This invention relates to an unloader for a tower grain dryer or the like, and more particularly to such an unloader which meters or positively unloads the dried grain from such a dryer in such manner that dried grain is substantially uniformly removed from all regions of the dryer outlet section.
Tower grain dryers are well known. Generally, they comprise a vertical tower of cylindrical or other shape. The tower has a plenum located within the tower and spaced from the inner surfaces of the outer walls of the tower. Typically, the walls of the tower and of the plenum are of porous construction such that air from within the plenum may be forced through the walls. Grain to be dried is conveyed to the upper reaches of the tower and fills the space between the outer tower wall and the plenum so as to form a drying path for the grain to be dried. As dried grain is continuously discharged from the lower end of the grain drying path, additional grain to be dried is loaded into the upper end of the drying path.
The plenum is supplied with heated air by means of one or more burner/blower assemblies. The heated air is forced from within the plenum through the porous or perforated walls of the plenum, through the grain in the drying path, and is forced through the porous outer wall of the tower carrying away moisture from the grain.
Reference may be made to the following U.S. Pat. Nos. which describe tower or other similar types of grain dryers of the type discussed above: 746,410, 3,333,348, 3,710,449, 3,766,664, 3,864,845, 3,896,562, 3,955,288, 4,004,351, 4,398,356, 4,423,557, 4,914,834, 5,129,164, and 5,136,791.
In certain of these prior art tower grain dryers, the lower portion of the drying path converges inwardly of the tower in a generally conical shape and is divided into a number of separate converging channels. The lower ends of the channels discharge the dried grain into the bottom of the tower to be unloaded. Unloading can be accomplished in a variety of ways. Of course, grain being a fluent material may flow by gravity out through gravity outlets. Alternatively, the grain may be swept from the base of the tower by a sweep auger or the like and conveyed by the sweep auger to a discharge outlet, as described in the above-noted U.S. Pat. No. 3,896,562. Still further, discharge augers may be located directly below the grain drying paths, as shown in U.S. Pat. No. 3,864,845, to unload the dried grain. In U.S. Pat. No. 3,333,348, a grain drying apparatus is disclosed having an inner wall and a spaced outer wall defining a grain flow path and having a pair of rotary agitator arms which extend out from the center of the dryer. In U.S. Pat. No. 4,004,351 uses rotary driven scoop arms to positively remove grain from the grain flow path.
However, it has been found that with tower dryers in which the grain drying path converges inwardly at the bottom of the tower and in which the grain drying path is divided into a number of converging channels, dried grain is oftentimes not uniformly removed from all of the channels. It has been found that grain will be removed at faster rates from some of the channels than from others. Because the speed at which the grain moves through the drying path (and hence the amount of time the grain is exposed to the drying air) varies in direct relation to the rate at which the dried grain is removed from the outlets of the channels, prior grain unloaders which did not uniformly remove dried grain from all of the grain channels caused some of the grain to move too fast through the dryer such that this faster moving grain might not be sufficiently dried, while other grain in the drying path might move too slowly such that this slower moving grain might become over dried. Of course, under dried grain is not desirable because it could lead to spoilage of the grain, and over dried grain is not desirable because it might become damaged from excessive exposure to the heated air which would waste energy and may damage the grain.
In the grain dryer described in the parent application of the present invention, now U.S. Pat. No. 5,566,470, dried grain is removed from the grain flow path by a rotary driven metering unloader body rotatably driven about a vertical axis and having a vertical wall for blocking the flow of grain from the grain flow path with the unloader wall having a grain inlet opening such that grain may enter the unloader body only by way of the grain inlet opening. Upon rotation of the unloader body, the grain within the unloader body is conveyed toward a center grain discharge outlet opening for removal from the dryer. While this unloader works well for its intended purpose, in order for it to vary the rate at which dried grain is unloaded, the rotary speed at which the unloader body is driven must be varied. This requires the use of a variable speed drive which is costly. In addition, the earlier metering unloader of this invention required a sweeping action to move the grain across the horizontal floor of the unloader to the grain discharge outlet. Therefore, there has been a need for a metering unloader body which does not require the use of variable speed drive and which does not require a sweeping action to discharge the grain.


This invention is concerned with the separation of a mixture of carbon dioxide and ethane derived from a prior separation or recovery stage or process. More particularly, the invention pertains to separation of a carbon dioxide-ethane azeotrope by freezing the carbon dioxide and removing the ethane with propane or a heavier hydrocarbon.
It is sometimes desirable to separate carbon dioxide from a gaseous mixture containing ethane, for example, in the treatment of natural gas or a reservoir injection gas, or in the preparation of synthetic natural gas. In one or more stages of these processes, carbon dioxide, ethane and heavier hydrocarbons are separated or recovered as a mixture. It is then desirable to separate the carbon dioxide from the remaining hydrocarbons, sometimes called NGL (natural gas liquids). When carbon dioxide is distilled or fractionated from the hydrocarbons, an azeotrope of carbon dioxide and ethane is formed at an overhead point in the distillation column. At this point no more ethane is separated from the carbon dioxide. Generally, unless it is desirable to recover the carbon dioxide, the carbon dioxide is vented unless the concentration of ethane in the azeotrope is such that environmental regulations make it necessary to burn the ethane-carbon dioxide mixture. Flaring is frequently an expensive and difficult process, especially in areas where the amount and concentration of the gas being flared randomly varies with various operating or producing conditions. In processes where it is desirable to recover the carbon dioxide, for example, tertiary recovery processes, the unseparated ethane is lost.
The ethane in the carbon dioxide is a valuable hydrocarbon. This invention is concerned with separating and recovering ethane along with the other hydrocarbons that might be in a carbon dioxide-ethane mixture derived from a prior process.


In the manufacture of transistors in a semiconductor substrate, such as a silicon wafer, several steps are required to form the gates of the transistors. A first layer of a gate oxide, e.g., silicon oxide, is deposited over the silicon substrate to protect it. Next a conductive, doped polysilicon layer is deposited, optionally followed by a layer of a conductive material such as a refractory metal silicide. A cap layer of silicon oxide or silicon nitride, preferably a silicon oxide produced by the chemical vapor deposition from tetraethoxysilane (TEOS), is also deposited.
A typical gate stack is shown in FIG. 1A wherein a silicon wafer 12 has a layer of gate oxide 13 thereon, followed by a first gate layer of conductive, highly doped polysilicon 14. A second gate layer 15 of a refractory metal silicide, such as titanium silicide or tungsten silicide, and a cap layer 16 of silicon oxide are also deposited.
The gate stack must now be etched to form a gate between the areas in the substrate in which the source and drain will be formed. The silicon oxide hard mask layer 16 is coated with photoresist, the photoresist is patterned, and the silicon oxide layer etched in conventional manner to form a "hard mask". Suitably the etchant for the hard mask is a fluorine-containing gas such as CHF.sub.3, C.sub.2 F.sub.6, CF.sub.4 and the like.
FIG. 1B illustrates the gate stack after it has been etched, the same numerals used as in FIG. 1A for the same layers. The silicon oxide hard mask and the gate oxide layer remain, and the two conductive layers are etched.
As devices become smaller and are placed closer together, the gates become correspondingly thinner and narrower. Thus wet etch techniques have been largely replaced by dry etching, particularly plasma etching, because plasma etching is more anisotropic and thus does not undercut the gate, particularly at its intersection with the substrate. Also, plasma etchants can be used that are highly selective; that is, they etch certain materials faster than others. In the case of a gate stack, the etchant must etch the silicide layer and the polysilicon layer, but not silicon oxide; thus the cap layers and the initial gate oxide layers remain intact, as shown in FIG. 1B. Plasma processing is also favored because processing can be carried out at comparatively low temperatures that will not damage the substrate or previously formed devices.
Various vacuum chambers have been designed to carry out plasma etching. One particular design has been disclosed by Ogle in U.S. Pat. No. 4,948,458. The etch apparatus forms a magnetically coupled planar plasma for treatment of a substrate such as a silicon wafer. This apparatus comprises a chamber having a dielectric window. A planar coil is mounted proximate to the window, and an RF power source is coupled to the coil, generally through an impedance matching circuit to maximize power transfer, and a timing circuit to provide resonance at the operating frequency, typically 13.56 MHz. Process gas is supplied to the chamber through an inlet port. When the RF power is turned on, a planar magnetic field is induced which extends into the interior of the chamber through the dielectric window. Thus a circulating flow of electrons is induced in the chamber in a plane parallel to the planar coil, limiting the transfer of kinetic energy in non-planar directions.
A surface support in the chamber supports the substrate to be processed parallel to the plane of the coil, and thus to the plasma. Since the plasma species have little velocity in non-planar directions, the kinetic impact of ionic species on the substrate is small and the predominant reaction is a chemical reaction between the plasma species and the layers on the substrate. This reaction takes place at low temperatures and low pressures.
A detailed description of the above apparatus is shown in FIGS. 2-4. Referring to FIGS. 2, 3 and 4, a plasma treatment system 100 suitable for etching individual semiconductor wafers 110, includes a chamber 112 having an access port 114 formed in an upper wall 116. A dielectric window 118 is disposed below the upper wall 116 and extends across the access port 114. The dielectric window 118 is sealed to the wall 116 to define a vacuum sealed interior 119 of the chamber 112. A planar coil 120 is mounted adjacent to the dielectric window 118. The coil 120 is formed as a spiral having a center tap 122 and an outer tap 124. The plane of the coil 120 is oriented parallel both to the dielectric window 118 and to the support surface 113 upon which the wafer 110 is mounted during etching. The coil 120 is able to produce a planar plasma within the interior 119 of the chamber 112 which is parallel to the wafer 110. A suitable distance between the coil 120 and the support surface 113 can be about 5-10 cm.
A radiofrequency (RF) generator 130 leads to a coaxial cable 132 to a matching circuit 134. The matching circuit 134 includes a primary coil 136 and a secondary loop 138 that may be positioned to adjust the effective coupling of the circuit and allow loading of the circuit at the frequency of operation. The primary coil 136 may be mounted on a disk 140 that can be rotated about a vertical axis 142 to adjust the coupling. A variable capacitor 144 is in series with the secondary loop 138 to adjust the circuit resonant frequency with the frequency output of the RF generator 130. Impedance matching maximizes the efficiency of the power transfer to the planar coil 120. An additional capacitor 146 is provided in the primary circuit to cancel part of the inductive reactance of the primary coil 136 in the circuit.
A second RF potential from a source 172 is applied to the wafer support 113. This RF generator 172 can be operated at a low frequency (below about 550 kHz) or a high frequency (13.56 MHz) but generally a low frequency is employed. The frequency of the RF generator 172 and that of the first RF generator 130 is generally different, and provides a resonant current flow in the coil 120. Thus if the primary RF generator 130 operates at 13.56 MHz, the second RF generator 172 operates suitably at 400 kHz for example. This two RF power source configuration allows control of the amount of energy introduced to the system 100 through the primary RF generator 130 and control of the power output of the RF generator 172 permits control of the velocity imparted to the reactive species in the plasma.
In order to maximize the density of the plasma, and therefore to reduce the time required to perform an etch step, comparatively high power is applied to the planar coil 120, on the order of 300-600 watts. A lower power is applied to the substrate support 113 of about 75-300 watts.
Thus high power provides fast etch rates at a low pressure in the chamber, i.e., 1 Torr or less. Further, since the kinetic energy of ions in such a plasma is low, there is less damage to the wafer.
However, we have found that charging of the wafers processed in the above planar coil apparatus is a problem. A net charge on the substrate support 113 is transferred to the wafer 110 being processed. It is believed this net charge is caused by non-uniformities in the plasma. Further, the selectivity of halogen-containing etchants, such as chlorine, is reduced by a high ion density in the plasma. The high density plasma can also result in undercutting of the wafer stack to be etched. For example, a high density plasma contains, of necessity, a high density of radical species that etch laterally as well as horizontally, causing undercutting of the gates, as shown in FIG. 5, discussed further hereinbelow. In order to reduce this undercutting, it has become common to provide sidewall protection of the gate during further plasma processing. During the course of the etching, to prevent lateral etching and undercutting of the etched gate stack, particularly at the base of the gate stack, it is also known to generate a plasma that, in addition to etching the gate stack, also deposits a protective film on the freshly etched sidewall surfaces. The formation of such layers, which can be polymeric, for example, improves the anisotropy of the etch and prevents undercutting. However, the thickness of this sidewall deposit is difficult to control; if it is too thin, it does not protect the etched sidewalls; and if it is too thick, it takes up more space on the substrate, and impairs the critical dimensions of the gates and their devices. This is unacceptable for submicron design rules.
To perform an etch step in the apparatus of FIGS. 2-4, a process gas is introduced into the chamber 112 through a port 150 formed in the side of the chamber 110. A vacuum exhaust system 152 maintains the pressure in the system and evacuates volatile by-product and unreacted gases.
Thus an improved method of etching gate stacks having good etch rates and good selectivity but improved anisotropy, would be highly desirable.


