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The present invention provides novel compounds, novel compositions, methods of their use and methods of their manufacture, where such compounds are generally pharmacologically useful as agents in therapies whose mechanism of action rely on theselective inhibition of the isozyme 5.alpha.-reductase 1.BACKGROUND OF THE INVENTIONCertain undesirable physiological manifestations, such as acne vulgaris, seborrhea, female hirsutism, male pattern baldness (alopecia) and benign prostatic hyperplasia, are the result of hyperandrogenic stimulation caused by an excessiveaccumulation of testosterone or similar androgenic hormones in the metabolic system. Early attempts to provide a chemotherapeutic agent to counter the undesirable results of hyperandrogenicity resulted in the discovery of several steroidal antiandrogenshaving undesirable hormonal activities of their own. The estrogens, for example, not only counteract the effect of the androgens but have a feminizing effect as well. Non-steroidal antiandrogens have also been developed, for example,4'-nitro-3'-trifluoromethyl-isobutyranilide. See Neri, et al., Endocrinol. 1972, 91 (2). However, these products, though devoid of hormonal effects, compete with all natural androgens for receptor sites, and hence have a tendency to feminize a malehost or the male ferns of a female host and/or initiate feed-back effects which would cause hyperstimulation of the testes.The principal mediator of androgenic activity in some target organs, e.g. the prostate, is 5.alpha.-dihydrotestosterone, formed locally in the target organ by the action of testosterone-5.alpha.-reductase. Inhibitors oftestosterone-5.alpha.-reductase will serve to prevent or lessen symptoms of hyperandrogenic stimulation in these organs. It is now known that a second 5.alpha.-reductase isozyme exists, which interacts with epidermal tissues, especially in scalptissues. This form is conventionally designated as 5.alpha.-reductase 1, while the isozyme that principall
United States Patent: 5621104 ( 1 of 1 ) United States Patent 5,621,104 Graham , et al. April 15, 1997 Substituted 3-phenanthridinone derivatives as 5-alpha-reductase inhibitors Abstract The present invention provides for the preparation of compounds,namely, 3-phenanthridinones and their derivatives and their unique ability to inhibit 5-alpha-reductase or their isozymes thereof in mammals enabling said compounds for treating hyperandrogenic conditions of acne, androgenic alopecia, male pattern baldness,female hirsutism,benign prostatic hyperplasia, prostatitis and prostatic cancer. Inventors: Graham; Donald W. (Mountainside, NJ), Hagmann; William K. (Westfield, NJ) Assignee: Merck & Co., Inc. (Rahway, NJ) Appl. No.: 08/522,350 Filed: September 15, 1995 PCT Filed: March 22, 1994 PCT No.: PCT/US94/03080 371 Date: September 15, 1995 102(e) Date: September 15, 1995 PCT Pub. No.: WO94/21614 PCT Pub. Date: September 29, 1994 Related U.S. Patent Documents Application NumberFiling DatePatent NumberIssue Date 36645Mar., 1993 Current U.S. Class: 546/108 ; 546/109 Current International Class: C07D 221/00 (20060101); C07D 221/12 (20060101); C07D 221/12 (); C07D 401/12 () Field of Search: 546/108,109 514/298 References Cited [Referenced By] U.S. Patent Documents 2227876 January 1941 Bolt 3239417 March 1966 Ditullio et al. 3264301 August 1966 Doorenboos et al. 3285918 November 1966 Doorenboos et al. 3567733 March 1971 Nomine et al. 4220775 September 1980 Rasmusson et al. 4317817 March 1982 Blohm et al. 4377584 March 1983 Rasmusson et al. 4596812 June 1986 Chidsey, III et al. 4732897 March 1988 Cainelli et al. 4760071 July 1988 Rasmusson et al. 4845104 July 1989 Carlin et al. 4859681 August 1989 Rasmusson et al. 4882319 November 1989 Holt et al. 4910226 March 1990 Holt et al. 5247091 September 1993 Mueller-Lehar Foreign Patent Documents 970692 Jul., 1975 CA 0004949 Oct., 1979 EP 0155096 Sep., 1985 EP 0200859 Nov., 1986 EP 0277002 Jun., 1988 EP 0289327 Nov., 1988 EP 0314199 May., 1989 EP 0343954 Nov., 1989 EP 0375344 Jun., 1990 EP 0375345 Jun., 1990 EP 0375347 Jun., 1990 EP 0375349 Jun., 1990 EP 1465544 Nov., 1965 FR WO91/12261 Aug., 1991 WO Other References Campbell et al., Syn. Commun. (1979), vol. 9, pp. 471-476, "A Novel Synthesis . . . : An Intermediate Useful in Terpene Synthesis". . Vila et al., Tet. Letters (1989), vol. 45, pp. 4951-4960, "Conformational Analysis of the 4a-Methyl Octahydrophenanthrene System". . Iida et al., Heterocycles (1983), vol. 20, pp.227-230, "A New Synthesis of Phenanthridine Derivatives". . Schultz et al., J. Am. Chem. Soc. (1978), vol. 100, pp. 2140-2149, "Heteroatom Directed Photoarylation. Synthetic Potential of the Heteroatom Sulfur". . Neri et al., Endo. (1972), vol. 91, No. 2, pp. 427-437, "A Biological Profile of a Non-steroidal Antiandrogen, SCH 13521 . . . ". . Nayfeh et al., Steroids, vol. 14 (1969), pp. 269-283, "Metabolism of Progesterone by Rat Testicular Homogenates-III". . Voight et al., Endo., vol. 92 (1973), p.1216, "The Antiandrogenic Action of 4-Androsten-3-one-17beta-Carboxylic Acid and its Methyl Ester on Hamster Flank Organ". . Doorenbos et al., J. Pharm. Sci., vol. 62, No. 4 (1973), pp. 638-640, "Synthesis & Antimicrobial Properties of 17Beta-Isopentyloxy-4-Aza-5 Alpha-Androstane and the 4-Methyl Derivative". . Doorenbos et al., J. Pharm. Sci., vol. 60, No. 8 (1971), pp. 1234-1235, "4,17 Alpha-Dimethyl-4-Aza-5 Alpha-Androstan-17 beta-ol Acetate & Related Azasteroids". . Doorenbos et al., J. Pharm. Sci., vol. 63, No. 4 (1974), pp. 620-622, "Synthesis & Evaluation of Antimicrobial Properties of Amidinoazaandrostanes and Guanidinoazaandrostanes". . Rasmusson et al., J. Med. Chem., vol. 29, No.11 (1986), pp. 2298-3115, "Aza Steroids: Structure-Activity Relationships . . . ". . Brooks et al., Prostate, vol. 9, No. 1 (1986), pp. 65-75, "Prostatic Effects Induced in Dogs by . . . 5 alpha-Reductase Inhibitors". . Brooks et al., Steroids, vol. 47, No. 1 (1986), pp. 1-19, "5 Alpha-Reductase Inhibitory . . . Activities of Some 4-Aza-Steroids in the Rat". . Liang et al., Endo., vol. 117, No. 2, (1986), pp. 571-579, "Species Differences in Prostatic Steroidal 5 Alpha-Reductases of Rat, Dog and Human". . Rasmusson et al., J. Med. Chem., vol. 27, No. 12 (1984), pp. 1690-1701, "Azasteroids as Inhibitors of Rat Prostatic 5 Alpha-Reductase". . Back et al., J. Org. Chem, vol. 46, No. 7 (1981), pp. 1442-1446, "N-Chloroazasteroids . . . ". . Liang et al., Chem. Abstracts, vol. 95, 109055j, "Inhibition of 5-Alpha-Receptor Binding . . . by a 4-Methyl-4-Aza-Steroid" (1985). . Kadohama et al., JNCL, vol. 74, No. 2 (Feb. 1985), pp. 475-481, "Retardation of Prostate Tumor Progression in the Noble Rat by 4-Methyl-4-Aza-Steroidal Inhibitors of 5 Alpha-Reductase". . Andriole et al., The Prostate, vol. 10 (1987), pp. 189-197, "The Effect of 4MA . . . on the Growth of . . . Human Tumors . . . ". . Bingham et al., J. Endocr., vol. 57 (1973), pp. 111-121, "The Metabolism of Testosterone by Human Male Scalp Skin". . Kedderis et al., Toxicol. Appl. Pharmacol., vol. 103 (1990), pp. 222-227, "Studies with Nitrogen-Containing Steroids . . . ". . Metcalf et al., Bioinorganic Chemistry, vol. 17 (1986), pp. 372-376, "Patent Inhibition of Human Steroid . . . by 3-Androstene-3-Carboxylic Acid". . Levy et al., Biochemistry, vol. 29 (1990), pp. 2815-2824, "Inhibition of Rat Liver Steroid 5 Alpha-Reductase . . . ". . Holt et al., J. Med. Chem., vol. 33 (1990), pp. 943-950, "Steroidal A Ring Carboxylic Acids . . . ". . Levy et al., J. Steroid Biochem., vol. 34, No. 1-6 (1989), pp. 571-575, "Interaction Between Rat Prostatic 5 Alpha-Reductase . . . ". . Holt et al., J. Med. Chem., vol. 33 (1990), pp. 937-942, "Steroidal A Ring Aryl Carboxylic Acids . . . ". . Metcalf et al., TIPS (Dec. 1989), vol. 10, pp. 491-495, "Inhibitors of . . . 