A shoe device having bimodal structures, configured to selectively snap the device to at least one of a second position and a first position, which selectively snaps the shoe into a first position upon being subjected to a first bending force, apt for placement or removal of a foot, and selectively snaps the shoe into a second position upon being subjected to a second bending force, apt for securement of a foot or having no foot. A forward leaning, flexible stadium arch structure, assembled to form a heel notch mechanism, connects to a sole. A morphing shoe collar portion connects to a heel. These are combined via vector changing devices for greater functionality.

It common for individuals to wear shoes, such as running shoes or tennis shoes. A shoe usually has a fastening arrangement that allows a user to fasten their shoe to their foot. For example, such fastening arrangements may include straps, shoe laces, or zippers.
However, existing shoes are problematic because their fastening arrangements are too complicated, unreliable, ugly, and take too much time to fasten shoes. For example, assuming a shoe lace is already threaded through a shoe, the shoe lace has to be pulled and tied in a doubly slipped reef knot formed by joining ends of the shoe lace. Straps with hook and loop fasteners are faster to secure than shoe laces, but straps are not durable and many consider them ugly. Zippers are uncomfortable to use and are known to break and come loose.
Other types of shoes have evolved that have no straps or fastening devices, and thus permit rapid donning, such as flip flops, sandals, or clogs. However, these shoe designs by lacking securement systems of the back heel often do not provide the necessary stability to the foot to permit safe running or active use. Further, these designs are often cited for causing numerous injuries and falls.
Other types of shoes have evolved that are rapidly donned that do have some kind of support provided to the back heel, such as shoes made of flexible material similar to pull-on water shoes, or shoes with flexible heel straps of varying designs, for example rubber clogs. However, these shoe designs require the dedicated use of hands, with the user required to sit or bend down to fasten the heel securing device.
Other types of shoes have evolved that are designed to be quicker and easier to don on and off, with minimal use of hands, without sitting or bending down to fasten or unfasten the shoe. However, these designs utilize complicated snaps, wheels, ratchets, magnets, mainsprings, pulleys, electric motors, common structures with loops and connection points, pivotally movable straps with support brackets, metal bands, metal springs, and other designs that are not cost effective to produce using single, widely used materials in the footwear industry such as natural, urethane, or silicone rubbers or ethylene-vinyl acetate and similar polymers.
Therefore there exists a need for an improved shoe that is quicker and easier to don and doff in comparison to existing shoe designs, with minimal use of hands, without sitting or bending down to fasten or unfasten the shoe, that permit the use of active motion such as running or active walking without possibility of injury or stumbling, have a functional bimodal spring mechanism activated by multiple pressure points that can be easily used by the consumer, and are cost effective to produce using single, widely used materials in the footwear industry such as natural, urethane, or silicone rubbers or ethylene-vinyl acetate and similar polymers.

Shoe device with bimodal structures for rapid entry and release


A downsized modular jack with high surface-mounting performance. The modular jack has a housing and a terminal holder assembled thereto. The housing has a rear wall formed with a terminal insertion through-hole extending through a thickness of the rear wall, and a latch section insertion through-hole positioned beside the terminal insertion through-hole. The latch section insertion through-hole has an engaged portion positioned within the thickness of the rear wall. The terminal holder has a connector terminal extending through the terminal insertion through-hole and a latch section engaged with the engaged portion and positioned within the thickness of the rear wall upon assembly of the terminal holder into the housing.

An electrical equipment such as a television is provided with a modular jack (modular connector) to which a LAN cable is connected for data transmission. Japanese Patent Application Publication No. H09-129294 discloses a modular jack having a main body and a terminal module assembled thereto. A connector of a LAN cable is inserted into the main body, and the terminal module includes terminals to be connected to the connector.


A scanning apparatus and method, the apparatus comprising: a light transmission means (90) having an exit tip; first and second drive means (92,94) for resonantly driving the light transmission means (90) in orthogonal directions; wherein the first and second drive means (92,94) are operable to move the tip in an elliptical pattern while varying the eccentricity of the elliptical pattern, whereby a portion of the elliptical pattern having a centre on the minor axis of the elliptical pattern approximates—at least in appearance—a raster pattern.

One existing scanning technique employs a resonant cantilever in order to achieve the high frequency scanning of an optical fibre tip, as a compact alternative to resonant mirror/galvanometer scanners. The high frequency or X scan is then combined with a slow or Y scan to produce a standard raster scanning pattern. The slow scan is usually not resonant and can have a sawtooth function, with relatively rapid retrace.
In such an arrangement, mechanical considerations require a resonant sinusoidal spot motion in the X or fast direction of the scan. Although a TV raster in both directions is more desirable (for optical dosage control and data gathering), a sawtooth scan at constant speed is feasible in only the slow or Y direction. As shown in FIG. 12, under practical conditions about half the scan area is available for data acquisition as indicated by the solid curves for a typical square image area. It is a matter of simple geometry to calculate that, at the end of the solid curves, the spot speed has fallen to 87% of the peak spot speed. The dotted portion of the scan, where spot speed is less than 87% of this maximum, is discarded. The 87% figure is derived from the 87% value for the maximum derivative of the cosine value. This value is somewhat arbitrary, but provides a basis for comparison between different scan patterns. The choice of 87% originates from the inventors' use of half of the amplitude of the sine wave for the raster scan, which corresponds to the ≧87% of maximum speed section of the raster pattern. This is also regarded, based on the inventors' experience, as the acceptable region in terms of image quality without undue distortion.
Typically in existing systems, the Y mechanism is in tandem with the X deflection system and has similar length. However, as demand increases for ever more compact scanners there is a need to develop a combined XY scanner of shortest possible length. If the fibre can itself be deflected in both X and Y directions, as a symmetrical cantilever, the scanner is more compact. The problem is that for practical forces only resonant operation is feasible. For this reason modulated circular patterns have been developed, such as is disclosed in U.S. Pat. No. 6,294,775 (Seibel and Furness).
U.S. Pat. No. 6,294,775 discloses a system in which a fibre tip is typically moved in a circle or ellipse, the radius of which is then modulated so that an area is progressively scanned. Suitably phased X and Y drives can produce the circular motion, effectively resonant in both X and Y directions. However, the modulation of the radius of the scanning circle or ellipse results in a large variation in scanning speed, and a singularity at the centre of the field. This scan pattern is very different from a raster scan, so the resulting circular pattern requires image processing, creating interface problems with standard systems. One pattern that can be produced with the system of U.S. Pat. No. 6,294,775 is shown schematically in FIG. 13. Only that portion of the scan shown with a solid curve would be used for imaging. The portion of the scan shown with a dotted curve corresponds to a spot speed of less than 87% of the peak scan speed and is discarded. Hence most of the central area cannot be accessed. The solid curve again corresponds to a spot speed of ≧87% of the peak spot speed which, in this spiral scan, corresponds to a radius of 87% of the maximum radius.


A chitosan membrane containing nanosize particles is disclosed in this invention. The chitosan membrane comprises a chitosan membrane and nano-inorganic particles. The nano-inorganic particles are uniformly embedded in the chitosan membrane. This invention also discloses a method for forming a chitosan membrane containing nanosize particles. The method comprises a grinding process, a dissolution process, a dispersion process, a blending process, an impurity removing process, a degassing process, a casting process, and a fixation process.

1. Field of the Invention
This present invention relates to a polymer membrane, and more particularly, to a chitosan membrane containing nano-inorganic particles and the method for forming the same.
2. Description of the Prior Art
Chitosan is a hydrophilic natural polymer, which has received much attention in recent years. Chitosan is a polysaccharide consisting of [(1,4)-2-amino-2-deoxy-β-D-glucan]. Usually, a deacetylation process is taken to produce chitosan from chitin. Chitin is also a natural polymer and consists of [(1,4)-2-acetamido-2-deoxy-β-D-glucan]. Chitin is the major constituent of the exoskeleton of insects and crustaceous aquatic animals, and also the major constituent of the cell wall of fungus. Chitosan is biodegradable and has the characteristics of excellent biocompatibility and almost no immunoreaction and no toxicity. Furthermore, because of the amino and hydroxyl groups in its molecular structure, chitosan is chemical reactive and is easy to be modified to from a variety of derivatives. For the above reasons, chitosan can be applied in many fields, such as: agriculture, medical and health care, food processing, fine chemicals, waste water treatment, and textile and paper-making industries.
Pervaporation is a membrane separation process that can be employed to separate liquid mixtures. It can be used to separate liquid mixtures with azeotrope. In addition, it comprises the advantages such as easy operation, energy saving, and others. Therefore, pervaporation attracts much attention in industry. The key of the development of pervaporation is the preparation of membranes with excellent separation performance. The separation mechanism is the difference in the penetration rate of each component in the feed to cross the membrane, and the permeation rate is determined by the solubility and the diffusivity of each component in the membrane. The diffusivity is related to the size of the molecule permeating through the membrane and the solubility is related to the affinity between the permeating molecules and the membrane. Thus, a strategy to improve pervaporation performance is to adjust the affinity between the preferred component and the membrane. For example, to synthesize a material with special hydrophilic property or to modify the commercial material for raising the hydrophilicity is practiced. Another application is to control the membrane structure for adjusting the diffusivity of the permeating components in the membrane. Because of its high hydrophilicity and good membrane-forming property, chitosan is a good material for preparation of pervaporations.
Chitosan can be prepared by a dry process, in which the chitosan/acid/water solution is evaporated to remove water and to form dense membranes. However, such membranes cannot be directly used in the pervaporation process because the chitosan membrane would re-dissolve when being in contact with aqueous solution, an effect caused by the residual acid in the membrane. Evan after the removal of the residual acid, the membrane would still be not stable when being applied to the pervaporation process, because of the swelling effect by the feed aqueous solution. Thus, a crosss-linking process is usually required. Sulfuric acid, aldehyde, and dialdehyde are common crosslinkers. After cross-linking, although the stability and permselectivuty are improved, the permeation flux is low (Uragami and Tadashi, U.S. Pat. No. 5,006,255), which limits the application of chitosan membranes to pervaporation. Therefore, a new process is still required to prepare chitosan membranes that posses high selectivity, high flux, and high stability for the pervaporation process.