Balloon angioplasty is a widely used procedure for expanding constricted body passageways, such as arteries and other blood vessels, or various ducts (e.g., of the biliary system). In an angioplasty procedure, an uninflated angioplasty balloon attached to a catheter is delivered to a constricted region of a body passageway. Once the balloon is in position at the constricted region, fluid is injected through a lumen of the catheter and into the balloon. The balloon consequently inflates and exerts pressure against the constricted region to expand the passageway. After use, the balloon is collapsed, and the catheter is withdrawn. Although treatment of constricted arteries in the vasculature is one common example where balloon catheters are used, this is only one example of how balloon catheters may be used and many other uses are possible. For example, balloon catheters may also be used to temporarily occlude vessels during medical procedures to prevent blood or other fluids from flowing through a vessel. Balloon catheters may also be used to expand other intraluminal devices without dilating the surrounding vessel wall, such as stent-grafts that may be used to treat aneurysms. The above-described examples are only some of the applications in which balloon catheters are used by physicians. Many other applications for balloon catheters are known and/or may be developed in the future.
Balloons have a number of important design parameters. One is rated burst pressure, which is the statistically-determined maximum pressure to which a balloon may be inflated without rupturing. In order to expand hard, calcified lesions, it is desirable that the balloon have a rated burst pressure of at least 15 atm. It is also desirable that the balloon have a low wall thickness to minimize the profile of the delivery system. A wall thickness of about 0.03 millimeters or lower is generally preferred. For a given balloon material, however, there is a trade-off between burst pressure and wall thickness, in that the burst pressure generally decreases when the wall thickness is reduced. Accordingly, there is a need for a means of increasing the strength of balloon materials to attain higher rated burst pressures at lower wall thicknesses.


DNA microarrays have been used to measure gene expression in samples from patients and to facilitate diagnosis of disease. Gene expression can reveal the presence of cancer in a patient in addition to the type, stage, and origin of the cancer. Gene expression may even have a role in predicting the efficacy of cancer therapies. In recent decades, the National Cancer Institute (NCI) has tested cancer therapeutics for their effect in limiting the growth of 60 human cancer cell lines. The NCI has also measured gene expression in those 60 cancer cell lines using DNA microarrays. Various studies have explored the relationship between gene expression and therapeutic effect using the NCI datasets.
During cancer treatment, critical time is often lost due to a trial and error approach to finding an effective therapy. In addition, cancer cells often develop resistance to a previously effective therapy. In such situations, patient outcome would be greatly improved by early detection of such resistance.
Thus, there exists a need in the art for methods and devices that can predict the responsiveness of cancer patients to a medical treatment.