5 Alpha-Reductase in Benign Prostatic Hyperplasia . . . ". . Murphy et al., Steroids, vol. 35, No. 3 (Mar. 1980), pp. 1-7, "Effect of Estradiol on a . . . Binding Protein in the Uterus of the Mouse". . Stone et al., Prostate, vol. 9 (1986), pp. 311-318, "Estrogen Formation in Human Prostatic Tissue . . . ". . Brooks et al., Steroids, vol. 47, No. 1 (1986), pp. 1-19, "5 Alpha-Reductase Inhibitory . . . Activities of Some 4-Azasteroids . . . ". . Labrie et al., Lancet, No. 8515 (1986), pp. 1095-1096, "Combination Therapy in Prostate Cancer". . Rittmaster et al., J. Clin. Endocrin & Metab., vol. 55, No. 1 (1987), pp. 188-193, "The Effects of . . . a 5 Alpha-Reductase Inhibitor . . . ". . Diani et al., J. Clin. Endoc. & Metab., vol. 74, No. 2 (1990), pp. 345-350, "Hair Growth Effects of Oral Administration of Finasteride . . . ". . Bruchovsky et al., J. Clin. Endoc. Metab., vol. 67, No. 4 (1988), pp. 808-816, "Kinetic Parameters of 5 Alpha-Reductase Activity in Stroma & Epithelium of Normal, Hyperplastic & Carcinomatous Human Prostates". . Hudson, J. Steroid Biochem., vol. 26, No. 3 (1987), pp. 349-353, "Comparison of Nuclear 5 Alpha-Reductase Activities in the Stromal and Epithelial Fractions of Human Prostatic Tissue". . Moore et al., J. Biol. Chem., vol. 251, No. 19 (1976), pp. 5895-5900, "Steroid 5 Alpha-Reductase in Cultured Human Fibroblasts". . Andersson et al., J. Biol. Chem., vol. 264, No. 27 (1989), pp. 16249-16255, "Expession Cloning & Regulation of Steroid 5 Alpha-Reductase, an Enzyme Essential for Male Sexual Differentiation". . Andersson et al., Proc. Nat'l Acad. Science, vol. 87 (1990), pp. 3640-3644, "Structural & Biochemical Properties of Cloned and Expressed Human and Rat Steroid 5 Alpha-Reductases". . Andersson et al., Nature, vol. 354 (Nov. 14, 1991), pp. 159-161, "Deletion of Steroid 5 Alpha-Reductase-2 Gene in Male Pseudohermaphroditism". . Wilson, Biol. of Reproduction, vol. 46 (1992), pp. 168-173, "Syndromes of Androgen Resistance". . Geldolf et al., Eur. J. Cancer, vol. 26, No. 2 (1990), pp. 188, "Enzyme Inhibitors in Hormone Dependent Prostate Cancer Growth". . Geldolf et al., J. Cancer Res. Clin. Oncol., vol. 118 (1992), pp. 50-55, "Consideration of the Use of . . . 4MA . . . in Prostate Cancer Research". . Brooks et al., The Prostate, vol. 18 (1991), pp. 215-227, "Effect of Castration, DES, Flutamide, and MK-906 on Growth of the Dunning Rat Prostatic Carcinoma". . Jones et al., J. Med. Chem., vol. 36 (1993), pp. 421-423, "Nonsteroidal Inhibitors of Human Type 1 Steroid 5alpha-Reductase". . Masubuchi et al., Eur. J. Pharm., vol. 183, No. 5 (1990), p. 1757, "Lack of DHT Inhibition . . . by Treatment of 4MA . . . ".. Primary Examiner: Rotman; Alan L. Assistant Examiner: Rotman; A. Attorney, Agent or Firm: Fitch; Catherine D. Winokur; Melvin Parent Case Text CROSS-REFERENCE This application is a 371 of PCT/US94/03080 filed Mar. 22, 1994, which is a continuation of Ser. No. 08/036,645 filed Mar. 24, 1993, (now abandoned). Claims What is claimed is: 1. A compound of the formula I ##STR4## or a pharmaceutically acceptable salt or ester thereof, wherein R.sub.1 and R.sub.3 are independently selected from the group consisting of hydrogen and C.sub.1-6 alkyl; R.sub.2 is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxyl and C.sub.1-6 alkylcarbonyloxy; X is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxyl, C.sub.1-6 alkoxy-C.sub.1-6 alkyl, halogen, cyano, C.sub.1-6 alkylcarbonyl, Ar-carbonyl, C.sub.1-6 alkoxycarbonyl, C.sub.1-6 alkylaminocarbonyl, Ar-aminocarbonyl and di-C.sub.1-6 alkylaminocarbonyl; and Ar is phenyl or pyridyl. Description FIELD OF THE INVENTION The present invention provides novel compounds, novel compositions, methods of their use and methods of their manufacture, where such compounds are generally pharmacologically useful as agents in therapies whose mechanism of action rely on the selective inhibition of the isozyme 5.alpha.-reductase 1. BACKGROUND OF THE INVENTION Certain undesirable physiological manifestations, such as acne vulgaris, seborrhea, female hirsutism, male pattern baldness (alopecia) and benign prostatic hyperplasia, are the result of hyperandrogenic stimulation caused by an excessive accumulation of testosterone or similar androgenic hormones in the metabolic system. Early attempts to provide a chemotherapeutic agent to counter the undesirable results of hyperandrogenicity resulted in the discovery of several steroidal antiandrogens having undesirable hormonal activities of their own. The estrogens, for example, not only counteract the effect of the androgens but have a feminizing effect as well. Non-steroidal antiandrogens have also been developed, for example, 4'-nitro-3'-trifluoromethyl-isobutyranilide. See Neri, et al., Endocrinol. 1972, 91 (2). However, these products, though devoid of hormonal effects, compete with all natural androgens for receptor sites, and hence have a tendency to feminize a male host or the male ferns of a female host and/or initiate feed-back effects which would cause hyperstimulation of the testes. The principal mediator of androgenic activity in some target organs, e.g. the prostate, is 5.alpha.-dihydrotestosterone, formed locally in the target organ by the action of testosterone-5.alpha.-reductase. Inhibitors of testosterone-5.alpha.-reductase will serve to prevent or lessen symptoms of hyperandrogenic stimulation in these organs. It is now known that a second 5.alpha.-reductase isozyme exists, which interacts with epidermal tissues, especially in scalp tissues. This form is conventionally designated as 5.alpha.-reductase 1, while the isozyme that principally interacts with the prostatic tissues is designated as 5.alpha.-reductase 2. Both isozymes are active in the prostatic tissues. Thus, in the treatment of hyperandrogenic disease conditions e.g. benign prostatic hyperplasia (BPH), it would be desirable to have one drug entity which is active against both isozymes in the prostate to significantly inhibit dihydrotesterone production, while also having another drug entity which is highly selective for inhibiting the isozyme 5.alpha.