pat. No. 6,142,914; U.S. Pat. No. 6,053,189; U.S. Pat. No. 5,870,774; U.S. Pat. No. 5,725,224; U.S. Pat. No. 5,427,391; U.S. Pat. No. 5,301,970; U.S. Pat. No. 3,833,256; U.S. Pat. No. 3,640,566; and U.S. Pat. No. 1,382,883.


A card output clearance adjusting device for card stacking machines, in particular a clearance adjusting device adapted for telephone cards and the like, including a receiving body, a conveyance device, and a press plate. The receiving body has a main frame and a support seat. The components of the conveyance device are disposed between the main frame and the support seat. The adjusting device has a securing plate formed by directly bending an upper portion of the main frame at an angle of 90 degrees, and a movable adjusting plate at a lower portion thereof The movable adjusting plate has guide track plates at both sides thereof movably inserted into corresponding guide tracks at both sides of the support seat. The upper surface of the movable adjusting plate is provided with four guide posts fitted with stop springs respectively. An upper end portion of each guide post extends into a corresponding hollow guide hole of the securing seat. An adjusting rotary knob is inserted via a through hole of the securing seat into a nut of the movable adjusting plate. By turning the adjusting rotary knob, micro-adjustment of a clearance between an inclined surface at the lower portion of the movable adjusting plate and a bottom plate of the support seat may be allowed to achieve optimal card output.

(a) Field of the Invention:
The present invention relates generally to a card outlet adjusting device for card stacking machines, and more particularly to an adjusting device in which a securing plate extended from an upper portion of a main frame of a receiving body and a movable adjusting plate movably provided at a front end of a support seat are provided and four guide posts fitted with stop springs and an adjusting rotary knob disposed between the securing plate and the movable adjusting plate are utilized to achieve precision adjustment of the card outlet clearance.
(b) Description of the Prior Art:
Telephone card vending machines are common today. Such vending machines may also be adapted to sell other cards. However, although the thickness of cards is quite uniform, minute difference in thickness may cause blocking or hinder the smooth discharge of cards from the vending machines. A card outlet adjusting device allowing micro-adjustment of the card outlet and of a simple construction is therefore desirable.
The inventor of the present invention has found that little difference in the thickness of cards will directly affect the smooth discharge of cards from card vending machines and conceived the present invention to solve this problem by providing a card outlet adjusting device after repeated experimentation.

Card outlet clearance adjusting device for card stacking machines


Pharmaceutical compositions comprising an antiarrhythmic agent for treatment of a heart condition via inhalation. Methods of treating a heart condition include administering by inhalation an effective amount of at least one antiarrhythmic pharmaceutical agent to a patient in need thereof. Nebulized drug product and kits are also disclosed.

Cardiac arrhythmia (also dysrhythmia) is a term for any of a large and heterogeneous group of conditions in which there is abnormal electrical activity in the heart. The heart beat may be too fast or too slow and may be regular or irregular.
Atrial arrhythmia therapy is a field with a high level of unmet clinical need. Many drugs used today have been on the market since the early 1980s and 1990s and are mostly inadequate due to either lack of efficacy or a side-effect profile that is often cardiac related, that necessitates extensive monitoring of the patient.
What is needed for fast and safe cardioversion (resolution of arrhythmia) is therapy that:                (a) causes little to no risk of acceleration of ventricular rate before cardioversion;        (b) slows atrio-ventricular (AV) conduction so that there is ventricular rate control and cardioversion at the same time;        (c) causes minimal to no effect in prolonging the QRS interval above the upper range of normal value (about 120 milliseconds) and should have a low risk of torsade de pointes; and        (d) causes minimal to no negative inotropic effect; it should have only mild negative chronotropic effect, without the risk of severe bradycardia when the patient reverts to sinus rhythm.        (e) causes minimal to no hypotension.        (f) causes no adverse event other than one that is mild, is transient (i.e. lasting no more than several minutes), does not require treatment, and has no sequelae.
None of the current approved drug products exhibit these characteristics. High oral and intravenous (IV) doses required to compensate for absorption, metabolism, and dilution result in blood high blood concentrations for an extended period of time that can cause the dangerous adverse cardiac events like pro-arrhythmias, QT prolongation, and torsade de pointes. FELDMAN et al., "Analysis of Coronary Response to Various Doses of Intracoronary Nitroglycerin," Circulation, 66:321-327 (1982); and BARBATO et al., "Adrenergic Receptors in Human Atherosclerotic Coronary Arteries," Circulation, 111:288-294 (2005). Comorbid conditions also limit use of ideal drugs in some patients, for example the case with intravenous adenosine. GAGLIONE et al., "Is There Coronary Vasoconstriction after Intracoronary Beta-adrenergic Blockade in Patients with Coronary Artery Disease," J Am Coll Cardiol, 10:299-310 (1987). Drugs like verapamil and diltiazem injections are second line of therapy requiring close monitoring of patients. NOGUCHI et al., "Effects of Intracoronary Propranolol on Coronary Blood Flow and Regional Myocardial Function in Dogs," Eur J Pharmacol., 144(2):201-10 (1987); and ZALEWSKI et al., "Myocardial Protection during Transient Coronary Artery Occlusion in Man: Beneficial Effects of Regional Beta-adrenergic Blockade," Circulation, 73:734-73 (1986).
Paroxysmal atrial fibrillation (PAF) is a subset of the overall atrial fibrillation (AF) population and is estimated to be 25-30% of the overall AF population. About 2.5 million patients are affected by AF in the United States. The population of PAF patients is estimated to be 900,000 to 1.5 million worldwide.
Paroxysmal supraventricular tachycardia (PSVT) is a type of arrhythmia that affects about 500,000 to 600,000 patients in the United States.
Ablation techniques, e.g., RF ablation, are often used to treat arrhythmias. But ablation is expensive with the cost typically ranging from about $25,000 to $36,000 per procedure. Despite the high expense, ablation may not completely correct the arrhythmia. Often, multiple ablation procedures are required to achieve a satisfactory therapeutic result.
Oral medications, e.g., pills, tend to require high doses and long time for onset of action. The oral dose for heart medications generally tends to be well over 1 mg. High doses increase the likelihood of side effects and drug-drug interactions as these patients typically take multiple medications. The time for onset for oral cardiovascular medications tends to be around 60 minutes. Oral antiarrhythmic medications have been predominantly developed for prevention whereas treatment being given intravenously.
Intravenous injection usually requires a hospital setting for administering a medicine and typically involves a visit to the emergency room (ER). These overheads result in this therapy being expensive compared to therapies where the patients can self-administer their medicines. Intravenous injection requires a dose that is higher than what is actually needed in the heart to compensate for dilution and metabolism. Drug injected by IV passes through the right side of the heart and then the lungs before reaching the left side of the heart. The drug remains in the blood stream at a high concentration bathing all the organs and tissues with this drug in a high concentration, until the drug gets excreted through the kidneys or through other metabolic routes (e.g., hepatic). As a result, IV drugs may cause unwanted side effects. Drugs administered via the IV route are significantly diluted in the venous blood volume and lungs before reaching the cardiac circulation.
Injecting a drug to the heart directly is usually a last-resort taken by a cardiologist as a life saving measure in an emergency. The doses of the drugs injected directly into the heart in this manner are usually less than their IV and/or oral doses.
In some cases, an unplanned surgery is necessary to save the patient's life. Of course, unplanned surgeries are expensive and risky to the patient.
Cardiac arrhythmias are associated with disabling symptoms like tightness around the chest, palpitations, feeling tired, shortness of breath, and sometimes chest pain.
In view of the above, arrhythmias frequently result in emergency room (ER) visits, where intravenous drugs are administered, sometimes necessitating an extended stay in the hospital and in some cases also leading to unplanned invasive procedures. Pipeline Insights: Antiarrhythmics, Datamonitor (June 2006); and TWISS et al., "Efficacy of Calcium Channel Blockers as Maintenance Therapy for Asthma," British J of Clinical Pharmacology (November 2001).
There remains, however, a need for improved compositions and methods for treating heart conditions. Accordingly, there also remains a need for methods of making these compositions.