Chitosan membrane containing nano-inorganic particles and the method for forming the same


A process for preparing an alkyl sulfonate derivative comprises causing a nitrogen-containing heterocyclic compound represented by the following formula (1): ##STR1## wherein X represents --O--, --S--, --NR.sup.1 --, --Se--, --Te-- or --CR.sup.2 R.sup.3 --, in which each of R.sup.1, R.sup.2 and R.sup.3 independently represents a hydrogen atom or a lower alkyl group, Y represents a hydrogen atom, a mercapto group, an arylthio group, an aralkyl group, a sulfo group, a halogen atom, an alkyl group, an alkylthio group, an alkylsulfonyloxy group or an arylsulfonyloxy group and each of R.sup.4, R.sup.5, R.sup.6, R.sup.7 and R.sup.8 represents a hydrogen atom, an alkyl group, an aryl group, an alkoxy group which may be substituted with a sulfo group, an aryloxy group, an alkylthio group, a haloalkyl group, a halogen atom, a cyano group, a carboxy group or a sulfo group, otherwise R.sup.4 and R.sup.5, R.sup.6 and R.sup.6, R.sup.6 and R.sup.7 and R.sup.7 and R.sup.8 are, in at least one of these combinations, bonded each other to form an aromatic ring or a cycloalkene ring; to react in the presence of Lewis acid with an aliphatic sultone to give an alkyl sulfonate derivative corresponding to the above formula (1).

It is already known that a cyanine dye of which the side chain of a mother nucleus (a heterocyclic ring directly bonded to a polymethine chain) is a sulfoalkyl group is used for a photographic material. The sulfoalkyl group is generally bonded to the quaternary nitrogen of a nitrogen-containing heterocyclic ring which constitutes the mother nucleus of the cyanine dye.
The above cyanine dye having the sulfoalkyl group directly bonded to the quaternary nitrogen is generally produced from a precursor, i.e., an alkyl sulfonate derivative having a heterocyclic ring, which has the following formula (5) or (7): ##STR2## wherein X represents --O--, --S--, --NR.sup.1 --, --Se--, --Te-- or --CR.sup.2 R.sup.3 -- (in which each of R.sup.1, R.sup.2 and R.sup.3 independently represents a hydrogen atom or a lower alkyl group which may have a substituent and R.sup.2 and R.sup.3 may form a ring by bonding each other), Y represents a hydrogen atom, mercapto group, an alkylthio group which may have a substituent and an alkyl group, n represents an integer of 0 to 6, and R represents a substituent, the substituents being the same or different from each other in the case of n of not less than 2. The cyanine dye obtained by the compound represented by the formula (5) or (7) is described in Japanese Patent Provisional Publications No. 1-187543 and No. 3-105339.
For example, an alkyl sulfonate derivative containing a nitrogen-atom can be prepared by causing a nitrogen containing compound (e.g., amine) to react with a chain alkyl sulfonate (salt) activated by introducing a halogen atom or sulfonyloxy group to bond the sulfoalkyl group to the nitrogen.
This method is considered to be applied to the preparation of the alkyl sulfonate derivative having a nitrogen-containing heterocyclic ring represented by the above formula (5) or (7). In more detail, it would be considered that a nitrogen-containing heterocyclic compound having the following formula (4) or (6): ##STR3## wherein Y, X, R, n and Z represent the meanings defined above; is caused to react with a chain alkyl sulfonate (salt) activated above to bond the sulfoalkyl group to the nitrogen, whereby the alkyl sulfonate derivative presented by the above formula (5) or (7) is obtained.
The activated alkyl sulfonate serves advantageously as a sulfoalkylated agent for a compound to be sulfoalkylated, in the case that the compound has a high nucleophilicity so that its sulfoalkylated reaction proceeds under relatively mild conditions. However, in the case that the nitrogen-containing heterocyclic compound of the above formula (4), which has not a benzene ring but a naphthalene ring, is caused to react with the activated chain alkyl sulfonate (salt), the reaction needs more heating due to its low reactivity so that the activated portion of the alkyl sulfonate is apt to eliminate. Hence, the alkyl sulfonate derivative represented by the above formula (5) can not be obtained using the alkylsulfonate.
Otherwise, as an sulfoalkylated agent having an activated hydrogen, an aliphatic sultone is already known. It is described in Japanese Patent Provisional Publication No. 1-187543 that the aliphatic sultone reacts with a nitrogen-containing heterocyclic compound such as a compound having the above formula (6) to introduce a sulfoalkyl group into the heterocyclic compound, whereby the alkyl sulfonate derivative of the above formula (5) is obtained. Generally, introduction of the sulfoalkyl group into the nitrogen-containing heterocyclic compound of the above formula (4) having a naphthalene ring is also conducted in the same manner as above. Thus, in the case that the sultone is caused to react with the nitrogen-containing heterocyclic compound of the above formula (4) or (6) to bond the nitrogen of the heterocyclic compound, the alkyl sulfonate derivative of the above formula (5) or (7) would be obtained. Because the elimination occurring in use of the activated chain alkyl sulfonate hardly occurs in the case of use of the sultone.
However, the study of the present inventor has revealed that the reaction of the sultone with the nitrogen-containing heterocyclic compound of the above formula (4) gives the derivative in an extremely low yield. The reason is deemed as follows:
A steric hindrance derived from a hydrogen atom or substituent which is bonded to 8.position carbon atom (on naphthalene ring) of the nitrogen-containing heterocyclic compound of the above formula (4), inhibits the sultone molecule from approach to the nitrogen atom of the nitrogen-containing heterocyclic compound.

Process for preparing an alkyl sulfonate derivative


A vehicle sensor assembly includes an optical sensor surface, at least two transducers arranged to input energy into the optical surface to produce an energy wave through the optical sensor surface and sense an attribute of an energy wave within the optical sensor surface. A controller arranged to drive the at least two transducers to input energy into the optical surface to produce an energy wave within the optical sensor surface to dislodge debris from the optical sensor surface.

Vehicles are increasingly implementing sensors for obtaining data utilized to adapt vehicle operations to a surrounding environment. Sensors can include RADAR, LIDAR and cameras. Commonly utilized sensors have an optical surface that provides input into the sensor. Debris on the sensor optical surface may impact sensor performance Conventional washing systems can require that large amounts of fluid be stored within the vehicle. Moreover, such fluid based systems are not operable if the fluid reserve is emptied. Cleaning with systems that utilize compressed air require costly additional devices within a vehicle and may not provide effective debris removal.
The background description provided herein is for the purpose of generally presenting a context of this disclosure. Work of the presently named inventors, to the extent it is described in this background section, as well as aspects of the description that may not otherwise qualify as prior art at the time of filing, are neither expressly nor impliedly admitted as prior art against the present disclosure.

Optical surface cleaning with directed energy waves


Methods, systems, and non-transitory computer readable medium are described for automated image measurement for process development and optimization. A method includes receiving an image of a product associated with a manufacturing process; determining, using a trained machine learning model, an image classification for the image; selecting, based on the image classification, one or more image processing algorithms for the image; pre-processing the image based on at least one of the one or more image processing algorithms to generate an enhanced image; measuring, using a first image processing algorithm of the one or more image processing algorithms, one or more attributes of the enhanced image to determine image measurements; and reporting the image measurements. The manufacturing parameters of the manufacturing process are to be updated based on the image measurements.

Large amounts of images (e.g., of wafers, etc.) are generated by different industries (e.g., semiconductor industry, biomedical industry, display industry, photovoltaic industry, etc.). For example, thousands of images may be generated every month in a semiconductor laboratory during process development. To perform image measurements, a setup (e.g., recipe setup) may be created for measuring attributes (e.g., product width, height, etc.) of a first image. The setup may be run on the remaining images to measure attributes of the remaining images. If the remaining images have variations (e.g., variation in structure of the product, variations due to change in process and imaging conditions, etc.), the setup created based on the first image may not apply and a system using the setup may fail to measure the attributes of the remaining images. Due to this failure, the remaining images may be manually measured by process engineers. The manual measurements may include errors, may be subject to variations from one engineer to another engineer, and may take up much engineer time.

Automated image measurement for process development and optimization


A chain comprising at least two links (15) having a generally oval or rounded shaped side profile, each of the links having a longitudinal axis (x-x) and linked together such that a force (16) is applied to each of the links when the chain is in tension, the force generally orientated along the longitudinal axis, each of the links having a cross-sectional profile (18) at the longitudinal axis and the cross-sectional profile having an outer width (19) generally along the longitudinal axis and an outer thickness (20) substantial transverse to the longitudinal axis, wherein the outer width is greater than the outer thickness. The cross-sectional profile may further comprise an inner thickness (30) substantially transverse to the longitudinal axis that is less than the outer thickness (29). The cross-sectional profile (26) may be substantially uniform around the link.

Link chains are well-known in the prior art. Generally, such chains are made from multiple links that are laced together. In such prior art chains, the links are manufactured from a circular cross-sectional profile of raw material such as steel wire or steel rod. These links generally are of an oblong shape with a parallel shank or barrel portions connected at either end by crown portions. Because a chain link under stress is subjected to bending forces around or at the ends of the link, the stress is mainly located in a radial manner, and concentrated in the central portions of the material between the inside and outside of the ends of the link. However, such chain links are not designed to address the stresses and strains to which the link is most commonly subjected. Thus, they typically are overbuilt in order to provide adequate strength at the critical areas of the link. Accordingly, there is a need for a lighter but stronger link chain.


