Methods and compositions for medical imaging, evaluating intracellular processes and components, radiotherapy of intracellular targets, and drug delivery by the use of novel cell membrane-permeant peptide conjugate coordination and covalent complexes having target cell specificity are provided. Kits for conjugating radionuclides and other metals to peptide coordination complexes are also provided.

1. Field of the Invention
The present invention broadly relates to the field of medicine. More specifically, the present invention relates to the fields of medical imaging, diagnostics, and pharmaceutical therapy. The present invention provides methods and compositions for medical imaging, evaluating intracellular processes, radiotherapy of intracellular targets, and drug delivery by the use of novel cell membrane-permeant peptide conjugate coordination and covalent complexes having target cell specificity. The present invention also provides kits for conjugating radionuclides and other metals to the peptide coordination complexes.
2. Description of Related Art
Radiopharmaceuticals in Diagnosis and Therapy
Radiopharmaceuticals provide vital information that aids in the diagnosis and therapy of a variety of medical diseases (Hom and Katzenellenbogen, Nucl. Med. Biol. 24:485-498, 1997). Data on tissue shape, function, and localization within the body are relayed by use of one of the various radionuclides, which can be either free chemical species, such as the gas 133Xe or the ions 123I−, and 201Tl−, covalently or coordinately bound as part of a larger organic or inorganic moiety, the images being generated by the distribution of radioactive decay of the nuclide. Radionuclides that are most useful for medical imaging include 11C (t1/2 20.3 min), 13N (t1/2 9.97 min), 15O (t1/2 2.03 min), 18F (t1/2 109.7 min), 64Cu (t1/2 12 h), 68Ga (t1/2 68 min) for position emission tomography (PET) and 67Ga (t1/2 68 min), 99mTc (t1/2 6 h), 123I (t1/2 13 h) and 201Tl (t1/2 73.5 h) for single photon emission computed tomography (SPECT) (Hom and Katzenellenbogen, Nucl. Med. Biol. 24:485-498, 1997).
SPECT and PET imaging provide accurate data on radionuclide distribution at the desired target tissue by detection of the gamma photons that result from radionuclide decay. The high degree of spatial resolution of modem commercial SPECT and PET scanners enables images to be generated that map the radionuclide decay events into an image that reflects the distribution of the agent in the body. These images thus contain anatomic and functional information useful in medical diagnosis. Similarly, if the radionuclides decay in such a manner as to deposit radiation energy in or near the target cells or tissues, the same approach would enable therapeutically relevant doses of radioactivity to be deposited within the tissues.
Many radiopharmaceuticals have been prepared whose tissue localizing characteristics depend on their overall size, charge, or physical state (Hom and Katzenellenbogen, Nucl. Med. Biol. 24:485-498, 1997). Other radiopharmaceuticals are synthesized with the intention to be ligands for specific hormone, neurotransmitter, cell surface or drug receptors, as well as specific high affinity transport systems or enzymes. As these receptors and enzymes are known to be involved in the regulation of a wide variety of vital bodily functions, effective imaging agents can be used in the diagnosis or staging of a variety of disease states, in which such receptors are functioning abnormally or are distributed in an abnormal fashion, or in the monitoring of therapy (Hom and Katzenellenbogen, Nucl. Med. Biol. 24:485-498, 1997). Effective therapeutic agents can also be used to deliver pharmacologically active doses of compounds to the same receptors and enzymes.
Recent advances in molecular, structural and computational biology have begun to provide insights in the structure of receptors and enzymes that should be considered in the design of various ligands. Two key issues derived from the structure and distribution of these receptors have a direct impact on the development of new radiopharmaceuticals: 1) the location of a receptor or enzyme activity in the body (i.e., peripheral sites versus brain sites), and 2) its subcellular location (i.e., on the cell surface versus intracellular) will determine whether a radiopharmaceutical injected intravenously will need to traverse zero, one, two or more membrane barriers to reach the target. The structure of the receptor and the nature of its interaction with the ligand will determine the degree to which large ligands or ligands with large substituents may be tolerated (Hom and Katzenellenbogen, Nucl. Med. Biol. 24:485-498, 1997). For example, radiopharmaceuticals which target cell surface receptors will encounter no membrane barriers to reach their target. Natural ligands for these receptors can be large, and often are charged and, consequently, large radiopharmaceuticals are tolerated. Conversely, for a radiopharmaceutical to reach intracellular receptors or enzymes, at least one membrane barrier, the cell plasma membrane, must be traversed, and if the target site is within the central nervous system, the radiopharmaceutical must also traverse the plasma membranes of endothelial cells of the brain which constitute the blood-brain barrier. Such a situation usually favors radiopharmaceutical designs that strongly minimize ligand size and molecular weight (Hom and Katzenellenbogen, Nucl. Med. Biol. 24:485-498, 1997). Thus, as the number of membrane barriers increases, a premium is placed on keeping the size of a conventional radiopharmaceutical small (<600 Da) and the lipophilicity intermediate (characterized by an octanol-water partition coefficient, log P ˜2) to enable the agent to traverse membranes (Dishino, et al., J Nucl Med 24: 1030-1038, 1983; Papadopoulos, et al., Nucl Med Biol 20:101-104, 1993; Eckelman, Eur J Nucl Med 22:249-263, 1995). This has conventionally precluded the use of peptide radiopharmaceuticals for intracellular targets.
There has been a great deal of research into the development of radiopharmaceuticals directed toward cell surface receptors whose natural ligands are peptides. Tc-labeled peptides can span the spectrum of size. The derivatizing group or chelation core of smaller peptides has been reported to impact the in vitro binding and in vivo distribution properties of these compounds (Babich and Fischman, Nucl Med Biol 22:25-30, 1995; Liu, et al., Bioconj Chem 7:196-202, 1996). For larger peptides or proteins, the labeling process can usually occur at one or more of several reactive sites, and thus, the final mixture of compounds is less chemically defined. Thus, for larger proteins, it is usually much less clear which of these sites, if any, might be more favorable for receptor interaction and whether or not specific labeling would increase biological activity of the agent (Hom and Katzenellenbogen, Nucl. Med. Biol. 24:485-498, 1997).
It is known that low molecular weight peptides and antibody fragments provide rapid tumor targeting and uniform distribution in tumor tissues (Yokota et al., Cancer Res 53:3776-3783, 1993). While such characteristics render low molecular weight peptides attractive vehicles for the delivery of radioactivity to tumor tissues and organs for both targeted imaging and radiotherapy, nonetheless problems have been encountered. High and persistent localization of the radioactivity is observed in the kidneys, which compromises tumor visualization in the kidney region and limits therapeutic potential (Buijs, et al., J Nucl Med 33:1113-1120, 1992; Baum, et al., Cancer (Phila) 73:896-899, 1994; Choi, et al., Cancer Res 55:5323-5329, 1995; Behr, et al., J Nucl Med 36:430-441, 1995). As discussed by Arano, et al. (Cancer Res 59:128-143, 1999), radiolabeled low molecular weight peptides and antibody fragments would become much more useful for targeted imaging and therapy if the renal radioactivity levels could be reduced without impairing those in the target tissue. Previous studies have indicated that radiolabeled low molecular weight peptides and antibody fragments are likely resorbed by proximal tubules via luminal endocytosis after glomerular filtration (Silberbagl, S. Physiol Rev 68:811-1007, 1988). The long residence times of the radiometabolites generated after lysosomal proteolysis of the radio labeled fragments in renal cells were also reported to be responsible for the persistent renal radioactivity levels (Choi, et al., Cancer Res 55:5323-5329; Rogers, et al., Bioconjugate Chem 7:511-522,1996).
There exists a continued need for peptide-based radiopharmaceuticals that are rapidly cleared and target intracellular receptors or enzyme activities.
Peptide-Based Metal Coordination Complexes
Small peptides can be readily prepared by automated solid phase peptide synthesis (Merifield et al., Biochemistry 21:5020-5031, 1982; Houghten, Proc Natl Acad Sci USA 82:5131-5135, 1985; Lin, et al., Biochemistry 27:5640-5645, 1988) using anyone of a number of well known, commercially available automated synthesizers, such as Applied Biosystems ABI 433A peptide synthesizer. Many combinations of natural and non-natural amino acids and peptide sequence mimetics (peptidomimetics) are possible, and selective engineering of favorable target-binding and pharmacokinetic properties can be accomplished with natural and unnatural peptides (Lister-James et al., Q. J: Nucl. Med., 41:111-118, 1997). Peptidomimetics are unnatural biopolymers that do not contain α-amino acids, but rather incorporate backbone structures with hydrogen-bonding groups (such as urea), chiral centers, side chain functionalities, and a sufficient degree of conformational restriction to behave similar to, or mimic the bioactivities of, a natural polypeptide. Peptide-based imaging agents are also well known (Lister-James et al., Q. J: Nucl. Med., 41:111-118,1997; Lister-James et al., J. Nucl. Med., 38:105-111, 1997), especially those that incorporate Tc-99m as the radionuclide, the most commonly used isotope in medical imaging.
The metallic character of Tc-99m requires that it be stabilized by a chelation system to be coupled to an imaging agent. This chelator may typically involve a multiple heteroatom coordination system, or the formation of a non-labile organometallic species. There are two broad strategies for binding metals for biological applications. These are "the pendant approach" and "the integrated approach," which have been recently reviewed by Katzenellenbogen and colleagues (Hom and Katzenellenbogen, Nucl. Med. Biol., 24:485-498, 1997). The pendant (or conjugate) approach involves the strategic placement of a Tc-99m-chelator-tether moiety at a site on the ligand that will not hinder binding of the ligand to its high affinity receptor. The integrated approach replaces a component of a known high-affinity receptor ligand with the requisite Tc-99m chelator such that there is a minimal change in the size, shape, structure, and binding affinity of the resultant molecule. Applications involving peptide-based imaging agents typically use the conjugate design, whereby an appropriate metal chelating moiety is affixed to the amino or carboxy terminus of the targeting peptide.
A variety of metal chelation systems have been developed for synthesis of radioisotopic and magnetic resonance peptide-based imaging agents. Peptide-based agents target extracellular or externally oriented membrane bound receptors (Hom and Katzenellenbogen, Nucl. Med. Biol., 24:485-498, 1997) because the charge, size, and pharmacokinetic properties of typical peptide structures do not allow diffusion across the lipid bilayer of the cell plasma membrane. This limitation has prevented peptide metal chelates from reporting the functional status or biological activity of intracellular receptors or enzymes or other homeostatic activities and intracellular targets. Although techniques and reagents for labeling antibodies and antibody fragments with metal-chelates are well known in the art (Hom and Katzenellenbogen, Nucl. Med. Biol., 24:485-498, 1997, and references therein), they target extracellular or externally oriented cell surface receptors.