This patent is subject to a terminal disclaimer.


A scaffolding enclosure for use with large structures such as water towers and the like is described. The scaffolding has a modular construction and is adapted to provide one or more enclosed work areas against the walls of the structure. The scaffolding has a movable horizontal top module, preferably extending from one side of the structure to the other, and a vertical module at one end or preferably both ends of the horizontal top module, extending downwardly therefrom adjacent the wall of the structure. Each vertical module has at least one work area and is enclosed on the back and the sides. The front face is open to the wall of the structure, and the edges of the work area are sealed against the wall of the structure. For water towers with undercut lower walls, inwardly angled lower modules may be attached to the vertical modules, the lower modules also having at least one work area.

1. Field of the Invention
This invention relates generally to apparatus for blasting, painting or otherwise treating the walls of large structures such as water towers, petroleum storage tanks, warehouses, factories, etc., and particularly to apparatus used to create a substantially sealed mobile work enclosure against the walls of such structures.
2. Description of the Prior Art
There is a growing consciousness regarding the environment and, in an attempt to protect the environment, the use and handling of certain materials is controlled.
Traditionally, blast cleaning operations were conducted in the open allowing the blast media and waste materials to become airborne and fall unheeded anywhere. Since the blast media is blown against the structure at high pressure, the blast media and waste material if not contained would fall over a large area and in high winds that area would be even larger. Such contamination is undesirable and accordingly many jurisdictions have imposed regulations to ensure that the blast media and waste materials are contained. Furthermore, some of the materials which are being removed are considered hazardous, such as lead-based paint, and it is therefore important to ensure that they are contained when removed.
In order to meet the requirements to contain the blast media and waste material, a number of systems have been proposed, including totally enclosing the structure, enclosed movable platforms, movable remote cleaning units, and hand-held vacuum blasters. These systems, however, are often difficult to use, costly and/or time-consuming to implement.
In prior art systems, in order to totally enclose a water tower, for example, a tarpaulin assembly has been used. The tarpaulin assembly includes a sock portion, a hat portion and supporting means. The supporting means includes a plurality of upper supports which are installed on the water tower, which is time-consuming. A plurality of supporting ropes are attached to the upper supports and the sock portion of the tarpaulin. The sock portion is then pulled up the side of the water tower. The hat portion of the tarpaulin which covers the top of the water tower is then attached to the sock portion. This tarpaulin assembly is very time-consuming and cumbersome to install and remove. It cannot be used in high winds since the wind load on the tarpaulin greatly increases the load on the water tower. Accordingly, in high winds the sock portion must be dropped and the work must be stopped even in only moderately high winds such as 20 miles per hour, so that there is enough time for the workers to get out and drop the sock before the wind increases further. Other problems include that it is difficult to maintain a sealed connection between the sock portion and the hat portion of the tarpaulin. Furthermore, the tarpaulin itself is costly and is susceptible to being ripped by high winds, as the tarpaulin is raised and lowered against guide wires.
Prior art movable platforms having enclosed platforms for use in cleaning buildings include those shown in U.S. Pat. No. 4,649,672 issued to Thomann on Mar. 17, 1987; U.S. Pat. No. 5,038,527 issued to Fastje on Aug. 21, 1990; and U.S. Pat. No. 4,949,512 issued to Thomann on Aug. 13, 1991.
Prior art remote-controlled units include for example the unit shown in U.S. Pat. No. 4,825,598 issued to Schlick on May 2, 1989. Such units are complex and intricate machines which are expensive to build and maintain and labor intensive to operate. Accordingly, they are expensive to operate.
The prior art hand-held vacuum blasters are mobile hand-held machines which both blast and contain the blast media. The nozzle of the blaster forms a seal against the structure so that no blast media or waste material can escape into the air. The hand-held vacuum blasters are particularly appropriate for spot blasting but they are too time-consuming to use for a large structure.
Other surface treatments, such as painting or chemical treatment, also may require an enclosed work area against the wall of the structure. Even where such an enclosure is not mandatory, it may be desirable for worker convenience and/or safety.
Accordingly there is a need for an apparatus which can be adapted to provide an enclosed work area against the walls of large structures. The apparatus should be readily adaptable to structures of different sizes and shapes, and should be relatively easy to install. It is also important that it be able to travel along or around the walls of the structure easily.