1. Field of Invention
This invention relates to molecules useful in determining minimal functional regions of IGFBP-3 and for antagonizing an IGF-I or IGF-II activity.
2. Description of Background and Related Art
The insulin-like growth factors I and II (IGF-I and IGF-II, respectively) mediate multiple effects in vivo, including cell proliferation, cell differentiation, inhibition of cell death, and insulin-like activity (reviewed in Clark and Robinson, Cytokine Growth Factor Rev., 7: 65–80 (1996); Jones and Clemmons, Endocr. Rev., 16: 3–34 (1995)). Most of these mitogenic and metabolic responses are initiated by activation of the IGF-I receptor, an α2β2-heterotetramer closely related to the insulin receptor (McInnes and Sykes, Biopoly., 43: 339–366 (1998); Ullrich et al., EMBO J., 5: 2503–2512 (1986)). The IGF-I and insulin receptors bind their specific ligands with nanomolar affinity. IGF-I and insulin can cross-react with their respective non-cognate receptors, albeit at a 100–1000-fold lower affinity (Jones and Clemmons, supra). The crystal structure describing part of the extracellular portion of the IGF-I receptor has been reported (Garrett et al., Nature, 394: 395–399 (1998)).
Unlike insulin, the activity and half-life of IGF-I are modulated by six IGF-I binding proteins (IGFBPs 1–6), and perhaps additionally by a more distantly related class of proteins (Jones and Clemmons, supra; Baxter et al., Endocrinology, 139: 4036 (1998)). IGFBPs can either inhibit or potentiate IGF activity, depending on whether they are soluble or cell-membrane associated (Bach and Rechler, Diabetes Reviews,3: 38–61 (1995)). The IGFBPs bind IGF-I and IGF-II with varying affinities and specificities (Jones and Clemmons, supra; Bach and Rechler, supra). For example, IGFBP-3 binds IGF-I and IGF-II with a similar affinity, whereas IGFBP-2 and IGFBP-6 bind IGF-II with a much higher affinity than they bind IGF-I (Bach and Rechler, supra; Oh et al., Endocrinology, 132: 1337–1344 (1993)). WO 01/75064 discloses additional human secreted IGFBP-like polypeptides that are encoded by nucleic acid sequences isolated from cDNA libraries from adrenal gland mRNA and thymus mRNA.
Structurally, IGF-I is a single-chain, 70-amino-acid protein with high homology to proinsulin. Unlike the other members of the insulin superfamily, the C region of the IGF's is not proteolytically removed after translation. The solution NMR structures of IGF-I (Cooke et al., Biochemistry, 30: 5484–5491 (1991); Hua et al., J. Mol. Biol., 259: 297–313 (1996)), mini-IGF-I (an engineered variant lacking the C-chain; DeWolf et al., Protein Science, 5: 2193–2202 (1996)),and IGF-II (Terasawa et al., EMBO J., 13: 5590–5597 (1994); Torres et al., J. Mol. Biol., 248: 385–401 (1995)) have been reported. It is generally accepted that distinct epitopes on IGF-I are used to bind receptor and binding proteins. It has been demonstrated in animal models that receptor-inactive IGF mutants are able to displace endogenous IGF-I from binding proteins and thereby generate a net IGF-I effect in vivo (Loddick et al., Proc. Natl. Acad. Sci. USA, 95: 1894–1898 (1998); Lowman et al., Biochemistry, 37: 8870–8878 (1998); U.S. Pat. Nos. 6,121,416 and 6,251,865). While residues Y24, Y29, Y31, and Y60 are implicated in receptor binding, IGF mutants thereof still bind to IGFBPs (Bayne et al., J. Biol. Chem., 265: 15648–15652 (1990); Bayne et al., J. Biol. Chem., 264: 11004–11008 (1989); Cascieri et al., Biochemistry, 27: 3229–3233 (1988); Lowman et al., supra).
Additionally, a variant designated (1–27,gly4, 38–70)-hIGF-I, wherein residues 28–37 of the C region of human IGF-I are replaced by a four-residue glycine bridge, has been discovered that binds to IGFBP's but not to IGF receptors (Bar et al., Endocrinology, 127: 3243–3245 (1990)).
A multitude of mutagenesis studies have addressed the characterization of the IGFBP-binding epitope on IGF-I (Bagley et al., Biochem. J., 259: 665–671 (1989); Baxter et al., J. Biol. Chem., 267: 60–65 (1992); Bayne et al., J. Biol. Chem., 263: 6233–6239 (1988); Clemmons et al., J. Biol. Chem., 265: 12210–12216 (1990); Clemmons et al., Endocrinology, 131: 890–895 (1992); Oh et al, supra). In summary, the N-terminal residues 3 and 4 and the helical region comprising residues 8–17 were found to be important for binding to the IGFBPs. Additionally, an epitope involving residues 49–51 in binding to IGFBP-1, -2 and -5 has been identified (Clemmons et al., Endocrinology, supra, 1992). Furthermore, a naturally occurring truncated form of IGF-I lacking the first three N-terminal amino acids (called des (1-3)-IGF-I) was demonstrated to bind IGFBP-3 with 25 times lower affinity (Heding et al., J. Biol. Chem. 271: 13948–13952 (1996); U.S. Pat. Nos. 5,077,276; 5,164,370; and 5,470,828).
In an attempt to characterize the binding contributions of exposed amino acid residues in the N-terminal helix, several alanine mutants of IGF-I were constructed (Jansson et al., Biochemistry, 36: 4108–4117 (1997)). However, the circular dichroism spectra of these mutant proteins showed structural changes compared to wild-type IGF-I, making it difficult to clearly assign IGFBP-binding contributions to the mutated side chains. A different approach was taken in a very recent study where the IGFBP-1 binding epitope on IGF-I was probed by heteronuclear NMR spectroscopy (Jansson et al., J. Biol. Chem., 273: 24701–24707 (1998)). The authors additionally identified residues R36, R37 and R50 to be functionally involved in binding to IGFBP-1.
Other IGF-I variants have been disclosed. For example, in the patent literature, WO 96/33216 describes a truncated variant having residues 1–69 of authentic IGF-I. EP 742,228 discloses two-chain IGF-I superagonists that are derivatives of the naturally occurring single-chain IGF-I having an abbreviated C domain. The IGF-I analogs are of the formula: BCn, A wherein B is the B domain of IGF-I or a functional analog thereof, C is the C domain of IGF-I or a functional analog thereof, n is the number of amino acids in the C domain and is from about 6 to about 12, and A is the A domain of IGF-I or a functional analog thereof.
Additionally, Cascieri et al., Biochemistry, 27: 3229–3233 (1988) discloses four mutants of IGF-I, three of which have reduced affinity to the Type 1 IGF receptor. These mutants are: (Phe23, Phe24, Tyr25) IGF-I (which is equipotent to human IGF-I in its affinity to the Types 1 and 2 IGF and insulin receptors), (Leu24) IGF-I and (Ser24) IGF-I (which have a lower affinity than IGF-I to the human placental Type 1 IGF receptor, the placental insulin receptor, and the Type 1 IGF receptor of rat and mouse cells), and desoctapeptide (Leu24) IGF-I (in which the loss of aromaticity at position 24 is combined with the deletion of the carboxyl-terminal D region of hIGF-I, which has lower affinity than (Leu24)IGF-I for the Type 1 receptor and higher affinity for the insulin receptor). These four mutants have normal affinities for human serum binding proteins.
Bayne et al., J. Biol. Chem., 264: 11004–11008 (1988) discloses three structural analogs of IGF-I: (1–62) IGF-I, which lacks the carboxyl-terminal 8-amino-acid D region of IGF-I; (1–27,Gly4, 38–70) IGF-I, in which residues 28–37 of the C region of IGF-I are replaced by a four-residue glycine bridge; and (1–27,Gly4, 38–62) IGF-I, with a C region glycine replacement and a D region deletion. Peterkofsky et al., Endocrinology, 128: 1769–1779 (1991) discloses data using the Gly4 mutant of Bayne et al., supra, Vol. 264. U.S. Pat. No. 5,714,460 refers to using IGF-I or a compound that increases the active concentration of IGF-I to treat neural damage.
Cascieri et al., J. Biol. Chem., 264: 2199–2202 (1989) discloses three IGF-I analogs in which specific residues in the A region of IGF-I are replaced with the corresponding residues in the A chain of insulin. The analogs are: (Ile41,Glu45,Gln46,Thr49,Ser50,Ile51,Ser53,Tyr55,Gln56)IGF-I, an A chain mutant in which residue 41 is changed from threonine to isoleucine and residues 42–56 of the A region are replaced; (Thr49,Ser50,Ile51)IGF-I; and (Tyr55,Gln56)IGF-I.
Sliecker et al., Adv. Experimental Med. Biol., 343: 25–32 (1994)) describes the binding affinity of various IGF and insulin variants to IGFBPs, IGF receptor, and insulin receptor.
IGFBPs are secreted by cells in culture and either inhibit or enhance IGF-stimulated functions (Clemmons et al., (1991) In Modern Concepts of Insulin-like Growth Factors. E. M. Spencer, editor. Elsevier, New York, N.Y. 475–486). Known forms of IGFBPs include IGFBP-1, having a molecular weight of approximately 30–40 kDa in humans. See, e.g., WO89/09792, published Oct. 19, 1990, pertaining to cDNA sequences and cloning vectors for IGFBP-1 and IGFBP-2; WO89/08667, published Sep. 21, 1989, relating to an amino acid sequence of IGFBP-1; and WO89/09268, published Oct. 5, 1989, relating to a cDNA sequence of IGFBP-1 and methods of expression for IGFBP-1.
IGFBP-2 has a molecular weight of approximately 33–36 kDa. See, e.g., Binkert et al., The EMBO Journal, 8: 2497–2502 (1989), relating to a nucleotide and deduced amino acid sequence for IGFBP-2.
IGFBP-3 has a non-glycosylated molecular weight of about 28 kDa. See, e.g., Baxter et al., Biochim. Biophys. Res. Com., 139:1256–1261 (1986), pertaining to a glycosylated 53-kDa subunit of IGFBP-3 that was purified from human serum; Wood et al., Mol. Endocrinol., 2:1176–1185 (1988), relating to a full-length amino acid sequence for IGFBP-3 and cellular expression of the cloned IGFBP-3 CDNA in mammalian tissue culture cells; WO 90/00569, published Jan. 25, 1990, relating to isolating from human plasma an acid-labile subunit (ALS) of IGFBP complex and the particular amino acid sequence for ALS pertaining to a subunit of IGFBP-3; and Schmid et al., Biochim. Biophys. Res Com., 179: 579–585 (1991), relating to effects of full-length and truncated IGFBP-3 on two different osteoblastic cell lines.
Although initially some inconsistencies in nomenclature for IGFBP4, IGFBP-5, and IGFBP-6 existed, in 1991 participants of the 2nd International IGF Symposium agreed upon an accepted IGFBP4, IGFBP-5, and IGFBP-6 nomenclature. Using accepted terminology, Mohan et al., Proc. Natl. Acad. Sci., 86:8338–8342 (1989) relates to an N-terminal amino acid sequence for an IGFBP-4 isolated from medium conditioned by human osteosarcoma cells, and Shimasaki et al., Mol. Endocrinology, 4:1451–1458 (1990) pertains to IGFBP cDNAs encoding IGFBP-4 from rat and human. WO92/03471 published Mar. 5, 1992, relates to an IGFBP4 (originally designated therein as IGFBP-5); and WO92/03470 published Mar. 5, 1992 relates to genetic material encoding IGFBP4 (originally designated therein as IGFBP-5).
WO92/12243 published Jul. 23, 1992, relates to IGFBP-5 (originally designated therein as IGFBP-6). Andress and Birnbaum, Biochim. Biophys. Res Com., 176: 213–218 (1991) relates to the modulation of cellular action of a mixture of affinity-purified IGFBPs from U-2-cell-conditioned media on IGFs. WO92/03469 published Mar. 5, 1992, relates to genetic material encoding IGFBP-6 (originally designated therein as IGFBP4); and WO92/03152 published Mar. 5, 1992, relates to an IGFBP-6 (originally designated therein as IGFBP-4). See also U.S. Appln. No. 2003/0082744 as well as U.S. Pat Nos. 6,025,465 and 5,212,074, which disclose IGFBP-6 and its fragments.
Zapf et al., J. Biol. Chem., 265:14892–14898 (1990) pertains to four IGFBPs (IGFBP-2, IGFBP-3, a truncated form of IGFBP-3, and IGFBP-4) isolated from adult human serum by insulin-like growth factor (IGF) affinity chromatography and high-performance liquid chromatography. Shimasaki et al., 2nd International IGF Symposium Abstract (January 1991) discusses amino-terminal amino acids for IGFBP4, IGFBP-5, and IGFBP-6.
When administered alone, i.e., without any IGF, the IGFBPs may also be therapeutically useful for blocking the adverse effects of IGFs, such as those that occur when IGFs are produced in excess, e.g. free IGFs secreted by certain cancer cells such as hormone-producing cancer cells such as breast or kidney cancer cells. More recently, it was demonstrated that U-2 human osteosarcoma cells secrete IGFBP-5 and IGFBP-6 (Andress and Birnbaum, supra; Shimasaki et al., J. Biol. Chem. 266: 10646–10653 (1991); Shimasaki et al., Mol. Endocrinol., 5: 938–948 (1991)). Although affinity-purified IGF-binding proteins derived from U-2-conditioned medium clearly enhanced IGF-I stimulated mitogenesis (Andress and Birnbaum, supra), it was unclear from those studies which protein was responsible for this effect. Mohan et al. demonstrated that IGFBP-4, purified from TE-89 human osteosarcoma cells, inhibits IGF-stimulated osteoblast mitogenesis (Mohan et al., Proc. Natl. Acad. Sci. (U.S.A.), 86: 8338–8342 (1989); see also LaTour et al., Mol. Endocrinol., 4: 1806–1814 (1990)). WO 03/068160 discloses use of IGFBP-3 for inhibiting tumor growth. WO 03/006029 discloses a method of inducing apoptosis in a cancer cell comprising increasing the expression of IGFBP-5 by the cell to an apoptosis-inducing amount. A method of killing cancer cells, a method of sensitizing cancer cells to agents that induce apoptosis, and a method of treating cancer in a patient are also described. U.S. Pat. No. 6,410,335 discloses a method of predicting risk for prostate cancer, and U.S. Application 2001/0018190 published Aug. 30, 2001 discloses a method of treating prostate cancer with, inter alia, IGFBPs, including IGFBP-3. U.S. Pat. No. 5,840,673 and EP 871,475 disclose a method of inhibiting growth of p53-related tumors by administering IGFBP-3 or a modulator of IGFBP-3 that upregulates IGFBP-3 expression or activity. WO 00/35473 discloses use of IGFBP-6 to treat inflammatory diseases including tumor angiogenesis. WO 94/22466 discloses use of any IGFBP-3 to treat cancer, including prostate cancer. WO 92/14834 discloses two IGFBPs isolated from rat serum, one identified as IGFBP-5 useful in treating cancer.
Exploitation of the interaction between IGF and IGFBP in screening, preventing, or treating disease has been limited, however, because of a lack of specific antagonists. The application of an IGF-1/IGF-2 antagonist as a potential therapeutic adjunct in the treatment of cancer is described by Pietrzkowski et al., Cancer Res., 52: 6447–6451 (1992). In that report, a peptide corresponding to the D-region of IGF-1 was synthesized for use as an IGF-1/2 antagonist. This peptide exhibited questionable inhibitory activity against IGF-1. The basis for the observed inhibition is unclear, as the D-region does not play a significant role in IGF-1 receptor (IGF-1R) binding but rather, in IGF-1 binding to the insulin receptor (Cooke et al., Biochem., 30: 5484–5491 (1991); Bayne et al., J. Biol. Chem., 264: 11004–11008 (1988); Yee et al., Cell Growth and Different., 5: 73–77 (1994)). IGF antagonists whose mechanism of action is via blockade of interactions at the IGF-1 receptor interface may also significantly alter insulin action at the insulin receptor, a disadvantage of such antagonists.
Certain IGF-1 antagonists have also been described by WO 00/23469, which discloses the portions of IGFBP and IGF peptides that account for IGF-1 and IGFBP binding, i.e., an isolated IGF binding domain of an IGFBP or modification thereof that binds IGF with at least about the same binding affinity as the full-length IGFBP. The patent publication also discloses an IGF antagonist that reduces binding of IGF to an IGF receptor, and/or binds to a binding domain of IGFBP.
Additionally, EP 639981 discloses pharmaceutical compositions comprising short peptides that function as IGF-1 receptor antagonists. The peptides used in the pharmaceutical compositions consist of less than 25 amino acids, comprise at least a portion of the C or D region from IGF-1, and inhibit IGF-1-induced autophosphorylation of IGF-1 receptors. Methods of inhibiting cell proliferation and of treating individuals suspected of suffering from or susceptible to diseases associated with undesirable cell proliferation such as cancer, restenosis, and asthma are disclosed.
Generation of specific IGF-1 antagonists has been restricted, at least in part, because of difficulties in studying the structure of IGF and IGFBP. Due to the inability to obtain crystals of IGF-1 suitable for diffraction studies, for example, an extrapolation of IGF-1 structure based on the crystal structure of porcine insulin was the most important structural road map for IGF-1 available (Blundell et al., Proc. Natl. Acad. Sci. USA, 75:180–184 (1978)). See also Blundell et al., Fed Proc., 42: 2592 (1983), which discloses tertiary structures, receptor binding, and antigenicity of IGFs. Based on studies of chemically modified and mutated IGF-1, a number of common residues between IGF-1 and insulin have been identified as being part of the IGF-1R-insulin receptor contact site, in particular the aromatic residues at positions 23–25. Using NMR and restrained molecular dynamics, the solution structure of IGF-1 was recently reported (Cooke et al., supra). The resulting minimized structure was shown to better fit the experimental findings on modified IGF-1, as well as the extrapolations made from the structure-activity studies of insulin. Further, De Wolf et al., Protein Sci., 5: 2193 (1996) discloses the solution structure of a mini-IGF-1. Sato et al., Int. J. Pept., 41: 433 (1993) discloses the three-dimensional structure of IGF-1 determined by 1 H-NMR and distance geometry. Torres et al., J. Mol. Biol. 248: 385 (1995) discloses the solution structure of human IGF-2 and its relationship to receptor and binding protein interactions. Laajoki et al., J. Biol. Chem., 275: 10009 (2000) discloses the solution structure and backbone dynamics of long-(Arg(3)) IGF-1.
Peptide sequences capable of binding to insulin and/or insulin-like growth factor receptors with either agonist or antagonist activity and identified from various peptide libraries are described in WO 01/72771 published Oct. 4, 2001.
U.S. Application No. 2003/0092631 published May 15, 2003 discloses peptides that antagonize the interaction of IGF-1 with its binding proteins, insulin receptor, and IGF receptor. These IGF antagonist peptides are useful in treating disorders involving IGF-1 as a causative agent, such as, for example, various cancers.
Regarding the structural information on the classical IGFBPs, they have a molecular mass ranging from 22 to 31 kDa and contain a total of 16–20 cysteines in their conserved amino-and carboxy-terminal domains (Bach and Rechler, supra; Clemmons, Cytokine Growth Factor Rev., 8: 45–62 (1997); Martin and Baxter, Curr. Op. Endocrinol. Diab., 16–21 (1994)). The central domain connecting both cysteine-rich regions is only weakly conserved and contains the cleavage sites for IGFBP-specific proteases (Chernausek et al., J. Biol. Chem., 270: 11377–11382 (1995); Clemmons, supra; Conover, Prog. Growth Factor Res., 6: 301–309 (1995)). Further regulation of the IGFBPs may be achieved by phosphorylation and glycosylation (Bach and Rechler supra; Clemmons, supra). There is no high-resolution structure available for any intact member of the IGFBP family. U.S. Pat. No. 6,500,635 discloses IGFBP-5 and its variants. U.S. Pat. Nos. 6,391,588 and 6,489,294 disclose truncated C-terminal IGFBP-5 fragments with reduced affinity for IGF-I as compared to full-length IGFBP-5. U.S. Pat. No. 6,369,029 discloses stimulating osteogenesis with C-terminal-truncated IGFBP-5. These compounds may be used for stimulating bone cell growth, for treating a bone disorder, or for stimulating mitogenic activity.
The NMR structures of two N-terminal fragments from IGFBP-5 that retain IGF-binding activity have recently been reported, showing that residues 40–92 of IGFBP-5 comprise the IGF binding site in the N-terminal domain of that protein (Kalus et al., EMBO J. 17: 6558–6572 (1998)). Other studies have found that N-terminal fragments (residues 1–88 and 1–97) of IGFBP-3 are also able to bind IGFs (Galanis et al., Journal of Endocrinology, 169 (1): 123–133 (2001); Vorwerk et al., Endocrinology, 143 (5): 1677–1685 (2002)).
In particular, Galanis et al. have synthesized both the amino-terminal (residues 1–88; N-88) and carboxyl-terminal (residues 165–264; C-165) domains of human IGFBP-3 in bacteria, as fusion proteins with a carboxyl-terminal FLAG peptide. Although only C-165 showed binding to IGF-I and -II by solution-binding assays, both N-88 and C-165 demonstrated binding to IGF-I and -II by biosensor analysis albeit with reduced affinities compared with full-length IGFBP-3. Only the carboxyl-terminal fragment (C-165) was able to form hetero-trimeric complexes with IGF-I and the acid-labile subunit (ALS).
Vorwerk et al. measured the binding of IGF-I and IGF-II to recombinant human N-terminal (residues 1–97; N-97) and C-terminal (residues 98–264; C-98) IGFBP-3 fragments and compared it with IGF binding to intact IGFBP-3 using biosensor analysis. Experiments were carried out either with binding protein or fragment immobilized or with IGF immobilized. These experiments showed that IGF-I and IGF-II bind to IGFBP-3 with affinities of 4–5×10−9 M and similar binding kinetics. The affinities of both N-97 and C-98 for IGF proteins were approximately three orders of magnitude less than that of full-length IGFBP-3.
U.S. Application No. 2003/0161829A1 published Aug. 28, 2003 and WO 03/025121 disclose fragments of IGFBP-3 that do not bind IGF-I to treat conditions characterized by immune stimulation rather than deficiency. The peptides target the CD74-homology domain sequence at the C-terminus of IGFBP-3 and activities localized to that region, having unique antigenicity. Peptides made to sequences in this region have previously been shown to interfere with the binding of IGFBP-3 to a number of its known ligands, including RXR-alpha, transferrin, ALS, plasminogen, fibrinogen and pre-kallikrein (Liu et al., J. Biol. Chem., 275: 33607–33613(2000); Weinzimeret al., J. Clin. Endocrinol. Metab., 86:1806–13 (2001); Campbell et al, Am. J. Physiol., 275: E321–E231 (1998); Campbell et al., J. Biol. Chem., 274: 30215–30221 (1999); Firth, et al., J. Biol. Chem., 273: 2631–2638, (1998)).
The IGFBP-3-derived met al-binding domain peptides differ from previously disclosed IGFBP-3-derived molecules including in their inability to bind IGF-I, their unique antigenicity, and the absence of the IGFBP-3 putative death receptor (P4.33) interaction domain of IGFBP-3 (so-called “mid-region”; amino acids 88–148). The P4.33 putative death receptor is described in WO 01/87238 (Genbank Accession Number BC031217; gi:21411477). For example, WO 02/34916 teaches the use of point mutants of IGFBP-3 in which the binding to IGF-I is impaired. However, the described molecules contain the mid-region of IGFBP-3 and would be expected to exert biological effects by interacting with the P4.33 putative receptor. WO 01/87238 teaches the use of P4.33 modulators for treating disease. The metal-binding peptides do not include the P4.33 putative interaction domain (mid-region of IGFBP-3).
U.S. Pat. No. 6,417,330, WO 99/63086, and U.S. application No. 2002/0072589 disclose IGFBP-3 variants modified to be resistant to hydrolysis. Also disclosed are variant IGFBP-3s where the nuclear localization signal (NLS) in native IGFBP-3 is altered. Additionally, amino-terminally extended IGFBP-3s are disclosed that include a variety of N-terminal extensions, including peptide and nucleotide binding domains, specific binding members such as ligand-binding domains from receptors or antigen-binding domains from immunoglobins, and peptide and protein hormones and growth factors. N-terminally extended IGFBP-3s may comprise hydrolysis-resistant or NLS-variant IGFBP-3s.
Some recent publications have described the use of IGFBP-3 peptides to treat cells in culture. The only peptides found to be active on breast cancer cells are derived from the mid-region of IGFBP-3 (McCaig et al., Br. J. Cancer, 86: 1963–1969 (2002); Perks et al., Biochim. Biophys. Res. Comm. 294: 988–994 (2002)).
U.S. Application No. 2003/0059430 published Mar. 27, 2003 discloses that the IGF-binding protein-derived peptides described above, including short peptides containing just 12–22 amino acids from the C-terminal domain of IGFBP-3, can mimic the full molecule's co-apoptotic, cell-penetrating, and metal-binding properties.
WO 03/052079 discloses mutants of IGFBP-3 that can inhibit DNA synthesis, can induce apoptosis, bind to neither human IGF-I nor human IGF-II, and comprise a mutation at Y57.
WO 02/098914 discloses a crystal suitable for X-ray diffraction, comprising a complex of IGF-I or -II and a polypeptide consisting of the amino acids 39–91 of IGFBP-1, the amino acids 55–107 of IGFBP-2, the amino acids 47–99 of IGFBP-3, the amino acids 39–91 of IGFBP4, the amino acids 40–92 of IGFBP-5, or the amino acids 40–92 of IGFBP-6 or a fragment thereof consisting at least of the 9th to 12th cysteine of IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4, or IGFBP-5 or at least of the 7th to 10th cysteine of IGFBP-6; methods for the determination of the atomic coordinates of such a crystal; IGFBP mutants with enhanced binding affinity for IGF-I and/or IGF-II, and methods to identify and optimize small molecules that displace IGFs from their binding proteins.
WO 02/34916 discloses mutant IGFBP-3 polypeptides and fragments thereof that have either no binding, or diminished binding to IGFs, yet retain their ability to bind to the human IGFBP-3 receptor (“P4.33”). The fragments are N-deletion fragments with 87 to 264 amino acids. The fragment 1–87 binds poorly to IGF-I, and the other fragments (1–46, 1–75, and 1–80) do not bind at all.
WO 00/23469 discloses IGFBP fragments that account for IGF-IGFBP binding. It provides an isolated IGF binding domain of an IGFBP or modifications thereof, which binds IGF with at least about the same binding affinity as the full-length IGFBP. It also provides an IGF antagonist that reduces binding of IGF to an IGF receptor. It especially relates to IGFBP-2 fragments, but also provides the isolated IGF binding domains of IGFBP-1, IGFBP-3, IGFBP4, IGFBP-5, and IGFBP-6. As with the IGF binding domain of IGFBP-2, the amino acid sequences comprising the IGF binding domain of the other IGFBPs could include modified forms so long as the binding affinity of the binding domain is about the same as that of the comparable native full-length IGFBP.
WO 99/32620 discloses IGFBP fragments and utilization thereof, i.e., peptides that are characterized in that the amino acid sequence parts thereof correspond to the amino acid sequence of IGFBP. The invention also relates to cyclic, glycosylated, phosphorylated, acetylated, amidated and/or sulfatized derivatives. These include C-terminal domains of IGFBP-3.
The use of gene fusions, though not essential, can facilitate the expression of heterologous peptides in E. coli as well as the subsequent purification of those gene products (Harris, in Genetic Engineering, Williamson, R., Ed. (Academic Press, London, Vol. 4, 1983), p. 127; Ljungquist et al., Eur. J. Biochem., 186: 557–561 (1989); and Ljungquist et al., Eur. J. Biochem., 186: 563–569 (1989)). Protein A fusions are often used because the binding of protein A, or more specifically the Z domain of protein A, to IgG provides an “affinity handle” for the purification of the fused protein. It has also been shown that many heterologous proteins are degraded when expressed directly in E. coli, but are stable when expressed as fusion proteins (Marston, Biochem J., 240: 1 (1986)).
Fusion proteins can be cleaved using chemicals, such as cyanogen bromide, which cleaves at a methionine, or hydroxylamine, which cleaves between an Asn and Gly residue. Using standard recombinant DNA methodology, the nucleotide base pairs encoding these amino acids may be inserted just prior to the 5′ end of the gene encoding the desired peptide.
Alternatively, one can employ proteolytic cleavage of fusion proteins (Carter, in Protein Purification: From Molecular Mechanisms to Large-Scale Processes, Ladisch et al., eds. (American Chemical Society Symposium Series No. 427, 1990), Ch 13, pages 181–193)).
There is a continuing need in the art for a molecule that can be used to elucidate binding epitopes on IGFBP-3 and other ligands, acts as an IGF antagonist to control the levels of circulating IGF as well as receptor response, for therapeutic or diagnostic uses, and can be used for other therapeutic, diagnostic, or assay purposes.