A precision targeting system for a firearm has an image capturing scope, a processor, and an actuator. In one embodiment, a user indicates when he wants to lock onto the target, and then readjust his aim after receiving feedback from the system. In another embodiment, the system automatically locks onto the target. After lock on, the system compares successive images, and determines if the target has moved in the firearm sight. If movement has occurred, the system calculates the degree of the movement, and sends appropriate signals to an actuator which corrects the aim of the firearm. The system thereby converts reasonably good aim into precision aim.

In military and law enforcement situations, marksmen and their firearms are expected to provide accurate and precise targeting at both short and long ranges. However, movements of the desired target and/or movements by the marksman may cause imprecise targeting and consequent missing of the target when the firearm is discharged.
Prior efforts to solve these problems all have their shortcomings. For example, some systems use gyroscopic technologies to combat these problems. In such systems, a gyroscope is implanted into the body or stock of a firearm. The marksman aims at the intended target, and locks the system onto the target by indicating to the system in some manner that the intended target is in the sight of the firearm. After that indication and locking onto the target, the gyroscope senses any movement in the firearm, either up and down, side to side, or a combination thereof, and through some mechanism corrects for that movement. There are at least two drawbacks to such gyroscopic systems however. First, they only correct movements of the firearm, and cannot adjust and correct for movements of the intended target. Second, since such systems are installed inside the stock or elsewhere in the firearm, they are not easy to either install or retrofit, and in most cases require at least some disassembly of the firearm.
The art is therefore in need of a precision targeting system for firearms that is effective, that is easy to install and retrofit without dismantling the firearm, and that will make corrections both for target movement and firearm movement.

BAE Systems Information and Electronic Systems Integration Inc.


IDDS is implemented as a kernel resident data source which provides per-system call audit records into user space in a timely manner. Each invocation of a system call is audited and a record of the activity is placed into a circular buffer in the kernel. A user-space process reads the data from the buffer via a device driver interface. A device driver provides a clean interface between the kernel and the IDS. The semantics of device drivers are familiar to most UNIX programmers, following the standard file-based open-read-write-close paradigm.

Intrusion detection data sources provide audit data to determine if an intrusion has occurred. Many previous sources only provided syslog data.
Previous intrusion detection data sources suffered from numerous deficiencies. For example, many sources always produce data, produce ambiguous data, the delivery of data is too slow, negatively impacts system throughput, and stores information from a system call in several records causing difficulty in accessing the records.

Method of generating and presenting kernel data

Hewlett-Packard Development Company, L.P.


Compounds which inhibit prenyl transferases, particularly farnysyltransferase and geranylgeranyl transferase I, processes for preparing the compounds, pharmaceutical compositions containing the compounds, and methods of use.

1. Field of the Invention
The present invention relates to novel peptidomimetics and other compounds which are useful as inhibitors of protein isoprenyl transferases (particularly protein farnesyltransferase and geranylgeranyltransferase) and as anti-cancer drugs, to compositions containing such compounds and to methods of use.
2. Background Information
Ras proteins are plasma membrane-associated GTPases that function as relay switches that transduce biological information from extracellular signals to the nucleus (29-31). In normal cells Ras proteins cycle between the GDP-(inactive) and GTP-(active) bound forms to regulate proliferation and differentiation. The mechanism by which extracellular signals, such as epidermal and platelet derived growth factor (EGF and PDGF), transduce their biological information to the nucleus via Ras proteins has recently been unraveled (29-31). Binding of the growth factors to tyrosine kinase receptors results in autophosphorylation of various tyrosines which then bind src-homology 2 (SH2) domains of several signaling proteins. One of these, a cytosolic complex of GRB-2 and a ras exchanger (m-SOS-1), is recruited by the tyrosine phosphorylated receptor where mSOS-1 catalyzes the exchange of GDP for GTP on Ras, hence activating it. GTP-bound Ras recruits Raf, a serine/threonine kinase, to the plasma membrane where it is activated. Raf triggers a kinase cascade by phosphorylating mitogen-activated protein (MAP) kinase/extracellular-regulated protein kinase (ERK) kinase (MEK) which in turn phosphorylates MAP Kinase on threonine and tyrosine residues. Activated MAP Kinase translocates to the nucleus where it phosphorylates transcription factors (31). Termination of this growth signal is accomplished by hydrolysis of Ras-GTP to Ras-GDP.
Ras oncogenes are the most frequently identified activated oncogenes in human tumors (1-3). In a large number of human cancers, Ras is GTP-locked because of mutations in amino acids 12, 13, or 61 and the above Ras pathway no longer requires an upstream growth signal and is uninterrupted. As a consequence, enzymes in this pathway such as Raf, MEK and MAP Kinase are constitutively activated.
In addition to its inability to hydrolyze GTP, oncogenic Ras must be plasma membrane-bound to cause malignant transformation (13). Ras is posttranslationally modified by a lipid group, farnesyl, which mediates its association with the plasma membrane (10-14).
Post-translational events leading to membrane association of p21ras have previously been disclosed (10-14). The p21ras proteins are first made as pro-p21ras in the cytosol where they are modified on cysteine 186 of their carboxyl terminal sequence CA.sub.1 A.sub.2 X (C=cysteine, A.sub.1 and A.sub.2 =isoleucine, leucine or valine and X=methionine or serine) by the cholesterol biosynthesis intermediate farnesyl pyrophosphate (FPP). This farnesylation reaction is then followed by peptidase removal of the A.sub.1 A.sub.2 X tripeptide and carboxymethylation of the remaining cysteine. The processed p21ras proteins associate with the inner surface of the plasma membrane (10-14).
p21Ras farnesyltransferase, the enzyme responsible for catalyzing the transfer of farnesyl, a 15-carbon isoprenoid, from FPP to the cysteine of the CA.sub.1 A.sub.2 X carboxyl terminus of p21ras, has been purified to homogeneity from rat brain (15,16). The enzyme is a heterodimer composed of .alpha. and .beta. subunits of molecular weights 49 and 46 kDa, respectively (17). The .beta. subunit has been shown to bind p21ras (17). Because p21ras farnesylation and subsequent membrane association are required for p21ras transforming activity (13), it has been proposed that p21ras farnesyltransferase would be a useful anticancer therapy target. Accordingly, an intensive search for inhibitors of the enzyme is underway (18-24, 33-44). Potential inhibitor candidates are CA.sub.1 A.sub.2 X tetrapeptides which have been shown to be farnesylated by p21ras farnesyltransferase and appear to be potent inhibitors of this enzyme in vitro (15,18,21-24). Competition studies have demonstrated that CA.sub.1 A.sub.2 X peptides with the greatest inhibitory activity are those where A.sub.1 and A.sub.2 are hydrophobic peptides with charged or hydrophilic residues in the central positions demonstrating very little inhibitory activity (18,21,23). A major drawback with the use of peptides as therapeutic agents is their low cellular uptake and their rapid inactivation by proteases.
The research efforts directed towards farnesyltransferase and the inhibition of its activity are further illustrated by the following patents or published patent applications:
U.S. Pat. No. 5,141,851 PA1 WO 91/16340 PA1 WO 92/18465 PA1 EPA 0456180 A1 PA1 EPA 0461869 A2 PA1 EPA 0512865 A2 PA1 EPA 0520823 A2 PA1 EPA 0523873 A1 PA1 Cys-Val-Leu-Ser PA1 Cys-Val-Ile-Met PA1 Cys-Val-Val-Met PA1 ii) lower alkyl; PA1 iii) alkenyl; PA1 iv) alkoxy; PA1 v) thioalkoxy; PA1 vi) halo; PA1 vii) haloalkyl; PA1 viii) aryl-L.sub.2 --, wherein L.sub.2 is absent, --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH(CH.sub.3)--, --O--, --S(O).sub.q wherein q is 0, 1, or 2, --N(R')-- wherein R' is hydrogen or lower alkyl, or --C(O)-- and aryl is selected from the group consisting of phenyl, naphthyl, tetrahydronaphthyl, indanyl and indenyl and the aryl group is unsubstituted or substituted; or PA1 ix) heterocyclic-L.sub.3 -- wherein L.sub.3 is absent, --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH(CH.sub.3)--, --O--, --S(O).sub.q wherein q is 0, 1 or 2, --N(R')-- wherein R' is hydrogen or loweralkyl, or --C(O)-- and heterocyclic is a monocyclic heterocyclic wherein the heterocyclic is unsubstituted or substituted with one, two, or three substituents independently selected from the group consisting of loweralkyl, hydroxy, hydroxyalkyl, halo, nitro, oxo (.dbd.O), amino, N-protected amino, alkoxy, thioalkoxy and haloalkyl; PA1 i) ##STR2## wherein R.sub.12a is hydrogen, loweralkyl or --C(O)O--R.sub.13, wherein R.sub.13 is hydrogen or a carboxy-protecting group and R.sub.12b is hydrogen or loweralkyl, with the proviso that R.sub.12a and R.sub.12b are not both hydrogen, PA1 ii) --C(O)NH--CH(R.sub.14)--C(O)OR.sub.15 wherein R.sub.14 is PA1 a) loweralkyl, PA1 b) cycloalkyl, PA1 c) cycloalkylalkyl, PA1 d) alkoxyalkyl, PA1 e) thioalkoxyalkyl, PA1 f) hydroxyalkyl, PA1 g) aminoalkyl, PA1 h) carboxyalkyl, PA1 i) alkoxycarbonylalkyl, PA1 j) arylalkyl or PA1 k) alkylsulfonylalkyl and PA1 iii) ##STR3## PA1 a) hydroxy, PA1 b) --SH, PA1 c) halo, PA1 d) oxo (.dbd.O), PA1 e) thioxo (.dbd.S), PA1 f) amino, PA1 g) --NHOH, PA1 h) alkylamino, PA1 i) dialkylamino, PA1 j) alkoxy, PA1 k) alkoxyalkoxy. PA1 l) haloalkyl. PA1 m) hydroxyalkyl, PA1 n) alkoxyalkyl, PA1 o) cycloalkyl, PA1 p) cycloalkenyl, PA1 q) alkenyl, PA1 r) alkynyl, PA1 s) aryl, PA1 t) arylalkyl, PA1 u) --COOH, PA1 v) --SO.sub.3 H, PA1 w) loweralkyl, PA1 x) alkoxycarbonyl, PA1 y) --C(O)NH.sub.2, PA1 z) --C(S)NH.sub.2, PA1 aa) --C(.dbd.N--OH)NH.sub.2, PA1 bb) loweralkyl-C(O)--, PA1 cc) loweralkyl-C(S)--, PA1 dd) formyl, PA1 ee) cyano, and PA1 ff) nitro.
Of the above disclosures, EPA 0520823 A2 discloses compounds which are useful in the inhibition of farnesyl-protein transferase and the farnesylation of the oncogene protein ras. The compounds of EPA 0520823 A2 are illustrated by the formula: EQU Cys-Xaa.sup.1 -dXaa.sup.2 -Xaa.sup.3
or pharmaceutically acceptable salts thereof, wherein Cys is a cysteine amino acid;
Xaa.sup.1 is an amino acid in natural L-isomer form;
dXaa2 is an amino acid in unnatural D-isomer form; and
Xaa.sup.3 is an amino acid in natural L-isomer form.
The preferred compounds are said to be CV(Dl)S and CV(Df)M, the amino acids being identified by conventional 3 letter and single letter abbreviations as follows:
______________________________________ Cysteine Cys C Glycine Gly G Isoleucine Ile I Leucine Leu L Lysine Lys K Methionine Met M Phenylalanine Phe F Serine Ser S Threonine Thr T Valine Val V ______________________________________
EPA 0523873 A1 discloses a modification of the compounds of EPA 0520823 A2 wherein Xaa.sup.3 is phenylalanine or p-fluorophenylalanine.
EPA 0461869 describes compounds which inhibit farnesylation of Ras protein of the formula: EQU Cys-Aaa.sup.1 -Aaa.sup.2 -Xaa
where Aaa.sup.1 and Aaa.sup.2 are aliphatic amino acids and Xaa is an amino acid. The aliphatic amino acids which are disclosed are Ala, Val, Leu and Ile. Preferred compounds are those where Aaa.sup.1 is Val, Aaa.sup.2 is Leu, Ile or Val and Xaa is Ser or Met. Preferred specific compounds are:
U.S. Pat. No. 5,141,851 and WO 91/16340 disclose the purified farnesyl protein transferase and certain peptide inhibitors therefor, including, for example, CVIM, TKCVIM and KKSKTKCVIM.
WO 92/18465 discloses certain farnesyl compounds which inhibit the enzymatic methylation of proteins including ras proteins.
EPA 0456180 A1 is directed to a farnesylprotein transferase assay which can be used to identify substances that block farnesylation of ras oncogene gene products while EPA 0512865 A2 discloses certain cyclic compounds that are useful for lowering cholesterol and inhibiting farnesylprotein transferase.
As will be evident from the foregoing, there is a great deal of research effort directed towards the development of inhibitors of farnesyltransferase. However, there still remains a need for improvements in this critically important area.
An enzyme closely related to farnesyltransferase, geranylgeranyltransferase I (GGTase I), attaches the lipid geranylgeranyl to the cysteine of the CAAX box of proteins where X is leucine (49,69). FTase and GGTase I are .alpha./.beta. heterodimers that share the .alpha. subunit (61,62). Cross-linking experiments suggested that both substrates (FPP and Ras CAAX) interact with the .beta. submit of FTase (17,63). Although GGTase I prefers leucine at the X position, its substrate specificity was shown to overlap with that of FTase in vitro (64). Furthermore, GGTase I is also able to transfer farnesyl to a leucine terminating peptide (65).
Although CAAX peptides are potent competitive inhibitors of FTase, rapid degradation and low cellular uptake limit their use as therapeutic agents. The stragegy of the present invention to develop superior compounds for inhibiting FTase and GGTase has been to replace several amino acids in the CAAX motif by peptidemimics. The rationale behind this strategy is based on the existance of a hydrophobic pocket at the enzyme active site that interacts with the hydrophobic "AA" dipeptide of the carboxyl termini CAAX of Ras molecules. In this regard, two very potent inhibitors of FTase (i.e. Cys-3AMBA-Met and Cys-4ABA-Met) were disclosed by us in an earlier U.S. patent application. The peptidomimetic Cys-4ABA-Met incorporates a hydrophobic/aromatic spacer (i.e. 4-aminobenzoic acid) between Cys and Met. The present application discloses several derivatives of Cys-4ABA-Met where positions 2 and 3 of 4-amino benzoic acid were modified by several alkyl, and/or aromatic groups, compounds that show great promise of ability to selectively antagonize RAS-dependent signaling and to selectively inhibit the growth of human tumors with aberrant Ras function.
Of the four types of Ras proteins (H--, N--, K4A--, and K4B-Ras) expressed by mammalian cells, K4B-Ras (also called K-Ras4B) is the most frequently mutated form of Ras in human cancers (1,3). Although several laboratories have demonstrated potent inhibition of oncogenic H-Ras processing and signaling (43,44), this disruption has not been shown with K-Ras4B. Previous studies have targeted H-Ras and not K-Ras4B as a target for the development of inhibitors. One recent report indicates that K-Ras4B can be geranylgeranylated in vitro, but with relatively low efficiency; its K.sub.m for GGTase I is 7 times higher than its K.sub.m for FTase (67). GGTase I CAAX-based inhibitors that can block geranylgeranylation processing have not been reported.
Recently, we have shown that a potent inhibitor of FTase disrupts K-Ras4B processing but only at very high concentrations that also inhibited the processing of geranylgeranylated proteins (66). This suggested that K-Ras4B may be geranylgeranylated, and that therefore inhibitors targeted at GGTase I would be effective in disrupting oncogenic K-Ras4B processing and signalling, and in treatment of cancers which were related to this form of Ras.