Scaffolding with enclosed movable work areas sealed against work surfaces


A slider and method of using the same is provided for facilitating the sliding of a load on a supporting surface. The slider includes a support platform having an upper surface for receiving the load thereon and a lower surface. A plurality of slider elements depend from the lower surface of the support platform. Each slider element has an outer surface engageable with the supporting surface. A lubricating pad extends from the support platform and is engageable with the supporting surface for lubricating the supporting surface during movement of the slider.

Sliders are often mounted to the bottom surface of a load to act as a buffer between the load and the surface on which the load rests. Typically, sliders take the form of convex discs mounted to the bottom surface of the load by means of adhesive, nails, or the like. The slider disperses the weight of the load over an enlarged area and allows the load to be slid over the supporting surface. Further, the slider prevents the scratching or marring of the supporting surface when the load is moved and prevents the forming of a depression in the supporting surface when the load remains in one place for an extended period of time.
While functional for their intended purpose, prior sliders have certain limitations. More specifically, repeated movement of the load along a supporting surface may cause the connection means that attaches the slider to the load to fail such that the slider may become detached from the bottom of the load. This, in turn, may result in the load engaging the floor and becoming damaged. Alternatively, prior sliders may not function properly on high friction surfaces such as a concrete factory floor. Consequently, prior sliders are not often used to move heavy loads across concrete factory floors. Further, if these floor sliders are used on a high friction floor, the load may become detached from the sliders and engage the floor. Once again, this may result in the load becoming damaged. Therefore, it is a highly desirable to provide a slider that may be simply and easily secured to the bottom surface of a heavy load and that facilitates sliding of such load along a high friction surface such as a concrete factory floor.
Therefore, it is a primary object and feature of the present invention to provide a slider that may be securely maintained beneath a bottom surface of a load.
It is a further object and feature of the present invention to provide a slider that is inexpensive to manufacture and simple to utilize.
It is a still further object and feature of the present invention to provide a slider that facilitates the sliding of a load over a wide variety of supporting surfaces.
In accordance with the present invention, a slider is provided for facilitating the sliding of a load on a supporting surface. The slider includes a base having an upper surface for supporting the load and a lower surface. A plurality of slider elements extends from the lower surface of the base. Each slider element has a generally arcuate outer surface that is engageable with the supporting surface.
The slider also includes a support having an upper surface and a lower surface interconnected to the upper surface of the base. A pad has an upper surface for engagement with the load and a lower surface interconnected to the upper surface of the support. The upper surface of the pad has a high co-efficient of friction. A rigid wire is positioned between the upper surface of the support and the lower surface of the pad. The wire partially overlaps the slider elements.
It is contemplated for each slider element to terminate at a generally flat apex. It is also contemplated for the slider to include a lubricating pad depending from the lower surface of the base. The lubricating pad is engageable with the supporting surface for lubricating the supporting surface. A first slider element of the plurality of slider elements may have a predetermined radius and a second slider element of the plurality of slider elements may also have a predetermined radius. The predetermined radius of the first slider is greater than the predetermined radius of the second slider.
The slider may also include a generally flat mat having an opening therethough. The base is receivable in the opening of the mat. The mat has an upper surface, a lower surface and on outer edge. A ramp may be operatively connected to the outer edge of the mat. The ramp has an upper edge lying in a generally common plane with the upper surface of the mat and a lower edge adjacent the supporting surface.
In accordance with a further aspect of the present invention, a slider is provided for facilitating the sliding of a load on a supporting surface. The slider includes a support platform having an upper surface for receiving the load thereon and a lower surface. A plurality of slider elements extends from the lower surface of the support platform. Each slider element has an outer surface engageable with the supporting surface. A lubricating pad depends from the lower surface of the supporting platform and is engageable with the supporting surface for lubricating the supporting surface.
The support platform includes an upper layer having an upper surface defining the upper surface of the support platform and a lower surface; an intermediate layer having an upper surface bonded to the lower surface of the upper layer and a lower surface; and a lower layer having an upper surface bonded to the lower surface of the intermediate layer and a lower surface defining the lower surface of the support platform. The upper layer is formed from a resilient pad such that the upper surface of the upper layer has a high co-efficient of friction. A rigid wire is positioned between the upper layer of the support platform and the intermediate layer of the support platform. The wire partially overlaps the slider elements.
It is contemplated for each slider element to terminate at a generally flat apex. It is also contemplated for a first slider element of the plurality of slider elements to have a predetermined radius and for a second slider element of the plurality of slider elements to also have a predetermined radius. The predetermined radius of the first slider is greater than the predetermined radius of the second slider.
The slider may also include a generally flat mat having an opening therethough. The support platform is receivable in the opening of the mat. The mat has an upper surface, a lower surface and on outer edge. A ramp may be operatively connected to the outer edge of the mat. The ramp has an upper edge lying in a generally common plane with the upper surface of the mat and a lower edge adjacent the supporting surface.
In accordance with a still further aspect of the present invention, a method is provided for sliding a load over a supporting surface. The method includes the steps of providing a slider having a first side for receiving the load thereon and a second side engageable with the supporting surface, and depositing a lubricant adjacent the slider as the load is slid on the slider over the supporting surface.
The slider includes a support platform having an upper surface for receiving the load thereon and a lower surface, and a plurality of slider elements extending from the lower surface of the support platform. Each slider element has an outer surface engageable with the supporting surface. The support platform includes a resilient pad having an upper surface that defines the upper surface of the support platform and a lower surface, and a base having an upper surface affixed to the lower surface of the pad and a lower surface that defines the lower surface of the support platform.
The method may include the additional steps of reinforcing the support platform and depositing the slider within an opening in a mat. The mat has upper and lower surfaces. Advertising indicia may be placed on the upper surface of the mat. The step of reinforcing the support platform includes the additional step of positioning a wire between the resilient pad and the base.