1. Field of the Invention
This invention relates to a novel compound and a chiral smectic C (SC*) liquid crystal composition containing the compound and being useful for liquid crystal display elements.
2. Description of the Related Art
At present, as to liquid crystal display elements, TN (Twisted Nematic) type display mode has been most broadly employed, but as far as the response speed is concerned, such TN type display elements are inferior to emissive type display elements (such as those of electroluminescence, plasma display, etc.). Although various improvements in this respect have been attempted, it appears that improvement to a large extent has not yet been realized. Thus, various liquid crystal display devices based on a different principle from that of TN type display elements have been attempted. As one of such devices, there is a display mode utilizing a ferroelectric liquid crystal (N. A. Clark et al: Applied Phys. lett., 36, 899 (1980)). This mode utilizes the chiral smectic C phase (hereinafter abbreviated to SC* phase) or the chiral smectic H phase (hereinafter abbreviated to SH* phase) of the ferroelectric liquid crystal, and those having these phases in the vicinity of room temperature are preferred.
These chiral smectic liquid crystal materials may be obtained by blending a plurality of single compounds each exhibiting a chiral smectic phase by itself, but it is known that the materials may be also obtained by adding an optically active liquid crystal compound, preferably a chiral smectic liquid crystal compound to an achiral smectic liquid crystal (exhibiting smectic C phase (SC phase), smectic H phase (SH phase), etc.).
Various kinds of compounds exhibiting SC phase have been known, but as to whether or not chiral smectic liquid crystal materials obtained by adding an optically active liquid crystal to the above-mentioned known compounds exhibit superior performances in liquid crystal display utilizing ferroelectricity, no ultimate evaluation thereof has been yet obtained. This is due to the fact that liquid crystal display utilizing ferroelectricity has not yet been technically completed. Thus it is necessary in the present situation to test various novel SC materials.


