Supported stereospecific catalysts and processes for the stereotactic propagation of a polymer chain derived from ethylenically unsaturated monomers which contain three or more carbon atoms or which are substituted vinyl compounds, specifically alpha olefins, particularly the polymerization of propylene to produce syndiotactic or isotactic polypropylene. The supported metallocene catalyst comprises a stereospecific metallocene catalyst and a co-catalyst component comprising at least one of an alkyl alumoxane and an alkylaluminum compound. Both the metallocene catalyst and the co-catalyst are supported on a particulate silica support comprising silica particles having an average particle size of 5–40 microns and an average effective pore size of 50–200 angstroms. The silica support further has a differential pore size distribution of a pore volume of at least 0.01 cm3/g. within a range having a maximum pore width of no more than 300 angstroms. The metallocene has a retention factor on this support of at least 90 wt. % after aging in tri-isobutylaluminum at a temperature of 25° C. for a period of 12 hours.

Numerous catalyst systems for use in the polymerization of ethylenically unsaturated monomers are based upon metallocenes. Metallocenes can be characterized generally as coordination compounds incorporating one or more cyclopentadienyl groups (which may be substituted or unsubstituted) coordinated with a transition metal. Various types of metallocenes are known in the art. They include bicyclic coordination compounds of the general formula:(Cp)2MeQn  (1)characterized by the isospecific metallocenes as described below and dicyclopentadienyl compounds of the general formula:Cp Cp′MeQn  (2)characterized by the syndiospecific metallocenes described below. In the aforementioned formulas the Me denotes a transition metal and Cp and Cp′ each denote a cyclopentadienyl group which can be either substituted or unsubstituted with Cp′ being different from Cp, Q is an alkyl or other hydrocarbyl group or a halogen and n is a number within the range of 1–3. The cyclopentadienyl groups are in a stereorigid relationship normally provided by a bridged structure between the metallocene rings (not shown in Formulas (1) and (2) above) although stereorigidity can be provided through substituent groups which result in steric hindrance, as described, for example, in U.S. Pat. No. 5,243,002 to Razavi. Also, while bridged metallocenes normally incorporate two cyclopentadienyl groups (or substituted cyclopentadienyl groups), bridged metallocenes incorporating a single cyclopentadienyl group which is bridged to a heteroatom aromatic group (both being coordinated with a transition metal) are also known in the art. For example, U.S. Pat. No. 5,026,798 to Canich discloses dimethylsilyl-bridged cyclopentadienyl—anilino or other heteroatom ligand structures with coordination to the transition metal being provided through the nitrogen atom of the anilino group.
As noted previously, isospecific and syndiospecific metallocene catalysts are useful in the polymerization of stereospecific propagation of monomers. Stereospecific structural relationships of syndiotacticity and isotacticity may be involved in the formation of stereoregular polymers from various monomers. Stereospecific propagation may be applied in the polymerization of ethylenically unsaturated monomers such as C3+ alpha olefins, 1-dienes such as 1,3-butadiene, substituted vinyl compounds such as vinyl aromatics, e.g, styrene or vinyl chloride, vinyl chloride, vinyl ethers such as alkyl vinyl ethers, e.g., isobutyl vinyl ether, or even aryl vinyl ethers. Stereospecific polymer propagation is probably of most significance in the production of polypropylene of isotactic or syndiotactic structure.
The structure of isotactic polypropylene can be described as one having the methyl groups attached to the tertiary carbon atoms of successive monomeric units falling on the same side of a hypothetical plane through the main chain of the polymer, e.g., the methyl groups are all above or below the plane. Using the Fisher projection formula, the stereochemical sequence of isotactic polypropylene is described as follows:
In structure (3) each vertical segment indicates a methyl group on the same side of the polymer backbone. Another way of describing the structure is through the use of NMR. Bovey's NMR nomenclature for an isotactic pentad as shown above is . . . mmmm . . . with each "m" representing a "meso" dyad, or successive pairs of methyl groups on the same said of the plane of the polymer chain. As is known in the art, any deviation or inversion in the structure of the chain lowers the degree of isotacticity and crystallinity of the polymer.
In contrast to the isotactic structure, syndiotactic propylene polymers are those in which the methyl groups attached to the tertiary carbon atoms of successive monomeric units in the chain lie on alternate sides of the plane of the polymer. Syndiotactic polypropylene in using the Fisher projection formula can be indicated by racemic dyads with the syndiotactic pentad rrrr shown as follows:
Here, the vertical segments again indicate methyl groups in the case of syndiotactic polypropylene, or other terminal groups, e.g. chloride, in the case of syndiotactic polyvinyl chloride, or phenyl groups in the case of syndiotactic polystyrene.
Syndiotactic polymers are semi-crystalline and, like the isotactic polymers, are insoluble in xylene. This crystallinity distinguishes both syndiotactic and isotactic polymers from an atactic polymer, which is non-crystalline and highly soluble in xylene. An atactic polymer exhibits no regular order of repeating unit configurations in the polymer chain and forms essentially a waxy product.
Yet another polymer configuration which has both isotactic and atactic features is exemplified by hemi-isotactic polypropylene. Hemi-isotactic polypropylene is characterized by every other methyl group being on the same side of the polymer with the remaining methyl groups randomly being on the same side or on the opposite side of the polymer backbone. Hemi-isotactic polypropylene can be characterized by the following Fisher projection formula in which, as indicated by the broken lines, alternate methyl groups have random steric configurations.
Thus, as shown in structure (5), the methyl groups indicated by the solid lines are in a mesa relationship with one another, with the alternating methyl groups indicated by the broken lines being randomly configured. Hemi-isotactic polypropylene, while having a semi-ordered structure, is primarily non-crystalline because of the disorder of the alternate methene units.
In most cases, the preferred polymer configuration will be a predominantly isotactic or syndiotactic polymer with very little atactic polymer. Catalysts that produce isotactic polyolefins are disclosed in U.S. Pat. Nos. 4,794,096 and 4,975,403. These patents disclose chiral, stereorigid metallocene catalysts that polymerize olefins to form isotactic polymers and are especially useful in the polymerization of highly isotactic polypropylene. As disclosed, for example, in the aforementioned U.S. Pat. No. 4,794,096, stereorigidity in a metallocene ligand is imparted by means of a structural bridge extending between cyclopentadienyl groups. Specifically disclosed in this patent are stereoregular hafnium metallocenes which may be characterized by the following formula:R″(C5(R′)4)2 HfQp  (6)In formula (7), (C5(R′)4) is a cyclopentadienyl or substituted cyclopentadienyl group, R′ is independently hydrogen or a hydrocarbyl radical having 1–20 carbon atoms, and R″ is a structural bridge extending between the cyclopentadienyl rings. Q is a halogen or a hydrocarbon radical, such as an alkyl, aryl, alkenyl, alkylaryl, or arylalkyl, having 1–20 carbon atoms and p is 2.
Catalysts that produce syndiotactic polypropylene or other syndiotactic polyolefins and methods for the preparation of such catalysts are disclosed in the aforementioned U.S. Pat. No. 4,892,851. These catalysts are also bridged stereorigid metallocene catalysts, but in this case, the catalysts have a structural bridge extending between dissimilar cyclopentadienyl groups and may be characterized by the formula:R″(CpRn) (CpR′m)MeQk  (7)In formula (7), Cp represents a cyclopentadienyl or substituted cyclopentadienyl ring, and R and R′ represent hydrocarbyl radicals having 1–20 carbon atoms. R″ is a structural bridge between the rings imparting stereorigidity to the catalyst. Me represents a transition metal, and Q a hydrocarbyl radical or halogen. R′m is selected so that (CpR′m) is a sterically different substituted cyclopentadienyl ring that (CpRn). In formula (8) n varies from 0–4 (0 designating no hydrocarbyl groups, i.e., an unsubstituted cyclopentadienyl ring), m varies from 1–4, and k is from 0–3. The sterically different cyclopentadienyl rings produce a predominantly syndiotactic polymer rather than an isotactic polymer. Like their isospecific counterparts, the syndiospecific metallocene disclosed in the '851 patent are used in combination with aluminum co-catalysts. The aluminum co-catalyst may take the form of an alumoxane and trialkyl aluminum or mixtures thereof. Specifically disclosed in the '851 patent is methylalumoxane and triethylaluminum (TEAL).
Specifically disclosed in U.S. Pat. No. 4,892,851 are bridged metallocene ligands having a dissimilar cyclopentadienyl group resulting from the reaction of 6,6-dimethyl fulvene with a substituted cyclopentadiene fluorene to produce a ligand characterized by an isopropylidene bridge structure. Preferably, this ligand structure is characterized as having bilateral symmetry such as indicated by the isopropylidene(cyclopentadienyl fluorenyl) structure as shown below:
As indicated by formula (8), the bilateral symmetry of the ligand structure is indicated by the balanced orientation about the broken line representing a plane of symmetry extending generally through the bridge structure and the transition metal atom.