A new I/O bus which may be used in constructing a multiple drive library computer system which is repairable while the system remains online. The I/O bus generally operates under a SCSI-type protocol. The bus comprises a primary I/O bus, and a plurality of secondary I/O buses, pigtailed to said primary bus. The pigtailed I/O buses are longer than the 100 mm stubs which are sanctioned under a SCSI protocol.

This invention pertains to a new I/O bus which may be used in constructing a multiple drive library computer system. With the newly invented I/O bus disclosed herein, repair of a failed drive may occur while one or more good drives in the library system remain online. In this manner, a host may have continual and uninterrupted access to information stored within the library.
Although the I/O bus disclosed herein is especially advantageous in removable media type multiple drive library computer systems, it may also be adapted to other multiple component computer systems as well.
The I/O bus disclosed herein may be used in conjunction with the Computer Frame Structure with Modular Housings and system and method of Online Drive Repair disclosed herein.
In a multiple drive library computer system, the first component to fail due to excessive use is often a storage drive. Typically, when a storage drive fails, the library undergoes a period of down time while the drive is repaired and/or replaced. During this down time, a host (whether it be a UNIX.RTM. work station, PC network server or otherwise) cannot access any of the information contained within the library.
Since loss of information access is unacceptable, efforts have been made to minimize library down time. These efforts include Redundant Array of Inexpensive Disks (RAID) and hot repair technologies.
The RAID technology involves a method of reconstructing data which is lost in the event of a drive's failure. Data is stored in a redundant array of nonremovable media type drives, such that when a failed drive is replaced, an error-correction operation can be applied to the data blocks of the remaining storage drives in the redundant array so that the data which was lost can be reconstructed. Although the RAID method helps to minimize library down time, the method is not applicable to removable media type libraries. In a removable media type library, failure of a drive does not result in loss of data. It only results in loss of access to data.
In a hot repairable system, storage drives are guided on rails into hot repair sockets. A failed drive may be removed from its socket without notification to the library system or a host. As the failed drive is pulled from its socket, a system of long and short pins is used to incrementally disconnect power to the drive, to notify the library system and the host that the drive is no longer available, and to make the necessary changes in system parameters to keep the library system online. However, there is a barrier to implementing hot repair technology in a removable media type library. The barrier exists due to the requirement of a removable media type library that the media inserting faces of its storage drives face a robotic media inserter. In order to keep such a system online, it is necessary to remove storage drives by pulling them away from the robotic inserter. To do this, the electrical connection faces of the storage drives (which in standard drives are opposite their media inserting faces) must be free of blockage (sockets, circuit boards, pins, etc.). To affect a hot repair of a removable media storage drive, a storage drive would need to be constructed wherein its media inserting face and electrical connection face were on adjacent sides, rather than on opposite sides. This is an added expense which is unnecessary in view of the online repairable system and method of online drive repair disclosed herein.
It is therefore a primary object of this invention to significantly reduce the down time of a multiple drive library computer system upon failure of one or more of the library's storage drives. In the case of a removable media type library, it is believed that library down time can be eliminated.
It is a further object of this invention to allow a host to have continual access to one or more good storage drives of a multiple drive library computer system while one or more failed drives of the library are repaired.