Tat Proteins and Peptides
Tat is an 86-amino acid protein involved in the replication of human immunodeficiency virus type 1 (HIV-1). The HIV-1 Tat transactivation protein is efficiently taken up by cells (Mann and Frankel, EMBO, 10:1733-1739, 1991; Vives et al., J. Virol., 68:3343-3353, 1994), and low concentrations (nM) are sufficient to transactivate a reporter gene expressed from the HIV-1 promoter (Mann and Frankel, EMBO, 10:1733-1739, 1991). Exogenous Tat protein is able to translocate through the plasma membrane and reach the nucleus to transactivate the viral genome (Frankel and Pabo, Cell 55:1189-1193, 1988; Ruben, et al, J Virol 63:1-8, 1989; Garcia, et al., EMBO J 7:3143, 1988; Jones, Genes Dev 11:2593-2599,1997).
A region of the Tat protein centered on a cluster of basic amino acids is responsible for this translocation activity (Vives et al., J Biol. Chem., 272:16010-16017, 1997). Tat peptide-mediated cellular uptake and nuclear translocation have been demonstrated in several systems (Vives, et al., J Biol Chem 272:16010-16017, 1997; Jones, Genes Dev 11:2593-2599, 1997). Chemically coupling a Tat-derived peptide (residues 37-72) to several proteins results in their internalization in several cell lines or tissues (Fawell, et at, Proc Natl Acad Sci USA 91:664-668, 1994; Anderson, et at, Biochem Biophys Res Commun 194:876-8884, 1993; Fahraeus, et al., Curr Biol 6:84-91, 1996; Nagahara, et al, Nat Med 4:1449-1452, 1998). A synthetic peptide consisting of the Tat basic amino acids 48-60 with a cysteine residue at the C-terminus coupled to fluorescein maleimide translocates to the cell nucleus as determined by fluorescence microscopy (Vives et al., J. Biol. Chem., 272:16010-16017, 1997). In addition, a fusion protein (Tat-NLS-β-Gal) consisting of Tat amino acids 48-59 fused by their amino-terminus to β-galactosidase amino acids 9-1023 translocates to the cell nucleus in an ATP-dependent, cytosolic factor-independent manner (Efthymiadis et al., J. Biol. Chem., 273:1623-1628, 1998).
While the literature teaches that Tat peptide constructs and similar membrane permeant peptides readily translocate into the cytosolic and nuclear compartments of living cells, little is known regarding the cellular retention characteristics over time once the permeant peptide constructs are no longer in contact with the cell surface from the extracellular fluid spaces. Furthermore, no information is available regarding the pharmacokinetic and distribution characteristics of membrane-permeant peptides within a whole living organism, animal or human.
Apoptosis
Chemotherapeutic drugs used in the treatment of cancer are thought to interact with diverse cellular targets in conferring lethal effects on mammalian cells. Recently, anticancer agents, irrespective of their intracellular target, have been shown to exert their biological effect in target cells by triggering a common final death pathway known as apoptosis (Fulda, et al., Cancer Res 57:3823-3829,1997; Fisher, Cell 78:539-542, 1994). Thus, there exists mounting evidence that many anticancer treatments may kill through apoptosis by activating intracellular death machinery in the target cell rather than by simply crippling various components of cellular metabolism (Fulda, et al., Cancer Res 57:3823-3829,1997; Fisher, Cell 78:539-542, 1994). In fact, the action of ionizing radiation, drug therapy, and withdrawal of physiological survival factors all appear to act as death stimuli in promoting execution of this common apoptotic pathway (Evan and Littlewood, Science 281:1317-1322, 1998; Ashkenazi and Dixit, Science 281:1305-1308, 1998). Thus, new models of resistance to therapy have begun to focus on mechanisms that antagonize execution of the apoptotic pathway.
Apoptotic stimuli can arise from the nucleus, cell membrane surface, or the mitochondria (Wyllie, Nature, 389:237-38, 1997). Ultimately, the stimuli converge on a process of activation of a family of interleukin 1β-converting enzymes {(ICE)-like cysteine proteases} known as cysteine aspartases ("caspases") (Thornberry et al., Science, 281:1312-16, 1998). Members of the caspase family are activated in apoptosis and have been shown to be necessary for programmed cell death in a number of biological systems (Yuan et al., Cell, 75:641-52, 1993; Thornberry et al., Science, 281:1312-16,1998). The caspase gene family, defined by sequence homology, is also characterized by conservation of key catalytic and substrate-recognition amino acids (Talanian et al., J. Biol. Chem., 272:9677-82, 1997). Thirteen mammalian caspases (1 through 13) have thus far been isolated, having distinct roles in apoptosis and inflammation (Thornberry et al., Science, 281:1312-16, 1998). In apoptosis, some caspases are involved in upstream regulatory events and are known as "initiators," while others are directly responsible for proteolytic cleavages that lead to cell disassembly and are known as "effectors." Evidence indicates that caspases transduce or amplify signals by mutual activation. For example, Fas-induced apoptosis is characterized by an early, transient caspase-1-like protease activity followed by a caspase-3-like activity, suggesting an ordered activation cascade (Enari et al., Nature, 380:723-26, 1996). Other data suggest that both caspase-3 and caspase-7 are activated by caspase-6 and caspase-10 (Thornberry et al., Science, 281:1312-16, 199; Fernandes-Alnemri, Proc. Natl. Acad. Sci. USA, 93:7464-69, 1996). Thus, while the activation cascade hypothesis remains to be absolutely proven (Villa et al., Trends in Biochem. Sci., 22:388-93, 1997), circumstantial evidence strongly points to caspase-3 as one key "effector" caspase, standing at the center of the execution pathway of the cell death program.
Caspases are some of the most specific of the proteases, showing an absolute requirement for cleavage after aspartic acid (Thornberry et al., Science, 281:1312-16, 1998). Recognition of at least four amino acids, amino terminal to the cleavage site, is also necessary for efficient catalysis. The preferred recognition motif differs significantly between caspases, thereby contributing to their biologically diverse functions (Talanina et al., J. Biol. Chem. 272:9677-82, 1997). In addition to high specificity, caspases are also highly efficient, with Kcat/Km values >106 M−1s−1 (Thornberry et al., Science, 281:1312-16, 1998). When viewed from the perspective of a molecular target for oncological imaging, this is a key property of the caspases that allows detection of caspase activity in vivo by radiosubstrates. Another advantage of the caspases as imaging targets centers on the nature of the biochemical reaction. Because normal cells have essentially non-detectable levels of caspase activity, and once activated, the "caspase cascade" amplifies reaction rates to maximal velocities (Thornberry et al., Science, 281:1312-16, 1998), the signal readout obtained by imaging is binary in character. That is, in the absence of caspase activity, the imaging signal will be low, and when activated, a highly amplified imaging signal will result. This renders the caspase-mediated enzymatic reaction essentially zero-order in situ and, therefore, independent of radiotracer concentration or specific activity, thus eliminating the complexities of first or higher order reaction rates.
Deregulation of apoptosis resulting in insufficient cell death can occur in cancer, allowing malignant tissues to grow (Thornberry et al., Science, 281:1312-16, 1998). Conversely, some diseases involve excess apoptosis, such as neurodegenerative disease, ischemia-reperfusion, graft-vs-host disease, and autoimmune disorders (Thornberry et al., Science, 281: 1312-16, 1998). Accordingly, two-fold strategies for therapeutic intervention are actively underway within the pharmaceutical industry, one to selectively induce apoptosis through caspase activation, the other to inhibit caspase activity. In order to assess the treatments to alter apoptosis, an accurate means to assess apoptoic activity in vivo is needed.
Inactive pro-caspases are constitutively expressed as pro-enzymes in nearly all cells, existing in latent forms in the cell cytoplasm (Villa et al., Trends in Biochem. Sci. 22:388-93, 1997). Thus, while caspase-3 can be readily identified by Western blots, this requires biopsy material and lysis of the cells. Furthermore, activation of caspase-3 is only inferred by observation of lower molecular weight cleavage fragments on the blot. Activation of caspase-3 has also been inferred from nuclear shifts of antigen by immunohistochemical analysis of biopsy material and shown to be associated with a more favorable prognosis in, for example, pediatric neuroblastoma (Nakagawara et al., Cancer Res. 57:4578-84, 1997). However, these indirect methods only imply activation. Thus, the simple determination of the presence or absence of caspase proteins is not necessarily diagnostically useful. A method to directly and non-invasively detect and quantify the enzymatic activity of caspases in order to monitor the commitment to cell death pathway is needed. Because caspases are cytosolic enzymes, new diagnostic and therapeutic compounds are required that can readily cross cell membranes, and whose specificity is based on the presence of protease activity.
Tat Peptide Complexes
Frankel et al. (U.S. Pat. Nos. 5,804,604; 5,747,641; 5,674,980; 5,670,617; 5,652,122) discloses the use of Tat peptides to transport covalently linked biologically active cargo molecules into the cytoplasm and nuclei of cells. Frankel only discloses covalently linked cargo moieties, and does not teach or suggest the attachment of metals to Tat peptides by metal coordination complexes. Specifically, Frankel does not teach the use of peptide chelators to introduce radioimaging materials into cells. In addition, while Frankel teaches the use of cleavable coupling reagents between the Tat protein and the cargo molecule, the cleavable linkers disclosed are non-specific, such that the retention of the cargo molecule is not limited to specific cells.
Anderson et al. (U.S. Pat. Nos. 5,135,736 and 5,169,933) discloses the use of covalently linked complexes (CLCs) to introduce molecules into cells. CLCs comprise a targeting protein, preferably an antibody, a cytotoxic agent, and an enhancing moiety. Specificity is imparted to the CLC by means of the targeting protein, which binds to the surface of the target cell. After binding, the CLC is taken into the cell by endocytosis and released from the endosome into the cytoplasm. In one embodiment, Anderson discloses the use of the Tat protein as part of the enhancing moiety to promote translocation of the CLC from the endosome to the cytoplasm. In another embodiment, Anderson discloses the use of CLCs to transport radionuclides useful for imaging into cells. The complexes described by Anderson are limited in their specificity to cells that can be identified by cell surface markers. Many biologically and medically significant cellular processes, for example caspase protease activities discussed above, are not detectable with cell surface markers. In addition, the attachment of enhancing moieties to the CLC is accomplished by the use of bifunctional linkers. The use of bifunctional linkers results in the production of a heterogeneous population of CLCs with varying numbers of enhancing moieties attached at varying locations. This can lead to the production of CLCs in which the biological activity of the targeting protein, the enhancing moiety, or both, are lost. Another disadvantage of CLCs is that the number and location of linked enhancing moieties will vary with each reaction, so that a consistent product is not produced.
There is a need in the art for cell membrane-permeant peptide complexes of uniform composition, capable of delivering radionuclides, other metals, diagnostic substances such as fluorochromes, dyes, etc., and therapeutic and cytotoxic drugs into cells in a specific and selective manner. Furthermore, rapid clearance of the complexes from non-target cells and tissues of the body would facilitate and enhance the utility of such complexes in vivo.