The foregoing structure may be contrasted with a metallocene which lacks bilateral symmetry which can be used in the production of hemi-isotactic polypropylene as described in the U.S. Pat. No. 5,036,034 to Ewen. An example of a compound indicating a lack of bilateral symmetry is isopropylidene (3-methyl cyclopentadienyl-1 fluorenyl) zirconium dichloride having the ligand structure shown by the following formula:
As explained in more detail in the aforementioned Ewen '034 patent, the lack of bilateral symmetry is indicated by the right side of the structure relative to the broken line being different from the left side because of the methyl group substituted at the distal position on the cyclopentadienyl group.
The various metallocene structures as described above can be used either as so-called "neutral metallocenes" in which case an alumoxane, such as methylalumoxane, is used as a co-catalyst, or they can be employed as so-called "cationic metallocenes" which incorporate a stable non-coordinating anion and normally do not require the use of an alumoxane. Syndiospecific cationic metallocenes are disclosed for example in U.S. Pat. No. 5,243,002 to Razavi. As disclosed there, the metallocene cation is characterized by the cationic metallocene ligand having sterically dissimilar ring structures which are joined to a positively-charged coordinating transition metal atom. The metallocene cation is associated with a stable non-coordinating counter-anion. Co-catalysts, such as disclosed in the aforementioned Ewen '851 and Ewen '034 patents, may also be employed with cationic metallocenes such as disclosed in the Razavi '002 patent. As disclosed in Razavi, alumoxanes such as methylalumoxanes normally will not be employed. However, alkyl aluminums, such as TEAL described previously, and other co-catalysts, such as trimethylaluminum, trialkoxy aluminums, dialkylaluminum halides, or alkylaluminum dihalides, may be employed as disclosed in the Razavi '002 patent.
The aforementioned Razavi '002 patent also discloses the establishment of a stereorigid relationship imparted by a sterically hindered relationship between substituted cyclopentadienyl rings which prevent rotation of the ring structures about their coordination axis. Alternatively, the cyclopentadienyl groups may be highly substituted such that a relatively low kinetic energy state is induced by the substituents in order to prevent rotation rings about their coordination axis at the temperature of the catalyst. Such cationic metallocenes also may, of course, like their neutral counterparts, be characterized by a stereorigid relationship imparted by means of a structural bridge between the cyclopentadienyl groups.
U.S. Pat. No. 5,225,500 to Elder et al. discloses stereorigid cationic metallocenes, including, inter alia, bridged metallocene catalysts useful for the production of syndiotactic polymers. The bridged metallocene catalysts of U.S. Pat. No. 5,225,500 comprise an unbalanced metallocene cation and a stable, non-coordinating counteranion for the metallocene cation. The metallocene cation is characterized by a cationic metallocene ligand having sterically dissimilar ring structures joined to a positively charged coordinating transition metal atom. The dissimilar cyclopentadienyl rings, at least one of which is substituted, are both in a stereorigid relationship relative to the coordinating metallocene of the metal atom catalyst, and, as noted previously, the stereorigid relationship may be imparted by means of a structural bridge between the dissimilar cyclopentadienyl rings.
While metallocene catalysts are often used as homogeneous catalysts, it is also known in the art to provide supported metallocene catalysts. As disclosed in U.S. Pat. Nos. 4,701,432 and 4,808,561, both to Welborn, a metallocene catalyst component may be employed in the form of a supported catalyst. As described in the Welborn '432 patent, the support may be any support such as talc, an inorganic oxide, or a resinous support material such as a polyolefin. Specific inorganic oxides include silica and alumina, used alone or in combination with other inorganic oxides such as magnesia, titania, zirconia and the like. Non-metallocene transition metal compounds, such as titanium tetrachloride, are also incorporated into the supported catalyst component. The inorganic oxides used as support are characterized as having an average particle size ranging from 30–600 microns, preferably 30–100 microns, a surface area of 50–1,000 m2/g, preferably 100–400 m2/g, a pore volume of 0.5–3.5 cm3/g, preferably about 0.5–2 cm3/g. Generally, the particle size, surface area, pore volume, and number of surface hydroxyl groups are said to be not critical to the Welborn procedure. Specifically disclosed in Welborn is a catalyst in which bis(cyclopentadienyl)zirconium dichloride (unbridged metallocene) is supported on a high surface area silica dehydrated in dry nitrogen at 600° C. and characterized as Davison D-952. The Welborn '561 patent discloses a heterogeneous catalyst which is formed by the reaction of a metallocene and an alumoxane in combination with the support material. The support in Welborn '561 is described similarly as the support in the Welborn '432 patent. A catalyst system embodying both a homogeneous metallocene component and a heterogeneous component, which may be a "conventional" supported Ziegler-Natta catalyst, e.g. a supported titanium tetrachloride, is disclosed in U.S. Pat. No. 5,242,876 to Shamshoum et al. Various other catalyst systems involving supported metallocene catalysts are disclosed in U.S. Pat. Nos. 5,308,811 to Suga et al. and 5,444,134 to Matsumoto. In both patents, the supports are characterized as various high surface area inorganic oxides or clay-like materials. In the patent to Suga et al., the support materials are characterized as clay minerals, ion-exchanged layered compounds, diatomaceous earth, silicates or zeolites. As explained in Suga, the high surface area support materials should have volumes of pores having radii of at least 20 angstroms. Specifically disclosed and preferred in Suga are clay and clay minerals such as montmorillonite. The catalyst components in Suga are prepared by mixing the support material, the metallocene, and an organoaluminum compound such as triethylaluminum, trirethylaluminum, various alkylaluminum chlorides, alkoxides, or hydrides or an alumoxane such as methylalumoxane, ethylalumoxane, or the like. The three components may be mixed together in any order, or they may be simultaneously contacted. The patent to Matsumoto similarly discloses a supported catalyst in which the support may be provided by inorganic oxide carriers such as SiO2, Al2O3, MgO, ZrO2, TiO2, Fe2O3, B2O2, CaO, ZnO, BaO, ThO2 and mixtures thereof, such as silica alumina, zeolite, ferrite, and glass fibers. Other carriers include MgCl2, Mg(0-Et)2, and polymers such as polystyrene, polyethylene, polypropylene, substituted polystyrene and polyarylate, starches, and carbon. The carrier has a surface area of 1–1,000 m2/g, preferably 50–500 m2/g, a pore volume of 0.1–5 cm3/g, preferably 0.3–3 cm3/g, and a particle size of 20–100 microns.
Of the various inorganic oxides used as supports, silica, in one form or another, is widely disclosed as a support material for metallocene catalysts. Silica, characterized as Davison D-948 or Davison D-952, appears as a conventional metallocene support. For example, U.S. Pat. No. 5,466,649 to Jejelowa discloses the use of dehydrated Davison D-948 silica as a support for various unbridged metallocenes used in conjunction with supported co-catalysts. U.S. Pat. No. 5,498,581 to Welch et al. discloses silica for use as a support for either bridged or unbridged metallocenes in which the silica is treated with carbon monoxide, water, and hydroxyl groups to inactive species. Specifically disclosed is the silica, Davison D-948, having an average particle size of 50 microns. Other silica-based supports are disclosed in U.S. Pat. Nos. 5,281,679 to Jejelowa, 5,238,892 to Chang, and 5,399,636 to Alt. The Chang and Jejelowa patent disclose the use of a silica support identified as Davison D-948, which is characterized as an amorphous silica gel containing about 9.7 wt. % water. As described in the Chang and Jejelowa patents, alumoxane is formed directly on the surface of the silica gel by direct reaction of an alkyl aluminum with silica gel which is undehydrated so as to ensure the conversion of the quantity of the alkyl aluminum to an alumoxane that has a high degree of oligomerization. The water-impregnated gel is characterized as having a surface range of 10–700 m2/g, a pore volume of about 0.5–3 cm3/g, and an absorbed water content of from about 10–50 wt. % in the case of the Jejelowa patent, and about 6–20 wt. % in the case of the Chang patent. The average particle size for the silica is described in Chang to be from 0.3–100 microns and in Jejelowa from about 10–100 microns. After the alumoxane silica gel component has been formed, the metallocene may be added to the wet slurry.
Other supported catalyst systems are disclosed in U.S. Pat. No. 6,166,153 to Shamshoum et al. Here, a silica support such as described above is pretreated with an alumoxane, such as methylalumoxane, followed by addition of a syndiospecific metallocene on the MAO-treated silica. The supported metallocene is used in conjunction with an organo-aluminum co-catalyst such as a monoalkyl or dialkyl aluminum halides as described previously, including trialkylaluminums such as trimethylaluminum, triethylaluminum or tri-isobutyl aluminum (TIBAL). In the supported catalyst disclosed in EP 819706, the silica support is a high surface area, small pore size silica which is first dried, slurried in a non-polar solvent, and then contacted with methylalumoxane in a solvent. The metallocene was then dissolved in a non-polar solvent, particularly the same as used as the solvent for the alumoxane. The solid metallocene supported on the alumoxane-treated silica is then recovered from the solvent, dried, and then incorporated into carrier liquid such as mineral oil. The Shamshoum European application also discloses a pre-polymerization step which can be used to decrease the aging time of the catalyst in the trialkyl aluminum or other aluminum co-catalyst.