A method collectively and yet individually assesses a parking area and locates a parking space which is energy-optimized with respect to a temperature control. A correspondingly equipped parking system carries out the method.

The invention relates to a method for collectively and yet individually rating a parking area and finding a parking space that is energy-optimized with regard to climate conditioning. Further, the present invention relates to an accordingly configured parking system. On top of that, a computer program product having control commands that implement the method and operate the proposed parking system is proposed.
DE 10 2014 001 554 B4 discloses an autonomous vehicle that takes the vehicle interior temperature and the expected time of arrival of the driver as a basis for independently choosing a parking space that results in an optimum interior temperature of the vehicle.
DE 10 2009 027 543 A1 discloses a method in which buildings and the position of the sun are taken as a basis for calculating the likely shadow pattern and this is visually indicated to the driver.
DE 10 2013 001 308 A1 discloses a method for providing information about a parking space. The invention also includes a navigation apparatus by means of which this information is made available to a driver of a motor car.
DE 10 2014 224 108 A1 discloses a method for operating a vehicle, wherein one or more vehicle components of the vehicle are operated on the basis of a prescribed time of collection of the vehicle at a collection position in a carpark such that the vehicle at the collection position has one or more prescribed states at the prescribed time of collection.
Saving energy has been an important factor in the development of vehicles for a long time. In the case of electric vehicles, however, intelligent energy management is even more important, because the range and hence the benefit to the customer can be increased directly. A fundamental component of this is temperature management in the vehicle interior.
The prior art shows detection of features of an individual parking space or static reading of previously stored features. When individual parking spaces are processed, over-specification can occur, however. Weather data typically relate to areas and hence it is disadvantageous to severely restrict the parking space search just to the local area.
It is an object of the present invention to provide an improved method that allows collective and yet individual rating of a parking area and finding of an energy-optimized parking space with little technical outlay. Further, it is an object of the present invention to provide an accordingly configured system arrangement and to provide a computer program product having control commands that implement the method and at least partially operate the proposed system arrangement.
Accordingly, a method for optimum climate conditioning when parking is proposed, involving specifying a parking area and a parking time, wherein the method is characterized in that there is provision for providing parking area information by way of a plurality of vehicles that are in this parking area in a period that comprises the parking time, and selecting a parking space within the parking area on the basis of vehicle parameters.
In the text that follows, aspects are sometimes depicted with reference to electrically operated vehicles, but this is not intended to be interpreted as limiting. Rather, the present invention is aimed generally both at electric vehicles and at vehicles having an internal combustion engine. In this respect, motor vehicles are generally developed further according to the invention. Suitable motor vehicles in this case are generally any motor vehicle, in particular an automobile.
According to the invention, it is possible to use an electrically operated vehicle to select a parking space such that energy consumption is optimized. As such, a battery does not simply power the air conditioning system, rather the applicable range of the electric vehicle also decreases when the air conditioning system is operated. In this regard, the driver can specify, for example by use of an application appliance, where he wishes to park and can optionally select a parking time. If a driver enters no parking time, then the current time can be set as standard or the route guidance is used to calculate when the vehicle will reach the destination area. It is therefore thus possible for the driver to select a complete road, a city zone or else a radius around a fixed point as a parking area. Therefore, it is thus not just possible to select individual parking spaces, but rather an entire area can be narrowed, which in turn increases the likelihood of a particularly suitable parking space being found.
It may thus be advantageous to travel further for an energy-optimized parking space rather than choosing a closer parking space that has unfavorable energy properties. An unfavorable energy property in this case is for example excessive heat or insolation in summer. By contrast, this is particularly advantageous in winter, since the vehicle needs to be heated less after a parking process. The same applies to the battery of an electric vehicle, which first needs to be brought to an operating temperature after parking.
It is therefore thus also possible to specify what form the parking space needs to take on the basis of the parking time. Therefore, it is also possible to take into consideration times of day and to take into consideration applicable weather conditions at the time of day. Since the weather can change quickly, a solution is proposed in the present case that is based on providing parking area information by means of multiple vehicles. Therefore, the specified areas are thus particularly advantageously rated, since the weather in such areas is typically always the same. On top of that, it is also possible for parking-space-individual features, such as for example a wind flow or a presence of buildings, to be taken into consideration. A building affects a parking space such that it results in shade and a particular wind behavior.
The parking area information can be provided by means of multiple vehicles that are either parked in the parking area or driving through it. This too can in turn accomplish rating of the applicable parameters, since a vehicle becomes particularly hot especially when parking. If just an ambient temperature is needed, then the measurement results from traveling vehicles can also be evaluated. Further, it is possible for other vehicles to provide route information and hence to specify that they will shortly be traveling and parking in the parking area. Therefore, the period can be used to set how current the information needs to be and, if need be, to provide expiry information. It is therefore possible for example for just data that are not more than 5 hours to be taken into consideration. As such, for example a wind is highly temporary weather that is no longer relevant if it took place on the day before.
A parking space can be selected on the basis of both provided vehicle parameters and other vehicles and vehicle parameters of the driver's own, searching vehicle. As such, applicable logic may be present that takes into consideration the provided vehicle parameters and compares its own, measured vehicle parameters against these. As such, a convertible with the top open heats up less than a closed vehicle. If the interior temperature thus needs to be optimized when parking, it is thus possible to take into consideration only those vehicles that are closed. If the vehicle looking for the parking space is a convertible, it is accordingly also possible to take into consideration parking area information from convertibles. Generally, vehicles can typically detect whether it is raining, and hence this information can be rated separately for a convertible. Since, according to the present invention, the ambient information is provided by a multiplicity of vehicles (subsequently referred to as a crowd), it is particularly advantageous that many different vehicle types can be taken into consideration. This affords the advantage over known methods that not every single parking space needs to be evaluated individually, because the IT system finds rules for how the weather influence is comparable for different designs of vehicles. As such, it is possible to filter out from the multiplicity of data whether a parking space is actually relevant. If for example an electrically operated vehicle is not supposed to become particularly hot, then it is already possible for all parking spaces or an area of parking spaces with a high level of heat to be filtered out.
This affords the advantage that efficient data processing can take place on the basis of both historic data in the form of a location-based and time-of-day-based model and realtime data. Over the entire duration of the observation history, the system uses the sum of all individual measurements to build up general information concerning the temperature and sequence of insolation for every parking space environment and every vehicle orientation. It is not just particularly advantageous that a multiplicity of actually measured data are available, but rather individual vehicle parameters can be taken into consideration and hence it is not just possible for the location of the parking space to be taken into consideration, but rather any vehicle per se can also be taken into consideration. In this case, it is particularly advantageous for the vehicle data of the searching vehicle also to be taken into consideration. If this is for example a car having an internal combustion engine, then this car has greater capacities for cooling a vehicle interior and does not need to bring a battery to an operating temperature. It is therefore thus possible for vehicle parameters of an electrically operated vehicle to be rated differently than data of a vehicle having an internal combustion engine. It is therefore thus possible for different information that does not appear relevant to be hidden from the existing database.
Using the collected data, the system provides the driver or the autonomous vehicle with a forecast of the optimum parking space in order to increase the energy efficiency of the vehicle for the customer. This is effected by means of the parking spot and the angle at which the vehicle is parked on the road. This passively controls the temperature of the vehicle, for example by virtue of the effect of weather such as shaded insolation, wind tunnels or vegetation effects. The suitable choice of parking space is derivable therefrom. This is therefore advantageous for the driver's cab, inter alia, and the air conditioning system is then relieved of load.
This has a similarly advantageous effect on the batteries in electric vehicles. Vehicle batteries have an optimum temperature range for their operation. To keep the battery in this temperature range, it needs to be heated or cooled, which can be optimized by means of the suitable parking space. All exposed components are open to the UV of insolation. If the insolation intensity or the vegetation effects can be located, the choice of location can help the customer to better preserve the components of the vehicle.
Instead of static building data, the collected data from vehicles that are already parked in this area are evaluated. This crowd solution means that there is no longer a reliance on building maps, which are sometimes not up to date. Additionally, the actual thermal radiation is predicted much more precisely, because, besides the buildings, there is also an influence by vegetation, air flows and temporary shade providers. It is also possible for statements contained in the crowd data to be made for each real vehicle type. The vehicle information number (VIN) allows the vehicle type, paint and the roof type (convertible, panorama glass roof) to be detected and processed in the crowd data as input parameters.
One is therefore independent of a supposedly correct and current building map. According to the invention, it is possible for reflections and wind flows, vegetation, to be taken into consideration and for temporary structures to be taken into consideration. Also, there is less computational complexity than with conventional methods.
According to one aspect of the present invention, the size of a parking area and/or the period are specified during a parking space search. This has the advantage that for example a radius or a city zone can be used to narrow the parking space search. Therefore, not only are individual parking spaces thus selected and analyzed, but rather a variable area can be taken into consideration, depending on the application scenario, and hence the likelihood of finding a suitable parking space can be increased. Further, a navigation system or the automatic derivation from the mobility pattern recognition can be used to set the time frame in which an arrival can be expected and hence to set the period. The period can also be used to set the up-to-dateness of the data.
According to a further aspect of the present invention, the vehicle parameters relate to at least one parked vehicle and/or to a parking vehicle. This has the advantage that vehicle parameters can be taken into consideration for the parking space search and hence it is possible to check which parameters of the parked automobiles are actually relevant to the searching vehicle. Further, it is possible to detect whether a vehicle is parking in the area or whether it is moving therein. Therefore, temperature information and information regarding wind can be interpreted correctly.
According to a further aspect of the present invention, the vehicle parameters describe an electric drive, an internal-combustion-engine-based drive, a state of charge, a fuel reserve, a bodywork design, a vehicle type, an external vehicle color, a vehicle paint, a roof design, a window arrangement and/or a stored vehicle parameter. This has the advantage that the relevant parameters can be read for the applicable application scenario. If primarily the temperature is relevant, then it is possible to detect which vehicle gets particularly hot under insolation, and to take these parameters into consideration. If characteristics are obtained from a window roof, these can likewise be taken into consideration. Generally, automobiles with an open top have different temperature properties than closed vehicles. In the case of an electric drive, the temperature is more important than in the case of an internal-combustion-engine-based drive, since the battery may need to be brought to operating temperature and heating or cooling is even disadvantageous for the range. Especially in the case of an electric vehicle with a low state of charge, it is important to use the air conditioning system as little as possible.
According to a further aspect of the present invention, the parking area information describes a temperature, an insolation angle, an insolation intensity, buildings, a vegetable, air flows, permanent shade providers and/or temporary shade providers. This has the advantage that parameters can be rated independently of one another. As such, for example a panoramic roof is more susceptible to heating of the vehicle than a completely closed roof. It is therefore possible for specifically data from vehicles having a panoramic roof to be evaluated if the vehicle to be parked has a panoramic roof just now. An insolation angle is less relevant to a panoramic roof than to a windshield.
According to a further aspect of the present invention, the parking area information is provided on the basis of optical sensors, temperature sensors, humidity sensors, wind sensors, brightness sensors, received information and/or stored information. This has the advantage that extended capture of the ambient parameters is possible, these not relating to a single parking space, but rather different parameters of an area can be captured.
According to a further aspect of the present invention, the parking vehicles and/or the vehicle to be parked provide a vehicle identifier and/or a vehicle information number VIN. This has the advantage that vehicle information or a vehicle parameter can already be read from such a number. As such, it is possible to detect what design is present and in this case to infer a particular behavior with regard to the parking area information.
According to a further aspect of the present invention, the parking area information is classified on the basis of at least one vehicle parameter, and the parking space is chosen on the basis of the relevant class of the vehicle to be parked. This has the advantage that clustering can be performed and merely relevant information can be processed. Therefore, it is not necessary for every vehicle to be evaluated individually, but rather the searching vehicle can provide its data and receives only parking space information for similar vehicles. As such, a particular size of parking automobiles can be hidden, since in this case there is the risk of a searching vehicle not actually being able to detect such a parking space on account of a lack of size. Therefore, allowance is made for a multiplicity of vehicles providing information on the basis of what is known as the crowd.
The object is also achieved by a parking system for optimum climate conditioning when parking, having a specification unit configured for specifying a parking area and a parking time, wherein the system is characterized in that there is provision for at least one provision unit configured for providing parking area information by means of a plurality of vehicles that are in this parking area in a period that comprises the parking time, and a selection unit configured for selecting a parking space within the parking area on the basis of vehicle parameters.
Therefore, a parking system having a map constructed historically from the crowd with parking position, vehicle orientation and vehicle states (convertible top open, sun visors up, windows open and the like) for forecasting optimum climate conditioning from historic and realtime data (Kalman filter) when parking is proposed.
The object is also achieved by a computer program product having control commands that carry out the method and operate the proposed arrangement or the parking system when they are executed on a computer.
According to the invention, it is particularly advantageous that the method can be used for operating the proposed apparatuses and units. Further, the proposed apparatuses and devices are suitable for carrying out the method according to the invention. Therefore, the respective unit implements structural features suitable for carrying out the applicable method. The structural features can also be in the form of method steps, however. The proposed method also has steps in store for implementing the function of the structural features.
Further advantages, features and details of the invention can be found in the description below, in which aspects of the invention are described in detail with reference to the drawings. In this context, the features mentioned in the claims and in the description can each be essential to the invention individually per se or in any desired combination. Similarly, the features mentioned above and those explained further below can each be used per se or in multiple combinations as desired. Functionally similar or identical parts or components are to a certain extent provided with the same reference signs. The terms "on the left", "on the right", "at the top" "at the bottom" used in the description of the exemplary embodiments relate to the drawings in an orientation with a normally readable designation of the figures or normally readable reference signs. The embodiments shown and described are not intended to be understood as conclusive, but rather have an exemplary nature for explaining the invention. The detailed description serves to inform a person skilled in the art, and therefore known circuits, structures and methods are not shown or explained in detail in the description in order to avoid making the present description more difficult to understand.
Other objects, advantages and novel features of the present invention will become apparent from the following detailed description of one or more preferred embodiments when considered in conjunction with the accompanying drawings.