-reductase 1 associated with the scalp, for use in treating conditions of the skin and scalp, e.g. acne and alopecia in males and hirsutism in females. Additionally, such a selective 5.alpha.-reductase 1 inhibitor could also be used in combination with finasteride (PROSCAR.RTM.), which is highly selective for 5.alpha.-reductase 2, for combination therapy in the treatment of BPH. Therefore it is an object of this invention to provide compounds that have sufficient activity in the inhibition of one or both 5.alpha.-reductase isozymes. It is an additional object of this invention to provide compounds that are useful in the treatment and/or prevention of benign prostatic hyperplasia. It is an additional object of this invention to provide compounds that are useful in the treatment of female hirsutism, male pattern baldness, acne, androgenetic alopecia, prostatic cancer, and insufficient plasma levels of high density lipoproteins. The compounds of the invention have utility in one or more of the aforementioned areas. SUMMARY OF THE INVENTION The compounds of the present invention are those of the general structural formula I: ##STR1## or a pharmaceutically acceptable salt or ester thereof, wherein R.sub.1 and R.sub.3 are independently selected from the group consisting of hydrogen and C.sub.1-6 alkyl; R.sub.2 is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxyl and C.sub.1-6 alkylcarbonyloxy; X is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxyl, C.sub.1-6 alkoxy-C.sub.1-6 alkyl, halogen, cyano, C.sub.1-6 alkylcarbonyl, Ar-carbonyl, C.sub.1-6 alkoxycarbonyl, C.sub.1-6 alkylaminocarbonyl, Ar-aminocarbonyl and di-C.sub.1-6 alkylaminocarbonyl; and Ar is phenyl or pyridyl. DETAILED DESCRIPTION OF THE INVENTION Salts encompassed within the term "pharmaceutically acceptable salts" refer to non-toxic salts of the compounds of this invention which are generally prepared by reacting the free base with a suitable organic or inorganic acid. Representative salts include the following salts: ______________________________________ Acetate Lactobionate Benzenesulfonate Laurate Benzoate Malate Bicarbonate Maleate Bisulfate Mandelate Bitartrate Mesylate Borate Methylbromide Bromide Methylnitrate Calcium Edetate Methylsulfate Camsylate Mucate Carbonate Napsylate Chloride Nitrate Clavulariate N-methylglucamine Citrate ammonium salt Dihydrochloride Oleate Edetate Oxalate Edisylate Pamoate (Embonate) Estolate Palmitate Esylate Pantothenate Fumarate Phosphate/diphosphate Gluceptate Polygalacturonate Gluconate Salicylate Glutamate Stearate Glycollylarsanilate Sulfate Hexylresorcinate Subacetate Hydrabamine Succinate Hydrobromide Tannate Hydrochloride Tartrate Hydroxynaphthoate Teoclate Iodide Tosylate Isothionate Triethiodide Lactate Valerate ______________________________________ The term "pharmacologically effective amount" shall mean that amount of a drug or pharmaceutical agent that will elicit the biological or medical response of a tissue, system, animal or human that is being sought by a researcher or clinician. The term "alkyl" shall mean straight or branched chain alkanes of one to ten total carbon atoms, or any specified numbers within this range. Whenever the term "alkyl" or its prefix root appears in a name of a substituent (e.g. aralkoxyaryloxy) it shall be interpreted as including those limitations given above for "alkyl". The compounds of the present invention can be administered in such oral dosage forms as tablets, capsules (each including timed release and sustained release formulations), pills, powders, granules, elixers, tinctures, suspensions, syrups and emulsions. Likewise, they may also be administered in intravenous (both bolus and infusion), intraperitoneal, subcutaneous or intramuscular form, all using forms well known to those of ordinary skill in the pharmaceutical arts. An effective but non-toxic amount of the compound desired can be employed as an antiandrogenic agent. The dosage regimen utilizing the compounds of the present invention is selected in accordance with a variety of factors including type, species, age, weight, sex and medical condition of the patient; the severity of the condition to be treated; the route of administration; the renal and hepatic function of the patient; and the particular compound or salt thereof employed. An ordinarily skilled physician or veterinarian can readily determine and prescribe the effective amount of the drug required to prevent, counter or arrest the progress of the condition. Oral dosages of the present invention, when used for the indicated effects, will range between about 0.05 to 1000 mg/day orally. The compositions are preferably provided in the form of scored tablets containing 0.5, 1.0, 2.5, 5.0, 10.0, 15.0, 25.0 and 50.0 mg of active ingredient. Effective plasma levels of the compounds of the present invention range from 0.002 mg to 50 mg per kg of body weight per day. Advantageously, compounds of the present invention may be administered in a single daily dose, or the total daily dosage may be administered in divided doses of two, three or four times daily. Furthermore, preferred compounds for the present invention can be administered in intranasal form via topical use of suitable intranasal vehicles, or via transdermal routes, using those forms of transdermal skin patches well known to those of ordinary skill in that art. To be administered in the form of a transdermal delivery system, the dosage administration will, of course, be continuous rather than intermittant throughout the dosage regimen. Other preferred topical preparations include creams, ointments, lotions, aerosol sprays and gels, wherein the concentration of active ingredient would range from 0.1% to 15%, w/w or w/v. In the methods of the present invention, the compounds herein described in detail can form the active ingredient, and are typically administered in admixture with suitable pharmaceutical diluents, excipients or carriers (collectively referred to herein as "carrier" materials) suitably selected with respect to the intended form of administration, that is, oral tablets, capsules, elixirs, syrups and the like, and consistent with conventional pharmaceutical practices. For instance, for oral administration in the form of a tablet or capsule, the active drug component can be combined with an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water and the like. Moreover, when desired or necessary, suitable binders, lubricants, disintegrating agents and coloring agents can also be incorporated into the mixture. Suitable binders include starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tragacanth or sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes and the like. Lubricants used in these dosage forms include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride and the like. Disintegrators include, without limitation, starch, methyl cellulose, agar, bentonite, zanthan gum and the like. The compounds of the present invention