Supported metallocene catalysts and their use in producing stereospecific polymers


Disclosed herein are an anti-biofilm composition and a method to inhibit or prevent cell adhesion and/or biofilm formation by a microorganism, in which use of 1,2,3,4,6-penta-O-galloyl-D-glucopyranose (PGG) is involved therein.

1. Field of the Invention
This invention primarily relates to a method to prevent or inhibit cell adhesion and/or biofilm formation by a microorganism, in which use of 1,2,3,4,6-penta-O-galloyl-D-glucopyranose (PGG) is involved therein.
2. Description of the Related Art
Nearly 99% of the microorganisms living in this planet thrive in microbial communities known as biofilms. They are formed by adhesion of cells to surfaces through an exopolymeric matrix. This matrix is important both in the formation and structure of the biofilm, and also to the protection of the cells since it may prevent the access of antimicrobials and xenobiotics to the cells inside the biofilm and confer protection against environmental stresses such as UV radiation, pH shifts, osmotic shock and desiccation. Fossilised biofilms of up to 3.5 billion years are among the oldest records of life on Earth. Biofilms are the planet's most successful form of colonialism as they live on soils, sediments, mineral, plant and animal surfaces, even under extreme environments, from glaciers to hot vents. Biofilms are even able to thrive in highly irradiated areas of nuclear power plants.
Cell aggregation is advantageous and required in several processes, namely in biological wastewater treatment and bioremediation systems. However, they constitute a serious problem in many industrial processes (e.g., paper, food, cosmetic and pharmaceutical industries) because they can cause corrosion and limit mass and heat transfer in pipes and tubes and mainly in water distribution systems and healthcare environments as they are a source of microbial infections. Furthermore, biofilms can also bioaccumulate metals and toxic compounds. Biofilms can contaminate contact lenses, catheters, endotracheal tubes, mechanical cardiac valves, prosthetic joints, surgical sutures, etc. Biofilms can result in surgical site infections, and cells in biofilms have higher resistance to antibiotics and biocides than planktonic cells and gene transfer is possible horizontally, which improves the exchange of genes between resistant and non-resistant strains.
Bacterial strains that do not produce exopolymeric substances (EPS) present lower adherent abilities than slime-producing strains. EPS is particularly valuable after the initial phase of adhesion in organisms, conferring protection against phagocytosis, interference with the cellular immune response and reduction of antibiotic potency. In fact, the host immune system is, in general, capable of rapidly killing non-adherent bacteria. The slow growth rate observed in biofilms and/or transport limitations of nutrients, metabolites and oxygen between the surface and the interior of the biofilm could be responsible for an increased antibiotic resistance over planktonic cells. Furthermore, the EPS matrix acts as an anchor, securing the cells and preventing their detachment under flow conditions, although detachment of cells may also be an important process for propagation and formation of new colonies.
The above is an excerpt from a review article, namely Carla C. C. R. de Carvalho (2007), Recent Patents on Biotechnology, 1, 49-57, which provides a thorough discussion of a number of scientific literatures and patent documents in relation to the prevention and control of biofilm proliferation in medical devices and water supply systems, as well as the development on anti-microbial surfaces, detergents and biocides. This review article and the references referred to therein are incorporated herein by reference in their entirety.
Biofilms can colonize on almost all surfaces, from glass to steel, and from cellulose to silicone, which are the main materials used to produce medical devices. Bacterial biofilms are frequently found in clinical and medical environments, and according to statistics, 65 percent of bacterial infections are associated with biofilms formed by bacteria. Many clinically important pathogens, such as Staphylococcus aureus, Pseudomonas aeruginosa, Streptococci, etc., have the ability to form biofilm. Inasmuch as bacteria living in biofilm have higher resistance to the attack of the host immune system and the toxic effect of antibiotics, it becomes difficult to treat infections of this kind. In particular, it is extremely hard to eradicate a bacterial biofilm once formed in an implanted medical device such as a cardiac catheter, a urethral catheter, a prosthetic joint, an artificial heart valve, an artificial blood vessel, etc., and replacing the biofilm-contaminated device with a new one is imperative, which leads to a year-by-year rise in medical expenses.
Amongst pathogens that cause nosocomial infections, Staphylococcus aureus is of great concern. Staphylococcus aureus forms biofilms on medical devices and causes pneumonia, meningitis, endocarditis, osteomyelitis and septicemia (Friedrich Götz (2002), Mol. Microbiol., 43 (6):1367-1378). Formation of biofilm by S. aureus is closely associated with the synthesis of an extracellular polysaccharide substance (EPS), namely polysaccharide intercellular adhesion (PIA), which is a β-1,6-linked N-acetyl (succinyl) glucosamine polymer synthesized by enzymes encoded by an ica operon (Sarah E. Cramton et al. (1999), Infect. Immun., 67 (10):5427-5433). In addition, the proteins of S. aureus that contribute to biofilm formation include fibronectin-binding proteins A and B (Eoghan O'Neill et al. (2009), J. Med. Microbiol., 58:399-402), collagen-binding protein (Patrick Ymele-Leki and Julia M. Ross (2007), Appl. Environ. Microbiol., 73 (6):1834-1841), SasG surface protein (Rebecca M. Corrigan et al. (2007), Microbiology, 153:2435-2446), and the biofilm associated protein bap (M. Ángeles Tormo et al. (2005), Microbiology, 151:2465-2475). Meanwhile, the pertinacious form of biofilm formation is inhibited by extracellular proteases produced by the organism (Elena Stary et al. (2010), Appl. Environ. Microbiol., 76 (3):680-687). These reports illustrate that factors on the bacterial surface facilitate attachment of bacteria and establishment of multilayered cell clusters on a solid surface, which are crucial to biofilm formation (Friedrich Götz (2002), supra). Owing to high resistance to antibiotics of biofilm-imbedded staphylococci (Kim Lewis (2001), Antimicrob, Agents Chemother., 45 (4):999-1007), biofilm-associated infections are extremely difficult to treat, necessitating the development of drugs that prevent and destroy biofilm.
In the last two decades, numerous investigators specializing in the research and development of anti-biofilm drugs and anti-biofilm medical instruments have identified several substances useful for preventing the formation or removal of staphylococcal biofilms. For example, lysostaphin, which is a peptidoglycan-degrading enzyme, prevents staphylococcal biofilm formation (Julie A. Wu et al. (2003), Antimicrob. Agents Chemother., 47 (11):3407-3414); N-acetylcysteine (NAC), which is a clinical drug, reduces EPS production, subsequently inhibiting biofilm formation (C. Pérez-Giraldo et al. (1997), J. Antimicrob. Chemother., 39:643-646); iodoacetamide (IDA) and N-ethyl maleimide (NEM), which are inhibitors of N-acetyl-D-glucosamine-1-phosphate acetyltransferase that catalyzes the biosynthesis of UDP-N-acetylglucosamine, i.e., a precursor of PIA, also inhibit biofilm formation (Euan Burton et al. (2006), Antimicrob. Agents Chemother., 50:1835-1840); and dispersin B, which hydrolyzes β-1,6-N-acetyl-glucosamine, disperses mature biofilm and is an agent potentially useful in anti-biofilm therapy (Yoshikane Itoh et al. (2005), J. Bacteriol., 187 (1):382-7). In addition, there have been researches investigating the use of different clinical antibiotics in combination to inhibit bacterial biofilm formation (Euan Burton et al. (2006), supra; and Saima Aslam et al. (2007), Antimicrob. Agents Chemother., 51 (4):1556-8).
While the target drugs or candidate drugs studied in the earlier reports are considered to have potential as an anti-biofilm agent (Saima Aslam et al. (2007), supra; Nicholas Beckloff et al. (2007), Antimicrob. Agents Chemother., 51 (11):4125-32; Ross P. Carlson et al. (2008), J. Biomater. Sci. Polymer Ed., 19 (8): 1035-1046; I. Raad et al. (2008), J. Antimicrob. Chemother., 62:746-650; Prabha Ramritu et al. (2008), Am. J. Infect. Control, 36 (2) 104-117; and Guo-Xian Wei et al. (2006), J. Antimicrob. Chemother., 57:1100-9), the greatest concern for enzymatic drugs to be used in clinic is the extremely high cost thereof, and drugs exhibiting bacterial-killing effect(s) are liable to induce resistant strains. Furthermore, the clinical efficacies of these target drugs or candidate drugs as studied in the above reports have yet to be verified.
There also exist numerous published patent documents disclosing a diversity of approaches to inhibit or prevent biofilm formation on various surfaces, including, e.g., WO 2008/132718 A2, WO 2010/072257 A1, WO 2010/112848 A2, WO 2010/144686 A1, U.S. Pat. No. 7,691,418 B2, US 20100152101 A1 (corresponding to TW200913996A), US 20090192192 A1, US 20090255536 A1, US 20090304621 A1, US 20100087769 A1, US 20100285084 A1, US 20100298208 A1, US 20110008402 A1, US 20110076312 A1, US 201100763332 A1, and US 20110086101 A1. These patent documents are incorporated herein by reference in their entirety.
In order to exploit anti-biofilm agents that are effective at low concentrations, non-toxic and biodegradable, health and environment friendly, and cost-saving, the applicants screened forty eight compounds isolated from plants commonly used in Chinese medicine, and surprisingly found that 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (β-PGG), either in a solution or coated on solid surfaces, did not inhibit the growth of tested microorganisms, yet prevented biofilm formation on solid surfaces. The α-anomer of β-PGG was also found to exhibit similar anti-biofilm effect. It is contemplated that PGG, either in the β-form or the α-form or a mixture of the α- and β-forms, may act as a potent anti-biofilm agent.

Inhibition of biofilm formation by 1,2,3,4,6-penta-O-galloyl-D-glucopyranose


Embodiments of variable structural members for a telecommunications equipment cabinet are presented herein. The variable structural members include an embedding surface configured to removably receive a structural insert to modify the characteristics of the equipment cabinet. A variety of removable structural inserts may be embedded in the embedding surface. The structural inserts may be arranged and rearranged to modify the structural characteristics of a cabinet such as at the time of manufacture and/or by a technician or user “in the field”.

Equipment within a telecommunications infrastructure may be maintained in variety of equipment housings. Traditionally, equipment housings have been designed with fixed dimensions for particular equipment, e.g., equipment of a particular type and/or having specific width and depth. Further mountings for equipment traditionally are incorporated into the structure of the equipment housings, e.g., mounting holes drilled into the supporting structure for equipment housing. In other words, equipment housings traditionally are designed to be static and are not intended to be modified after manufacture. However, new and different arrangements of telecommunications equipment are often required for a variety of reasons such as to handle increased demands for service, due to technology changes, to accommodate new or different equipment, and so forth. Updating static equipment housings to accommodate new equipment and/or equipment arrangements may be time consuming, costly, frustrating and even impossible.
Accordingly traditional techniques produce telecommunication housings which are inflexible, may be difficult or impossible to modify to accommodate new equipment and/or new equipment configurations, and may be more costly to manufacture or update.


A computing system including network elements arranged in at least one group. A plurality of the network elements are designated as spines and another plurality are designated as leaves, the spines and leaves are interconnected in a bipartite topology, and at least some of the spines and leaves are configured to: receive in a first leaf, from a source node, packets destined to a destination node via a second leaf, forward the packets via a first link to a first spine and to the second leaf via a second link, in response to detecting that the second link has failed, apply a detour path from the first leaf to the second leaf, including a detour link in a spine-to-leaf direction and another detour link a leaf-to-spine direction, and forward subsequent packets, which are received in the first leaf and are destined to the second leaf, via the detour path.