Membrane-permeant peptide complexes for medical imaging, diagnostics, and pharmaceutical therapy


A system for constructing devices for chucking workpieces in defined and reproducible positions on machine tools and measuring machines includes a mounting pipe which has grid points formed at regular coordinate distances and is provided in the longitudinal direction of the pipe with chamfers uniformly distributed over the circumference, wherein the grid points are formed on the chamfers in the form of concave spherical recesses, and wherein the center points of the spherical recesses are located on lines which extend parallel to the chamfers outside of the pipe body and which describe the ideal pipe shape.

1. Field of the Invention
The present invention relates to a system for constructing devices for chucking workpieces in defined and reproducible positions on machine tools and measuring machines. In addition, the invention relates to a mounting pipe for such a system with grid points arranged at regular coordinate distances, and a corresponding base plate. The invention also relates to a connecting element and a connecting adapter for connecting such mounting pipes to each other, to a base plate or to an adapter plate.
2. Description of the Related Art
EP 222 147 B1 discloses a system of the above described type. The mounting pipes and the base plate of this known system have locating bores arranged at regular coordinate distances. These locating bores form grid points which establish a grid spacing. This grid spacing is provided in all three planes x, y and z.
The locating bores or transverse bores forming the grid points of this known system are provided in the mounting pipes so as to intersect in the four surfaces in a large number and with great precision, wherein the mounting pipes preferably have a parallelepiped shape with rectangular or square cross-section, and wherein these mounting components and possibly appropriate base plates make it possible to construct various spatial structures for mounting and measuring workpieces. The mounting pipes are manufactured from high-strength and extruded aluminum pipes which are subsequently mechanically processed for achieving the necessary precision. The section modulus of the components is reduced by the large quantity of locating bores and transverse bores.
Pipes of aluminum having not such a high strength can be drawn more precisely, however, the precision which is possible in mechanical processing cannot be achieved.

Horst Witte Entwicklungs- und Vertriebs-KG


The synthesis and biological activity of benzoisoindoloisoquinolone compounds are described. The synthesis and biological activity of C-11-substituted indenoisoquinolones are also described. Indenoisoquinolones substituted at C-11 are prepared by McMurry reactions of 11-ketoindenoisoquinolones with aldehydes.

The cytotoxicity profile of the topoisomerase I (top 1) inhibitors camptothecin (3) and indenoisoquinoline 2 (see FIG. 3) has been described by Kohlhagen et al. in Mol. Pharmacol. 54:50-58 (1998); Pommier et al. in Biochem. Biophys. Acta, 1400:83-105 (1998); and Pommier in Opinion in Oncologic, Endocrine & Metabolic Investigational Drugs, 1:168-169 (1999), the disclosures of which are incorporated herein by reference. The synthesis of indenoisoquinoline 2 is accomplished by treatment of the cis-substituted isoquinolone 1 (FIG. 3) with thionyl chloride, as described by Cushman & Cheng in J. Org. Chem. 43:3781-83 (1978), the disclosure of which is incorporated herein by reference. Both camptothecin (3) and indenoisoquinoline 2 were also shown to be inhibitors of DNA religation reactions occuring after DNA cleavage by the enzyme, i.e., top1-catalyzed single strand breakage. Both camptothecin (3) and indenoisoquinoline 2 might be better classified as a top1 poisons than a top1 suppressors because camptothecin (3) and indenoisoquinoline 2 showed the ability to stabilize the cleavable complexes. However, the DNA single-strand breaks induced by indenoisoquinoline 2 were more stable than those induced by camptothecin (3). Furthermore, the cleavage site specificity of 2 was different from that of camptothecin (3).
Although several camptothecin (3) derivatives such as irinotecan and topotecan are clinically useful anticancer agents, they are unstable due to opening of the lactone ring present on each of these compounds; thus, subsequent rapid reversibility of the cleavage complexes is observed after drug removal. Consequently, there is a present need for additional therapeutic agents that inhibit top1 like the camptothecins, but that induce novel DNA cleavage patterns, have modified toxicity profiles and extended durations of action, and display different antitumor spectra relative to the camptothecins themselves. A number of analogs of the indenoisoquinoline 2 have been synthesized, as described by Strumberg et al. in J. Med. Chem. 42:446-457 (1999); Cushman et al. in J. Med. Chem. 43:3688-3698 (2000); and Jayaraman et al. in J. Med. Chem. 45:242-249 (2002).

Cytotoxic indeno and isoindoloisoquinolones

The United States of America as represented by the Secretary of the Department of Health and Human Services


A liquid discharge head includes piezoelectric members including: a pressure chamber applying a pressure for discharging liquid to liquid; a first electrode provided on an inner surface side of the pressure chamber; and a second electrode provided outside the pressure chamber, the piezoelectric members being arranged in a first direction intersecting with an ink flow direction and in a second direction crossing the ink flow direction and the first direction so that the flow directions of the liquid flowing through the pressure chamber of the piezoelectric members are arranged along one another. The head includes first common wiring lines connected to the first electrodes arranged in the first direction; and second common wiring lines connected to the second electrodes 23 arranged in the second direction. The first common wiring lines are arranged in the second direction and the second common wiring lines are arranged in the first direction.

Conventionally, an ink jet recording apparatus which discharges ink on a recording medium to record an image has been known as a recording apparatus. The ink jet recording apparatus incorporates a liquid discharge head for discharging ink.
As a mechanism for discharging ink from the liquid discharge head, there is known a piezoelectric member which introduces and discharges ink by changing the volume of a pressure chamber included in the liquid discharge head. The pressure chamber is provided with a liquid supply channel for supplying ink to the pressure chamber, and nozzles for discharging ink from the pressure chamber. When the volume of the pressure chamber is contracted, the ink contained in the pressure chamber is discharged as ink droplets from the nozzles, and when the volume of the pressure chamber is expanded, the ink is introduced into the pressure chamber from the liquid supply channel.
The piezoelectric member is composed of a diaphragm that forms at least one wall surface of the pressure chamber and a piezoelectric element provided on the diaphragm. The volume of the pressure chamber can be expanded or contracted by deforming the piezoelectric element.
In particular, a cylindrical piezoelectric member has been previously proposed in which a cylindrical piezoelectric element is used to form a pressure chamber. The cylindrical piezoelectric member contracts toward the center in a radial direction of the cylindrical shape. Accordingly, the ink accumulated in the pressure chamber is uniformly pressurized in a direction toward the center from the outer periphery of the piezoelectric member. This allows the ink to be discharged from the nozzles with a larger flying force.
Meanwhile, in order to obtain a higher resolution while maintaining a printing speed in performing printing with the liquid discharge head using the piezoelectric member, it is necessary to dispose multiple nozzles at a higher density in the liquid discharge head. Correspondingly, the piezoelectric members provided in association with the respective nozzles are required to have a structure that is small and can be disposed at a high density.
In this regard, PTL 1 discloses a liquid discharge head in which multiple cylindrical piezoelectric members are arranged in a staggered two-dimensional matrix form, thereby increasing the density of nozzles. PTL 1 also discloses a method for manufacturing the liquid discharge head in which a piezoelectric material is filled in a mold having multiple recesses and the piezoelectric members are integrally formed. The integral formation of the piezoelectric members can improve accuracy of the layout of the nozzles and simplify a process for manufacturing the piezoelectric members.
PTL 2 discloses, as a method for manufacturing a liquid discharge head in which piezoelectric members are disposed at a high density, a method for stacking multiple plates each having multiple grooves with groove extending directions aligned with each other and cutting the plates in a direction perpendicular to the groove extending direction. The plates are each formed of a piezoelectric material, and each groove portion serves as a pressure chamber.
In the manufacturing method disclosed in PTL 2, a pressure chamber having a greater depth than the manufacturing method disclosed in PTL 1 can be formed while the density of the disposed nozzles is maintained. The volume of the pressure chamber and the amount of contraction thereof can be increased by increasing the depth of the pressure chamber. Accordingly, both the flying force of ink and the high-density layout of nozzles can be obtained.