can also be administered in the form of liposome delivery systems, such as small unilamellar vesicles, large unilamellar vesicles and multilamellar vesicles. Liposomes can be formed from a variety of phospholipids, containing cholesterol, stearylamine or phosphatidylcholines. Compounds of the present invention may also be delivered by the use of monoclonal antibodies as individual carriers to which the compound molecules are coupled. The compounds of the present invention may also be coupled with soluble polymers as targetable drug carriers. Such polymers can include polyvinylpyrrolidone, pyran copolymer, polyhydroxypropyl-methacrylamide-phenol, polyhydroxyethylaspanamidephenol, or polyethyleneoxidepolylysine substituted with palmitoyl residues. Furthermore, the compounds of the present invention may be coupled to a class of biodegradable polymers useful in achieving controlled release of a drug, for example, polylactic acid, polyepsilon caprolactone, polyhydroxy butyric acid, polyorthoesters, polyacetals, polydihydropyrans, polycyanoacrylates and cross-linked or amphipathic block copolymers of hydrogels. The compounds of the present invention can be prepared readily according to the following reaction Schemes and Examples or modifications thereof using readily available starting materials, reagents and conventional synthesis procedures. In these reactions, it is also possible to make use of variants which are themselves known to those of ordinary skill in this art, but are not mentioned in greater detail. ##STR2## The carbonyl of a phenanthrone such as 1 is protected as the ketal 2 by reaction with ethylene glycol in the presence of an acid with removal of water. The double bond which moves out of conjugation with the aforementioned carbonyl is oxidized to the ozonide which is subsequently oxidized with hydrogen peroxide. The resulting acid 3 is converted to the acyl azide 5 via the acid chloride 4. Heating of 5 results in a Curtius rearrangement to the isocyanate which, along with the ketal protecting group, is hydrolyzed in the presence of aqueous acid to the dione 6 which will spontaneously cyclize to the 3-phenanthridinone 7. Alkylation of the nitrogen with an alkyl iodide results in the formation of 8. ##STR3## In Scheme II, Michael addition of N-alkyl homophthalimide to phenylthiomethyl vinyl ketone in the presence of base gives the adduct 9. The side chain carbonyl is protected as the ketal and one of the ring carbonyl groups is reduced with sodium borohydride and eliminated to form the isocarbostyril or isoquinolone-like compound 11. Subsequent ketalization of the side chain carbonyl followed by reduction and cyclization yields the substituted 3-phenanthridinone 12. Oxidative elimination of the phenylthio group gives the desired product 13. The most preferred compounds of the invention are any or all of those specifically set forth in these examples. These compounds are not, however, to be construed as forming the only genus that is considered as the invention, and any combination of the compounds or their moieties may itself form a genus. The following examples further illustrate details for the preparation of the compounds of the present invention. Those skilled in the art will readily understand that known variations of the conditions and processes of the following preparative procedures can be used to prepare these compounds. All temperatures are degrees Celsius unless noted otherwise. EXAMPLE 1 BIOLOGICAL ASSAYS Preparation of Human prostatic and scalp 5.alpha.-reductases Samples of human tissue were pulverized using a freezer mill and homogenized in 40 mM potassium phosphate, pH 6.5, 5 mM magnesium sulfate, 25 mM potassium chloride, 1 mM phenylmethylsulfonyl fluoride, 1 mM dithiothreitol (DTT) containing 0.25 M sucrose using a Potter-Elvehjem homogenizer. A crude nuclear pellet was prepared by centrifugation of the homogenate at 1,500 xg for 15 min. The crude nuclear pellet was washed two times and resuspended in two volumes of buffer. Glycerol was added to the resuspended pellet to a final concentration of 20%. The enzyme suspension was frozen in aliquots at -80.degree. C. The prostatic and scalp reductases were stable for at least 4 months when stored under these conditions. 5.alpha.-reductase assay The reaction mixture contained in a final volume of 100 .mu.l is: 40 mM buffer (human scalp, potassium phosphate, pH 6.5; human prostatic 5.alpha.-reductase, sodium citrate, pH 5.5), 0.3-10 .mu.M.sup.14 C-T (or .sup.3 H-T), 1 mM DTT, and 500 .mu.M NADPH. Typically, the assay was initiated by the addition of 50-100 .mu.g prostatic homogenate or 75-200 .mu.g scalp homogenate and incubated at 37.degree. C. After 10-50 min the reaction was quenched by extraction with 250 .mu.l of a mixture of 70% cyclohexane: 30% ethyl acetate containing 10 .mu.g each DHT and T. The aqueous and organic layers were separated by centrifugation at 14,000 rpm in an Eppendorf microfuge. The organic layer was subjected to normal phase HPLC (10 cm Whatman partisil 5 silica column equilibrated in 1 ml/min 70% cyclohexane: 30% ethyl acetate; retention times DHT, 6.8-7.2 min; androstanediol, 7.6-8.0; T, 9.1-9.7 min). The HPLC system consisted of a Waters Model 680 Gradient System equipped with a Hitachi Model 655A autosampler, Applied Biosystems Model 757 variable UV detector, and a Radiomatic Model A120 radioactivity analyzer. The conversion of T to DHT was monitored using the radioactivity flow detector by mixing the HPLC effluent with one volume of Flo Scint 1 (Radiomatic). Under the conditions described, the production of DHT was linear for at least 25 min. The only steroids observed with the human prostate and scalp preparations were T, DHT and androstanediol. EXAMPLE 2 A solution of 4a-methyl-4,4a,9,10-tetrahydro-2(3H)-phenanthrone 1 (7 g, 33 mmol; prepared by the method of A. L. Campbell and J. D. McChesney, Syn. Commun. 1979, 9, 471-479) is dissolved in anhydrous benzene (300 mL) and ethylene glycol (16 mL) and p-toluenesulfonic acid (0.7 g, 4 mmol) added. The solution is refluxed with the removal of water in a Dean-Stark trap according to the method of A. J. Vila, R. A. Spanevello, A. C. Olivieri, M. G. Sierra, and J. D. McChesney, Tet. Lett. 1989, 45, 4951-4960 to form the ketal, 2-ethylenedioxy-4a-methyl- 1,2,3,4,4a,9-hexahydrophenanthrene 2. A solution of 2 is dissolved in methylene chloride and cooled to -78.degree. C. and a stream of ozone is passed through it until a pale blue color persists. A solution of water containing 30% hydrogen peroxide is added and the mixture warmed to 0.degree. C. for 2 hr, then to room temperature for 48 hr. Ethyl acetate is added and the solution successively washed with 2% aqueous sodium bisulfite solution, water, and saturated salt solution. The organic solution is dried over anhydrous sodium sulfate and the solvent removed by rotoevaporation to yield 2-(4'-ethylenedioxy-1 '-methyl-2'-oxocyclohexyl)-phenylacetic acid 3. The acid 3 is dissolved in