Communication networks used in applications such as High-Performance Computing (HPC) systems and datacenters typically comprise a large number of network elements interconnected by links. A high-reliability communication network should be able to recover quickly from link failure events.
Methods for recovery from link failures are known in the art. For example, a white paper by Mellanox® Technologies, 2019, describes a solution called SHIELD™—(Self-Healing Interconnect Enhancement for Intelligent Datacenters), which takes advantage of the intelligence already built into the latest generation of InfiniBand switches. By making the fabric capable with self-healing autonomy, the speed with which communications can be corrected in the face of a link failure can be sped up by 5000×, fast enough to save communications from expensive retransmissions or absolute failure.
Aspects of the SHIELD solution are described, for example, in U.S. Pat. No. 9,729,473, which describes a method in a network element that includes multiple interfaces for connecting to a communication network. The method includes receiving via an ingress interface packets that are not allowed to undergo re-routing and that are addressed to a destination via a first egress interface. The packets are forwarded via the first egress interface when there is a valid path from the first egress interface to the destination. When there is no valid path from the first egress interface to the destination, a second egress interface is selected from a group of multiple egress interfaces that have respective paths to the destination and are assigned to packets for which re-routing is allowed, and the packets are forwarded via the second egress interface until recovering a path to the destination.
U.S. Pat. No. 9,137,143, describes a multiprocessor computer system comprising a dragonfly processor interconnect network that comprises a plurality of processor nodes and a plurality of routers. The routers are operable to adaptively route data by selecting from among a plurality of network paths from a target node to a destination node in the dragonfly network based on one or more of network congestion information from neighboring routers and failed network link information from neighboring routers.

Deadlock-free rerouting for resolving local link failures using detour paths


A method of recording information in a phase-change recording medium, including the steps of conducting a test recording, using a laser beam including a plurality of pulse trains, each pulse train including alternately (a) a comb-shaped pulse train portion and (b) a flat pulse-free portion, or using a laser beam including a comb-shaped pulse train pulse train portion without including the flat portion, with a duty ratio of the comb-shaped pulse train portion being changed, thereby recording a plurality of signals or laser-beam applied portions in the recording medium, reproducing the plurality of recorded signals, or measuring the light intensities reflected by the laser-beam applied portions and converting the measured light intensities to voltages and obtaining the relationship between the amplitudes of the signals reproduced from the recorded signals or the voltages and the duty ratios corresponding thereto in order to specify a pulse strategy for recording information in the phase-change recording medium, and a phase-change recording medium produced by this method of recording are proposed.

Japanese Patent Application No. 11-273061 filed Sep. 27, 1999 is hereby incorporated by reference.
1. Field of the Invention
The present invention relates to a method of recording information in a phase-change recording medium comprising a phase-change material in a recording layer thereof, which phase-change material is capable of recording information in a rewritable manner and reproducing recorded information by being subjected to phase change at the irradiation with a laser beam. The present invention also relates to a phase-change recording medium produced by the method of recording information of the present invention, such as a rewritable compact disk (CD-RW), and other recording media for use in optical memory appliances.
2. Discussion of Background
As described in Japanese Laid-Open Patent Application 63-29336, there is conventionally known a method of recording information signals in an optical disk, using an optical disk recording apparatus, by causing a laser beam to scan the optical disk in such a manner that the surface of the optical disk is irradiated with a light spot of the laser beam, for instance, with the light spot of the laser beam being subjected to power modulation with information signals.
Furthermore, there is conventionally known a method of determining or setting optimum recording conditions such as recording (light) power, and the pulse width of recording (light) power by reproducing the information signals recorded in the optical disk and monitoring the reflection amplitudes of the reproduced signals or the length of a recording mark.
Various recording compensation methods have been disclosed for improving the quality of recording signals in the phase-change recording.
For example, in Japanese Laid-Open Patent Application 63-26632, as an effective method for improving the quality of recording signals, there is disclosed a method of recording long amorphous marks, using a pulse train in a PWM (pulse width modulation) method by use of a recording film with a high crystallization speed.
Furthermore, in Japanese Laid-Open Patent Application 63-266633 and U.S. Pat. No. 5,150,352, there is disclosed a method of controlling the fluctuations of the positions of the edge portions of a recording mark for marking an improvement in the reduction of the jitters by increasing the laser energy at the leading edge and the tail-end edge of a pulse train, or by lengthening laser irradiation time.
Orange Book Part III (ver 2.0) provides the standard of CD-RW for line recording at one to quadruple speeds (1.2 to 5.6 m/s). Such low line speeds take a long time for recording, so that there has been a demand for a rewritable compact disk capable of performing rewritable recording at higher speed.
Due to the above disclosed prior art, phase-change disks and optical disk drives having excellent performance have been made available. However, there has been desired further improvement on the technology for producing the optical disk and optical disk drive in order to obtain an optical disk which is securely compatible with CD-R(recordable), and an optical disk drive for use with the optical disk, which have completely satisfactory performance in overall aspects thereof, and which can create a new market of optical disk and optical disk drive.
By use of the conventional methods, however, it is extremely difficult to find most appropriate recording conditions without fail even if information signals are recorded in the conventional optical information recording media by a conventional, ass-produced optical information recording and reproducing apparatus for the following reasons:
In the above-mentioned conventional methods, there is known a method for determining a most appropriate recording power for each optical information recording and reproduction apparatus by monitoring the amplitudes of recording signals, that is, the difference between a signal level in an unrecorded portion and a signal level in a recorded portion of the recording medium, which amplitude constitutes a representative reproduction signal in the optical information recording medium.
However, it is known that the value of the amplitude of the recording signal is varied not only by the recording power, but also by the wavelength of the LD (laser diode) of the recording and reproduction apparatus, the numerical aperture of an optical pickup, the rim intensity (the intensity distribution of a laser beam which enters a condenser lens), the size or the shape of a light spot, and the pollution of the optical system with time, so that the optimum recording laser power and the quality of recorded signals are largely varied. Therefore, the conventional optical drives for the optical disk recording apparatus have been designed so as to be made compatible with different types of optical disks produced by different manufacturers thereof.
It is therefore a first object of the present invention to provide a method of recording information in a phase-change recording medium, which is free of the above-mentioned shortcomings of the conventional recording methods, and has the following features: The method includes a test recording step and is capable of attaining high recording performance without resort to a particularly selected combination of a rewritable compact disk and a compact disk drive, and also is capable of significantly improving the initial characteristics and overwrite characteristics of the rewritable compact disks and compact disk drives used therewith. The method is also suitable for performing recording and erasing of information, using a compact disk with a rotation speed in a wide range of 1.2 m/s to 22.4 m/s in terms of line speed.
A second object of the present invention is to provide a phase-change recording medium which is produced by the above-mentioned recording method.
The first object of the present invention can be achieved by a method of recording information in a phase-change recording medium comprising the steps of:
conducting a test recording with the application of a laser beam to the phase-change recording medium, the laser beam comprising a plurality of pulse trains, each pulse train comprising alternately (a) a comb-shaped pulse train portion and (b) a flat pulse-free portion, with a duty ratio of the comb-shaped pulse train portion being changed, thereby recording a plurality of signals in the recording medium,
reproducing the plurality of recorded signals, and
obtaining the relationship between the amplitudes of signals reproduced from the recorded signals and the duty ratios corresponding thereto in order to specify a pulse strategy for recording information in the phase-change recording medium.
More specifically, the first object of the present invention can be achieved by a method of recording information in a phase-change recording medium with a predetermined recording line speed, comprising the steps of:
conducting a test recording with the application of a laser beam to a predetermined portion of the phase-change recording medium, the laser beam comprising a plurality of pulse trains, each pulse train comprising alternately (a) a comb-shaped pulse train portion comprising a plurality of pairs of pulses, one with a pulse width T1 and a recording power P1, and the other with a pulse width T2 and a recording power P3, and (b) a flat pulse-free portion with a recording power P2, wherein P1, P2 and P3 are in the relationship of P1 greater than P2xe2x89xa7P3 in terms of the intensity of the light of the laser beam, and each of the comb-shaped pulse train portion and the flat pulse-free portion has the same duration width, with a duty ratio of the comb-shaped pulse train portion, defined by T1/(T1+T2) wherein 1/(T1+T2) is a clock frequency, being changed, thereby recording a plurality of signals in the recording medium,
reproducing the plurality of recorded signals to obtain reproduced signals corresponding to the plurality of recorded signals and to determine the amplitudes of the respective reproduced signals, and
obtaining the relationship between the amplitudes of the respective reproduced signals and the duty ratios corresponding thereto in order to specify a pulse strategy for recording information in the phase-change recording medium.
By use of the above-mentioned method, an appropriate recording pulse can be selectively set to such a degree of precision that is sufficient for use in practice, without optical information recording and reproducing apparatus, in particular, a mass-produced one, suffering any effects of the amplitude of a recording signal and a recording power offset, which effects are apt to become evident among such optical information recording and reproducing apparatus.
The above-mentioned method may further comprise the step of selectively designating (1) at least one amplitude with a magnitude of at least 80% of that of a maximum amplitude from the amplitudes of the respective reproduced signals and (2) the duty ratio corresponding thereto, whereby an appropriate pulse strategy for recording information can be specified efficiently, with higher precision, and the production costs for the optical information recording and reproducing apparatus for use with this method can be reduced.
The above-mentioned method can also include the step of recording as an information code in the phase-change recording medium the above-mentioned relationship between the amplitudes of the respective reproduced signals and the duty ratios corresponding thereto, or at least one of (1) at least one amplitude with a magnitude of at least 80% of that of a maximum amplitude from the amplitudes of the respective reproduced signals and (2) the duty ratio corresponding thereto, whereby the recording can be carried out without the test recording for each recording medium can be avoided, and exclusive tracks for the test recording can be eliminated the phase-change recording medium.
Furthermore, the above-mentioned method may further comprise the step of recording the recording power P1 in advance as an information code in the phase-change recording medium, whereby the mechanism of the optical information recording and reproducing apparatus for use with this method can be simplified, and the speed of the recording operation thereof can be increased.
The first object of the present invention can also be achieved by a method of recording information in a phase-change recording comprising the steps of:
conducting a test recording with the application of a laser beam to the phase-change recording medium, the laser beam comprising a comb-shaped pulse train, with a duty ratio of the comb-shaped pulse train being changed, thereby forming laser-beam applied portions in the recording medium,
applying light to the laser-beam applied portions to measure the intensities of the light reflected from the laser-beam applied portions, and
obtaining the relationship between the intensities of the light and the duty ratios corresponding thereto in order to specify a pulse strategy for recording information in the phase-change recording medium.
More specifically, the first object of the present invention can also be achieved by a method of recording information in a phase-change recording medium with a predetermined recording line speed, comprising the steps of:
conducting a test recording with the application of a laser beam to a predetermined portion of the phase-change recording medium, the laser beam comprising a comb-shaped pulse train which comprises a plurality of pairs of pulses, one with a pulse width T1 and a recording power P1, and the other with a pulse width T2 and a recording power P3, wherein P1 and P3 are in the relationship of P1 greater than P3 in terms of the intensity of the light of the laser beam, with a duty ratio of the comb-shaped pulse train, defined by T1/(T1+T2) wherein 1/(T1+T2) is a clock frequency, being changed, thereby forming laser-beam applied portions in the recording medium,
applying light to the laser-beam applied portions to measure the intensities of the light reflected from the laser-beam applied portions, and
obtaining the relationship between the intensities of the light and the duty ratios corresponding thereto in order to specify a pulse strategy for recording information in the phase-change recording medium.
The above-mentioned method may further comprise the step of selectively designating (1) at least one intensity of the light which is at least 80% of a maximum intensity of the light from the intensities of the light and (2) the duty ratio corresponding thereto.
The above-mentioned method can also include the step of recording as an information code in the phase-change recording medium the above-mentioned relationship between the intensities of the light and the duty ratios corresponding thereto, or at least one of (1) at least one intensity of the light which is at least 80% of a maximum intensity of the light from the intensities of the light and (2) the duty ratio corresponding thereto.
Furthermore, the above-mentioned method may further comprise the step of recording the recording power P1 in advance as an information code in the phase-change recording medium.
The first object of the present invention can also be achieved by the first mentioned method of recording information in a phase-change recording medium, with the addition of the steps of:
designating one duty ratio from the relationship between the amplitudes of the respective reproduced signals and the duty ratios corresponding thereto,
conducting a test recording with the application of a laser beam to a predetermined portion of the phase-change recording medium, the laser beam comprising a plurality of pulse trains, each pulse train comprising alternately (a) a comb-shaped pulse train portion comprising a plurality of pairs of pulses, one with a pulse width T1 and a recording power P4, and the other with a pulse width T2 and a recording power P6, and (b) a flat pulse-free portion with a recording power P5, wherein P4, P5 and P6 are in the relationship of P4 greater than P5xe2x89xa7P6 in terms of the intensity of the light of the laser beam, and each of the comb-shaped pulse train portion and the flat pulse-free portion has the same duration width, with the recording power P4 being changed, thereby recording a plurality of signals in the recording medium,
reproducing the plurality of recorded signals to obtain reproduced signals corresponding to the recorded signals and to determine the amplitudes of the respective reproduced signals, and
obtaining the relationship between the amplitudes of the respective reproduced signals and the recording powers P4 corresponding thereto in order to specify a pulse strategy for recording information in the phase-change recording medium, in which P4, P5 and P6 may be respectively the same as or different from P1, P2, and P3 in the first mentioned method.
The above-mentioned method may further comprise the step of selectively designating (1) at least one amplitude with a magnitude of at least 80% of that of a maximum amplitude from the amplitudes of the respective reproduced signals and (2) the recording powers P4 corresponding thereto.
Furthermore, the above-mentioned method may further comprise the step of recording as an information code in the phase-change recording medium the relationship between the amplitudes of the respective reproduced signals and the recording powers P4 corresponding thereto.
Furthermore, the above-mentioned method may further comprise the step of recording as an information code in the phase-change recording medium at least one of (1) at least one amplitude with a magnitude of at least 80% of that of a maximum amplitude from the amplitudes of the respective reproduced signals and (2) the recording power P4 corresponding thereto.
The second object of the present invention can be achieved by a phase-change recording medium produced by any of the above-mentioned methods for use in a method of recording information in an optical information recording medium with a predetermined recording line speed, wherein any of the above-mentioned information codes is recorded in advance in a predetermined portion of the phase-change recording medium.