The disclosure of Japanese Patent Application No. HEI 11-87167 filed on Mar. 29, 1999 including the specification, drawings and abstract are incorporated herein by reference in its entirety.
1. Field of Invention
The invention relates to a control system for starting an engine installed in a vehicle, and more particularly to a control system provided with a plurality of starting systems.
2. Description of Related Art
An engine, such as a gasoline engine is constructed such that fuel-air mixture goes through an intake stroke and a compression stroke before being ignited to cause an explosive combustion, and the pressure generated thereby moves the piston to generate power, and the power is then transmitted to a crankshaft. The control system for the engine is provided with a starting system for rotating the crankshaft at a rotational speed equal to or greater than a predetermined rotational speed when starting the engine.
Japanese Patent Laid-Open No. HEI 9-117012 discloses a vehicle provided with such a starting system. The vehicle includes an electric motor, an engine, and a generator, which serve as power sources for driving the vehicle, and the generator is connected to the engine. The generator is operated as an electric motor to rotate the engine from a stopped state up to a predetermined idle speed. When the engine speed reaches the idle speed, the fuel is supplied to the engine and then ignited. Then, the generator is no longer operated as an electric motor.
In addition to the aforementioned publication, there is also suggested a start control system of a vehicle equipped with an electric motor for driving auxiliaries of a vehicle and a starter motor provided exclusively for engine start, wherein at least one of the electric motor and the starter motor can be used for starting the engine.
However, because a single generator is used to serve as the electric motor for starting the engine, the startability of the engine is adversely affected due to nonconformance of the rotational speed or the torque of the electric motor with the state of the vehicle. Also, because a single generator is used to serve as the electric motor, the startability of the engine is adversely affected when the state of charge of the battery for supplying electrical energy to the electric motor is insufficient to start the engine. Moreover, a pair of large and small spur gears are usually employed as means for power transmission between the starter motor and the engine. Accordingly, there exists the possibility of noise being generated at engine start depending on specifications of the spur gear mesh and the selection of the engine starting mode.
The invention has been made in the light of the aforementioned circumstances and therefore it is an object of the invention to provide a start control system capable of improving the engine startability in conformance with the state of a vehicle.
In a first aspect of the invention, an engine start control system includes a plurality of starting systems capable of starting the engine, and a controller. The controller determines a first associated amount associated with the rotational resistance of the engine, and then selects the mode of starting the engine by the plurality of starting systems in accordance with the determination results. The first associated amount refers to a phenomenon or a state which allows a direct or indirect determination of the engine rotational resistance.
According to the first aspect, the first associated amount associated with the engine rotational resistance is determined, and the starting mode of the engine is selected based on the determination result of the first associated amount. For example, the starting mode of the engine is selected such that a torque corresponding to the rotational resistance of the engine is obtained. That is, when the rotational resistance of the engine is comparatively high, the starting mode of the plurality of starting systems is selected so that a high starting torque can be obtained. This improves the startability of the engine irrespective of the rotational resistance of the engine.
The first associated amount may be the viscosity of the engine oil or the temperature of the engine cooling water. The rotational resistance of the engine is estimated based on the viscosity of the engine oil or the temperature of the engine cooling water.
In a second aspect of the invention, the engine start control system provided with a plurality of starting systems capable of starting the engine is also capable of driving a functional device other than the engine using either one or more of the starting systems. The controller of the engine start control system further determines a drive state of the functional device and selects the mode of starting the engine by the plurality of starting systems based on the determined drive state. The drive state of the functional device may be the rotational speed of the functional device, for example.
According to the second aspect, the drive state of the functional device is determined, and the mode of starting the engine by the plurality of starting systems is selected based on the determination result. For example, the starting mode of the engine is selected so that a rotational speed appropriate for starting the engine can be obtained. That is, when the functional device is driven by either one or more of the starting systems and when the rotational speed of the starting system is comparatively high, the engine can be rotated by a starting system that is driving a functional device after the engine is rotated by a starting system that is not driving a functional device. This makes it possible to gradually increase the engine rotational speed, whereby the startability of the engine is improved.
According to a third aspect of the invention, an engine start control system includes a plurality of starting systems capable of starting the engine, a plurality of energy sources which supply energy to respective starting systems, and a controller that determines the states of the plurality of energy sources, and selects the mode of starting the engine by the plurality of starting systems based on the determined states of the plural energy sources.
According to the third aspect, the states of the plurality of energy sources are determined, and the mode of starting the engine by the plurality of starting systems is selected based on the determination result. For example, the starting mode of the engine is selected so that an energy appropriate for starting the engine can be obtained. That is, by selecting a starting mode for starting the engine with a starting system having a higher energy state, the startability of the engine can be improved and a decrease in the energy amount of a starting system having a lower energy state can be suppressed.
According to a fourth aspect of the invention, an engine start control system includes a power transmission member which transmits power from the engine or from at least one of the power sources other than the engine, a plurality of starting systems capable of starting the engine, and a controller that determines a second associated amount associated with the vehicle speed in a state where the vehicle is run by power from the power source, and then selects for selecting the mode of starting the engine by the plurality starting systems based on the determined second associated amount. The second associated amount refers to a phenomenon or a state which allows a direct or indirect determination of the vehicle speed.
According to the fourth aspect, a difference between the engine rotational speed and the rotational speed of the power transmission member is estimated based on the second associated amount associated with the vehicle speed, and the starting mode of the engine is selected based on the estimation result.
In accordance with the first through fourth aspects of the invention, the selection of the starting mode of the engine involves selection of which starting system function (rotational speed, torque, and the like) to use, the number of starting systems employed for starting the engine, and the timings for driving and stopping each starting system when a plurality of starting systems are used.
According to a fifth aspect of the invention, an engine start control system includes a first starting system capable of starting the engine by transmitting power to the engine via a gear transmission, a second starting system capable of starting the engine by transmitting power from the engine via a belt transmission, and a controller that, upon starting the engine, first drives the first starting system, then drives the second starting system and continues driving the second starting system even after the first starting system is stopped.
According to the fifth aspect, upon engine start, first, the first starting system is driven and the power is transmitted to the engine via the gear transmission. Then, the second starting system is driven, and the power is transmitted to the engine via the belt transmission. The engine is driven by the power transmitted from the second starting system after the first starting system is stopped. For example, the drive time of the first starting system, which transmits power to the engine via the gear transmission, is set short, so that the generation of noise due to engine start can be suppressed. The belt transmission, which transmits power from the second starting system to the engine, prevents generation of gear noise and abnormal sounds due to backlash as compared to the gear transmission upon engine start. Also, the belt transmission does not require lubricating oil for cooling and lubricating the engaging portions because the device does not contain any engaging portions such as in the gear transmission. Accordingly, temperature increase or power loss caused by agitation of the lubricating oil is eliminated. Also, the construction of the belt transmission is simple because it does not require a lubricating system.
According to a sixth aspect of the invention, an engine start control system includes a first starting system connected to a crankshaft of the engine, a second starting device connected to the crankshaft of the engine, and a controller that, upon starting the engine, first drives the first starting system, then drives the second starting system before driving of the first starting system is terminated.
According to the sixth aspect, the engine is started by drive of the first and the second starting systems in parallel, whereby the startability of the engine is improved.