This invention provides an electro-optical module with reduced noise in driving voltage. The invention can include a power supply substrate that is arranged separately from the flexible substrate having a driver, so that the noise of the driving voltage supplied from the power supply substrate is reduced.

1. Field of Invention
The invention relates to an electro-optical module, a power supply substrate, a wiring substrate, and an electronic apparatus.
2. Description of Related Art
A type for mounting an electro-optical panel having an electro-optical element, such as a liquid crystal device, on an electronic apparatus, such as cellular phone and television has been known in the related art. See, for example, Japanese Unexamined Patent Application Publication No. 10-209581.
In order to safely drive the electro-optical element on the electro-optical panel, a method for mounting the electro-optical panel, a method for connecting the electro-optical panel to a wiring substrate, configuration or structure of the electro-optical module need to be considered in addition to the configuration of the electro-optical panel itself. As the electro-optical panel has been densely integrated, problems, such as noise or a delay, in control signal or instability of the driving voltage need to be solved in consideration of the mounting type.
An object of the invention is to provide the electro-optical module and related components which are designed to solve the above-mentioned problem.

Electro-optical module, power supply substrate, wiring substrate, and electronic apparatus


A printed circuit board apparatus comprises a printed circuit board. The printed circuit board includes a first and a second surface and a hole portion. A printed pattern is formed on the first surface, and a parts having a lead is mounted on the second surface. The printed circuit board apparatus also includes an eyelet and plural solder entering portions. The eyelet includes a curling portion and a head portion positioned on the first and second surfaces of the printed circuit board, respectively, and a cylindrical portion, connecting the head and curling portion, inserted into the hole of the printed circuit board. A plurality of solder entering portions are formed at equal intervals on the curling portion. From the solder entering portions, solder enters into space between the curling portion and the first surface face of the printed pattern surrounding the hole of the printed circuit board and the eyelet.

1. Field of the Invention
The present invention relates to a printed circuit board apparatus and, in particular, to a printed circuit board and a method and apparatus for mounting heavy or high heat generating components thereon.
2. Description of the Related Art
Generally, printed patterns such as a copper leads are formed on one side of a printed circuit board; components having leads are mounted on the other side. The leads pass through holes on the circuit board and are soldered to lands of the printed patterns.
In mounting heavy parts or high heat components on the circuit board, eyelets are first mounted into holes of the circuit board. This is done to prevent the possible breakage of the circuit board due to separation of the copper leaf from the board caused either by the weight of the components or by the heat deterioration of the circuit board.
FIG. 1 is a perspective view of a printed circuit board apparatus of the prior art. A heavy component or part 20 with leads 22 is mounted on one side (i.e. a part mounting side) 24 of a circuit board 26. Printed patterns 28 are formed on the other side (i.e. printed pattern side) 30 of circuit board 26. Eyelets 32 are fixed to board 26 by positioning them through holes 34 formed on board 26. The ends portion of leads 22, from part mounting side 24, are inserted through holes (cylindrical portions) in eyelets 32 and are soldered to lands 36 of printed patterns 28.
FIGS. 2 (A) through (D) are perspective, sectional and plan views of eyelet 32 shown in FIG. 1. The manner of fixing eyelet 32 to the circuit board is described below with reference to FIG. 2. Eyelet 32, shown in FIG. 2(A), is inserted through hole 34 of printed circuit board 26 from part mounting side 24 (FIG. 2(B)); the end of eyelet 32 projects from printed pattern side 30. One end of eyelet 32 is then curled by a saw-tooth punch, for example, the present punch shown in FIG. 10. By utilizing this curling process, eyelet 32 is fixed to the circuit board, as shown in FIG. 2(C). Curling portion 38 is formed in a continuous ring-shaped or annular configuration on printed pattern side 30, as shown in FIG. 2(D).
FIGS. 3 and 4 are perspective views of curling portion 38 after utilizing the prior art curling method. As shown in these Figures, portion 38 has a generally annular and convex configuration. FIG. 3 shows eyelet 32 with four interrupted sections 381 of curling portion 38 caused by breakage during the curling process. FIG. 4 shows eyelet 32 having a substantially continuous ring-shaped portion 38.
FIG. 5 shows a sectional view of a printed circuit board using an eyelet mounted by the present method. After the curling of eyelet 32, and lead 22 of component 20 is inserted in the hole of eyelet 32, solder 40 is then applied from printed pattern side 30. Soldering is implemented by using, for example, an automatic flow soldering machine. Due to the high viscosity of solder, it is difficult for solder to enter into curling portion 38 whether eyelet 32 has interrupted sections 381 (see FIG. 3) or substantially continuous section (see FIG. 4). As a result, a cavity 42 will form in many cases. The presence of cavity 42 will contribute to breaking of the soldered joint if either a load is added to lead 22 or repeated thermal expansion occurs.
For example, in TVs using printed circuit boards, it is desirable to decrease the length of lead cords, and preferably position them on the circuit board to facilitate assembly and reduce cost. In the event that heavy or high heat generating components are mounted on the boards, breaking of the soldered joints can occur.