Method of recording information in phase-change recording medium and recording medium for use in the method


A method of virtualizing an application to execute on a plurality of operating systems without installation. The method includes creating an input configuration file for each operating system. The templates each include a collection of configurations that were made by the application during installation on a computing device executing the operating system. The templates are combined into a single application template having a layer including the collection of configurations for each operating system. The collection of configurations includes files and registry entries. The collections also identifies and configures environmental variables, systems, and the like. Files in the collection of configurations and references to those files may be replaced with references to files stored on installation media. The application template is used to build an executable of the virtualized application. The application template may be incorporated into a manifest listing other application templates and made available to users from a website.

1. Field of the Invention
The present invention is directed generally to methods of virtualizing an application so that when the application is executed on a computing device having an operating system, the application is at least partially isolated from the operating system and executes on the computing device without having been installed or having administrator privileges.
2. Description of the Related Art
Installation of a typical application on a computing device usually requires a long setup and configuration process, which includes copying files, registering software components, installing runtimes, installing third-party components upon which the application is dependent, configuring setup files, and so forth. Additionally, user configuration including setting up user preferences, and other customization is also typically required.
Further, more than one application is typically installed on the computing device. Interactions between shared components and different versions of the same application frequently introduce errors when applications are installed, uninstalled, or upgraded.
Within an organization, applications are typically installed by Information Technology ("IT") personnel and systems administrators. To protect information stored on networked computing devices, it may be desirable to configure the organization's computing devices with security measures. Unfortunately, many applications do not function properly on secured, locked-down desktops. Thus, IT personnel and systems administrators may be forced by the needs of the organization to compromise network security for application compatibility.
One method of deploying (installing and executing) an application that avoids these above problems includes preparing and executing a virtualized copy of the application (a "virtual application"). A virtual application is a virtual machine image pre-configured with all of the files, registry data, settings, components, runtimes, and other dependencies required for a specific application to execute immediately and without installation on the host computing device. Virtual applications allow application publishers and IT administrators to reduce the costs and complexity associated with development, setup, configuration, deployment, and maintenance of software applications.
For example, a publisher of an application based on the Microsoft .NET Framework or Java runtime engine might create a virtual application that combines the application with the required runtime engine. Using this virtual application, an end-user can run the application immediately, even if the user has not installed the required runtime engine, or has an incompatible runtime engine installed. This improves both the user experience and reduces both test and support complexity associated with deployment of the application.
Furthermore, because each virtual application is an isolated execution environment, virtual applications may be concurrently executed that would otherwise interfere with one another. For example, applications that overwrite system DLLs or require different runtime engine versions can be executed simultaneously on a single host computing device. As an additional advantage, virtual applications can provide access to internal virtualized copies of privileged system resources, allowing unprivileged users to execute applications without encountering security exceptions or irritating Vista User Account Control ("UAC") prompts.
Therefore, a need exists for methods and systems for preparing virtualized applications. A further need exists for a method of allowing an end user to build and configure the virtualized application. A virtual application configured to effectively share memory between processes is also desirable. The present application provides these and other advantages as will be apparent from the following detailed description and accompanying figures.

Method and system for virtualization of software applications


The invention relates to a method for applying to a carrier a marking serving to measure length, angle cr the like, such as, for example, a magnetic tape (4), by means of which the accuracy of the measurements is improved. In the case of such methods, in one marking step a means for producing a track with markings, for example a writing head (9), is guided over the carrier and, by virtue of the fact that the carrier is acted upon, markings, for example magnetic north and south poles, are applied therein at predetermined positions of the carrier. According to the invention, it is proposed that in this method the actual positions of a reference point (16), the difference between the the marking of the track are measured with respect to measured actual positions and desired positions are determined, and, when differences are present, corrected marking are applied to the same track of the carrier in a further marking step, positions of markings of the first marking step being changed with respect to positions of markings of the second marking step by values depending on the differences.