diethyl ether and dimethylformamide and thionyl chloride is added. The solution is stirred at room temperature for 1 hr and poured into ice water. The ether layer is separated and dried over anhydrous sodium sulfate. The solvent is removed by rotoevaporation and the product, 2-(4'-ethylenedioxy-1'-methyl-2'-oxocyclohexyl)-phenylacetyl chloride 4, is dissolved in acetone. Sodium azide is added and the solution stirred for 20 min. Water is added and the mixture extracted with diethyl ether and the organic layer dried over anhydrous sodium sulfate. The solvent is removed by rotoevaporation to yield 2-(4'-ethylenedioxy-1'-methyl-2'-oxocyclohexyl)-phenylacetyl azide 5. The acyl azide 5 is dissolved in dimethylformamide and heated to 100.degree. C. until nitrogen evolution ceases. The solution is cooled and treated with aqueous acetic acid to form 2-(2', 4'-dioxo-1'-methyl-cyclohexyl)-benzyl amine 6. Diethyl ether is added and the solution is washed successively with saturated sodium bicarbonate solution, water, and saturated salt solution and dried over anhydrous sodium sulfate. The solvent is removed by rotoevaporation to yield 1,2,3,4,4a,5,6,10b-octahydro- 10b-methyl-3-phenanthridinone 7. A solution of 7 in dimethylformamide at 0.degree. C. is treated with 1 equivalent of sodium hydride followed by methyl iodide. After stirring at room temperature, diethyl ether is added and the solution successively washed with water and saturated salt solution. The solvent is removed by rotoevaporation to yield 1,2,3,4,4a,5,6,10b-octahydro-5,10b-dimethyl-3-phenanthridinone 8. EXAMPLE 3 3(2H)-Phenanthridinone derivatives have been prepared from homophthalimide by the method of H. Iida et al., (Heterocycles 1983, 20, 227-30). 2-Methyl-homophthalimide is reacted with phenylthiomethyl vinyl ketone (prepared by the method A. G. Schultz et al.,J. Am. Chem. Soc. 1978, 100, 2140-9) in the presence of Triton B according to the described method to form 2-methyl-4-(3'-oxo-4'-phenylthiobutyl)-homophthalimide 9. Reaction of 9 with ethylene glycol and p-toluenesulfonic acid in refluxing anhydrous benzene with removal of water by a Dean-Stark trap gives 4-(3'-ethylenedioxy-4'-phenylthiobutyl)-2-methylhomophthalimide 10 which is reduced with sodium borohydride and treated with aqueous hydrochloric acid to form 2-methyl-4-(3'-oxo-4'-phenylthiobutyl)-isocarbostyril 11. Ketalization of 11 with ethylene glycol in the presence of p-toluenesulfonic in reluxing benzene follows as above. Reaction of the ketal with lithium aluminum hydride in diethyl ether followed by treatment with concentrated hydrochloric acid at 100.degree. C. gives 5-methyl-1,2,3,4,4a,5,6,10b-octahydro-4-phenylthio-3-phenanthridinone 12. Treatment of 12 with basic hydrogen peroxide gave 5-methyl-1,2,3,4,4a, 10b-hexahydro-3-phenanthridinone 13. While the invention has been described and illustrated with reference to certain preferred embodiments thereof, those skilled in the art will appreciate that various changes, modifications and substitutions can be made therein without departing from the spirit and scope of the invention. For example, effective dosages other than the preferred dosages as set forth herein above may be applicable as a consequence of variations in the responsiveness of the mammal being treated for any of the indications for the compounds of the invention indicated above. Likewise, the specific pharmacological responses observed may vary according to and depending upon the particular active compound selected or whether there are present pharmaceutical carriers, as well as the type of formulation and mode of administration employed, and such expected variations or differences in the results are contemplated in accordance with the objects and practices of the present invention. It is intended, therefore, that the invention be limited only by the scope of the claims which follow and that such claims Be interpreted as broadly as is reasonable. * * * * *
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"Substituted 3-phenanthridinone Derivatives As 5-alpha-reductase Inhibitors - Patent 5621104"Please download to view full document


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This Cuisinart Stainless Steel Bar Wall Pot Rock is a lovely way to store and display your pots and pans. Made of brushed stainless steel, it comes with 4 stainless steel hooks and a limited lifetime manufacturer's warranty. Measures 33" l x 3" w x 3" h. This bar-style pot rack is great for kitchens of all shapes and sizes. The sleek profile and universal pot hooks work wonderfully for storing your most used pots and pans.
product information
- Comes with 5 stainless hooks
- Simple to install and designed to last a lifetime
product details
SKU 00148664 model no CRBW-33B product dimensions 33" x 1.5" x 3" shipping weight 4 brand Cuisinart color No material stainless steel MFG: product manual N/A MFG: warranty N/A MFG: specs N/A
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subset: commoncrawl


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At South by Southwest, HBO creates an interactive installation where "Game of Thrones" fans can take portraits in the Iron Throne and play a game that lets them hone their sword-wielding skills.
As supplies of the coveted collectibles dwindle, enthusiasts besiege the Lollipop pop-up booth at Mobile World Congress in a last-ditch effort for complete satisfaction.
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lizlovelust Model
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You refer to 'people' when you should be using 'I'. You're applying your needs and desires onto everyone else and you're factually wrong as evidenced by sales.
That's where they went wrong to begin with, attempting to do that at all...
The concept of hybrid laptops is pretty amazing. Too bad no OEM has managed to do it properly.
A separate OS for tablets would have been wiser, leaving the traditional desktop/laptop OS as is.
Now Microsoft has stated ARM is the future for the Desktop.
Windows RT is the future vision of Microsoft for the mainstream users...
A separate OS for tablets would have been wiser, leaving the traditional desktop/laptop OS as is.
Octavean:Im not sure you understand where I am coming from. When talking about Apple Computers and Laptops, they are running x86 hardware for the most part the same as a Desktop PC.However the Apple Store based systems :ie the IPhone, Ipad, etc are running IOS in most cases ARM based systems.
Anyway, I think Intel can and will bring the fight to ARM devices in due time. It does sort of make some sense for AMD to make ARM chips and X86 / X64 chips as well though. There are even rumors that Intel foundries are in talks for ARM manufacturing too,...
1 recommendation
I don't know what you would be willing to bet, but I have a beard I'd be willing to place on the line if Windows doesn't have some semblance of a Start Menu either in Beta or final form by the end of the third quarter.