Use of twin screw extrusion to further enhance the uniformity of crosslinked rubber dispersion in thermoplastic vulcanizates (TPVs) to improve elastic properties of TPVs is disclosed. Most specifically, this invention employs intermeshing twin screw extruders to further homogenize dynamically vulcanized rubber dispersions in TPVs so that their particle size dispersion index (PSDI), or the ratio of weight average equivalent dispersion particle diameter to number average equivalent dispersion particle diameter, can be lowered to less than 1.6 or 1.57 with corresponding elastic property improvements by having lower hysteresis, higher elongation to break, and higher retractive force. TPV products having lower PSDI and improved elastic properties, and apparatus for conducting the disclosed method, are also provided.

The first commercial thermoplastic vulcanizate (TPV) was Santoprene™, and was introduced in the early 1980s. Thermoplastic vulcanizates are thermoplastic elastomers, not thermoset rubbers, and can be processed or re-processed as thermoplastics. Thermoplastic vulcanizates differ from thermoplastics at least by inclusion of dispersed vulcanized rubber particles. Vulcanization, or crosslinking, of rubbers in TPVs is necessary to keep the rubber, which is the majority blend component, as the dispersed phase instead of the continuous phase. Following the Paul-Barrow continuity criterion (D. R. Paul and J. W. Barlow (1980) J. Macromol. Sci., Rev. Macromol. Chem., C18(1), 109-168), where phi 1/phi 2=eta 1/eta 2, the phase with infinite viscosity, such as crosslinked rubbers, would stay dispersed. This allows the packing of a maximum amount of rubber dispersion in a plastic matrix without rubber phase inversion. The maximum packing volume percent is limited by packing physics and is typically less than 70 vol. %. By squeezing in greater than 60 vol. % of crosslinked rubber dispersions inside a plastic matrix, the plastic matrix becomes inter-connecting plastic ligaments sandwiched in between dispersed crosslinked rubber particles.
Without being bound by any theory, the elasticity of a TPV is thought to derive from these thin plastic ligaments sandwiched between dispersed rubber particles. Based on experimental findings and theoretic modeling (e.g. as by M. C. Boyce, S. Socrate, K. Kear, O. Yeh, and K. Shaw, J. Mech. Phys. Solids, 49, 1323, (2001), and J. Mech. Phys. Solids, 49, 1343, (2001)), these thin plastic ligaments kink or plastic flow during TPV deformation by the incompressible deformation of sandwiching crosslinked rubber dispersions. Subsequently, these plastic ligament kinks act as spatial registrations to allow elastic recovery and to deliver elasticity. Thinner plastic ligaments would be easily deformed and also yield easily, for plastic flow/kink formation, relative to thick plastic ligaments. If the plastic matrix has plastic patches that are relatively large between dispersed rubber particles, these plastic flows and kink developments are not possible and this leads to poorer elastic properties. Rubber dispersion size and uniformity are important to create a uniform plastic ligament network; large particle size and/or a dispersion of particle size that is less uniform degrades the elastic properties of a TPV.
The particle size and uniformity of the rubber dispersion in a TPV can thus constrain the selection of plastic and rubber components for the preparation of a TPV. For a Santoprene™ TPV, which is a TPV based on isotactic polypropylene (iPP) plastic matrix and crosslinked ethylene-propylene-diene terpolymer (EPDM) rubber dispersions, it is important to use fractional melt-flow rate (MFR) iPP to blend with EPDM in a mixer or extruder before the introduction of curatives. Since EPDM typically has much higher molecular weight (MW) than that of an iPP, low MFR and high MW iPP is helpful to provide viscosity matching during initial blending. Viscosity matching allows stress transfer across blend interfaces for finer dispersions (L. A. Utracki, "Polymer Alloys and Blends—Thermodynamics and Rheology", Hanser Publishers, New York, (1990)); in this case, it is to ensure fine iPP dispersions inside the EPDM matrix. Once the curatives are introduced, phase inversion occurs and crosslinked EPDM becomes the dispersed phase. Although decent dispersion of crosslinked rubber can be obtained in a TPV by judicious selections of plastic and rubber components (for viscosity matching) and of twin screw extrusion elements (for phase inversion and rubber dispersion), crosslinked rubber dispersion uniformity in a TPV can be further improved for better elastic properties by certain improvements to the processing of the TPV composition as described herein below.