1. Field of the Invention
The invention relates to a method for applying to a carrier a marking serving to measure length, angle or the like, in which in one marking step a means for producing a track with markings is guided over the carrier and, by virtue of the fact that the carrier is acted upon, permanent markings are applied therein at predetermined positions of the carrier.
2. Description of Related Art
In many fields of technology, it is necessary to determine positions of machines, machine components etc. A multiplicity of measuring methods have already become known for this purpose. A first example in this respect is the measuring method using transmitted light or reflection with the aid of glass scales which have alternating bright/dark markings. A further example is magnetic measuring methods with north and south poles applied in an alternating fashion to a carrier. Finally, measuring methods have also become known in which the xe2x80x9cmarkingsxe2x80x9d are scanned inductively. This enumeration of measuring methods for which the present invention is suitable is only exemplary and not final.
Common to all these measuring methods is that they use markings which have different physical properties. These differences are detected by suitable sensors. Since the length of each individual marking is known in advance, the desired measurement of length or angle can be carried out by means of the number of the detected xe2x80x9cchanges in propertyxe2x80x9d.
A substantial source of error in all these measuring methods consists, however, in that the individual markings do not have the desired properties. For example, a length measurement is not exact whenever one of the marking is located at a position other than that provided, or its length does not correspond to the prescribed length.
It is therefore the object of the present invention to create a method and a device with the aid of which the measuring accuracy of such measuring methods can be improved.
According to the invention, this object is achieved in the case of a method named at the beginning by virtue of the fact that actual positions of the markings of the track are measured with respect to a reference point, the differences between measured actual positions and desired positions are determined and, when differences are present, corrected markings are applied to the same track of the carrier in a further marking step, positions of the markings of the first marking system being offset with respect to positions of markings of the second marking step by values depending on the differences.
The object is also achieved by means of the system shown in FIG. 1. This system includes a marking device (8) for writing a multiple markings track, a clamping device (2) for positioning a carrier within the system and a positioning device with causes relative movement between the carrier and the writing element (9), a measuring device (10) which determines the actual positions or specific points of the markings, means for storing the measured actual positions, means for 1) comparing the actual positions or specific points of the markings with prescribed desired positions of the markings or specific points and 2) determining the deviation between the actual and desired positions, and a controller for controlling the application of the markings to the carrier a new. The positions of these further markings are corrected in each case by a value which depends on the previously determined deviations.
Thus, according to the invention a compensation of positioning errors of the markings is carried out. The accuracy of such measuring methods can be increased by correcting the positions or the length or other physical properties of markings already produced in at least one further marking step. It is decisive for the accuracy of the measuring method that, for example, transitions from a magnetic north pole to a following south pole or vice versa, or transitions of other property changes are now located at the prescribed positions. The result of this is a constant length of the poles or markings, which correspond to the respectively provided incremental division.
In the case of a measuring method which uses a track like the markings produced using the method according to the invention, it is usual to proceed from a reference point and to count only the number of the changes in property. Consideration may be given as changes in property to, for example, the change in the direction of the magnetic field strength or magnetic field induction, and thus to the change from one pole to another pole. By multiplying by the size of the incremental division, the position or the positioning path of the measuring device can be determined more accurately. Since the accuracy of the positioning of the transitions from one marking of the track to the following marking is thereby completely decisive for the accuracy of the measuring method itself, it is preferred according to the invention that in the case of the production of the track, as well, it is chiefly the deviations of the transitions from their desired positions which are corrected.
This method for applying markings constitutes a break with the previously applied direction of development for the purpose of improving the measuring accuracy. To be precise, said direction provided either always attempts to increase the positioning accuracy in the case of a single marking step per track, or to apply a further correction track in addition to the measuring track. Moreover,xe2x80x94otherwise than with previous marking methodsxe2x80x94this method assumes that essentially only the positions of those changes in property or pole are decisive which are to be observed in the form of a prescribed uniform raster. The poles whose lengths are of only secondary importance and are yielded from the raster are to be arranged in this raster.
So that the second and each further marking step for compensating errors from one or more preceding marking steps can be carried out particularly simply and with the smallest possible outlay, it can be provided that in these marking steps all the previously produced markings of the track are traversed and marked once again. The further marking step carried out recently in this way therefore differs from the preceding marking step only in that a correction is carried out with the aid of the difference between the desired and actual values in the case of those markings for which a deviation is determined between the desired and actual values of the length, positions or other properties.
The marking method according to the invention can be applied both in xe2x80x9canaloguexe2x80x9d and in xe2x80x9cdigitalxe2x80x9d measuring methods. In this connection, xe2x80x9canaloguexe2x80x9d measuring methods are to be understood as those methods in which the strength or intensity of markings can be changed by repeated marking. An example of this is magnetic measuring methods. xe2x80x9cDigitalxe2x80x9d measuring methods are to be understood, by contrast, as those methods whose markings permit only two states, specifically marked or not marked. An example of this is the optical measuring methods, already mentioned, based on glass scales. A further example is methods which use markings produced by punchings and in which the measuring principle is based on the determination of material present yes/no.
In conjunction with analogue marking methods, it has proved to be preferable if when carrying out a further marking step the value for compensating the positioning or application error has the absolute value of twice the difference between the value of the desired and the actual positions. The correction direction is in this case always opposite to the determined direction of deviation of the application error. An (arithmetic) mean value which corresponds exactly to the prescribed desired value is therefore set up by the superimposition of the two last marking steps.
In connection with digital marking methods, it is preferred to form and use for compensating application errors a value which correspond to the single difference between the desired value and the measured value of the respective physical variable. Since it is not a superimposition which takes place here, but only an overwriting, and the new position of the corresponding marking corresponds to the actual position produced by the last marking step, the single value of the difference originally present suffices for correcting the deviation.
The method according to the invention and the system according to the invention can be used in principle independently of the later purpose for which the markings are used. Thus, it is possible to produce tracks which are used for relative or for absolute measuring methods. Absolute measuring methods are distinguished usually by the fact that a plurality of tracks are present whose divisions are of different size. Moreover, in the case of absolute measuring methods a length or an angle is measured with reference to a permanently prescribed, and as a rule unchangeable, reference quantity (zero point). The method according to the invention can be applied for each of these tracks of an absolute measuring method. Of course, however, it is necessary to carry out more than one marking step only in the case of those tracks for which application error are determined. If application errors are measured in the case of a plurality of tracks, the further marking steps for each of these tracks can also be carried out simultaneouslyxe2x80x94just like the first marking and measuring steps.
The method according to the invention can also be used in the case of xe2x80x9cquasi-absolutexe2x80x9d measuring methods which use a track of spacing-coded reference marks. These are marks which are arranged at different, but specific spacings from one another. Since the spacings of sequential markings are known, the point at which the sensor of the measuring system is located can be determined by traversing two of these markings. The measuring method with spacing-coded reference marks is described, for example, in DE-C 24 16 212.
Likewise, the method can be applied for marking tracks of relative measuring methods. In these measuring methods, it is not spacings referred to a permanently prescribed reference point which are measured, but spacings from an arbitrary first mark to an arbitrary second mark.

Method for applying and correcting measuring marks on a carrier


A method for forming a three-dimensional reconstructed image acquires two dimensional measured radiographic projection images over a set of projection angles, wherein the measured projection image data is obtained from an energy resolving detector that distinguishes first and second energy bands. A volume reconstruction has image voxel values representative of the scanned object by back projection of the measured projection data. Volume reconstruction values are iteratively modified to generate an iterative reconstruction by repeating, for angles in the set of projection angles and for each of a plurality of pixels of the detector: generating a forward projection that includes calculating an x-ray spectral distribution at each volume voxel, calculating an error value by comparing the generated forward projection value with the corresponding measured projection image value, and adjusting one or more voxel values using the calculated error value and the x-ray spectral distribution. The generated iterative reconstruction displays.

A computerized tomography (CT) imaging apparatus operates by acquiring multiple 2D images with a rotating imaging ensemble or gantry that has an x-ray source and, opposite the x-ray source, an imaging sensor rotating about a fixed axis relative to the patient. CT imaging allows the reconstruction of 3D or volume images of anatomical structures of the patient and is acknowledged to be of particular value for obtaining useful information for assisting diagnosis and treatment.
There is considerable interest in the use of CT imaging in dental and ear-nose-throat (ENT) applications, as well as for other imaging of the patient's head. A number of volume imaging system designs have been proposed for this purpose. Among proposed solutions are hybrid systems that combine panoramic imaging and CT imaging. For example, U.S. Pat. No. 6,118,842 entitled "X-RAY IMAGING APPARATUS" to Arai et al. discloses an X-ray imaging apparatus that supports both imaging modes. The apparatus includes an X-ray source, an X-ray detector for detecting X-rays having passed through the subject, and supporting means for supporting the X-ray source and the X-ray detector so that they are spatially opposed to each other across the subject; and mode switching means for switching between a CT mode and a panorama mode. To detect X-rays, only one large area X-ray detector is used. The X-ray imaging apparatus can obtain both types of images by switching modes during the imaging session. However, the proposed imaging apparatus requires an expensive detector capable of carrying out both imaging functions in a satisfactory manner. Additionally, systems of this type typically compromise image quality by using a uniform distance between the X-ray source and detector, even though different distances would be more advantageous.
By way of example, FIG. 1 shows an embodiment of a conventional CT imaging apparatus 40. A column 18 is adjustable for height of the subject. The patient 12 or other subject, shown in dotted outline, is positioned between an x-ray source 10 and an x-ray imaging sensor panel 20, also termed an imaging detector. X-ray imaging sensor panel 20 rotates on a rotatable mount 30 in order to position a CT sensor 21 for obtaining the exposure. CT sensor 21 is positioned behind the subject, relative to x-ray source 10. The operator rotates CT sensor 21 into this position as part of imaging setup. With rotation of mount 30, sensor 21 and source 10 revolve about the head of the patient, typically for some portion of a full revolution. Still other dental imaging system solutions combine CT, panoramic, and cephalometric imaging from a single apparatus. With such combined systems, the required amounts of radiation exposure can be a concern, particularly for CT imaging, which can require numerous images, each from a separate exposure.
Conventional digital radiography detectors have some limitations related to how attenuation of radiation energy at a single exposure is interpreted. For example, it can be very difficult, from a single exposure, to distinguish whether an imaged object has a given thickness or a given attenuation coefficient. To resolve this ambiguity, some systems provide separate, sequential low-energy and higher energy exposures and use the resulting difference in image information to distinguish between types of materials. However, in order to provide this information, this type of imaging requires that the patient be subjected to additional radiation for the second exposure. This problem can be compounded for CT imaging, in which multiple images are obtained, one from each of a number of angles of revolution about the patient.
Computed tomography (CT) and cone beam computed tomography (CBCT) systems reconstruct volume image data from a series of 2D x-ray images, termed "projection images", obtained at different angular positions about the imaged subject. An iterative reconstruction method is employed to use data from the 2D images for this purpose.
Cone beam scanners generally use polychromatic X-ray sources because of their lower cost and availability as compared with monochromatic X-ray sources which either require a synchrotron or an X-ray monochromator. The broad-spectrum radiation that is emitted from the polychromatic X-ray source is attenuated by the material that is being imaged, according to its x-ray attenuation coefficient, which varies with the type of material.
Among the problems encountered in obtaining image data for accurate 3D reconstruction is beam hardening. Beam hardening occurs as the polychromatic or polyenergetic radiation progresses through the subject material. Energy of different wavelengths is absorbed at different rates, according to the irradiated subject material. As a result of energy absorption of particular wavelengths by the material, the energy spectrum of the polychromatic X-ray radiation varies with location or depth in the scanned object and this variation depends on both the spatial characteristics or depth of the object and the relative location of the X-ray source. Because lower-energy radiation (at lower frequencies or longer wavelengths) is attenuated more strongly than higher-energy radiation (at higher frequencies or shorter wavelengths), the radiation beam is "hardened". For a uniform cylindrical phantom, for example, X rays passing through the middle portion of the phantom pass through more material than X-rays passing through edge portions. As the X-ray energy encounters more material, its spectral content changes and is considered to be more "hardened" than the same energy directed through less material; the proportion of higher energy to lower energy increases as the radiation travels further through the object. From a spectral aspect, the energy spectrum changes along the beam path that the radiation follows through the material, even where the object is of uniform depth and material composition. This change in the spectral content of the beam causes artifacts such as cupping, in which the middle of the subject experiences different radiation levels than portions of the edge of the subject. These beam hardening artifacts can appear as dark bands between highly attenuating parts of the imaged object.
Beam hardening complicates the task of 3D image reconstruction in CBCT and other volume imaging modalities. The 2D image content that is used to reconstruct a particular 3D voxel can be affected differently according to the angle at which the 2D image is obtained and the location of the voxel within the imaged object. Thus, there is a need for image processing methods that compensate for beam hardening in 2D images and in 3D image reconstruction.
In conventional CBCT volume reconstruction, the volume image that is generated provides only a single data value for each voxel, according to the total amount of attenuation measured at each position within the object. This single data value is not sufficient for determining the material composition at that voxel; only a rough guess of the material combination can be made. It would be of particular value to be able to obtain additional information for each voxel. Attenuation coefficients at two or more different energy levels, for example, would provide sufficient information to allow a more accurate estimate of the material composition of the reconstructed data.