Optimum temperature control during parking

Bayerische Motoren Werke Aktiengesellschaft


Semiconductor devices including dual gate structures and methods of forming such semiconductor devices are disclosed. For example, semiconductor devices are disclosed that include a first gate stack that may include a first conductive gate structure formed from a first material, and a second gate stack that may include a dielectric structure formed from an oxide of the first material. For another example, methods including forming a high-K dielectric material layer over a semiconductor substrate, forming a first conductive material layer over the high-K dielectric material layer, oxidizing a portion of the first conductive material layer to convert the portion of the first conductive material layer to a dielectric material layer, and forming a second conductive material layer over both the conductive material layer and the dielectric material layer are also disclosed.

Semiconductor devices including dual gate structures that include dual metal electrodes, or gates, on high-K dielectrics are expected to be a basis for the next generation of memory devices. However, reliable manufacturing and integration of dual metal gates having two different work functions has been a challenge. For example, conventional methods of forming dual metal gates having two different work functions require etching a metal layer over a portion of the high-K dielectric material before applying another metal layer, which may cause etch-induced damage to the high-K dielectric material.
For the reasons stated above and other reasons that will become apparent to those of ordinary skill in the art upon reading and understanding the present specification, there is a need in the art for improved semiconductor devices including dual gate structures and methods of forming such semiconductor devices.


A system for adjusting content display orientation on a screen is disclosed. The system may include a processor that may detect both eyes and a body part of a user that is proximal to one or more of the user's eyes. The system may then determine an eye gaze plane based on the positions of the first and second eyes of the user. The eye gaze plane may be determined by identifying a first line of sight extending from the first eye and a second line of sight extending from the second eye. Additionally, the eye gaze plane may bisect a center of the first eye and a center of the second eye of the user. Once the eye gaze plane is determined, the system may adjust the orientation of content displayed on a display device based on the eye gaze plane and on the position of the body part.

In today's society, people have been increasingly adopting use of devices such as mobile phones, computer tablets, interactive displays, and laptops over traditional personal computers for a variety of things including work, entertainment, or other tasks. With such widespread acceptance, engineers and scientists have had to develop a variety of technologies and systems to ensure that the users can view and access content on such devices as effectively and as easily as possible. For example, technologies have been developed to automatically adjust the display orientation of media content at 90 degree increments based on a device's position relative to the force of gravity. Many smartphones or computer tablets, which often have a rectangular shape, often utilize technology that allow them to change the orientation of content that is displayed at 90 degree increments based on the smartphone or tablet being held in a particular position. Such smartphones or tablets typically use internal gyroscopes to sense the position of the device relative to the force of gravity and adjust the orientation of the content displayed on the screen of the smartphone or tablet at 90 degree increments only when the position of the smartphone or tablet is changed by more than a predetermined threshold position variable. In addition to using gyroscopes, some technologies utilize accelerometers to measure the rate of acceleration and use the measure rate of acceleration to adjust the orientation of the content by 90 degree increments only.

This patent is subject to a terminal disclaimer.

Adjusting content display orientation on a screen based on user orientation


The scissor sharpening machine includes a honing disc with a curved blade guide and a blade clamp assembly which slides axially along the blade guide. The curvature of the blade guide corresponds to the conventional curvature along the lengths of the blades of a pair of high quality scissors or shears, and assures that they are sharpened properly. The blade clamp assembly includes a series of predetermined stops to set the proper bevel angle during the sharpening process. However, the blade may be rocked about its longitudinal axis to the limit set by the stop, in order to provide a convex curvature to the blade edge if so required. The apparatus may include a cabinet with motor controls and other components, and the blade guide and blade clamp assemblies may be adjusted and repositioned to allow sharpening of either left hand or right hand scissors and shears.

1. Field of the Invention
The present invention relates generally to sharpening tools and equipment. More specifically, the present invention comprises a scissor sharpening machine which retains the conventional curvature along the length of the scissor blade, while simultaneously providing the proper bevel angle or convex edge across the edge of the blade during the sharpening process.
2. Description of the Related Art
High quality scissors and shears are conventionally constructed with the cutting edges of the blades having a large radius curvature along their lengths, in order to provide a more constant included angle between the two blades as they close upon one another during the cutting operation. The radius of curvature used is nearly universally 800 millimeters, or about 31.5 inches. This is particularly true of scissors and shears used in the hair cutting and beauty salon fields, where the scissors used are nearly always quite costly to purchase and of very high quality.
Some of these scissors may cost as much as a few hundred dollars to purchase. Naturally, the owners of such costly scissors are concerned that when they are periodically sharpened, that the sharpening operation be conducted properly. This is not always the case with many conventional sharpening machines and operations. Many of the existing scissor sharpening machines available do not follow the true curvature along the length of the scissor blade, but rather form a series of straight edges with slight angles therebetween. Other sharpening machines have been constructed to follow the 800 mm curvature along the length of the blade, but cannot provide an accurate bevel angle along the blade edge, or form the required convex curvature of the blade edge where such curvature is required.
The present inventor is aware of various scissor sharpening machines and tools which have been developed in the past. One such device is described in Japanese Patent Publication No. 59-115,151 published on Jul. 3, 1984, comprising a manually powered device having a guide roller for the honing stone with the guide roller having a convex curvature along its length in order to follow the curvature of the blade along the length of its cutting edge. While the angle of the scissor blade may be set to form a specific bevel along the blade edge, there is no means to provide a convex edge, as is required for some scissor blades.
Japanese Patent Publication No. 2-036,057 published on Feb. 6, 1990 describes (according to the drawings and English abstract) two sets of rotary grindstones having a variably adjustable angle between the axes of the two sets. This allows the angle of the cutting edge to be adjusted according to that originally manufactured for the blade. However, this device cannot follow the 800 mm (or other) curvature along the length of a scissor blade, nor can it allow the blade to be rotated about its elongate axis during the sharpening operation in order to form a convex curvature along the cutting edge of the blade.
None of the above inventions and patents, taken either singly or in combination, is seen to describe the instant invention as claimed. Thus, a scissor sharpening machine solving the aforementioned problems is desired.