1. Four million desktop apps need to run somewhere. Back in 2010, at the International CES in Las Vegas, Microsoft CEO Steve Ballmer noted that four million desktop programs run on Windows 7. All of those programs run on Windows 8, too. Backward compatibility is the lifeblood of Windows. The idea that those legacy apps will be orphaned in a single release is ludicrous.2. Corporate customers and OEMs would mutiny. Corporate customers need to write custom apps that run on Windows. Those apps need to do things that arent possible in the highly constrained Windows 8 app model. And those corporate customers with their volume licenses pay billions of dollars in license fees to Microsoft every year for Windows. Say what you want about Steve Ballmer, but dont try to tell me hes going to willingly give up one of Microsofts most lucrative revenue streams. And if you think that, well, then you probably think Richard Stallman is next in line to be Chief Technical Officer of Microsoft.3. Refactoring old-fashioned dialog boxes into a more touch-friendly interface is an evolutionary step. The whole point of Windows 8 is to enable touch as a primary user input mechanism, alongside the mouse and keyboard. That makes it possible for Microsofts PC-building OEM partners to build hybrid devices that can smoothly shift from conventional PC to tablet and back again. (I looked at three such devices just a few weeks ago.) In the first release of Windows 8, a limited selection of Control Panel functions were converted to the new modern/Metro UI. Did anyone not expect that the long-term goal was to move more and more of these functions to the modern UI? Yes, that means the old desktop Control Panel is being deprecated, and that Windows users will probably need to drop to the desktop less often in Blue. It doesnt mean the desktop is vanishing.4. Removing the desktop would be more trouble than its worth. Many hundreds of thousands of words have been written about the complexity of Windows. Windows developers have spent years making the OS simpler, and more modular, with some success. But ripping out the desktop completely is, if not impossible, at least highly unlikely. Maybe in a decade the need for the desktop will vanish. But that day wont come this year or next.5. Microsoft already has a no desktop option: Windows RT. When Windows 8 shipped last October, Windows RT shipped right alongside it. Microsoft is committed to both platforms. One has the ability to run Windows desktop apps; the other doesnt. Does anyone really believe that Microsoft would dump the OS that sold 60 million copies in its first two months and put all its chips on the one that has sold perhaps a million or two copies in the same period? If so, I want to play poker with you.
Given that though....if WinRT becomes what Microsoft is shifting everyone to....Windows will be nothing more than a locked down OS where you can only get/upgrade programs/apps from the Microsoft Store. I'll easily go to Linux if that happens and I hope it would blowback hard in MS's face.
Linux, what is that? Last time I check »gs.statcounter.com/#os-ww-monthl ··· 2-201302 it had less then 1% of the world's desktops and has been pretty much flat lined forever despite all the 'this will be the year of Linux'.


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2nd Season Of At The Paley Center To Feature Glenn Close, Marlo Thomas
The Paley Center for Media and WNET will bring legendary voices and footage to New York metro area public television viewers in the second season of the interview series At the Paley Center premiering 8:30 p.m. on THIRTEEN beginning January 19th, Tuesdays at 10:30 p.m. on WLIW21 beginning on January 24 and Tuesdays at 10:00 p.m. on NJTV beginning on January 24.
For this second season, the Paley Center and WNET are launching a special initiative called "She's Making Media," a new series of programs that puts a slightly different lens on the subject of women's role in media. At the Paley Center will celebrate women who are making media - media with a purpose. Hosted by Pat Mitchell, President and CEO of The Paley Center for Media, each half-hour episode of the new six-part series concentrates on a woman who has used media in new and innovative ways, including Glenn Close (January 19), Marlo Thomas (January 26), Jane Fonda (February 2), Arianna Huffington (February 9), Eve Ensler (February 16), and Maria Elena Salinas (February 23).
About the show: In each unique and compelling half hour episode, the guest's life-story is intertwined with numerous examples of her work, taking advantage of the Paley Center's Collection. Mitchell also speaks with each guest about the enormous impact of the media on women. A unique, signature element of At The Paley Center is a short performance, reading, or monologue selected and performed by the guest: for example, Marlo Thomas reads an excerpt from her autobiography about her marriage to Phil Donahue; Jane Fonda reads an excerpt from her book about her decision to end her marriage to Ted Turner; Eve Ensler performs a short monologue; and Glenn Close sings an a cappella rendition of a lullaby she co-authored for her current film, Albert Nobbs. This very personal coda to the show is selected by each guest.
Episodes of At the Paley Center will stream online after each week's premiere at www.thirteen.org/paleycenter.
At the Paley Center is a production of The Paley Center for Media and a presentation of Creative News Group in association with WNET.ORG. Executive Producers for The Paley Center for Media are Pat Mitchell, Diane Lewis, John Wolters, and Susan Lester for LesterMedia. For Creative News Group Mary Lockhart is Executive Producer and Stephen Segaller and Neal Shapiro are Executives in Charge. The series is funded by Rosalind P. Walter.
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Science & Health
7:18 am
Tue January 14, 2014
Cold Weather Returning
BIRMINGHAM, Ala. (AP) — Forecasters say there's a chance for rain and snow showers across parts of northern Alabama late Tuesday night into Wednesday morning. However, little snow accumulation is expected. The National Weather Service says new snow accumulation of less than a half-inch is possible in the Birmingham area. Cooler temperatures are also in store for Alabama for the second half of the week. Lows temperatures of around 19 degrees are expected in the Huntsville and Florence areas by early Saturday. In the Birmingham metro area, temperatures are expected to begin sliding Wednesday toward overnight lows of around 21 degrees by the weekend. Lows in the Montgomery and Mobile areas are expected to be in the lower to mid-20s by the weekend.


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Can Someone Identify Whats Eating My Dahlias?
I am hoping that someone will be able to help me. Some type of insect is eating my dahlias. Either the edges of the leaves have turned black or the leaves are eaten off completely. Also the new growth at the tops of the plants are being eaten too. I have not seen any kind of insect although I have looked several times both on the stem and under the leaves. I have been spraying with Malathion?sp but whatever it is must love it and just keeps on eating. Out of 15 plants only one has blooms on it and it seems to be the only one this pest doesn't like to eat! Any help would be greatly appreciated. I would attach a photo but I don't see where I can do that.
Earwigs. At the first sign of problem, this pest is number one on the list.
Try this; put a short lenght of hose...about 12 to 18 inches in the vicinity of the plants. Early in the a.m. go out with a bucket of soapy water, lift the hose and tap it over the soap. See what falls out.
Earwigs is the one big reason why I never try to take dahlia inside, they are a beggar since they hide in amongs the petals.
The earwigs like it moist and munch at night, but hide during daylight hours. Trying to see them during the day is pretty well impossible.
Another method if you dont have a handy hose to destroy....roll up a newspaper section....place it in the vicinity and dampen it. In the morning, go out and collect your newspaper.
Sometimes too, just like catching slugs and snails, lay a board....about 6" wide...12" long near the plants. In the early morning, peek under it. They're fast movers so be prepared.


text:
Destination: Destin
Area: Miramar Beach - Scenic 98
Type: Condo/Villa
Number of Floors: 5
Bedrooms: 2
Baths: 2
Classic coastal living is yours to enjoy at this exciting resort in Miramar Beach. This beautiful new 4-story condominium resort sits directly across from the beach with breathtaking unobstructed views of the Gulf. Mediterranea features lovely manicured gardens and fountains, a heated pool & spa, community clubhouse, fitness center, tennis, underground parking and a boardwalk & gazebo leading to the beach. The luxurious 2-bedroom units feature designer interiors, master bath Jacuzzi, washer/dryer, plus multiple balconies for taking in the gulf views.
|Pool/Hot Tub/Sauna
|Complex Features
|Parking Features
|Services Available
The property has the following accessibility features. For additional information regarding any other accessibility features, please call (888)-909-6807
|This property has an accessible public entrance.
|There is an accessible route to the meeting room/ballroom area.
|There is an accessible route to the exercise facilities.
|There is an accessible route to one or more swimming pools.
|This property has accessible parking spaces for cars.
|This property's exercise facility is accessible.
|This property has an accessible swimming pool.
|Closest Airport: VPS
|Nearest City: Panama City Beach
|"Mediterranea" Check-In Office
|Check-In Information
|Check-In Office Name: Miramar Beach Office
11125 Highway 98 West
Miramar Beach, Florida
Check-In Time: 4:00 PM
Check-Out Time: 10:00 AM
Open: Sunday - Thursday 9:00AM - 5:00PM
Friday & Saturday 9:00AM - 7:00PM
850-654-6340 (check-in line)
850-654-6340 (office)
After Hours Check-In Procedure:
Pick up telephone next to office door. Telephone automatically rings to after hours call center. Customer service agents assists with check-in via lock box next to telephone.