1. Technical Field
This application relates to surgical staplers, and more particularly, to an apparatus for sequentially applying a plurality of surgical fasteners to body tissue.
2. Background of Related Art
Surgical devices wherein tissue is first grasped or clamped between opposing jaw structure and then joined by means of surgical fasteners are well known in the art. In some instruments a knife is provided to cut the tissue which has been joined by the fasteners. The fasteners are typically in the form of surgical staples however, two part polymeric fasteners are also utilized.
Instruments for this purpose can comprise two elongated members which are respectively used to capture or clamp tissue. Typically, one of the members carries a cartridge which houses a plurality of staples arranged in at least two lateral rows while the other member comprises an anvil which defines a surface for forming the staple legs as the fasteners are driven from the cartridge. Where two part fasteners are used, this member carries the mating part, e.g. the receiver, to the fasteners driven from the cartridge. Generally, the stapling operation is effected by a pusher which travels longitudinally through the cartridge carrying member, with the pusher acting upon the staples to sequentially eject them from the cartridge. A knife may travel with the pusher between the staple rows to longitudinally cut and/or open the stapled tissue between the rows of staples. Such instruments are disclosed in U.S. Pat. No. 3,079,606 and U.S. Pat. No. 3,490,675.
A later stapler disclosed in U.S. Pat. No. 3,499,591 applies a double row of staples on each side of the incision. This is accomplished by providing a cartridge assembly in which a cam member moves through an elongate guide path between two sets of staggered staple carrying grooves. Staple drive members are located within the grooves and are positioned in such a manner so as to be contacted by the longitudinally moving cam to effect ejection of the staples. Other examples of staplers are disclosed in U.S. Pat. Nos. 4,429,695, 5,065,929, and 5,156,614.
Many of the prior art linear stapling devices discussed above include a significant number of moving parts, small components and machined structural elements that are costly to fabricate and time consuming to assemble. These factors add to the overall cost of the stapling devices and thus increase the costs incurred by hospitals and health care professionals, and ultimately, the patient upon which the devices are utilized. A linear stapler that could be manufactured and assembled less expensively would provide great benefits.
The subject application is directed to a linear surgical stapler that is constructed from fewer, less expensive components than known prior art staplers configured to sequentially apply a plurality of surgical staples to body tissue. The stapler includes a first body portion supporting an anvil plate which defines a fastener forming surface and a second body portion configured to releasably mate with the first body portion. In the detailed description which follows, the first and second body portions of the stapler are also referred to as the xe2x80x9canvil half-sectionxe2x80x9d and xe2x80x9ccartridge half-sectionxe2x80x9d, respectively.
A disposable loading unit is removably supported in the second body portion and includes a cartridge defining a plurality of slots and a tissue contacting surface, a plurality of surgical fasteners disposed in the slots of the cartridge, a plurality of ejectors or pushers positioned adjacent the surgical fasteners. A wedged actuator provided in the disposable loading unit is positioned and configured to enter and translate through the cartridge to sequentially interact with the pushers.
The stapler in a preferred embodiment, further includes an elongated actuation member mounted for longitudinal movement within the second body portion and releasably engagable with the wedged actuator, whereby longitudinal movement of the actuation member causes the wedged actuator to interact with the ejectors, driving the surgical fasteners from the cartridge to be formed against the anvil plate.
The first body portion preferably includes an elongate anvil support member and a pivoting lever handle. The anvil plate is preferably formed separate from the anvil support member and includes a plurality of staple forming pockets defining the anvil forming surface. The anvil plate also includes means for engaging the anvil support member during assembly of the surgical stapler to securely fasten the anvil plate to the support member. A notched area is defined adjacent a proximal end of the anvil support member and correspondingly positioned detents are formed adjacent a proximal end of the second body portion. The notched area and the detents cooperate to facilitate relative pivotal movement of the first and second body portions when they are mated with one another.
Preferably, a pair of upstanding flanges are formed on the disposable loading unit proximal of the tissue contacting surface thereof. The flanges define a structural tissue stop to limit the movement of body tissue. The flanges are also dimensioned to engage a pair of corresponding apertures formed in the anvil plate to maintain the first and second body portions in alignment with one another when the surgical stapler is in a closed or clamped position.
The wedged actuator of the disposable loading unit is preferably monolithically formed from a planar piece of sheet metal during a stamping process and includes a planar base and a pair of upstanding parallel cam wedges. An upturned flange is formed at a distal end of the actuation member for releasably engaging a complementary slot formed in the base of the wedged actuator. The wedged actuator preferably further includes an upstanding support flange to which a knife blade is fastened. The knife blade is provided to form an incision in the stapled body tissue.
A retaining channel depends from a distal end of the second body portion for supporting the disposable loading unit. Preferably, the disposable loading unit and the retaining channel include complementary engagement structures for releasably securing the disposable loading unit in the retaining channel. Opposed bearing structures are formed in the retaining channel at a proximal end thereof for abutting the anvil support beam when body tissue is clamped between the anvil plate and the tissue contacting surface of the cartridge. The bearing structures serve to inhibit the anvil support beam from bending as a result of the compressive forces generated during clamping.
Further features of the surgical apparatus of the subject application will become more readily apparent to those skilled in the art from the following detailed description of the apparatus taken in conjunction with the drawings.


A product picking apparatus picks up product items according to a first spacing (e.g., product items arriving on a conveyor) and releases the product items according to a second spacing (e.g., product items placed into a carton). Known product picking apparatuses have used belts or endless tracks to frictionally engage and propel product pickers in a cyclical movement. The contacting surfaces responsible for generation of the friction that drives the product pickers are typically wear parts. Therefore, their condition is constantly changing. Accordingly, the movement of the product pickers is subject to slight variation over time. Such variations can result in “missed pickups” by one or more product pickers. This can result in production line shutdowns and/or cartons or cases that are “light” on product.