Liquid discharge head and method for manufacturing liquid discharge head


A multilayer ceramic capacitor comprises plural ceramic dielectric layers laminated one on another, and at least two internal electrodes separated by the ceramic dielectric layer and alternately terminated at the opposite sides of the laminated ceramic dielectric layers. The ceramic dielectric layers is composed of a complex oxide including a component (A), a component (B) and copper, wherein the component (A), is at least one element selected from the group consisting of Pb, Ca, Sr and Ba, but contains Pb at the least, wherein the component (B) is at least two elements selected from the group consisting of Mg, Ni, Zn, Ti, Ta, Nb and W, the molar ratio of the component (A) to component (B) being not less than 0.985, but not more than 1.110, and wherein the content of said copper in the complex oxide is more than 0.650 wt %, but not more than 2.200 wt % in terms of Cu.sub.2 O. The internal electrodes are composed of copper or an alloy mainly comprising copper.

1. Field of the Invention
The present invention relates to a multilayer capacitive element and a method for its production. More particularly, it relates to a multilayer ceramic capacitive element utilizing a lead-based complex perovskite for forming dielectric layers and comprising internal electrodes of copper or an alloy mainly comprising copper. Moreover, the invention relates to a method for manufacturing such multilayer capacitive elements.
2. Description of the Prior Art
Recently, multilayer ceramic capacitors have been widely popularized as there is an increasing demand for small-sized, large capacitance capacitors with severe requirements for size reductions of electronic devices as well as with increase in operating frequencies of electronic devices. In general, such a multilayer ceramic capacitor comprises a plurality of ceramic dielectric layers laminated one on another, and a plurality of internal electrodes separated by the ceramic dielectric layer and alternately terminated at opposite sides of the laminated ceramic dielectric layers.
In the production of such multilayer capacitors, green ceramic sheets are respectively applied with an internal electrode, laminated on one another, and then fired with internal electrodes at a sintering temperature of the dielectric ceramic material. Since the dielectric material conventionally used for multilayer capacitors are of a barium titanate system which has a sintering temperature of about 1300.degree. C., and since the internal electrodes are subjected to such a high sintering temperature, it is required to use, as a material for internal electrodes, a metal which does not react with dielectric and which has a high melting point and high resistance to oxidation. For that reason, noble metals such as gold, platinum, palladium and the like have widely been used for the internal electrodes. However, use of such a noble metal has led to increase in production cost of multilayer ceramic capacitors.
To solve that problem, it has recently proposed to produce multilayer ceramic capacitors utilizing a low sintering dielectric ceramic material together with an inexpensive internal electrode material. For example, Japanese patent application laid-open No. 62-210613 and No. 63-265412, and U.S. Pat. No. 4,752,858 disclose a multilayer ceramic capacitor comprising a plurality of dielectric layers of a lead-based complex perovskite, and internal electrode layers composed of copper or an alloy mainly containing copper, said lead-based complex perovskite containing a component (A) and a component (B), the component (A) being the one selected from the group consisting of Pb, Ca, Sr and Ba, but containing Pb at the least, the component (B) being at least two elements selected from the group consisting of Mg, Ni, Zn, Ti, Ta, Nb and W, the molar ratio of said component (A) to component (B), i.e., A/B, being not less than 1.00. In addition to the above application and patent, Japanese patent applications laid-open Nos. 62-115817, 62-128513 and 62-203321 each discloses a method for production of such multilayer ceramic capacitors.
The dielectric ceramic materials of the prior art can be fired at a relatively low sintering temperature of less than 1080.degree. C. in a reducing atmosphere, thus making it possible use copper or its alloy as a material for internal electrodes. It is, however, difficult to obtain dense ceramic dielectric which possess high specific resistance even at high temperatures, thus making it impossible to produce multilayer ceramic capacitors which possess high reliability even at high temperatures and high humidities.
To solve this problem, it has been proposed to incorporate a small amount of copper oxides (namely, 0.03 to 0.65 wt % in terms of Cu.sub.2 O) into the above lead-based complex perovskite dielectric material, for example, in U.S. Pat. No. 4,885,661.
In the production of such multilayer capacitors, however, it is required to fire the capacitors in a reducing atmosphere containing a reducing gas such as, for example, hydrogen, carbon monoxide, ammonia or the like with a low partial pressure of oxygen, as well as that disclosed in the above Japanese patent applications. For that reason, it is required to keep the partial pressure of oxygen in the firing atmosphere constant, thus making it considerably difficult to control the firing atmosphere. This may result in failure of mass production of multilayer ceramic capacitors with high reliability.
One idea to solve that problem is to fire green multilayer ceramic capacitors in a neutral atmosphere consisting essentially of nitrogen, but this has lead to problems. If the multilayer ceramic capacitors are fired in the nitrogen atmosphere, a part of copper in the electrode layers diffuses into the dielectric layers through the contacting surface between them during firing, resulting in a considerable difference in the content of copper oxides between the contacting and noncontacting areas of each dielectric layer with the electrode layer. Such a difference in the content of copper oxides causes production of cracks in the dielectric layers, and has led to decrease in the life characteristics of capacitors under the conditions of a high temperature and a high humidity.

Matsushita Electric Industrial Co., Ltd.


A receiving device of an embodiment has a receiver, a demultiplexer, and an interference detector. The receiver receives a multiplexed signal. The demultiplexer demultiplexes the multiplexed signal into a plurality of signals. The interference detector, with referring to bit transitions of the plurality of signals in a predetermined time period, detects interference in the multiplexed signal.

In a receiving device, deterioration of communication quality of a desired signal caused by an interfering or jamming signal, and deterioration of communication quality of a desired signal caused by deterioration of the communication transmission path hinder normal reception. Duplication of the transmission path and comparison of the two information received in duplicate using the result to detect abnormalities has been proposed as a method of detecting the deterioration of communication quality.
However, in a method such as this, it is necessary to have a duplicated transmission path, thereby increasing the overhead, and there have been cases in which the transmission efficiency was poor.

Receiving device, communication system, and interference detection method


Apparatus is provided for adjustably leveling a machine base, such as a postal scale, wherein the machine base does not have to be turned over to accomplish the leveling adjustment. The apparatus includes a threaded support shaft having a non-circular configuration at one end and a leveling wheel having a threaded passage capable of receiving and mating with the threaded support shaft. A retaining structure is capable of retaining the rotational movement of the threaded support shaft and is capable of restricting movement of the threaded support shaft relative to the base.

This invention relates to an adjustable leveling foot assembly which is capable of varying support on the underside of a housing. More particularly, this foot assembly is provided for purposes of leveling a postal scale.
When placing items, for example envelopes or packages, on top of a postal scale it is desirable that the weighing platform be level so as not to encourage slippage or movement of the mailpiece while atop the platform. Leveling is also desirable in order to provide a strictly normal force on the postal scale load cell transducer thereby avoiding errors due to any horizontal components. Often at the underside of a scale housing is located a plurality of leveling feet for the purpose of leveling the upper top portion of the housing.
U.S. Pat. No. 4,219,089 discloses leveling feet which are on threaded shafts and received at the base of the housing. Typically when adjusting the feet for leveling in these prior art systems, the user must turnover the housing to reduce the weight pressure on the feet in order to turn the feet in the desired direction to adjust the height of the feet. Adjusting of the feet typically becomes a trial and error process which can lead to numerous overturns of the housing until satisfactory leveling is achieved.
Numerous overturns of the housing being made over time is detrimental to the electronic circuitry, displays, and the like which comprise parts of the scale unit. Long-term stability and accuracy of these parts is reduced.
Assuming adjustment of the feet is sought in this prior art system without overturning the housing unit, weight pressure will produce strain on each of the feet rendering it difficult to easily rotate the feet. Additionally, the access to such feet in order to rotate is difficult and time-consuming depending upon the relative location of the feet in proximity to the periphery of the housing.
It is therefore an object of the present invention to provide a leveling foot assembly which permits the user to easily and quickly adjust the desired height of each foot.


According to example embodiments of inventive concepts, a method of fabricating a 3D semiconductor device may include: forming a stack structure including a plurality of horizontal layers sequentially stacked on a substrate including a cell array region and a contact region; forming a first mask pattern covering the cell array region and defining openings extending in one direction over the contact region; performing a first etching process with a first etch-depth using the first mask pattern as an etch mask on the stack structure; forming a second mask pattern covering the cell array region and exposing a part of the contact region; and performing a second etching process with a second etch-depth using the second mask pattern as an etch mask structure on the stack structure. The second etch-depth may be greater than the first etch-depth.

Example embodiments of inventive concepts relate to a method of fabricating a semiconductor device and/or a semiconductor device fabricated using the same and, more particularly, to a method of fabricating a three-dimensional semiconductor device including a stepped stack structure and/or a three-dimensional semiconductor device fabricating using the same.
Semiconductor devices are becoming more highly integrated to meet the desires of customers (e.g., in order to provide high performance and low costs thereof).
The integration density of the semiconductor memory devices may directly affect the costs thereof. Thus, the high integration density of the semiconductor memory devices may be increasingly demanded. The integration density of conventional two-dimensional (2D) or planar semiconductor memory devices may be mostly influenced by a planar area in which a unit memory cell occupies. Thus, the integration density of the conventional 2D or planar semiconductor memory devices may be influenced by a process technology for forming fine patterns. However, improving the process technology for forming the fines patterns may be limited the cost of equipment and/or difficulties of the process technology.
Three-dimensional (3D) semiconductor memory devices have been proposed. However, a process technology capable of reducing cost per bit than the 2D semiconductor memory devices and of improving reliability may be demanded for mass production of the 3D semiconductor memory devices.