GPS: Longitude -86.359491 Latitude 30.381590
877-497-6208(after hours phone)
Mediterranea - by Wyndham Vacation Rentals
Rachel K. | 01/09/2014
Tyler | 12/09/2009
15% Off For Spring Break
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Minimum Night Stay: 3
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Promo Code: MILITARY
Travel Start Date: 01/01/2015
Travel End Date: 12/31/2015
Bedrooms: 2
Extra Sleeping Area: Den
Baths: 2 Full + 1 Half
Type: Condo/Villa
Sleeps: 6
Proximity: Across the Street from Beach
1 - 3 BR | 1 - 3 BA | Sleeps 6 - 10
1 - 4 BR | 2 - 4 BA | Sleeps 5 - 10


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Should Roth IRA $ be taxed twice?
Hi everybody,
Several years ago my husband changed jobs and the new company he joined hadn't set up their 401K plan yet, so we rolled the 401K balance from his former employer into a traditional IRA. We also opened and deposited money into a Roth IRA. Then, in 2003 after his new company had established their own 401K and much of the money he'd rolled into the IRA had evaporated, he closed the IRA and rolled the balance into the 401K. At the same time, we withdrew what was left in the Roth IRA because we were steadily losing money, couldn't roll it into the 401K, and didn't want to continue our relationship with the broker.
When I filed our 2003 taxes, I apparently didn't document the IRA rollover or withdrawal correctly and as a result, I recently received a letter from the IRS showing a large balance owed. In response, I provided the IRA with evidence of the rollover along with a check for a 10% penalty plus interest on the Roth IRA withdrawal amount. I've now received another letter demanding additional $$$ because the IRS recalculated our 2003 income to include the Roth IRA withdrawal amount. Is this correct? I mean, the money we deposited in the Roth IRA had already been taxed. How can they tax me twice on the same income?
Your prompt advice would be very much appreciated. Thanks!
A basic principle of taxation in the USA is every dollar is taxed once and only once. (Qualifying Roth IRA withdrawals can be an exception.)
Your contributions to the Roth IRA should not be taxed again by the IRS because you already paid taxes on those contributions when you put them into the Roth IRA. The earnings on the Roth IRA may or may not be taxable depending on your circumstances. For example, how old are you, how long were the funds in the IRA, were there any circumstances that existed in your life that would qualify you for an exception to the 10% penalty for early withdrawal?
Page 58 of the pub linked to below should help you answer your questions.
In my 12 years of preparing taxes, one of my favorite things to do is prove the IRS wrong when they assess additional taxes.
Good luck.
Here is a link that might be useful: IRS Pub 590


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Floor Plans and Pricing
1 Bedroom
|$505 - $515
|1 Bathroom
|623 Sq. Ft.
2 Bedrooms
|$545 - $555
|1 Bathroom
|731 Sq. Ft.
|$680 - $710
|1 Bathroom
|870 Sq. Ft.
|$740 - $770
|1.5 Bathrooms
|1060 Sq. Ft.
3 Bedrooms
|2 Bathrooms
|1270 Sq. Ft.
Property Features
- Property Overview
- Special Features
- Community Features
- Apartment Amenities
- Local Schools
- Pet Policy
University Woods in Fairborn, OH
As you walk through a lush forest at the University Woods Apartment Homes, you will notice 1 & 2 bedroom apartments, 2 & 3 bedroom town homes and luxurious villas. Each home is equipped with air conditioning, Broadband Internet Access, cable, access on an on-site laundry facility, and balconies. Residents also head to the pool to relax with friends and neighbors. We welcome your pets too! Conveniently located in Fairborn with easy access to Wright Patterson Airforce Base, Wright State University, The Mall @ Fairfield Commons, I-675 and I-35. Call today to schedule your personal tour.
Special Features
- Beautiful L-Shaped Pool
- Washer Dryer Hook-Ups In Select Units
- Attached Garages With Select Styles
- Laundry Facilities
- Luxurious Townhomes and Villas
- Fully Equipped Kitchens
- Caring Staff
- Beautiful Wooded Views
- Close to I-675, The Mall @ Fairfield Commons & WSU
- Private Entryways
- Full Equipped Kitchen
- Clubhouse with Billiards
Community Features
- Apartment
- Club House
- Garages
- Laundry Facility
- Pool
- Townhouse
Apartment Amenities
- Air Conditioning
- Cable or Satellite
- Carpet
- Dishwasher
- Garbage Disposal
- Patio or Balcony
- Washer Dryer Hookup
- Window Covering
Local Schools
- Fairborn High School
- Fairborn Intermediate School
- Fairborn Primary School
We believe school data to be accurate, but do not guarantee that. Please be sure to verify where your children will attend school before making your housing decision.
Pet Policy
Pet Friendly...Some Breed Restrictions!
- Cats Allowed
- Pets Allowed
- Small Dogs Allowed
Web Reviews
Contact University Woods
University Woods
Office HoursMon - Fri: 9 AM to 5 PM Sat : 10 AM - 4:30 PM
Welcome home to University Woods! Located in Fairborn, Ohio our community offers convenient access to I-675, SR-35, OH-444, The Mall @ Fairfield Commons, WPAFB, WSU and nearby suburbs like Beavercreek, Xenia and Yellow Springs. University Woods has 1, 2 & 3 bedroom apartments, villas and townhomes some with attached garages. Our community features a sparkling L-shaped swimming pool, clubhouse, laundry facilities & an abundance of green space. Call today & make University Woods your new home.
Please call for specific driving directions.
As you search for your perfect apartment, please keep in mind that rental rates (including specials and discounts) and availability are very fluid in the apartment industry. Based on many factors, the rental rates (including specials and discounts) and availability can actually change not just daily, but hourly, if not even more quickly. While our advertisers do take steps to keep their information current, the rental rates or availability you may find here now at ForRent.com may not be the same as when you contact the communities.
Quick Links For Your Apartment Search
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- 45324
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text:
SALADO, Texas (AP) — Emergency crews are responding to a reported bridge collapse along an interstate in Central Texas.
If you just have to have it now, as in one hour, you can, at least in the Dallas area, as Amazon.com Inc. announced Thursday it will offer Prime Now.
Downtown Fort Worth's dining scene is about to get spicier with the opening of a new restaurant featuring Latin-inspired coastal cuisine.
Texas unemployment fell to 4.3 percent during February for the sixth straight month of declines, the Texas Workforce Commission reported Friday.
The future of a redevelopment plan for the 50-year-old Westchester Plaza on Fort Worth's Near Southside is unclear.
FRISCO, Texas (AP) — FC Dallas has reached a long-term agreement with Toyota for the naming rights to the club's suburban Dallas home stadium and extended soccer complex.