Crosslinked rubber dispersion in thermoplastic vulcanizates


The invention, belonging to the field of biological treatment of pollutants and functional materials, presents a non-dissolved redox mediator biofilm carrier and its preparation method. The graphene oxide and/or carbonylation modified graphene oxide are used as the non-dissolved redox mediator, which is called as the functional material, and the extrusion grade polyethylene/polypropylene particles are used as the basic material. The non-dissolved redox mediator biofilm carrier is prepared by the screw extrusion process, which is a simple, flexible and controllable method, and possesses strong adaptability. The reactor with these biofilm carriers has high removal efficiency of refractory organic pollutants.

Refractory organic pollutants are those that can hardly be degraded by microorganisms, or have a very long time required for degradation. They are easily accumulated in natural media such as water bodies and soils, such as halogenated compounds, monocyclic aromatic compounds, phenols, phthalates, polycyclic aromatic hydrocarbons, nitrogen compounds, polychlorinated biphenyls, organochlorine insecticides, organophosphorus insecticides, urethane insecticides and herbicides. Their environmental hazards have been the world's concern. Control of refractory organic pollutants is an important issue in the field of water pollution prevention and control. Recent studies have shown that the addition of artificial redox mediators can accelerate the biodegradation of refractory organic pollutants and shorten the degradation time. Therefore, the redox mediator has potential application value and been caused more and more attention worldwide.

Non-dissolved redox mediator biofilm carrier and its preparation method


Based on an actual temperature upstream of a roll stand, a predicted temperature is estimated for when strip sections of the strip will roll through the roll stand. The predicted temperature is used to predict material moduli, which is used to control a regulating device that influences a roll gap for the roll stand and to parameterize a roll gap control system. A roll gap profile is predicted based on the predicted temperatures, and is compared with a nominal roll gap profile. A regulating variable that influences a profile of a roll gap is set. The regulating variable is then corrected based on the comparison with the nominal roll gap profile. The predictions are made using a prediction horizon corresponding to a plurality of consecutive sections of the strip. Control is performed for both an operator side and a drive side of the strip.

The present invention relates to a control method for a rolling mill train, wherein an adjusting device acting on a first roll stand of the rolling mill train is controlled during rolling of strip sections taking at least one control parameter into account.
The present invention also relates to a computer readable storage medium, a control computer and a rolling mill train.
Temperature fluctuations over the width and length of the strip can result in considerable malfunctions during rolling. The changing material hardness causes variations in the rolling force which can in turn lead to other roll stand reactions which, for their part, result in a change in the roll gap profile. Examples of such roll stand reactions are roll flattening, roll deflection and stand spring. Added to these are a change in the roll crowning due to contact of the work rolls with the differentially heated strip. This also affects the roll gap geometry. If such changes in the roll gap profile are not taken into account, this will result in gauge, profile and flatness defects.
The known setpoint value calculation for rolling mill trains (pass schedule calculation) can only make limited provision for temperature variations in the longitudinal direction (head, strip and tail temperature) and none at all in the strip width direction. Until now, such effects have sometimes been compensated using automatic gauge control (AGC) which at least partly corrects the setting deviations due to roll stand reaction. In addition, techniques are known in which a rolling force measurement in the first roll stand of a multi-stand rolling mill train is used for feed-forward control of the remaining stands.
Both procedures have their disadvantages. For example, automatic gauge control (AGC) cannot react to variations in the temperature profile across the width of the strip. Above all, any asymmetry in material strength (e.g. caused by a temperature wedge) and, associated therewith, any roll stand reaction asymmetry is not taken into account. Feed-forward control of the stands of a multi-stand rolling mill train by rolling force measurement in the first roll stand of the rolling mill train cannot, by its very principle, be used for a single-stand train.
This problem is particularly prevalent in continuous casting and rolling plants where there is little or no way to compensate for temperature variations in the strip, so that temperature profiles (over the length and/or the strip width) have not evened out before the strip reaches the roll stand or stands. Temperature variations can also occur in hot-rolled wide strip trains, e.g. due to the so-called skidmarks or uneven through-heating of the cast slab in the furnace.
DE 101 56 008 A1 and, with identical content, US 2004/205 951 A1 disclose a control method for a rolling mill train,                wherein a strip section temperature is determined in each case for strip sections upstream of the first roll stand,        wherein the strip section temperatures for the time of rolling of the respective strip section in the first roll stand are included in the calculation in real time by a strip model.
In DE 101 56 008 A1, the temperature behavior and possibly also the phase transformation of the strip sections are determined purely with the aim of suitably adjusting strip heating and/or strip cooling. DE 101 56 008 A1 makes no provision for using the determined temperature in connection with the rolling process as such.
WO 2008/043 684 A1 discloses a control method for a rolling mill train,                wherein a strip section temperature is determined in each case for strip sections upstream of a first roll stand of the rolling train,        wherein the strip section temperatures for the time of rolling of the respective strip section in the first roll stand are predicted by a strip model on the basis of the temperatures determined,        wherein, using the predicted temperatures of the strip sections, at least one respective control parameter for rolling of the strip sections in the first roll stand is determined,        wherein an adjusting device acting on the first roll stand is controlled during rolling of the respective strip section taking the respective control parameter determined into account.
The Patent Abstracts of Japan for JP 61 289 908 A disclose a control method for a rolling mill train whereby—in addition to the features mentioned above in connection with WO 2008/043 684 A1—the following features are implemented:                a respective current operator-side and a respective current drive-side material modulus is predicted for the strip sections using the temperatures predicted for the time of rolling of the respective strip section in the first roll stand,        a roll gap of the first roll stand can be influenced on the operator- and drive-side by the adjusting device,        the material moduli correspond to the control parameters and are used by the adjusting device at the time of rolling of the respective strip section in the first roll stand for parameterizing an operator-side and drive-side roll gap control system, and        the temperatures of the strip sections for the time of rolling of the respective strip section in the first roll stand are predicted by the strip model using a first prediction horizon.
From DE 35 15 429 A1 it is known to take account of the temperature distribution of the strip to be rolled across the width of the strip for determining the anticipated roll wear.
EP 2 301 685 A1 discloses a control method for (among other things) a rolling mill train,                wherein a strip section temperature is determined in each case for strip sections upstream of a first roll stand of the rolling train,        wherein the strip section temperatures for the time of rolling of the respective strip section in the first roll stand are predicted by a strip model on the basis of the temperatures determined,        wherein, using the predicted temperatures of the strip sections, at least one respective control parameter for rolling of the strip sections in the first roll stand is determined,        wherein an adjusting device acting on the first roll stand of the rolling mill train is controlled during rolling of the respective strip section taking the respective control parameter determined into account.