Method of fabricating three-dimensional semiconductor device and three-dimensional semiconductor device fabricated using the same


Provided is a novel system for delivery of a gas from a liquefied state. The system includes: (a) a cabinet having a first and second panel disposed therein; (b) at least one compressed liquefied gas cylinder corresponding to each panel disposed in the cabinet; (c) temperature and/or pressure sensors disposed on each the cylinder; and (d) a controller for monitoring and adjusting the energy input into each of the cylinders based on the temperature and/or pressure in each of the cylinders sensed by the temperature and/or pressure sensors.

1. Field of the Invention
The present invention relates to a system for delivery of gas from a liquefied state, and to a method for delivery of gas at a high flow rate in a controlled manner.
2. Description of the Related Art
In the semiconductor manufacturing industry, high purity gases stored in cylinders are supplied to process tools for carrying out various semiconductor fabrication processes. Examples of such processes include diffusion, chemical vapor deposition (CVD), etching, sputtering and ion implantation. The gas cylinders are typically housed within gas cabinets. These gas cabinets also contain means for safely connecting the cylinders to respective process gas lines via a manifold. The process gas lines provide a conduit for the gases to be introduced to the various process tools.
Of the numerous gases utilized in the semiconductor manufacturing processes, many are stored in cylinders in a liquefied state. A partial list of chemicals stored in this manner, and the pressures under which they are typically stored, is provided below in Table 1:
TABLE 1 Vapor Pressure of Gas at 20.degree. C. Chemical Name Formula (psia) Ammonia NH.sub.3 129 Boron Trichloride BCl.sub.3 19 Carbon Dioxide CO.sub.2 845 Dichlorosilane SiH.sub.2 Cl.sub.2 24 Hydrogen Bromide HBr 335 Hydrogen Chloride HCl 628 Hydrogen Fluoride HF 16 Nitrous Oxide N.sub.2 O 760 Perfluoropropane C.sub.3 F.sub.8 115 Sulfur SF.sub.6 335 Hexafluoride Tungsten WF.sub.6 16 Hexafluoride
The primary purpose of the gas cabinet is to provide a safe vehicle for delivering gas from the cylinder to the process tool. The gas cabinet typically includes a gas panel with various flow control devices, valves, etc., in a configuration allowing cylinder changes and/or component replacement in a safe manner.
Variations in pressure of the relatively low volume cylinders stored in gas cabinets depend upon the rate of gas withdrawal from the cylinder (and the removal of the necessary heat of vaporization) as well as the transfer of ambient energy to the cylinder. Such effects are not typically present in bulk storage systems. In bulk storage systems, the thermal mass of the stored chemical is sufficiently large that liquid temperature variation occurs relatively slowly. Gas pressure in bulk systems is controlled by the temperature of the liquid. That is, the pressure inside the container is equal to the vapor pressure of the chemical at the temperature of the liquid.
In gas delivery systems based on cylinders, the need to control cylinder pressure by controlling cylinder temperature is recognized in the art. Gas cylinder heating/cooling jackets have been proposed for controlling cylinder pressure through the control of cylinder temperature. In such a case, a heating/cooling jacket can be placed in intimate contact with a cylinder. The jacket is maintained at a constant temperature by a circulating fluid, the temperature of which is controlled by an external heater/chiller unit. Such jackets are commercially available, for example, from Accurate Gas Control Systems, Inc.
Control of cylinder temperature coupled with thermal regulation of the entire gas piping system to prevent recondensation in the gas delivery system has been proposed for gases having low vapor pressures in U.S. Pat. No. 5,761,911 to Jurcik et al, hereby incorporated by reference in its entirety. The requirement for thermal regulation of the piping system is a result of the greater than ambient temperature of the cylinder caused by the heating/cooling jacket. If the gas line is not thermally controlled, recondensation of the gas flowing therethrough can occur when it passes from the heated zone into a lower temperature zone. Heating/cooling jackets coupled with thermal regulation is not favored due to the complications associated with system maintenance (e.g., during cylinder replacement) and the added expense.
To meet the requirements of the semiconductor processing industry and to overcome the disadvantages of the related art, it is an object of the present invention to provide a novel system for controlled delivery of gases from a liquefied state which allows for accurate control of the flow rate, while simultaneously providing safety features that allow shut down of the system at unacceptable temperatures for the gas employed.
It is a further object of the present invention to provide a method for delivery of gases at a variable flow rate and in a controlled manner.
It is another object of the present invention to provide a method for delivery of gases at a high flow rate over a period of time as required by the application carried out downstream.
It is yet another object of the present invention to provide a system for the delivery of a gas at consistently high purity and high flow rate, when needed and increasing the longevity of the cylinders from which the gas is withdrawn.
Other objects and aspects of the present invention will become apparent to one of ordinary skill in the art upon review of the specification, drawings and claims appended hereto.

System and method for controlled delivery of liquefied gases including control aspects


A miter saw is provided having a support arm that is pivotally mounted to a base for adjustment of a pivot angle, the saw including a detent mechanism to provide pivot stops at common bevel angles, such as at 45xc2x0 L, 0xc2x0 (vertical), and 45xc2x0 R. The detent mechanism includes a step-shaped, arcuate detent block mounted to the support arm in an adjustable manner to permit the accurate setting of the block in a home position. In an embodiment, a pair of set screws acts against opposite ends of the detent block, permitting precise adjustment in either direction. An axially movable detent pin is mounted to the base to contact against stepped surfaces of the block. The arm is free to pivot within a bevel angle range defined by one of the surfaces. Steps between surfaces act as a pivot stops, abutting the pin at a corresponding predetermined angle of the arm.

The invention generally relates to power tools and more particularly relates to a miter saw having a pivotable support arm with a detent mechanism to provide pivot stops at certain bevel angles.
Power miter saws are generally known. Typically, a power miter saw includes a base having a fixed support platform having a rip fence and a turntable that is rotatably mounted to the base, a movable arm assembly extending from the turntable, and power saw unit mounted to the arm for cutting a workpiece on the turntable. To make standard miter cuts, the arm holds the saw unit so that its circular blade is generally vertical.
A compound miter saw additionally includes a bevel angle joint that permits the angular adjustment of the arm to hold the blade at a bevel angle, generally between 0-45 degrees from vertical. Detent mechanisms are generally known for locking the bevel angle joint at common angles, for example 0, 33.9 or 45 degrees, however, an improved detent mechanism is desired. Some known detent mechanisms include steps integrated into the structure of the support arm, wherein the bevel angle is limited by contact of one of the steps against detent pin. It is desirable to provide a miter saw having a step-like detent mechanism that permits easy adjustment of the position of one or more of the steps relative to the arm to facilitate fine adjustment of a corresponding pivot stop position.
The invention provides an improved compound miter saw which permits precise adjustment of detent steps that correspond to bevel angle stops. For example, in an embodiment, a compound miter saw is provided which includes: a base; a movable support arm assembly for holding a tool unit, the support arm having a hub portion that is rotatably mounted to the base to permit rotation of the support arm relative to the base along an axis; a detent block having a plurality of generally parallel, planar surfaces adjacent surfaces are positioned at different axial depths relative to each other so that the adjacent surfaces are separated by a respective step; a detent pin carried by the base for movement in a direction generally parallel to the axis and generally perpendicular to the surfaces; and a biasing element urging the detent pin into contact against one of the surfaces; wherein each surface defines a range of possible bevel angle positions of the support arm, and the step can abut the pin to limit a pivoting of the support arm at a corresponding predetermined bevel angle and wherein the detent block is adjustably mounted to the support arm to permit adjustment of the position of the step relative to the support arm. Preferably, each of the steps is planar and radially oriented relative to the axis.
In an embodiment, the hub portion includes a recess shaped to receive the block and to provide space for adjustment of the block either clockwise or counterclockwise relative to a center of the hub. The hub further includes fasteners, such as set screws, to secure the detent block at a desired position.
In an embodiment, the compound miter saw further includes a linkage operable to move the detent pin. With the linkage, a user can retract the detent pin to clear one of the steps, permitting the support arm to move to a bevel angle beyond the pivot stop defined by the respective step. Preferably, the linkage includes a handle is positioned generally at a side of the base which is generally opposite of the hub.
In an embodiment, the detent block is generally arcuate, and wherein the detent block is mounted to the hub generally concentrically to the axis.
In an embodiment, at least one of the steps includes a threaded bevel angle adjustment bolt to adjust the bevel angle at which the step contacts the detent pin.
An advantage of the present invention is that it provides an improved compound miter saw.
Another advantage of the present invention is that it provides a compound miter saw in which a xe2x80x9chomexe2x80x9d bevel angle position, such as a vertical (0xc2x0) position, is precisely adjustable.
A further advantage of the present invention is that it provides a compound miter saw that has few parts and which is simple to assemble in a precise manner.
Yet another advantage of the present invention is that it provides a compound miter saw having a tiltable support arm, wherein pivot stops can be released by a linkage actuatable from a front of a saw. A related advantage is that the miter saw of the invention provides enhanced safety, avoiding a need for a user to reach around or over the saw to move a detent pin located near a rear of the saw.

Bevel angle detent system for a compound miter saw


Provided is a solid-state imaging device including a first photoelectric-conversion-portion selectively receiving a first wavelength light in incident light and performing photoelectric conversion; and a second photoelectric-conversion-portion selectively receiving a second wavelength light which is shorter than the first wavelength, wherein the first photoelectric-conversion-portion is laminated above the second photoelectric-conversion-portion in an imaging area of a substrate so that the second photoelectric-conversion-portion receives the light transmitting the first photoelectric-conversion-portion, wherein a transmitting portion is formed in the first photoelectric-conversion-portion so that the second wavelength light transmits the second photoelectric-conversion-portion more than other portions, and wherein the transmitting portion is formed to include a portion satisfying the following Equation within a width D defined in the direction of the imaging area, a refraction index n of a peripheral portion of the transmitting portion, and the longest wavelength λc of the second wavelength range selectively photoelectrically-converted in the second photoelectric-conversion-portion:λc/n≦2D.