Saturated and unsaturated heteroarylcycloalkylmethyl-amine compounds corresponding to formula I,

Depression is an affectivity disorder with which a depressive syndrome occupies the foreground, depressive meaning associated with depression or of a sad mood. Depressive diseases include unipolar mild depressions, dysthymia, melancholy, bipolar depressions, severe depressions with or without madness and moderate depressions (bipolar disease I, mania and severe depression; bipolar disease II, hypomania and severe depressions; cyclothymic personality disorders, hypomania and mild depressions). Those antidepressants of which the antidepressant action is based on an inhibition of the re-uptake of the monoamines noradrenaline (NA) or serotonin (5-HT) are widely used for therapy of depressions (Pacher, P., Kohegyi, E., Kecskemeti, V., Furst, S., Current Medicinal Chemistry 2001, 8, 89-100). Inhibitors of the re-uptake of monoamines are also used for treatment of anxiety disorders (Goddard, A. W., Coplan, J. D., Gorman, J. M., Charney, D. S., in: Neurobiology of mental illness, Charney, D. S., Nestler, E. J., Bunney, B. S. (eds.), Oxford University Press, New York, 1999, p. 548-563). Anxiety disorders are classified into generalized anxiety disorders, panic attacks, obsessive syndromes, social anxiety disorders, simple phobias, agoraphobias and posttraumatic stress disorders (PTSD).
In addition to the actual antidepressant action, inhibitors of the re-uptake of noradrenaline and serotonin also lead to an independent analgesic action by activating descendant pain inhibition paths at the level of the spinal cord. Inhibitors of the re-uptake of monoamines are employed clinically for monotherapy, and also as an adjuvant for treatment of chronic pain (inter alia neuropathic pain) (Sindrup, in: Yaksh, T. L. et al., Anesthesia. Biological foundations. Philadelphia: Lippincott-Raven, 1997, 987-997). There is still an urgent need for treatment of chronic pain in particular which is appropriate for the patient. Conventional opiates have a good action in the therapy of severe to very severe pain, while their activity on neuropathic pain is unsatisfactory.
The use of inhibitors of the re-uptake of monoamines is limited by side effects, such as e.g. accommodation disorders, serotonin syndrome or QT lengthenings.

Saturated and unsaturated heteroarylcycloalkylmethyl amines as anti-depressants

Abstract: processes for their preparation, pharmaceutical formulations comprising these compounds and the use of saturated and unsaturated heteroarylcycloalkylmethyl-amines for the preparation of pharmaceutical formulations. pharmaceutical formulations and related methods of treatment or prophylaxis of certain condition, especially depression and/or pain, are also disclosed.


According to an aspect, a network system comprises a ring-type network, and a master transmission apparatus. The master transmission apparatus includes blocking unit, conversion unit and transmission unit. The blocking unit prohibits relay of the transmission frame received through a first virtual transmission line and a second virtual transmission line. The conversion unit changes transmission path information included in the transmission frame from the first virtual transmission line to the second virtual transmission line. The transmission unit transmits the transmission frame including the transmission path information changed by the conversion unit.

1. Field of the Invention
Embodiments described herein relate generally to a network system formed as, for example, a ring type.
2. Description of the Related Art
Conventionally, a ring-type network system is used as a network system that periodically transmits data to a plurality of terminal apparatuses. Such a network system is preferably capable of transmitting data that should be periodically transmitted without any loss even when, for example, a failure has occurred on part of the transmission path. In addition, using an apparatus employing Ethernet® for the physical layer and the data link layer as a network transmission apparatus is advantageous for the cost and member availability from the viewpoint of the degree of technical maturity and popularization. If an error has occurred on the apparatus or transmission line in the network system using such a network transmission apparatus, the transmission path is changed to avoid the error.
However, the conventional network system has the following problems. That is, an apparatus for monitoring the presence/absence of an error is necessary. Switching to change the path after the occurrence of an error is time-consuming. To shorten the switching time, the transmission apparatus becomes complex. Data may be lost at the time of switching. In addition, the network system may have physically duplexed transmission lines to improve the reliability of transmission. However, installing a plurality of transmission lines is expensive.


A security monitor apparatus and method using a smart card are provided. The apparatus, which is connected to a system and displays a signal generated by the system, includes an interface that is used to communicate with the smart card containing personal identification information, a detector that detects a signal through the interface to determine insertion of the smart card into the monitor, and a controller that reads the personal identification information via the interface from the smart card and controls turning the display of the monitor on or off, when the insertion of the smart card is detected. The insertion of a smart card containing personal identification information into a monitor apparatus enables immediate screen protection and power savings.

1. Field of the Invention
The present invention relates to computer security, and more particularly, to a security monitor apparatus and method using a smart card that contains personal information.
2. Description of the Related Art
As environmental protection and energy savings are matters of major concern, screen protection and energy conservation are becoming increasingly important considerations in a system that includes a monitor. For instance, a screen saver or Display Power Management Signaling (DPMS) is commonly used in a display apparatus, such as a monitor, in order to reduce power consumption.
A power-saving screen saver for a computer monitor changes the current monitor mode to screen protection mode when user input e.g., through a mouse or keyboard is lacking for a predetermined time. While in a screen protection mode, computer activation requires user input or a predetermined password.
DPMS is an international standard focused on achieving a reduction in monitor power consumption. The standard defines four types of power modes corresponding to Advanced Power Management (APM) employed by the main body of a computer. APM is an API developed by INTEL and MICROSOFT allowing power management to be written into the system BIOS. The APM's four types of power modes are an on-mode, a stand-by mode, a suspend mode, and an off-mode. In the on-mode, vertical and horizontal synchronization signals are input from a computer to a display apparatus via a connector. During the on-mode, a video signal is input to the computer and displayed on a screen, operating at full power. In the stand-by mode, only a vertical synchronization signal is input from the computer to the display apparatus via the connector. Nothing is displayed on the screen due to the blanking of the video signal. The screen operates at partial power usage, resulting in little power consumption. In the suspend mode, only a horizontal synchronization signal is input from the computer to the display apparatus via the connector. Once again, nothing is displayed on the screen due to the blanking of the video signal. The screen operates at minimal power usage, resulting in little power consumption. In the off-mode, the power supply is completely shut off, and the vertical and horizontal synchronization signals are not input to the display apparatus. The video signal is blanked, resulting in maximum power savings.
However, the aforementioned screen saver, DPMS-type monitor protection, and energy saving modes unfortunately are not operational until a lack of user input has been detected after a predetermined time. Therefore, actions for monitor protection cannot be immediately taken. Also, once screen saver mode has been set, the existing screen saver mode requires the input of a predetermined password, creating an inconvenience to the user.

Security monitor apparatus and method using smart card


In one embodiment, a method for optimization using multi-dimensional data includes receiving a problem instance to be solved using an optimization engine. The problem instance is specified in a multi-dimensional format associated with a multidimensional data model that includes multiple data dimensions each including a hierarchy of members. The problem instance includes an objective function, an optimization operator, and one or more constraints. The optimization engine is unable to solve the problem instance including the objective function, the optimization operator, and the one or more constraints in the multi-dimensional format. The method also includes, using a transformation module, transforming the problem instance including the objective function, the optimization operator, and the one or more constraints into a format appropriate for the optimization engine and communicating the transformed problem instance including the objective function, the optimization operator, and the one or more constraints to the optimization engine to be solved.

1. Technical Field of the Invention
This invention relates to the field of optimization, and more particularly to optimization using a multi-dimensional data model.
2. Background
The data associated with a business is often stored in a number of different locations and formats. A business may integrate and manage this data by creating one or more multi-dimensional data models that organize the data hierarchically in one or more data dimensions. The use of such a multi-dimensional data model allows a user to readily and generically store, access, and manipulate the data associated with the business. For example, the user may specify particular data by referring to a particular level in the hierarchy of a dimension or by specifying the intersection of a member in each dimension.

Optimization using a multi-dimensional data model


A wheel hub is provided for use in combination with conventional depressed center grinding wheels. The hub includes a generally cylindrical aperture bushing. A disc shaped flange extends radially from a medial portion of the bushing and terminates at a peripheral lip. The bushing is adapted to extend through a central bore of the wheel so that the lip engages the backing face of the wheel proximate an outermost circumference of the depressed center. A grinding face end of the bushing is flangeable radially outward to engage the front grinding face of the wheel and mechanically capture the wheel between the grinding face end and the flange. The flange, lip and backing face form a cavity into which epoxy resin is placed to chemically bond the hub to the wheel. The combination of mechanical fastening and chemical bonding adequately secures the hub to the wheel, nominally without requiring the flange to extend over the stub. The present invention thus advantageously enables the wheel to be ground nominally to the stub, to provide improved wheel utilization.