Volume image reconstruction using data from multiple energy spectra


The present invention relates to a method of preparing adhesive coated articles and cold seal bonded laminates therefrom. Specifically, it relates to a method wherein certain polychloroprene based adhesive compositions are used to form adhesive coated substrates that are non-blocking and pressure sealable at ambient temperature. In a preferred embodiment, the invention relates to a method for the preparation of coated substrates and articles that are particularly useful for the manufacture of medical packaging and tamper evident applications.

The invention is directed to cold sealable adhesive articles. The present invention relates to a method of preparing adhesive coated articles and cold seal bonded laminates therefrom. Specifically, it relates to a method wherein certain polychloroprene based adhesive compositions are used to form adhesive coated substrates that are non-blocking and pressure sealable at ambient temperature. In a preferred embodiment, the invention relates to a method for the preparation of coated substrates and articles that are particularly useful for the manufacture of medical packaging and tamper evident applications.
It is generally known that water-based "cold seal" adhesives can be used to form dry-bond laminates for protective packaging. The terminology "cold seal" refers to a class of adhesives which possess the ability to form bonds to themselves at  ambient temperature with pressure, yet are essentially tack free to the touch, allowing coated substrates to be wound upon themselves and stored without adhering to the opposing face of the substrate backing. Adhesives of this type have been employed in a variety of packaging applications including food (i.e. flexible packaging for candy wrappers, chips etc.); medical packaging; self-seal and tamper evident envelopes; banding for paper money, napkins, and clothing; and protective packaging such as fold over "blister" packages for hardware and small parts. Additionally, the cold seal adhesives have found utility as anti-skid coatings and for release-paper free tapes such as tab-less diaper tapes.
Natural latex based products have dominated the cold seal market for quite some time, since uncompounded natural latex exhibits properties amenable to cold seal applications. Natural latex based cold seals have several deficiencies. For example, in medical device packaging, natural latex based cold seals contain proteins that have been identified as skin sensitizers. Additionally, natural latex based cold seals often discolor, e.g, yellow, and oxidized upon aging resulting in undesirable aesthetics and reduced bond strength of the coated substrates and articles.
Furthermore, the adhesion characteristics of natural latex based cold seals are often reduced by irradiation, which is required for the sterilization of packaged medical bandages and devices. It is believed that irradiation causes the natural latex to crosslink, significantly changing the bond properties.
For medical device packaging it is often desirable that the adhesive coated article resist yellowing when subjected to heat. Yellowing is often undesirable because the discoloration can diminish the aesthetics of the packaging.
Several references that disclose water-based synthetic cold seals, and their method of use, are described below:
The Bayer Corporation Division of Fibers, Organics, and Rubber provides product literature describing "Dispercoll C Polychloroprene Laticies—General Information On Properties And Compounding For Adhesive Applications". The polychloroprene latex peel strength, on canvas duck, are evaluated using a room temperature bond method wherein the aqueous polychloroprene latex is coated onto the substrate and air dried. The canvas is then folded onto itself and immediately pressed in platen at 200 psi for 15 seconds.
U.S. Pat. No. 4,889,884 issued to Dust et al., Dec. 26, 1989 claims a cold-seal adhesive composition comprising about 45 to 70% by wt. of a synthetic base polymer and about 30 to about 55% by wt. of a synthetic secondary polymer, wherein the base polymer comprises a synthetic copolymer, a synthetic copolymer, or any mixture thereof characterized in that it possesses a Tg of about −40 to about −60° C. and a Williams plasticity number of about 2.5 to 2.9; and the secondary polymer comprises a styrene-acrylic copolymer, a synthetic styrene-acrylic resin or any mixture thereof, or an admixture of one or more styrene-acrylic copolymers or styrene acrylic resins, or any mixture thereof with one or more synthetic polymer, copolymers, or synthetic resins, characterized in that it possess a Tg of about −35 to about 5° C. and a plasticity number of about 5.0 to about 5.6. At column 2, lines 41-47 it is states that, "Virtually any synthetic polymer meeting these criteria (Tg and Williams plasticity) can be used in the adhesive compositions of this invention, but preferred polymers include acrylic copolymers such as a copolymer comprising 60% (by wt.) butyl acrylate, 30% (by wt.) 2-ethylhexyl acrylate and 105 vinyl acetate; and styrene butadiene rubbers."
Similarly, U.S. Pat. No. 4,902,370 issued Feb. 20, 1990 as a divisional of the '884 claims a method of forming a cold seal bond on a substrate by applying the recited adhesive, drying said emulsion to form a dried film, and subsequently bringing the coated portion of the substrate in contact with each other such that a bond is effected.
U.S. Pat. No. 5,314,944 issued to Chao, May 24, 1994 relates to a pressure sensitive adhesive that is tack-free to the touch, but forms a permanent bond under moderate pressure. The pressure sensitive adhesive contains a tacky adhesive latex, a non-tacky latex or polymer, and an inert filler. The tacky adhesive latex provides the sealing properties, the non-tacky latex or polymer provides blocking resistance and the filler absorbs oil that may adversely affect the sealing properties. The tacky adhesive latex is generally an acrylic type adhesive latex. The non-tacky latex may be an acrylate latex or a styrene-butadiene latex or a non-tacky polymer such as polyvinyl alcohol, starch and cellulose derivatives.
U.S. Pat. No. 5,567,773 issued to McGee et al., Oct. 22, 1996 is directed to an adhesive coating which is pressure sealable to itself and non-blocking to a dissimilar coating comprising a blend of a) a soft polymer having a measured glass transition temperature below room temperature; and b) a hard polymer having a measured glass transition temperature which is higher than the measured glass transition temperature of the soft polymer in a low blocking, pressure sealable coating formable proportion.
U.S. Pat. No. 4,888,395 issued to Min, Dec. 19, 1989 relates to core/shell polymers containing a rubber core and thermoplastic shell acrylate-vinylacetate-acrylic terpolymer having excellent cold seal strength properties. The core/shell polymer contain about 1 to 50% by weight of a rubber core. At Column 3, lines 54-60, this reference states "Typical rubbers which can make up of the core include polyisoprene, polybutene, polychloroprene (neoprene), poly (1,3-butadiene), natural rubber, butadiene/styrene and the like." Hence, this reference is also directed to cold seal compositions containing a blend of polymers.
Additionally, aqueous polychloroprenes have been used as an ingredient in contact adhesives. For example, U.S. Pat. No. 5,476,896 issued to Pereira et al. Dec. 19, 1995 relates to a water-based contact adhesive comprising a carboxylated polychloroprene latex which provides elastomeric properties, a carboxylated poly (vinyl acetate-ethylene) aqueous emulsion which provides toughness to the adhesive, a tackifier resin dispersion, an organic water soluble crosslinking agent for the carboxyl functionality of the polychloroprene and poly (vinyl acetate-ethylene); and optionally an adhesion promoter. The compositions exemplified contain at least 10% rosin ester dispersion.
Contact adhesives differ substantially from cold seal compositions. As exemplified in Pereira et al., contact adhesives generally comprise tackifying resins. Whereas cold seal compositions require a proper balance of properties such that the adhesive will form a bond to itself with pressure yet do not exhibit tendencies to adhere to other substrates once dried, contact adhesives may either be permanently pressure sensitive or unable to form a bond without heat activation once dried. Further, contact adhesive typically refers to an adhesive that is coated on at least one substrate and adheres to itself upon contact and drying, whereas cold seal compositions are coated on both surfaces intended to be bonded and the coated surfaces are not contacted until after the adhesive is completely dried.