1. Field of the Invention
The present invention relates to a solid-state imaging device, a method of manufacturing thereof, and an electronic apparatus.
2. Description of the Related Art
Electronic apparatuses such as a digital video camera and a digital still camera include solid-state imaging devices. For example, as the solid-state imaging device, a CMOS (Complementary Metal Oxide Semiconductor) type image sensor, a CCD (Charge Coupled Device) type image sensor, or the like is included.
In the solid-state imaging device, a plurality of pixels is arrayed in a matrix shape on an imaging area of a semiconductor substrate. Each pixel is provided with a photoelectric conversion portion. For example, photodiodes are disposed as the photoelectric conversion portions.
Among solid-state imaging devices, in the CMOS type image sensor, the pixel is configured to include semiconductor devices such as a pixel transistor other than the photoelectric conversion portion. With respect to the pixel transistors, a plurality of transistors are configured so as to read out signal charges generated by the photoelectric conversion portions and to output electric signals to signal lines.
In the solid-state imaging device, when photographing a color image, the photoelectric conversion portion generally receives light incident through color filters on a light-receiving plane and performs photoelectric conversion to generate the signal charges.
For example, the color filters of the three primary colors of red, green, and blue are disposed in a Bayer array on the imaging area, so that light of each color transmitting the color filter of each color is received by the photoelectric conversion portion in each pixel. In other words, by considering the pixel which the red color filter is disposed above, among the light incident as a subject image, the light of the green and blue components are absorbed and only the light of the red component transmits the red color filter, so that the transmitted red light is received by the photoelectric conversion portion disposed at the lower layer thereof.
Miniaturization of the solid-state imaging device and an increase in the number of pixels are necessary. Therefore, as the size of one pixel is further reduced, it is difficult to receive a sufficient light amount, and the image quality of the photographed image is not easily improved.
In order to solve these problems, a "lamination type" is proposed where the photoelectric conversion portions which selectively receive the light of the colors are not disposed in the direction parallel to the imaging area but the photoelectric conversion portions of the colors are disposed to be laminated in the direction perpendicular to the imaging area.
In the "lamination type", for example, it is proposed that three layers of the organic photoelectric conversion layers are laminated as the photoelectric conversion portion so as to sequentially receive the three primary color light included in the incident light. In this case, a portion of the incident light is absorbed in the photoelectric conversion portion disposed in the upper portion so that the photoelectric conversion is performed. Then, a portion of the light which is not absorbed in the photoelectric conversion portion disposed in the upper portion is absorbed in another photoelectric conversion portion disposed in the lower portion so that the photoelectric conversion is performed. For example, the photoelectric conversion portion of the uppermost layer absorbs green light; the photoelectric conversion portion of the middle layer absorbs blue light; and the photoelectric conversion portion of the lowermost layer absorbs red light. In addition, in each photoelectric conversion portion, the photoelectric conversion is performed so that signal charges are generated (for example, refer to Japanese Unexamined Patent Application Publication No. 2005-347386).
Besides, in the "lamination type", for example, it is proposed that a photoelectric conversion portion is disposed in an internal portion of the semiconductor substrate and an organic photoelectric conversion layer as a photoelectric conversion portion is disposed above thereof. For example, it is proposed that photodiodes receiving blue light and red light are formed at different depths in the semiconductor substrate and a photoelectric conversion layer receiving green light is formed on the surface of the semiconductor substrate (for example, refer to Japanese Unexamined Patent Application Publication Nos 2005-353626 and 2008-258474).
In this manner, in the "lamination type", each pixel receives not only mono-colored light but also a plurality of colored light. Therefore, it is possible to improve the light usage efficiency, so that it is possible to easily implement miniaturization. For example, in the case where three organic photoelectric conversion layers are laminated to receive the three primary color light of red, green, and blue, since the light usage efficiency is increased by three times, the area per pixel may be reduced, for example, by ⅓ times. In addition, in the case of the "lamination type", since a demosaic process is not necessary in comparison with the case where pixels are arrayed in a Bayer array, it is possible to suppress the occurrence of a false color.

Solid-state imaging device, method of manufacturing thereof, and electronic apparatus


LEDs (7) are arranged on at least opposite two corners of a bottom surface of a box body (11) of a tray shape whose bottom surface is quadrilateral, whose upper side is open, on an inner surface of which a light reflection member (11b) is provided, and whose side walls (11c) are inclined outward, so as to irradiate inside of the box body, wherein a plurality of LEDs (71) are arranged so that a region irradiated by each of the LEDs (71) rotates sequentially in a specific direction (same direction). As a result, there can be obtained a surface light source having high brightness and uniformity in an arbitrary size whether the light source is small or large while using semiconductor light emitting devices (LEDs), and an electrically illuminated signboard using the surface light source, which is thin and capable of uniform display and which operates with low electricity consumption.

In recent years, liquid crystal display devices are used as display screens, being accompanied with thinning of monitors for television receivers, personal computers or the like, and furthermore the television receivers or the like have a tendency of enlarging. Cold cathode ray tubes are generally used as the backlights for the liquid crystal display devices, but recently, it has been studied to use semiconductor light emitting devices (hereinafter referred to as LEDs) which can be operated with a low drive voltage. In this case, as shown in FIG. 11, a backlight is formed by introducing light of LEDs 112 or the like from sides of a light guide plate 111 and by taking out the light from a surface side of a light reflection surface provided on a back surface of a light reflection plate (cf. for example, Japanese Patent Application Laid-Open No. HEI7-320514), or, is formed, as shown in FIG. 12A and 12B, by arranging the light emitting devices 112 (chips or LED products) provided on the light reflection plate, so that intensity (brightness) of the light in a surface at a position of a light diffusion member 114 is uniformed by spontaneous diffusion of the light, and that the light of uniform brightness is irradiated from the surface of the light diffusion member 114.
In the former case, although brightness in almost entire surface can be uniformed by the light guide plate in a liquid crystal panel of a small type having a side of, for example, approximately 50 mm or less, a light source of a large type can not be obtained without arranging a number of the light guide plates because uniformity in a surface can not be achieved perfectly in the liquid crystal display devices having a screen larger than that described above. Here, as the light should be introduced from a side to the light guide plate 111, a light source of a large type and uniform brightness can not be obtained by arranging light guide plates (ununiformity of brightness in a surface occurs at a part of the LEDs 112), because a part of the light sources (LEDs 112) makes obstruction. Namely, a surface light source of a desired size can not be obtained by arranging (tiling) a number of light guide plates. On the other hand, being accompanied with enlarging television receivers of a thin type, enlarging of backlights for liquid crystal display devices is indispensable.
A constitution in the latter case has been employed for backlights of recent liquid crystal television receivers of a large type or the like, because a surface light source of a desired size can be obtained by arranging LEDs up to a number for making a necessary size. On the contrary, since the light from each of LEDs is irradiated to a liquid crystal panel directly through the light diffusion member 114, a distance d from a bottom surface of the LEDs 112 to the light diffusion member 114 should be approximately 70 mm in order to uniform brightness between adjacent LEDs 112, because if not, brightness at a middle part of the LEDs 112 decreases (even if the light diffusion member is provided, it eliminates directionality of light but has no function of mixing lights which the light guide plate has). Furthermore, there occurs a problem that uniform chromaticity can not be obtained, since chromaticity of each LED varies even among white LEDs and since a distance to the light diffusion member 114 should be larger because lights are not mixed perfectly in case of making white light by mixing colors by using each of LEDs of R, G, and B.
Electrically illuminated signboards used for advertisement in stations or the like have a structure, as shown for example in FIG. 13, in which several straight fluorescent lamps (hereinafter referred to as fluorescent lamps) 101 or the like are arranged in a light reflection casing (housing) 102 so as to irradiate a display panel 104 or the like through a light diffusion plate 103 or directly. The housing is formed of, for example, stainless steel, aluminum or the like in a shape of a box having an opening at a top surface side, and the fluorescent lamps 101 or the like are provided therein. Then, the housing is formed by coating a light reflection material inside so that the light from the fluorescent lamps irradiates the display panel 104 provided at a front side without being wasted (cf. for example, Japanese Patent Application Laid-Open No. 2003-330394). In case of using LEDs for the light sources, there rise same problems as that in backlights for liquid crystal display devices as described above.
As described above, in the surface light source which irradiates the light from a surface of a light guide plate by introducing the light of LEDs from a side of the light guide plate, as a part of a light source projects, arranging (tiling) a number of them can not be carried out in order to enlarge an area of the surface light source. Here, even if an upper surface of LEDs 112 are covered with a light reflection plate not to expose the light source at a surface, the brightness can not be matched with a part of the light guide plate because the portion is not a region irradiating the light. Uniform irradiation from an entire surface by diffusing the light in the light guide plate is hardly obtained because the light is apt to travel straight even if it is made easy to introduce the light into the light guide plate by using LEDs of a dome type and by narrowing directionality of the light. On the contrary, if the directionality is widened, the light can not be taken into the light guide plate because total reflection increases due to increasing of oblique incident light to the side of the light guide plate. Therefor, the light emitted from the LEDs can not be utilized efficiently, and there exists a problem that the surface light source of high brightness, uniformity and a large type can not be obtained. In LEDs of a chip type not in LEDs of a dome type, a surface light source of high brightness and a large type has not been achieved because of small amount of light flux and its indirect light.
On the other hand, in case of a right-under type in which LED chips or the like are arranged side-by-side directly at a back side of the light diffusion member 114, fine color images can not be displayed since variation of each chromaticity appears because the light of each of the LEDs 112 is irradiated directly without being mixed, and thinning can not be achieved at the same time since the LED chips and the light diffusion plate should be parted by a distance of approximately 70 mm depending on an interval between the LEDs, taking it into consideration to mix colors of R, G, B or the like. Furthermore, when the distance from the light source is large, efficiency of using the light decreases because the brightness decreases in inverse proportion to a square of the distance and, for example, LEDs of a high out put power of approximately 1 W should be arranged through an interval of 35 to 45 mm. Therefor, increasing of input power results in a large long-term change of LEDs by heat generation, necessity of heat dispersion and necessity of a space for setting a heat sink, being against to thinning, but such backlights having the heat sink (50 to 60 mm thick) has been employed in actual television receivers of a large type.
After all, there are problems that in a conventional surface light source using LEDs, a surface light source of a large type can not be obtained simply by using a light guide plate, and that in the right-under type of arranging the LEDs directly under a display plate in matrix structure, thinning the surface light source can not be achieved because a means for dispersing heat becomes necessary as output power of the LEDs is increased to make a distance from a position of the LEDs to a light diffusion member large. Further, in the right-under type, there rises still a problem that a production cost is raised significantly, since LEDs of certain brightness and chromaticity should be used by selecting the LEDs because the lights of each of the LEDs can be hardly mixed.