1. Field of the Invention
The present invention relates to a lithium battery, and more particularly to a lithium primary battery having coiled electrode members for use in supplying high current.
2. Description of the Prior Art
In a conventional coiled type lithium battery (FIG. 1), an electrode body of a cylindrical shape of the battery is formed in such a manner that a negative electrode plate 1 made of a strip sheet of lithium or lithium alloy and a positive electrode 2 made of metal charge collecting mesh holding a positive electrode agent are laminated through a separator 3 made of a non woven cloth, such as polypropylene fibers, and are coiled in a roll.
Moreover, in order to avoid collapse of the roll of the electrode members, the outer end part of the separator 3, wound around the outer cylindrical surface of the electrode body, is adapted to contact with the inner cylindrical surface of a negative electrode can except for a portion of an adhesive tape wound around the central portion of the outer cylindrical surface of the roll of the electrode body. At the inner central portion of the roll of the electrode body, namely at the beginning of the winding of the electrode body, a rolled portion 3a of only the separator 3 is formed and the stripe-like positive electrode 2 is disposed outside of the rolled portion 3a and the strip-like negative electrode 1 is disposed outside of positive electrode 2 through the separator 3.
The inner end 1a of the strip-like negative electrode plate 1 ends beyond the inner end 2a of the positive electrode plate 2 toward the inner portion of the roll of the electrode body in order to prevent slip of the respective members of the electrode body and to facilitate winding of the electrode body when the electrode body is wound by a winding machine by clamping the inner end of the separator 3 by the rotation spindle of the machine. Accordingly, as shown by 3a, only the separator 3 is rolled along some length (normally 90.degree. to 180.degree.) from the inner end la of the strip-like negative electrode plate 1.
As the collecting mesh of the positive electrode, there is used an expanded metal plate made of stainless steel which metal plate is cut by a number of slits directed in one direction and the metal plate is expanded in a direction perpendicular to the slit to open the slits. Conventionally, the stripe-like positive electrode plate is formed in such a manner that the expanded metal is sandwiched by positive electrode agent sheets made of a positive active agent, electrically conductive powder and a binder with the positive electrode agent sheets bonded to the expanded metal by a rolling machine.
However, according to recent developments in the wide field of use of the battery, there are increasing cases of wrong use of the battery of this kind such that the battery, despite the fact that the battery is a primary battery, is erroneously subjected to charging or forced discharging by an external power source. An example of forced discharging, which occurs many times, is that one or more old batteries, which are already used and the discharging capacity thereof is depleted or small, are connected with one or more new batteries of which the discharging capacity is plentiful. In this case, if the battery of which the discharging capacity is depleted is forced to be discharged, the battery is loaded with a minus voltage by the current supplied from the other healthy battery.
In the conventional coiled type lithium battery, if such error occurs, the battery is apt to generate heat due to an internal short circuit and there are many cases of the batteries catching fire.
The holding of the positive electrode agent in the positive electrode is done mainly by bonding of the positive electrode mix, carried on the expanded metal on both sides of the slit. However, in case of expanded metal, if the slit is opened too wide, the expanded metal is apt to be cut off. Therefore, in general, the opening rate of the expanded metal is small, about less than 70%, whereby the bonding areas are insufficient, the sufficient holding force can not be obtained and therefore there is a problem that the positive electrode mix can be easily separated from the expanded metal at the time of formation of the coiled electrode body.
In case the pressing force of the positive electrode agent sheet is increased for increasing the bonding force of the positive electrode agent and electric collecting ability, there is such a problem that rigid deformation of and cut-off in the expanded metal sheet easily occur. There is a further disadvantage that since the edge of the opened slit and the cut off edge are acute in the expanded metal sheet, the separator is apt to be damaged.
It has also been discovered that when the lithium batteries are subjected to work using relatively large current, the batteries generate a lot of heat and the temperature of the battery becomes higher at the central portion, and the insulation layer 3a is molten, whereby an internal short circuit occurs at the inner end 1a of the negative electrode plate 1 and the inner end 2a of the positive electrode 2 and a further large amount of current flows there with the generation of further heat, causing the lithium and lithium alloy to become molten resulting in burning or an explosion of the battery.


Organic excreta, whether from domestic, stray or wild animals, often has a substantial adverse impact on otherwise pleasant modem lifestyles. The same also represents a significant health threat, due to the plethora of diseases often found in animal excrement. While nature will, over time, degrade the organic components of excreta, such action is relatively very long-term. Moreover, while the same is occurring, excreta poses a health hazard, gives off unpleasant odors, and appears and is repulsive to most individuals. At the same time, solid excreta also present the possibility of being picked up underfoot and spread, sometimes even into the home, office or commercial environment. Finally, excreta while it is deteriorating naturally over a long period of time tends to damage lawns due to heat and other prolonged effects.
In an effort to avoid the dangers and unpleasantness associated with the same, numerous jurisdictions have implemented so-called “pooper scooper” laws which require, for example, a dog owner to clean up after a pet, for example, while it is being given its required daily walk. However, in addition to the fact that pet owners are not all fastidious about cleaning up after their animals, numerous sources of excreta, not controllable by pooper scooper regulations abound. These range from problems created by Canadian geese on golf courses and waterfront properties to the excreta of wild deer beside houses in the suburbs, and leavings of stray animals in urban locations.


Systems and applications for delivering computer-based training (CBT) have existed for many years. However, CBT systems historically have not gained wide acceptance. A problem hindering the reception of CBTs as a means of training workers and learners is the inflexibility of courses and training material to adapt to the need of individual learners.
Some CBTs were based on hypermedia systems that statically linked content. User guidance was given by annotating the hyperlinks with descriptive information. The trainee could proceed through learning material by traversing the links embedded in the material. The structure associated with the material was very rigid, and the material could not be easily written, edited, or reused to create additional or new learning material.
Newer methods for intelligent tutoring and CBT systems are based on special domain models that must be defined prior to creation of the course or content. Once a course is created, the course material may not be easily adapted or changed for specific training needs of different learners. As a result, the course often fails to meet the needs of the trainee and/or trainer.
In addition, CBT systems do not provide for collaborative learning that is typically associated with classes taught in a classroom. Practically all CBT courses are constructed according to the paradigm of individual learning that at best is enhanced by an environment that enables users to communicate with each other. For example, a typical web-based course may include an elaborate hyper media structure. The structure is embedded into an environment that provides general tools for communication (e.g., chat rooms or video conferencing). However, content and collaboration are not integrated.
Therefore, for the above and other reasons, new methods and technologies are needed to supplement traditional computer based training and instruction.


1. Field of the Invention
This invention relates to a catheter and, more particularly, to an electrode catheter having a remotely curvable tip.
2. Description of the Related Art
The advantages of steerable catheters are known. Such catheters are inserted into a blood vessel or other body area and their distal end guided in various directions to reach areas of the body which would otherwise be inaccessible. Examples of steerable catheters are disclosed in U.S. Pat. Nos. 3,749,086 to Kline et al.; 3,773,034 to Burns et al., 3,552,384 to Pieric and 3,521,620 to Cook.
A steerable catheter should have both flexibility for steering the catheter tip and rigidity to control steering. Known prior art catheters have been unable to successfully combine these two characteristics, tending instead to sacrifice one of these characteristics at the expense of the other. It is also desirable to limit the direction of bending of the distal end of the catheter to provide better steering control.
Catheters having electrode means for monitoring parts of the body, such as the heart, by transmitting electrical signals for analysis on an external monitor are also known. Currently a need exists for an electrode catheter which is steerable to access areas of the heart which could not be reached by a non-bendable catheter. It would be desirable to provide an electrode catheter with a steerable tip that combines sufficient flexibility to allow steering of the catheter to desired areas with good torsional rigidity and steering control.


In recent years, optical devices, such as light-emitting diodes (LED), laser diodes, and UV photo-detectors have increasingly been used. Group-III nitride compounds, such as gallium nitride (GaN) and their related alloys, have been known suitable for the formation of the optical devices. The large bandgap and high electron saturation velocity of the group-III nitride compounds also make them excellent candidates for applications in high-temperatures and high-speed power electronics.
Due to the high equilibrium pressure of nitrogen at typical growth temperatures, it is extremely difficult to obtain GaN bulk crystals. Therefore, GaN layers and the respective LEDs are often formed on other substrates that match the characteristics of GaN. Sapphire (Al2O3) is a commonly used substrate material. FIG. 1 illustrates a cross-sectional view of an LED package component. LED 2, which includes a plurality of GaN-based layers formed on sapphire substrate 4. Sapphire substrate 4 is further mounted on lead frame 6. Electrodes 8 and 10 electrically connect LED 2 onto lead frame 6 through gold wires 12.
Sapphire has a low thermal conductivity. Accordingly, the heat generated by LED 2 cannot be dissipated efficiently through sapphire substrate 4. Instead, the heat is mostly dissipated through the top end of LED 2 and through gold wires 12. However, the necessary length of gold wires 12 to extend to lead frame 6 renders the heat-dissipating efficiency low. In addition, electrode 10 occupies chip area and reduces the total chip area available for LED light output.


Monosaccharide is a generic term for a hydrocarbon having a carbon chain of 3 or more carbon atoms, and in nature there are a number of monosaccharides as much as 40 or more species in a variety of forms including free forms or derivatives of metabolites or biosynthetic products as well as complex carbohydrates, oligo-saccharides or polysaccharides. Industrially most important monosaccharide is D-glucose, of which the process for production has been established on an industrial scale using a method of hydrolysis of starch with an enzyme such as amylase, and has been industrially most widely used in the fields of foods, cosmetics and pharmaceuticals in large quantities. Further, D-fructose which is produced by conversion of D-glucose with isomerase is an industrially important sugar. Other industrially applied process for production of some monosaccharides includes production of L-sorbose from sorbitol by an acetic acid bacterium, production of D-galactose from lactose by β-galactosidase, and production of D-xylose from xylan by acid hydrolysis. A large number of other monosaccharides are difficult to produce in industrially large quantities because of industrial and economical limitation in raw materials, generative reaction and yield, and they almost have not yet been utilized industrially.
The present inventors have paid attention to such expensive and rarely available monosaccharides and gave a name of rare sugars to these monosaccharides; and they have continued to assiduously study the generative reaction of rare sugars for a long period of years. The present inventors have conducted a study for development on monomeric rare sugars including both D-psicose and D-allose. They, as mentioned in the non-patent document 1, have developed a process for producing D-psicose directly from D-glucose in combination of an industrially used D-xylose isomerase with D-ketohexose 3-epimerase discovered by the inventors, and thus opened a new route to a process for the continuous production of D-psicose.
D-Psicose which is generally known to exist in molasses of sweet potatoes in small quantities, is one of industrially expected sugars, particularly in food industry, since it has a sweet taste of good quality similar to D-fructose and is best suited as hardly fermentative and low calorie sugar. That is, D-psicose draws attention as a sugar which does not promote the synthesis of fat and does not accumulate body fat, particularly intraperitoneal fat in comparison with monosaccharides such as D-glucose or D-fructose (non-patent document 2). Further, it has been reported that the available energy value of D-psicose is approximately zero (non-patent document 3).
Thus, based on their success in producing D-psicose, they have succeeded in large scale production of a rare sugar D-allose by isomerization of D-psicose using L-rhamnose isomerase. In this connection, the present inventors have discovered L-rhamnose isomerase (also referred to as “L-RhI”) produced by Pseudomonas stutzeri LL-172 strain, and further elucidated that this enzyme works to catalyze the isomerization reaction of L-rhamnose to L-rhamnurose as well as L-rhamnurose to L-rhamnose. L-Rhamnose isomerase produced by Pseudomonas stutzeri LL-172 (IPOD FERM BP-08593) also acts on isomerization between D-allose and D-psicose, and thus this enzyme is capable of producing D-allose from D-psicose. In this situation, it is necessary to use an enzyme of the Pseudomonas stutzeri LL-172 origin in order to produce D-allose from D-psicose (patent document 1). Because of discovery of this enzyme, practical use of the reaction for production of rare sugars aimed by the present inventors took a great step forward; particularly, this was remarkable in production of D-allose from the substrate D-psicose on a large scale. Since it became apparent that this D-allose has various physiological activities, the research is rapidly developing. At present, it has become apparent that D-allose has an effect such as cancer cell inhibition or anti-oxidant effect important in a medical field (patent document 2).
The production of D-allose, however, includes the most expensive bottleneck step for separating D-allose from D-psicose during the course of production. In order to produce D-allose as a single product, the product contained in a mixture of sugar solutions formed due to the property of the enzyme has to be separated from the raw materials. In the reaction with L-rhamnose isomerase, D-psicose and D-allose reach to an equilibrium state of 7:3, from which mixture of sugar solutions D-allose is separated by column chromatography. Though this operation for separation is naturally required as an essential step for purification of a monomeric sugar, it is also true that the time and labor are required as the production scale of rare sugar becomes huge.
On the other hand, “sugar solution of grape sugar/fruit sugar” containing D-glucose and D-fructose has practically been used as a mixture of sugars at present. The sugar solution of grape sugar/fruit sugar has industrially produced as alternative sugar having a compositional ratio similar to ordinary sugar by converting approximately a half of D-glucose to D-fructose using xylose isomerase, and is commercialized as gum syrup for use in coffee or tea. The mixed sugar solution of D-glucose and D-fructose is difficult to crystallize and utilized in a liquid form not as crystals. This is considered because of very high solubility of D-fructose in water, requiring much time and labor and producing a disadvantage in production cost; thus, it has been utilized as such without crystallization. The name of isomerized sugar usually indicates a mixed sugar solution of D-glucose and D-fructose. This is owing to the reason that at present only the sugar solution produced by isomerization reaction of D-glucose as raw material with xylose isomerase has been industrially made fit for practical use.    Non-patent document 1: Journal of Fermentation and Bioengineering, 80, p 101, 1995    Non-patent document 2: Asia Pacific J. Clin. Nutr. 10, 233-237,    Non-patent document 3: J. Nutr. Sci. Vitaminol 48, 77-80, 2002    Patent document 1: PCT WO2004/063369 A1)    Patent document 2: PCT WO03/097820 A1