Method for the preparation of non-blocking adhesive coated articles and cold seal bonded laminates


Spin trapping compositions in general have now been discovered to be effective in treating a variety of disorders, including disorders such as those arising from ischemia, infection, inflammation, exposure to radiation or cytotoxic compounds, not just of the central and peripheral nervous systems but of peripheral organ disease having a wide variety of etiologies. In the preferred embodiment, the compositions for treating tissue damage from ischemia contain PBN, or active derivatives thereof, in a suitable pharmaceutical carrier for intravenous, oral, topical, or nasal/pulmonary administration. Other preferred spin-trapping agents include 5,5-dimethyl pyrroline N-oxide, (DMPO), .alpha.-(4-pyridyl-1-oxide)-N-tert-butylnitrone, (POBN), and (TEMPO) spin-trapping derivatives thereof. Examples of derivatives of PBN include halogenated derivatives, bifunctional derivatives, conjugates with drugs or targeting molecules, dimers and cyclodextran polymers of PBN. Many different disorders can be treated using these compounds, including diseases or disorders of the central and peripheral nervous systems, and disorders arising from ischemia, infection, inflammation, oxidation from exposure to radiation or cytotoxic compounds, as well as due to naturally occurring processes such as aging.

The present invention is a method and compositions containing spin trapping agents for the treatment of dysfunctions and disease conditions arising from oxidative damage.
Oxygenated tissue suffers damage, in many cases permanent damage, if it becomes ischemic and is then reperfused. The brain appears to be highly susceptible to ischemia/reperfusion injury. Certain areas of the brain, for example, the hippocampus and spinal cord, are more susceptible than other regions of the brain. As a result, ischemia/reperfusion injury to brain may have a multiplicative effect simply because of the necessity for complete integrity of all regions in order to have proper functioning.
Free radicals have been postulated to be mediators of reperfusion damage. The most likely sites for production of such radicals as the superoxide (O.sup.-2) and hydroxyl (OH.sup.-) species, and the precursor oxygen species, H.sub.2 O.sub.2 are the mitochondrial respiratory chain specific enzymes and the sequences catalyzed by cyclooxygenase and lipoxygenase. However, radicals are also formed during autoxidation of many compounds (e.g., catecholamines). Ischemia appears to favor a spurt of free-radical formation, resulting in oxidation of polyenoic free fatty acids, release and reuptake of catecholamines, and oxidation of hypoxanthine by xanthine oxidase. Despite these events occurring during recirculation, when the O.sub.2 supply is restored, they represent metabolic cascades triggered by agonist-receptor interactions, energy failure, and/or calcium influx during the insult.
Although free radical formation has been postulated to be a likely cause of ischemic damage, it was difficult to directly demonstrate that such formation occurs and/or that it was sufficiently pronounced to overwhelm the antioxidative defense of the tissue, as reviewed by Curran, et al., Mol. Cell. Biol.5, 167-172 (1985). Phenyl butyl nitrone (PBN) has been used in a number of these in vitro research studies using spin trapping to look for free radicals, but until demonstrated by the data in U.S. Ser. No. 07/422,651, now U.S. Pat. No. 5,025,032 there has been no data to support the proposition that it could be useful in vivo, particularly with respect to treatment of tissue damage in the central nervous system. In vivo, the drug must be able to both cross the blood brain barrier and act in a manner which reduces tissue damage during or following ischemia.
In U.S. Ser. No. 07/589,177, abandoned on Apr. 20, 1993 the use of PBN and related compounds, as well as 5,5-dimethyl pyrroline N-oxide (DMPO) and .alpha.-(4-pyridinyl-1-oxide)-N-tert -butylnitrone (POBN), for treatment of aging was described. Age related changes in central nervous system function have generally been associated with the loss of cells, a widening of lateral ventricles and deficits in short term memory. The precise mechanisms of functional changes as a result of aging, or other diseases associated with aging, have not generally been agreed upon, including several mechanisms for the generation of oxidized material in the brain. A marked reduction in certain neurotransmitter receptor systems has been associated with increased oxidation of proteins. For example, decreases in muscarinic receptors and other cholinergic systems have been characterized as they relate to alterations in functions in Alzheimers disease. It is now known that the processes of aging and Alzheimer's disease are associated with oxidation of brain proteins. It has also been hypothesized that aging is associated with multiple minor periods of ischemia (multi-infarct conditions or transient ischemia attacks) which, over a period of time, may give rise to the production of oxidized protein.
The demonstration in a variety of systems, both neural and nonneural, that there is an age related enhancement of the level of oxidized protein in tissue gives rise to the possibility that age related dysfunctions in the central nervous system may be associated with the build-up of oxidized proteins and oxidized macromolecules within neurons throughout the central nervous system. The hypothesis is that cells which have a buildup of oxidized protein are less functional and less able to maintain the specified role of those cells in that particular area of the central nervous system. The data presented in U.S. Ser. No. 07/589,177 abandoned on Apr. 20, 1993 was the first report of substantial investigations in which alterations in the oxidized protein burden of the central nervous system was manipulated and correlated with a functional outcome on the part of the animal. There are a number of other disorders and diseases which have now been postulated to be associated with oxidation of proteins, including many central nervous system (CNS) diseases besides stroke and aging, including Parkinsonism, trauma, vascular headaches, cerebral palsy, diabetic neuropathy,and neuroanesthesia adjunct, as well as peripheral nervous system diseases such as diabetic peripheral neuropathy and traumatic nerve damage, as well as peripheral organ diseases. Examples of peripheral organ diseases include atherosclerosis, pulmonary fibrosis, pancreatitis, angioplasty, multiple organ failure, burns, decubitus ulcers, and ischemic bowel disease.
It is therefore an object of the present invention to provide spin-trapping compositions and methods for use thereof which are useful in preventing or reversing ischemic damage in vivo, in the CNS, resulting from diseases such as stroke, aging, Parkinsonism, concussion, Berry aneurysm, ventricular hemorrhage and associated vasospasm, spinal cord trauma, vascular headaches, and neuroanesthesia adjunct.
It is another object of the present invention to provide spin-trapping compositions, and methods for use thereof, which are useful in treating damage in vivo resulting from peripheral nervous system diseases, including diabetic peripheral neuropathy and traumatic nerve damage.
It is still another object of the present invention to provide spin-trapping compositions, and methods for use thereof, which are useful in preventing or reversing free radical damage in vivo resulting from injury, infection and inflammation, especially peripheral organ diseases such as chronic obstructive pulmonary disease (COPD), atherosclerosis (both diabetic and spontaneous), pulmonary fibrosis due to anti-cancer treatment, drug treatment, pancreatitis, angioplasty, multi-organ failure following trauma, burns (chemical, thermal, and radiation), the progressive loss of myocardial cells leading to cardiac failure as a result of age-related oxidation, and ischemic bowel disease.
It is another object of the present invention to provide spin-trapping compositions for use in the process of organ transplantation and preservation.
It is a further object of the present invention to treat disorders not associated with oxidation, such as undesirable HDL/LDL ratios, as well as the treatment of damage arising from exposure to cytotoxic compounds and radiation.

Spin trapping pharmaceutical compositions and methods for use thereof

University of Kentucky Research Foundation


In some implementations, an electronic device includes an actuator having a coil and a magnet, at least one of which may be movable relative to the other. The coil may receive a drive current to cause movement of at least one of the magnet or the coil, such as to provide a haptic output, motivate a loudspeaker, or the like. A transceiver electrically coupled with the coil through a connection circuit may use the coil as an antenna for at least one of sending or receiving a radio frequency communication through the coil. Additionally, or alternatively, the coil may be placed into proximity to a source of a magnetic field to induce an electric current in the coil. The induced electric current may be passed from the coil to a power management system, such as to charge a battery or the like.

People commonly use electronic devices for communicating with others, consuming digital media content, executing applications, and performing numerous other functions. Examples of such electronic devices may include eBook reader devices, cellular telephones and smart phones, tablet computers, portable media players, laptop and netbook computers, personal digital assistants, and navigation devices, to name a few. As these electronic devices continue to increase in popularity, providing ways to enhance the functionality of these devices within a limited form factor continues to be a priority.


An input/output subsystem of a computing environment is configured as a plurality of input/output subsystem images, each of which appears to a program as an independent input/output subsystem. An input/output subsystem image includes one or more communications adapters used for communicating within the computing environment. A communications adapter is identified by hardware of the computing environment by using a first identifier, and it is identified by a program of the computing environment by using a second identifier. The identifiers can be of different sizes.

In various computing systems, such as the eServer zSeries, S/370-XA, ESA/370 and ESA/390 systems, offered by International Business Machines Corporation, Armonk, N.Y., each system footprint, referred to as a central processing complex (CPC), is limited to a maximum configuration of 256 I/O paths, such as, for example, 256 channel paths. One of the reasons for the constraint is that the unique identifier for each channel path configured to the CPC, referred to as the Channel Path Identifier (CHPID), is defined as an 8-bit binary number, which provides 256 unique CHPID values from zero to 255. Since this value is only 8-bits, only 256 paths with unique identifications are possible. One solution is to increase the size of the CHPID; however, this has serious consequences for the many programs that use the CHPID.
This 256-channel path limitation has restricted the ability to provide significant increases in the overall CPC in terms of the maximum processing capacity of the central processors provided by the CPC. Further, computing systems are being created in which the total computing capacity of the systems is increasing past the point where 256 channel paths are sufficient in order to provide adequate I/O bandwidth and I/O configuration flexibility necessary to fully utilize the increased numbers of central processors.
Thus, a need exists for a capability to extend the functionality of an input/output subsystem. In one example, a need exists for a facility that can provide more than 256 I/O paths in a manner that is minimally disruptive to the programs using the paths.

Method, system and program products for identifying communications adapters of a computing environment