A powder inhaler for administering powder by inhalation comprising: a flow path defined by a plurality of surfaces through which a stream of air is in use drawn on inhalation by a user; and dosing means (18) for providing a dose of powder to the flow path for entrainment in the stream of air; characterized in that the inhaler further comprises dislodging means for dislodging powder accumulated on a surface of the flow path downstream of the dosing means (18).

A number of powder inhalers are known which use different systems for introducing a dose of powder into an air stream. Typically, the powder is inhaled into the lungs of a patient in order to treat, for example, asthma.
One such powder inhaler is disclosed in EP-A-0237507. This inhaler comprises an inhalation channel and a mouthpiece comprising an air chamber and an outlet nozzle, which together define a flow path through which a stream of air is drawn during inhalation by a user. This inhaler further comprises means for introducing powder into the inhalation channel. During inhalation air is first drawn into and through the inhalation channel so as to pick up powder. The stream of air containing powder is then drawn through the air chamber and out of the outlet nozzle of the mouthpiece.
FIG. 1 illustrates such a powder inhaler. The inhaler comprises a mouthpiece 2 comprising an outlet nozzle 4, an inhaler body 6 and a rotatable grip portion 8 for operating a dosing mechanism for providing doses of powder for inhalation. The inhaler body 6 is provided with an opening 10 which is filled with a window 12 through which an indicating wheel 42 is visible so as to provide an indication as to the usage of the inhaler.
FIG. 2 illustrates in exploded view component parts disposed within and to the inhaler body 6. The inhaler body 6 is capped with a divider 14 which is fixed thereto. For aesthetic reasons the inhaler body 6 is an opaque moulding. The divider 14 is a transparent moulding which has a depending tongue 15, a part of which forms the window 12.
Within the inhaler body 6 are housed the component parts of the dosing mechanism. These component parts include a dosing unit 16 which comprises a member 17 having a planar surface in which a plurality of dosing means 18 are provided and a shaft 20 which extends axially from the centre of the member 17, an inhalation unit 22 which comprises an inhalation channel 24 and a storage unit 26 which comprises a storage chamber 28 for storing powder. The above-mentioned component parts of the dosing mechanism are assembled by passing the inhalation channel 24 through an opening 30 in the storage unit 26 and passing the shaft 20 through central openings 32, 34 in the inhalation unit 22 and the storage unit 26 respectively. When so assembled, the upper ends of the inhalation channel 24 and the storage chamber 28 pass respectively through first and second openings 36, 38 in the divider 14. In this way, the inhalation unit 22 and the storage unit 26 are fixed in position in relation to one another and the dosing unit 16 can be rotated relative thereto.
In this inhaler the storage unit 28 is open at the bottom such that in use powder is provided to the dosing unit 16 under the action of gravity and the inhalation unit 22 further comprises scrapers 40 which are resiliently biased against the surface of the member 17 in which the dosing means 18 are provided. In this way, as the dosing unit 16 is rotated, the dosing means 18, which in this inhaler comprise a plurality of through holes, are filled with powder by the scrapers 40. Powder is prevented from passing through the dosing means 18 by a plate (not illustrated) which is disposed beneath the dosing unit 16.
As illustrated in FIG. 2, the divider 14 further comprises supporting means 41 for rotatably supporting an indicating wheel 42. The indicating wheel 42 has a plurality of teeth 44 disposed around the periphery thereof which engage with a spiral groove or protrusion 46 on the end face of the shaft 20. The supporting means 41 is configured to align the indicating wheel 42 such that a part of the periphery thereof is disposed adjacent the inner surface of the window 12. In use, as the dosing unit 16 is rotated, the spiral groove or protrusion 46 engages with one or more of the teeth 44 on the indicating wheel 42 so as to rotate the same. In this way, by providing a coloured marking on the periphery of the indicating wheel 42, it is possible to provide the user with a visible indication at the window 12 as to the usage of the inhaler.
As illustrated in FIG. 4, the mouthpiece 2 is fixed to the divider 14. The mouthpiece 2 comprises first and second parts 48, 50, the first part 48 being the part which is gripped by the lips of a user and the second part 50 being an insert fitted within the first part 48. The second part 50 comprises a tubular section 52, which includes one or more spirally or helically shaped projections 54 that act to deflect the air drawn therethrough and thereby deagglomerate any larger particles of entrained powder, and a substantially radially-directed flange 56, which provides a surface that together with upper surface of the divider 14 defines an air chamber 58 that is in fluid communication with the inhalation channel 24 through which air containing powder is drawn on inhalation by a user.
In use, as described hereinabove, powder is transferred from the storage chamber 28 to one of the dosing means 18, and, with rotation of the dosing unit 16, the one dosing means 18 provides a dose of powder to the inhalation channel 24. In this inhaler the dosing unit 16 is rotated by rotating the grip portion 8 in the counter-clockwise sense between first and second angularly-spaced positions. For this purpose the dosing unit 16 comprises wedge-shaped elements 60 disposed around the periphery of the member 17 and the grip portion 8 comprises a resilient member (not illustrated) which is configured to engage with an axially-directed surface 60a of a respective one of the wedge-shaped elements 60 so as to rotate the dosing unit 16 by pushing the respective wedge-shaped element 60. On rotation of the grip portion 8 in the opposite, clockwise, sense between the second and the first angularly-spaced positions, the dosing unit 16 remains stationary and the resilient member is located behind the axially-directed surface 60a of the adjacent wedge-shaped element 60; the resilient member riding over an inclined surface 60b of the adjacent wedge-shaped element 60.
Although the above-described known powder inhaler functions quite adequately, powder may accumulate on surfaces in the flow path through the inhaler.