Surface light source and electrically illuminated signboard


The log washer with staggered paddles is a device for washing and separating aggregates, such as sand, gravel, ores, etc., from waste material. The log washer has a water tank or trough having one end inclined or raised relative to horizontal. A pair of shafts are mounted for rotation in bearings in the end walls of the tank, and connected to a driver by appropriate gearing so that the shafts rotate in opposite directions. Each shaft has a plurality of paddles mounted thereon, each paddle being mounted at an angle to the shaft to raise washed aggregates up the inclined trough to a discharge hopper or conveyor belt. Further, the paddles on each shaft are grouped in sections, the radial angle formed by adjacent sections with the shaft being staggered, the paddles on adjacent shafts being offset so that the aggregate material is ground between the paddles.

1. Field of the Invention
The present invention relates to apparatus for separating and washing clay, shale, and other contaminants from gravel, and particularly to a log washer having staggered paddles.
2. Description of the Related Art
Gravel is a commonly used material in the construction industry, being used in concrete, in paving, in landscaping, and as a component in other materials and the performance of other functions. Gravel may be obtained by strip mining techniques, from quarries, by dredging operations, and other methods. Typically gravel obtained by such methods will be mixed with clay mud balls or other soils, often containing grass, roots, and small wood or tree branch fragments, or with shale, sand, sandstone, limestone, or other earthen materials. In order to prepare gravel for market, it is necessary to separate the gravel from the earthen materials in which it is found, and to wash the gravel so that it is free from such contaminants.
Fine grades of gravel are usually separated and washed in devices which use a screw conveyor or auger, having a continuous, smooth, helical spiral blade about its circumference similar to the thread of a screw. Examples of such devices are shown in U.S. Pat. No. 1,695,021, issued Dec. 11, 1928 to Puryear (two parallel screws driven by planetary gears, with improved arrangement of water jets and valves for directing the flow of water in the tank), and in U.S. Pat. No. 2,025,841, issued Dec. 31, 1935 to Young (trough with screw conveyors and a novel de-shaling hopper for removing shale from gravel by water jets). Sometimes notches will be cut into the threads at regular intervals to break up clumped material, e.g., the cut-flight conveyor shown in FIG. 31 at page 1426 of Marks"" Mechanical Engineers"" Handbook (4th ed., 1941), U.S. Pat. No. 4,448,678, issued May 15, 1984 to Gentry (lignite separator with a single, hybrid shaft having a spiral lower end and a notched upper end).
Coarse gravel is usually separated and washed using log washers. Typical log washers have a water tank or trough mounted at an inclined angle relative to horizontal, with a pair of parallel shafts or logs mounted bearings in the end walls of the trough so that they are free to rotate. A motor is connected to one end of the shafts by appropriate gearing to drive the shafts to rotate in opposite directions. Each shaft has a plurality of paddles or blades mounted thereon, usually mounted to the shaft at an angle, the paddles on adjacent shafts being staggered so that mud balls and other clumps of material broken down by grinding between the blades of adjacent shafts, and so that the shafts carry solid rock and gravel material towards the raised end of the shaft, where the separated and washed gravel is discharged to an appropriate hopper or conveyor belt. Typically, in a conventional log washer, the paddles on a single shaft are mounted in long rows at equally spaced angular distances about the axis of the shaft, e.g., at 90xc2x0 intervals.
Examples of conventional log washers with proposed improvements are disclosed in U.S. Pat. No. 1,609,652, issued Dec. 7, 1926 to McQueen (log washer with improved method of attaching the paddles to the shaft using keyways and aligned slots), and U.S. Pat. No. 3,807,558, issued Apr. 30, 1974 to Hamm (gravel separator using both sand screw and log washer where material introduced to trough lateral to screw or log washers into high velocity stream of water). U.S. Pat. No. 2,336,991, issued Dec. 14, 1943 to Leveke, shows a gravel washer with a single shaft having multiple sections of different diameters, one section being square in section, in which the sections are mounted eccentrically relative to the bearing to produce greater agitation in the trough.
The problem with conventional log washers is that the paddles on each shaft are mounted in straight rows. This configuration means that each time a row of paddles completes a revolution, the load in the tank of trough will be thrown or shifted laterally against the sidewalls of the tank. The lateral shifting of the load in the tank creates agitation and vibration along the entire length of the tank, at least four times per revolution in the case of log washers having four rows of paddles. The vibrations cause rocking in the tank supports, requiring that more time and effort be expended in preparing the foundation or supports for the tank or trough, and potentially result in greater wear and stress being placed on the bearings and/or the shaft. The present invention is directed towards a log washer shaft having staggered sections of paddles along each row, in order to reduce load shifting stresses, resulting in less strain and stress being placed upon the tank supports.
Other forms of separators are known for separating other mixtures of solids, having structures less related to the present invention, such as those described in the following patents: U.S. Pat. No. 1,972,195, issued Sep. 4, 1934 to Lacy, Jr. (ore washer with a chain and sprocket with buckets mounted on the chain to scoop material in a trough); U.S. Pat. No. 2,050,458, issued Aug. 11, 1936 to Ovestrud et al. (portable separator with a scrubber and a screen, but no log washers); U.S. Pat. No. 2,324,549, issued Jul. 20, 1943 to P. L. Wigton (separator with a spiral ribbon mounted on a shaft where the shaft is supported by a chain or belt); U.S. Pat. No. 2,489,161, issued Nov. 22, 1949 to Scholes (endless belt separator with improved seals); U.S. Pat. No. 4,234,415, issued Nov. 18, 1980 to de Tuya Casuso (ore separator with rotating drum); U.S. Pat. No. 5,868,256, issued Feb. 9, 1999 to Teppo (clay refiner with rotating drum); and International Patent No. WO 97/16253, published May 9, 1997 (rotating drum with inner and outer chambers).
None of the above inventions and patents, taken either singularly or in combination, is seen to describe the instant invention as claimed. Thus a log washer with staggered paddles solving the aforementioned problems is desired.
The log washer with staggered paddles is a device for washing and separating aggregates, such as sand, gravel, ores, etc., from clay, dirt, organic waste matter, and other impurities. The log washer has a water tank or trough having one end inclined or raised relative to horizontal. A pair of shafts are mounted for rotation in bearings in the end walls of the tank, and connected to a driver by appropriate gearing so that the shafts rotate in opposite directions. Each shaft has a plurality of paddles mounted thereon, each paddle being mounted at an angle to the shaft to raise washed aggregates up the inclined trough to a discharge hopper or conveyor belt. Further, the paddles on each shaft are grouped in sections, the radial angle formed by adjacent sections with the shaft being staggered, the paddles on adjacent shafts being offset so that the aggregate material is ground between the paddles.
The adjacent sections of paddles on each shaft are separated by transition zones characterized by an absence of paddles. The transition zones provide for enhanced scrubbing of the aggregate material.
Accordingly, it is a principal object of the invention to reduce the vibration in a log washer caused by shifting loads through staggering sections of paddles on the log washer shafts.
It is another object of the invention to relieve stress and strain on the supports of a log washer tank by staggering sections of paddles on the log washer shafts.
It is a further object of the invention to provide a log washer which separates aggregates from waste materials and washes the aggregate having smoother operation through staggering shifting loads in the log washer water tank.
Still another object of the invention is to reduce wear and tear on log washer tank supports, log washer shafts, and shaft bearings by offsetting sections of paddles in each row of log washer paddles.
It is an object of the invention to provide improved elements and arrangements thereof for the purposes described which is inexpensive, dependable and fully effective in accomplishing its intended purposes.
These and other objects of the present invention will become readily apparent upon further review of the following specification and drawings.


A wire section (1) inserted into a patient includes a wire (4) connected with a snare (3) at the front end thereof, and an outer tube (8) which retractably passes the wire (4) and the snare (3) therein. A remote control section (2) not inserted into the patient's body includes a bar-like main body (9) with a hollow inside; an operating member (11) connected to the main body (9) so as to be slidable in L and R direction and sled to enter or exit the snare (3) into and from the outer tube (8); and a pinching mechanism (15) built in the main body (9) and connected to the operating member (11) for detachably pinching the pipe (6) connected to the rear end of the wire (4). The wire section (1) and the remote control section (2) are connected when the pipe (6) is pinched by the pinching mechanism (15), and the wire section (1) and the remote control section (2) are separated when the pipe (6) is released from the pinching mechanism (15).