1. Field of the Invention
This invention relates to abrasive grinding wheels, and more particularly to an improved wheel hub for mounting a grinding wheel to a grinding apparatus.
2. Background Information
Grinding machines that utilize abrasive grinding wheels mounted therein may be employed to perform many distinct grinding operations. The varied operations have led to the development of a wide variety of grinding wheel shapes and sizes. One type of grinding wheel in particular is the depressed center wheel, characterized by the central portion of the wheel being offset in the axial direction from the wheel periphery. The wheel thus has a concavo-convex stub portion in which a grinding face has a depressed or concave central portion and an opposite backing face has a raised or convex central portion. This design allows a user to perform face grinding operations using the grinding face having the depressed central portion. Often, such operations are performed on metal, masonry or concrete surfaces and the like, using portable grinding machines. Depressed center wheels are classified by the American National Standards Institute (ANSI) as Type 27 and 28 grinding wheels.
The means by which a grinding wheel is secured to the grinding machine spindle is particularly important with depressed center wheels. In general, the mounting means must be capable of holding the wheel perpendicular to the spindle during grinding operations, and must provide support to the wheel to distribute stresses away from the central mounting aperture, where stresses tend to concentrate. The mounting means also must be firmly secured to the abrasive wheel, to prevent any slippage therebetween. In addition, the mounting means for Types 27 and 28 wheels have generally been provided with extra support to the wheel periphery, as well as to the central portion of the backing (non-grinding) face of the wheel to resist the additional stresses imposed by face grinding operations.
To satisfy these requirements, it is common to provide Type 27 and 28 wheels with a hub having a flange that extends over the central raised portion, the concavo-convex stub portion, and onto and in contact with the peripheral portion of the wheel, to resist side pressure or otherwise uneven force applied to the grinding face of the wheel. The opposite face of the wheel is provided with a flange contained completely within the depressed area thereof.
Although such hub construction may produce satisfactory results in many instances, it is not without drawbacks. In particular, extension of the flange beyond the raised stub portion of the backing face tends to limit the useful life of the wheel. In this regard, the wheel must be replaced before it is ground down to the diameter of the backing flange to avoid potentially damaging contact between the backing flange and the workpiece. Accordingly, grinding wheels that utilize this hub construction tend to be discarded with a substantial portion of valuable and otherwise usable abrasive remaining thereon. Such relative under-utilization of the wheel tends to add undesirable expense to grinding operations in terms of both wheel cost and labor costs associated with the frequency of wheel removal and installation.
A need thus exists for an improved grinding wheel hub that overcomes the drawbacks of the prior art.


A method and apparatus are provided whereby a person not familiar with programming or programming languages can create a wizard to interface between an application program and the user to guide the user through the interaction with the application program. This allows non-programmers to create intuitive and sensible user interfaces without the requirement of learning how to write software.

With the use of personal computers becoming pervasive throughout society, a need has arisen to allow those who have not been specifically trained in computers to enter, develop and maintain information without requiring a significant amount of training. Many solutions have been proposed to this problem.
Help systems such as balloon help, which will create a bubble with context sensitive helpful information when a particular key sequence is entered, and hover help, which also provide pop-up, context sensitive help when the cursor remains over an active field for a certain period of time became popular to assist an untrained or novice user in performing such tasks. While these help systems are a significant improvement over the legacy methods of providing assistance such as providing hard copy documentation or providing a link to online books, they still can be voluminous and do not guide the user through the task which they are attempting to complete.
Another approach to solving the problem of assisting untrained users is the tutorial approach. Before a user attempts to complete an unfamiliar task, they are asked to complete a tutorial which will take them through the steps which they are about to perform. This allows the user to actually see what the panels are and understand a sample of the task to be performed, but it does not assist them when they become confused part way through their execution of the task.
There are several additional solutions to the problem of designing easy to use interfaces to guide users through application programs, three of them are coaches, cue cards and agents.
Coaches are programs that guide a user through an existing interface, teaching the user how to do a task with a particular product. A coach teaches the user how to use a products interface, guiding you from one step to the next and protecting you from making mistakes. An example of this is that a coach might disable every menu item except one, drawing a box around the one enabled menu item that the user should chose. Coaches are different than cue cards in that coaches are more than information. They provide application logic to guide the user through the task.
Cue cards are small help panels that appear along side an existing interface, teaching the user how to do a task with a particular product. Cue cards differ from coaches in that they are informational only; they tell the user what to do but don't guide or restrict the user in any way. It leaves the responsibility to the user to read the information in the cue card and apply that information to the task.
Agents, in the present sense, are autonomous pieces of code that perform a task for the user. Agents typically work in the background and have very little user interface. They are designed to do something without interaction from the user and are typically executed automatically when a predetermined event occurs or a predetermined condition becomes true.
The newest approach to this problem is the creation of wizards. Wizards are interfaces designed to do tasks for users. They are different from the prior art in that they are not necessarily meant to teach or instruct. Wizards are meant to simplify the user interface. Wizards reside between the user and an application program and guide the user through tasks. Examples of this are, for instance, a wizard that allows a form to have pop-up options for each of the fields to be entered. Another example is the Rapid Test product from Mercury Interactive Corp. which uses a plan wizard, a script wizard and a cycle wizard to provide a self-guided visual interface for specifying test requirements and test cases. Wizards were first divulged in a patent assigned to Microsoft Corporation entitled `Method and System for Controlling the Execution of an Application Program`, U.S. Pat. No. 5,301,326.
Wizards are traditionally written in programming languages such as C or C++. Since the wizards are written in programming languages, they require programmers to write them. There is a need in the industry for an intuitive means of creating a wizard without requiring a programmer, a means for creating a wizard that is easy to understand so that a person familiar with the user interface of the application program can easily write a wizard for executing that application program. This would significantly reduce the training costs for those who create user front-ends for application programs.

Non-programming method and apparatus for creating wizards with a script

International Business Machines Corporation


This invention pertains to therapeutic antibacterial/antifungal-wound healing compositions comprising a therapeutically effective amount of antibacterial agents and/or antifungal agents and/or wound healing composition alone. In one embodiment, the wound healing composition comprises (a) zinc oxide; (b) calcium channel blocker, and (c) fat-soluble vitamins admixed with antibacterial and antifungal agents. The therapeutic antibacterial/antifungal-wound healing compositions may be utilized in a wide variety of pharmaceutical products and administered orally or topically.

Wound Healing
Wounds are internal or external bodily injuries or lesions caused by physical means, such as mechanical, chemical, viral, bacterial, fungal and other pathogenic organisms, or thermal means, which disrupt the normal continuity of tissue structure. Such bodily injuries include contusions, wounds in which the skin is unbroken, incisions, wounds in which the skin is broken cutting instrument, and lacerations, wounds in which the skin is broken by a dull or, blunt instrument. Wounds may be caused by accident, surgery, pathological organisms, or by surgical procedures. Patients who suffer wounds could benefit from an antibacterial/antifungal-wound healing composition.
Wound healing consists of a series of processes whereby injured tissue is repaired, specialized tissue is regenerated, and new tissue is reorganized. Wound healing consists of three major phases: a) an inflammation stage (0-3 days), b) proliferation stage (3-12 days), and c) a remodeling phase (3 days to 6 months).
During the inflammation phase, platelet aggregation and clotting from a matrix which traps the plasma proteins and blood cells to induce the influx of various types of cells. During the cellular proliferation phase, new connective or granulation tissue and blood vessels are formed. During the remodeling phase, granulation tissue is replaced by a network of collagen and elastin fibers leading to the formation of scar tissue.
When cells are injured or killed as the result of a wound, a wound healing step is desirable to resuscitate the injured cells and produce new cells to replace the dead cells. The healing process requires the reversal of cytotoxicity, the suppression of inflammation, and the stimulation of cellular viability and proliferation. Wounds require low levels of oxygen in the initial stages of healing to suppress the oxidative damage and higher levels of oxygen in the later stages of healing to promote collagen formation by fibroblasts.
Mammalian cells are continuously exposed to activate oxygen species such as superoxide (O.sub.2—), hydrogen peroxide (H.sub.2.0.sub.2.), hydroxyl radical (OH), and singlet oxygen (.sup.1O.sub.2.). In vivo, these reactive oxygen intermediates are generated by cells in response to aerobic metabolism, catabolism of drugs and other xenobitics, ultraviolet and x-ray radiation, and the respiratory burst of phagocytic cells (such as white blood cells) to kill invading bacteria such as those introduced through wounds. Hydrogen peroxide, for example, is produced during respiration of most living organisms especially by stressed and injured cells.
These active oxygen species can injure cells. An important example of such damage is lipid peroxidation which involves the oxidative degradation of unsaturated lipids. Lipid peroxidation is highly detrimental to membrane structure and function and can cause numerous cytopathological effects. Cells defend against lipid peroxidation by producing radical scavengers such as superoxide dismutase, catalase, and peroxidase. Injured cells have a decreased ability to produce radical scavengers. Excess hydrogen peroxide can react with DNA to cause backbone breakage, produce mutations, and alter and liberate bases. Hydrogen peroxide can also react with pyrimidines to open the 5,6-double bond, which reaction inhibits the ability of pyrimidines to hydrogen bond to complementary bases, Hallaender, et al. (1971). Such oxidative biochemical injury can result in the loss of cellular membrane integrity, reduced enzyme activity, changes in transport kinetics, changes in membrane lipid content and leakage of potassium ions, amino acids and other cellular material.
Antioxidants have been shown to inhibit damage associated with active oxygen species. For example, pyruvate and other Alpha-keotacids have been reported to react rapidly and stoichiometrically with hydrogen peroxide to protect cells from cyt9olytic effects, O'Donnell=Tormey et al., J. Exp. Med., 165, pp. 500-514 (1987).

Method of healing skin wounds in mammals and a composition therefor