Inhaler with vibrational powder dislodgement


An electric nail gun includes a muzzle seat, a safety component being movable relative to the muzzle seat, and a cylinder unit connected to the muzzle seat and including a striking cylinder, at least one storage chamber that is adapted for storing pressurized air, and a sealing cap that is coupled to the striking cylinder and the at least one storage chamber. The electric nail gun further includes an air valve disposed in the cylinder unit and being directly and solely movable by the safety component from a closed position to an open position to allow the pressurized air to flow into the striking cylinder, and a nail-striking unit driven movably by the pressurized air for striking a nail when the air valve is at the open position.

Referring to FIG. 1, a conventional electric nail gun 1 disclosed in U.S. Pat. No. 8,011,547 includes a machine body 11, a guide member 12, a lifter 13, a gas cylinder 14, a piston 15 and a striking member 16.
The guide member 12 is connected to the machine body 11 and is adapted for loading a nail 2. The lifter 13 is mounted to the machine body 11 and is drivable by electric power to rotate counterclockwise. The gas cylinder 14 is mounted in the machine body 11, and defines a cylinder space 140. The piston 15 is disposed in the cylinder space 140 of the gas cylinder 14, divides the cylinder space 140 into an upper section 141 and a lower section 142, and is movable relative to the machine body 11 such that volumes of the upper and lower sections 141, 142 are variable. The striking member 16 is co-movably connected to the piston 15, and extends through the lower section 142 of the cylinder space 140 into the guide member 12. The striking member 16 has a striking portion 161 that is distal from the piston 15 and that is for striking the nail 2, and a cogged portion 162 that is disengageably engaged with the lifter 13.
When the lifter 13 is powered by electric power to rotate counterclockwise, due to the engagement between the cogged portion 162 and the lifter 13, the striking member 16 and the piston 15 are both driven by the lifter 13 to move upwardly. The upward movement of the piston 15 reduces the volume of the upper section 141 of the cylinder space 140 and pressurizes air therein. As the lifter 13 continues to rotate to a specific orientation, it disengages the striking member 16. The disengagement of the striking member 16 from the lifter 14 prompts the pressurized air in the upper section 141 of the cylinder space 140 to push the piston 15, urging the striking portion 161 of the striking member 16 to strike the nail 2.
By repeating the above-mentioned process, the conventional electric nail gun 1 is able to perform high-speed consecutive nailing cycles since the air in the upper section 141 of the cylinder space 140 is constantly in direct contact with the piston 15, either before or after being pressurized. However, such configuration has its downsides. Without anything functioning as a safeguard or buffering the interaction between the piston 15 and the pressurized air, the striking member 16 may strike the nail 2 by accident if any of the lifter 13 and the striking member 16 malfunctions and breaks the engagement therebetween, causing safety issues for users.
In addition, during each nailing cycle, the pressurized air in the upper section 141 of the cylinder space 140 is released completely after the striking, that is, an output of kinetic energy is not adjustable. Therefore, energy excess may occur when the conventional electric nail gun 1 is used with different types of nail 2 or workpieces, resulting in excessive recoil and impact that may shorten the lifespan of the nail gun.


Gaming devices, systems, and methods include a gaming device that includes a display device and an image capture device to capture a plurality of images of an eye of a player of the gaming device at a plurality of respective times. The gaming device generates, for each image of the plurality of images, gaze direction data indicative of a gaze direction of the eye of the player at the respective time corresponding to the image. The gaming device accesses a player database including player data for a plurality of players, the player data including, for each player, stored gaze data. Based on the gaze direction data and the stored gaze data, the gaming device determines a player parameter value corresponding to a player parameter for the player. Based on the player parameter value, the gaming device modifies a game feature of a wagering game at the gaming device.

Embodiments described herein relate to the field of gaming devices, such as in a casino environment, and in particular to determining a player's emotional state using player gaze movement at gaming devices. In casinos and other establishments, players may play wagering games using electronic gaming machines (EGMs), such as video gaming terminals, and other gaming devices. EGMs may include other types of systems, such as online gaming systems that enable users to play games using computer devices, such as desktop computers, laptops, tablet computers or smart phones, computer programs for use on a computer device, gaming consoles that are connectable to a display, such as a television or computer screen, and others.
EGMs may be configured to enable players to provide input via buttons, keyboards, touch interfaces, and other input devices. Such input may be used by the EGM to identify the player, to enable or disable game features, or to perform other functions of the EGM. Many conventional gaming devices employ relatively simple input devices, such as buttons or keypads, which limit the features and functionality that can be offered at the gaming device.

Determining a player's emotional state using player gaze movement at gaming devices