The present disclosure relates to crystalline silicon solar cell manufacturing, and more particularly, to a method for texturing a crystalline silicon substrate utilizing an aqueous alkaline etchant solution which includes a nanoparticle slurry as one of the components thereof.
A photovoltaic device is a device that converts the energy of incident photons to electromotive force (e.m.f.). Typical photovoltaic devices include solar cells, which are configured to convert the energy in the electromagnetic radiation from the Sun to electric energy.
In a typical solar cell, single-crystalline silicon is generally used as one of the components of the cell. In such applications, the single-crystalline silicon needs to have a non-planar surface to improve light capture. Typically, the non-planar surface has concave and convex patterns with a minute pyramid (i.e., square pyramid) shape. In such solar cells, the light reflected from one spot impinges again to another spot on the surface of the crystalline solar cell by virtue of the ‘textured’ surface, penetrating into the solar cell to be effectively absorbed in the solar cell. Although a portion of the impinging light that has not been fully absorbed, but arrives at the back face of the solar cell, is reflected back to the surface again, that portion of impinging light can be reflected again at the surface comprising steeply inclined pyramidal surfaces, thereby confining the light in the solar cell to improve absorption of light and to enhance power generation.
In conventional single-crystalline silicon solar cells, the textured structure is formed by immersing the exposed (100) face of a single-crystalline silicon wafer into an alkaline solution, i.e., sodium hydroxide (NaOH) or potassium hydroxide (KOH), which may also include 5 to 30% by volume of isopropyl alcohol and/or 0.3 to 1.5% by weight of silicon. The silicon is etched into the bath as a bath conditioner.
The etching rate in anisotropic etchants of the kind described above depends on the crystallographic orientation of the silicon surface being etched. The etching rate on the (111) face is significantly lower than the other crystallographic orientations. Accordingly, the (111) face with the slowest etching rate is advantageously left on the surface. Since this (111) face is inclined by about 54 degree against the (100) face, pyramidal projections constituted of the (111) face and its equivalent faces are formed. The pyramid size and density depends on the KOH or NaOH concentration, the amount of silicon already dissolved in the bath, and additive such as isopropyl alcohol.


1. Field of the Invention
The present invention relates generally to an apparatus and method for the testing of a USB device, and in particular, to a USB device whose USB communication ports can also be used for testing of the USB device.
2. Background Art
USB is commonly used to interface data communications or connections between a host or hub (such as a personal computer (PC)) and peripheral devices (such as printers and scanners, among others). FIG. 1 is a simple schematic diagram illustrating a conventional USB device 10, such as a scanner, and how the USB device 10 is tested by the manufacturer of the USB device 10 prior to delivery of the USB device 10 to a customer.
The USB device 10 has an integrated circuit (IC) 12. Any conventional IC can be utilized, but in many cases, the IC can be a conventional ASIC as is well-known in the art. The IC 12 is coupled to a motor 14 to control the operation of the motor 14. In addition, the IC 12 is coupled to a sensor 16, which can be CCD sensor. The sensor 16 is utilized by the scanner 10 to scan documents, as is well-known in the art, and the signals representing the scanned information are provided to the IC 12 for processing.
Although the USB device 10 is being described herein as being a scanner, the principles of the present invention are equally applicable to any device or peripheral which has the capability for USB communication with a host device. Such devices and peripherals include keyboards, computer mice, printers, monitors, etc. In most cases, the host device would be a PC, which operates in conjunction with an operating system such as xe2x80x9cWindowsxe2x80x9d(trademark) to issue a series of commands to the USB device 10 to control the operation of the USB device 10. As a result, each USB device 10 requires one corresponding PC to enable the USB device 10 to be operated.
The testing of a USB device 10 usually includes a conventional burn-in test as is well-known in the art. FIG. 1 illustrates a testing unit 20 that has a processor 22 that is coupled via conventional USB lines (D+, Dxe2x88x92) to the IC 12 to perform the testing. The processor 22 is typically a PC operating in a xe2x80x9cWindowsxe2x80x9d(trademark) operating system (such as Windows 98). However, since each USB device 10 needs to be separately controlled by a dedicated PC, the manufacturer of the USB device 10 will need to have on hand a large number of PCs to perform testing. For example, a scanner manufacturer may need to utilize up to a few hundred PCs. Since each burn-in test can take up to three hours to complete for each USB device 10, the testing becomes cumbersome, time-consuming, and therefore quite expensive. As a result, many USB devices 10 are not tested prior to release.
To overcome this problem, some manufacturers have attempted to use smaller and less complex processors instead of an entire PC system to perform the testing. These smaller processors are less expensive than a conventional PC system because they omit many of the components (e.g., certain boards, cards, etc.) of a PC, and do not need to be supported by a xe2x80x9cWindowsxe2x80x9d(trademark) operating system. As a result, the manufacturer may be able to afford to hook up a few hundred smaller processors at any given time to perform the needed testing for the USB devices 10. One example of such a smaller processor is an MCU 8051, manufactured and sold by Intel Corporation, which is well-known in the art. To use the 8051, the USB device 10 would have two dedicated testing ports (such as an 12C protocol bus) that are only used for testing purposes. These testing ports are usually pins and connectors that are typically provided on the IC 12, and the processor would issue commands to the IC 12 via these testing ports to perform the testing procedures. Unfortunately, these dedicated testing ports cannot be used during the normal use and operation of the USB device 10. These open ports are often aesthetically unpleasant, and are often not tolerated by consumers. In addition, these open testing ports use up precious space on an IC 12, and increase the complexity of the design of the IC 12.
Thus, there still remains a need for an apparatus and method for testing USB devices that avoid the above-mentioned problems.
It is an object of the present invention to provide an IC and method for use in a USB device that does not need to be tested by PCs.
It is another object of the present invention to provide an IC and method for use in a USB device that does not utilize dedicated testing ports.
It is yet another object of the present invention to provide an IC and method for use in a USB device where the same pins and connectors can be used for both testing and normal operation.
To accomplish the objectives of the present invention, there is provided an apparatus and method of testing a USB device. The present invention provides a first USB communication line and a second USB communication line. Separate first and second paths are created between an external device and a controller in the USB device, with both paths including the first and second USB communication lines. The apparatus detects whether a USB connection exists over the first and second USB communication lines. If a USB connection exists over the first and second USB communication lines, USB communication is routed via the first path. Otherwise, testing communication is routed via the second path. The external device can be either a USB host or a testing unit.


1. Field of the Invention
This invention relates to the measurement of the flow rate of weak cell liquor produced in a chlor-alkali cell. It further concerns the use of a weir-type flow meter for the purpose indicated.
2. Description of the Prior Art
In the operation of a cell room containing a plurality of chlor-alkali cells, it has not been usual to determine, regularly and with accuracy, the rate of production of weak cell liquor from an individual cell. When such a determination has been made, it has been usual to use merely a bucket and stop watch. Such a practice is inconvenient and somewhat dangerous, in that it involves the handling of a hot (approximately 90.degree. Centigrade) solution of caustic.
The rate of production of weak cell liquor from an individual cell gives an important indication of how well or poorly an individual cell is currently performing. In one kind of commercial cells of the diaphragm type, the flow rate of weak cell liquor being withdrawn from the cell may range from about two to seven liters per minute. In other cells, the range may be somewhat different. Typically, a cell which has recently been renewed by having its diaphragm replaced will give a flow rate on the higher end of the range mentioned above, and as the cell operates for several weeks or months, the observed flow rate tends to decrease. From time to time, it is possible, in the operation of a diaphragm-type cell, to adjust (increase slightly) the level of the head on the anolyte side of the cell and thereby increase the flow rate. Ultimately, however, because of the buildup of a gel or of insoluble particles of alkaline-earth hydroxides which are formed because of alkaline-earth metal ions contained as an impurity in the brine fed to the cell, the rate of flow through the diaphragm decreases, even when the maximum available head is used, to a value such that further operation becomes uneconomical. In order to keep a cell room containing a great number of such individual cells operating on a smooth and satisfactory basis, it would be highly desirable to have a convenient means whereby the rate of flow of weak cell liquor leaving each individual cell could be easily and conveniently determined.