A remote controlled medical instrument for remote controlling an actuator inserted into the body and treating an object in the body includes a polypectomy instrument for resecting the polyp formed in the body, a body tissue collecting instrument for collecting a malignant or benign tissue of the body and an internal foreign object extracting instrument for extracting a foreign object taken inside the body.
The polypectomy instrument, serving by way of example as the above remote controlled medical instrument, conventionally includes a monopolar type and a bipolar type. The monopolar type includes instruments such as that disclosed in Japanese Laid-Open Patent Publication No. 05-337130, and the bipolar type includes instruments such as that disclosed in Japanese Laid-Open Patent Publication No. 10-137261. FIG. 10 is a view showing the above mentioned monopolar polypectomy instrument. In FIG. 10, the polypectomy instrument 50 includes a wire section 51 inserted into the stomach or the intestine through an endoscope, and a remote control section 52 with which the doctors performing the surgery control the wire section 51 outside of the body. H is a high-frequency generator for flowing high-frequency current to the polypectomy instrument 50.
In the wire section 51, 53 refers to a snare serving as an actuator for resecting the polyp P formed at the wall W of the stomach or the intestine (the intestine herein). The snare 53 is an electrode formed by forming a steel stranded wire into a loop shape, and a high-frequency current is flowed out from the high-frequency generator H, as hereinafter described. 54 is a wire made of a steel stranded wire with the snare 53 coupled to the front end, and the rear end of the wire 54 is coupled to the remote control section 52. 55 is a tube through which the wire 54 and the snare 53 pass in a freely entering and exiting manner and is made of a flexible plastic. Here, only the wire 54 is passed through the tube 55, but by pulling the wire 54 in the R direction, the snare 53 is deformed and accommodated inside the tube 55.
In the remote control section 52, 56 is a rod-shaped main body having a hollow inside, and a slit 56a extending in the longitudinal direction L and R of the main body 56 is formed at the side face. A cap 57 for holding the rear end of the tube 55 to the front end of the main body 56 is attached to the front end (L direction side) of the main body 56, and the wire 54 is passed through the cap 57. 58 is an operating member slidably coupled to the main body 56 in the L and R direction, and is formed with finger inserting holes 58a, 58b through which the forefinger and the middle finger are inserted. 59 is a male jack coupled to the operating member 58, and the rear end of the wire 54 is coupled to the root of a terminal 59a at the center. Thus, when the operating member 58 is slide operated in the L and R direction, the wire 54 coupled to the jack 59 is moved in the L and R direction, causing the snare 53 to project out from the inside of the tube 55 or retract inside the tube 55. Further, the jack 59 is fitted with a female jack 60, and is thereby connected to the high-frequency generator H by way of a cable C1. The high-frequency current generated at the high-frequency generator H thereby flows out through the cable C1 and the jacks 60, 59 to the wire 54, and from the wire 54 to the snare 53. M is an external electrode attached to the abdomen or the buttocks of the patient, and is connected to the high-frequency generator H by way of a cable C2. 61 is a pipe coupled to the operating member 58, and is arranged inside the main body 56. The pipe 61 passes the wire 54 therein and leads it to the operating member 58. 62 is a finger holder coupled to the rear end (R direction side) of the main body 56, and is formed with a finger inserting hole 62a through which the thumb is inserted. When the thumb is inserted into the finger inserting hole 62a, and the forefinger and the middle finger are inserted into the finger inserting holes 58a, 58b of the above mentioned operating member 58, the operating member 58 is slide operated in the L and R direction by the forefinger and the middle finger while holding the main body 56.
The steps of resecting the polyp P formed at the wall W of the intestine and the operations of each part in the above polypectomy instrument 50 will now be explained. First, two jacks 59, 60 are fitted together, and the external electrode M is attached to the abdomen or the buttocks of the patient. Next, the wire section 51 is inserted into the intestine of the patient with the endoscope (not shown). Here, the operating member 58 is sled to a position shown with a dotted line, the pipe 61 and the wire 54 are pulled in the R direction, and the snare 53 is retracted inside the tube 55. When the front end of the wire section 51 is inserted to a location where the polyp P is located, the operating member 58 is sled to a position shown with a solid line. The pipe 61 and the wire 54 are thereby pushed in the L direction, causing the snare 53 to project out from the inside of the tube 55, and the projected snare 53 then encircles the base Pa of the polyp P. Here, in FIG. 10, since the projecting direction (U direction herein) of the polyp P and the loop surface of the snare 53 are parallel, even if the snare 53 is moved in the D direction, the snare 53 does not encircle the polyp P, and thus the polyp P is rotated with the entire intestine with respect to the snare 53 by having the patient change the body position to have the projecting direction of the polyp P perpendicular to the loop surface of the snare 53, and the snare 53 then encircles the polyp P.
Further, when a polypectomy instrument 70 equipped with a rotating mechanism part 71 is used as shown in FIG. 11, the snare 53 easily encircles the polyp P without having the patient change the body position. The reference characters of each part shown in FIG. 11 are the same for parts similar to those in FIG. 10. In FIG. 11, the rotating mechanism part 71 is arranged on the middle of the wire section 51, and is configured from a grip 72 gripped by the hand, a supporting pipe 73 rotatably supported at the middle of the grip 72, and a roller 74 fixed to the peripheral surface of the supporting pipe 73. The supporting pipe 73 passes the wire 54 therein and holds the wire 54. Due to such rotating mechanism part 71, by rotating the roller 74 with the axis of the supporting pipe 73 as the rotating center, the supporting pipe 73 and the wire 54 are rotated in the same direction as the roller 74, and the rotational torque of the wire 54 is transmitted to the snare 53, thus rotating the snare 53 in the same direction as the roller 74. Therefore, the snare 53 is rotated with respect to the polyp P without having the patient change the body position to have the projecting direction of the polyp P perpendicular to the loop surface of the snare 53, and the snare 53 then encircles the polyp P. Further, the surgery can be performed without having the patient change the body position, and thus the load on the patient can be removed.
When the snare 53 encircles the polyp P as above, the high-frequency current is flowed out from the high-frequency generator H to the snare 53 through the wire 54. Thus, the high-frequency current is conducted from the base Pa of the polyp P encircled by the snare 53 through the body of the patient and to the external electrode M, and heat generation as well as burning occurs at a portion of the polyp P having the smallest cross sectional area. Subsequently, when the operating member 58 is gradually sled to the R direction, the pipe 61 and the wire 54 are pulled in the R direction, causing the snare 53 to gradually retract inside the tube 55, and thus the base Pa of the polyp P is tightened by the snare 53. Finally, the base Pa of the polyp is burnt off by the burning by the high-frequency current and the tightening force of the snare 53, and the polyp P is resected from the wall W of the intestine.
In the conventional polypectomy instrument 50, 70, the wire section 51 inserted into the body of the patient is discarded after the surgery in view of infection of disease and hygienic problems. However, since the remote control section 52 and the rotating mechanism part 71 are integrally coupled to the wire section 51, the remote control section 52 and the rotating mechanism part 71 not inserted into the body of the patient are also discarded with the wire section 51, and thus the entire instrument 50, 70 is disposable. This is a great waste when using the instrument, and is a factor in the increase of facility cost of hospitals and the like.


A valve body for a valve has an envelope surface with a bell-shaped cross section contour in a longitudinal direction of the valve body. The envelope surface is provided with a guide region for guiding the valve body in a valve seat and is further provided with a sealing region for contacting fluid-tightly the valve seat. The sealing region adjoins in the longitudinal direction the guide region. The bell-shaped cross section contour in the longitudinal direction from the guide region to the sealing region is open at one side and increases strictly monotonously. The valve body is formed of a thermoplastic polyhalogen olefin. A crankcase ventilation device is provided that is provided with a valve provided with such a valve body.

The invention concerns a valve body for a valve with an envelope surface which comprises a bell-shaped cross section contour in a longitudinal direction of the valve body, comprising a guide region for guiding the valve body in a valve seat and a sealing region for fluid-tight contact at the valve seat.
Moreover, the invention concerns a valve with a valve seat and a valve body according to the invention, which are arranged in a valve housing.
Finally, the invention concerns a crankcase ventilation device with at least one valve according to the invention.
The invention will be disclosed in the following based on the example of its use in an internal combustion reciprocating piston engine.
In such internal combustion engines, it is not possible to achieve a complete sealing action at the piston rings between the piston and the cylinder wall. The requirement of a low friction between these components and the requirement of a sealing action as complete as possible between them are contrary here. A compromise must be found between these two requirements. This means that no complete sealing action can be achieved. Oil-containing leakage gas (so-called "blow-by") can thus bypass the piston and reach the crankcase. In this context, in principle three different paths for escape of the leakage gas can be differentiated: On the one hand, the leakage gas can escape through gaps in the piston rings, on the other hand, it can escape between the piston ring and the cylinder wall, and, finally, between the piston ring and the piston. The oil-containing leakage gas that has escaped in such a way into the crankcase must now be supplied again to the combustion process. This is performed in closed crankcase ventilation devices (closed crankcase ventilation—CCV).
Such crankcase ventilation devices, depending on the field of application, can be constructed differently. In an exemplary embodiment of such a crankcase ventilation device, the oil-containing leakage gas is first guided into an oil separator in whose return line an oil return flow check valve can be arranged. This oil return flow check valve prevents that oil is accidentally sucked in (which could cause damages in the internal combustion engine). Moreover, further pressure regulating valves (for purified leakage gas) or other non-return check valves that are required for regulating the pressure in the crankcase can be provided downstream of the oil separator.
These different valves are typically embodied differently in regard to construction. Therefore, they comprise typically also a different closure behavior, respectively. In this context, for an efficient crankcase venting action, a closing of the valves as early as possible already for very minimal vacuum values must occur and an oil drainage already at very low oil quantity weights.