Officials of the Major League Soccer franchise announced Tuesday that their field in Frisco will be named Toyota Stadium while 17 other fields adjacent to the stadium will be called Toyota Soccer Center.
The terms of the deal were not revealed.
The complex covers 145 acres adjacent to downtown Frisco and in addition to being home to FC Dallas, the stadium hosts international soccer matches, concerts and other events. The surrounding fields are used primarily for youth soccer.
The announcement comes 1½ years after the expiration of the team's original naming-rights deal with Plano, Texas-based Pizza Hut. The stadium opened in 2005 as Pizza Hut Park.
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Rinse and Hold or Half Load Option?
I'm torn between SHE3AR76UC and SHE3ARF6UC (lowes exclusive).
Both are Bosch Ascenta's, but the lowe's exclusive model replaces the half rack wash option with rinse and hold.
Pros/cons of each?
I'm not really sure how much use the half load option will get from us, our current habit is fill as much as possible and run.
From what I've read rinse and hold keeps down the smell level and helps with pre-rinsing as you fill your dishwasher to do a full load (saw recommendation of running once a day until full).
I'm leaning toward rinse and hold now, but any suggestions form those who have these options?
I would opt for the half load option over rinse and hold. I had a Bosch from 2007, SHE58. It had the half load option. I used it sometimes, I try to run a full load as much as possible. I reduces water and time, plus you can put dishes anywhere in the machine and was available on most cycles. It gave me good wash results. My current Miele LaPerla 2 has a prerinse that I've never used in the two yrs I've had the dw.
I've had a half-load option for 2 or 3 years, and I think I've only used it once. I thought when my sons went off to college we wouldn't have as many dishes, but we still manage to fill the whole dishwasher in a short time.
Of the two, it sounds like half load is the much better choice of the two.


text:
Nomi Network Reviews
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October 11, 2012
I am a Social worker and have 4.5 years of experience in development sector specially i worked with the trafficked and vulnerable women of Bihar. I met Nomi Network people at Forbeshganj, Araria district of Bihar, and I was very happy to see that at least these young women from US came here to change the life of the trafficked/vulnerable women by providing them Vocational Education Training Program. Good work and hats off for this team.
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The windows and door of Krazy Mike's are all silvered over and reflective, so there's no way of seeing from ...More Details >
Invisible War
Invisible War: UALR's Gender Studies Program, in conjunction with the Clinton School of Public Service, will screen a new, award-winning documentary The Invisible War. The documentary will examine sexual assaults in the military and will be followed by a question-and-answer session with Kirby Dick, the documentary's producer. The free film will begin at 6 p.m. in the auditorium of UALR's Engineering and Information Technology Building. For more information, contact Sarah Beth Estes at (501) 569-3191.
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Internet Software and Services
Company Overview of FIRE Solutions, Inc.
Company Overview
1001 Avenue of the Americas
11th Floor
New York, NY 10018
United States
Founded in 1999
Key Executives for FIRE Solutions, Inc.
FIRE Solutions, Inc. Key Developments
FIRE Solutions, Inc. announced that respected industry veteran James Shorris has joined the company's Board of Directors, effective immediately. Mr. Shorris was appointed to the Board by unanimous vote at this morning's quarterly Board meeting. Mr. Shorris is currently Executive Vice President and Deputy General Counsel for Regulatory Affairs at LPL Financial. Prior to joining LPL, he was EVP/Executive Director of Enforcement at FINRA.
FIRE Solutions, Inc. announced that it has entered into agreement with Financial Industry Regulatory Authority to deliver FINRA's E-Learning courseware effective January 1. Starting January 1, representatives and firms can purchase access to individual courses or the entire FINRA E-Learning library by going to https://forms.firesolutions.com/enroll/finra. Pricing is identical to what FINRA had formerly charged: $45 annually for access to the entire library per student or $12.50 for individual courses.
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The result was a groundbreaking bill that bought together diverse fans from different musical backgrounds. Filmed at Irvine Meadows Amphitheatre in Southern California Live Noise captures Anthrax' performance during that tour. The show incorporates approximately one hour of live performance with back stage footage that includes Public Enemy. The encore is an extended rockin' version of Bring The Noise, metal and rap at last fusing into a seamless whole.
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Tissue Fluid And Rapid Testing
Here's a taste of what TheBody.com has to offer on this topic:
Get the Facts
IRIS: A Concern for People Starting HIV Therapy...serious condition that can occur shortly after a person starts HIV therapy for the first time. It can also occur in people who restart their meds after a time being off them. IRIS happens when your immune system recovers too quickly. It can start to "overwork" and respond to other infections that may or may not have been diagnosed before starting therapy, even ones that may have already been under control. When your immune system responds in...
Ask the Experts
one positive rapid test followed by 10 negative rapid test..Dear sir i am very much thankful to your forum. My question is i had unprotected frottage with a sex girl in bangkok. When i returened to india i took two rapid test at 3rd and 6th week after exposure and the results came back negative. AT...
Response from Robert J. Frascino, M.D.
The Robert James Frascino AIDS Foundation...tests. You've had 10 negative rapid tests since your "positive" test. HIV is not your problem. No way. No how. No further HIV testing is warranted or recommended. False-positive HIV screening tests are not uncommon. You can read much more about... Read more »
Positive Elisa, Indeterminate Western Blot, Negative Rapid Test HIV test was indeterminate?(INDETERMINATE HIV TESTS, 2009) (PREGNANCY, 2009)Hi, Doctor - Around 2 weeks ago during my annual OBGYN appointment, I received a HIV test. The Elisa came back repeatedly positive and the Western Blot was indeterminate with traces of P24. Freaking out, I then went to my local health clinic 4 days...
Response from Robert J. Frascino, M.D.
The Robert James Frascino AIDS Foundation...Western Blot in my wife. We spoke to a infectious disease doctor and they were surprised by the latest results and ordered more testing. I am pretty confident that there is some type of error in the last test, but am going out of my mind. Can you... Read more »
rapid test negative and lab test positive, how come ?I live in Hong Kong,I did an HIV test, first they made a rapid test (taking blood from my finger) and the result after 20 minutes comes out NEGATIVE. In same time they take sample of my blood to do other lab test (I think the classic ELISA or...
Response from Robert J. Frascino, M.D.
The Robert James Frascino AIDS Foundation...Hello,Unfortunately I cannot explain the logic (or lack thereof) of your recent testing in Hong Kong! Certainly if you had a negative rapid test three months or longer from your last potential HIV exposure, I would Read more »
3 HIV Elisa test + 1 inconclusive WB 1 negative WB(same clinic) 4 rapid test - (2 different clinics)Dr BobThis all started back in july of 08 when i got my first + elisa and a inconclusive on the WB, I was retested a week later at the same place elisa + WB NEG. Had a uni-gold test done that day as well was neg. March of this yesr had another...
Response from Robert J. Frascino, M.D.
The Robert James Frascino AIDS Foundation...that a positive ELISA plus a negative Western Blot is considered a "negative HIV test!" You've had way too many tests. Stop testing. You have essentially no HIV risk and the sum of your multiple tests to date confirms your HIV-negative status.Why... Read more »
2009 H1N1 Flu (Swine Flu) and You...is the 2009 H1N1 virus sometimes called "swine flu"? This virus was originally referred to as "swine flu" because laboratory testing showed that many of the genes in the virus were very similar to influenza viruses that normally occur in pigs... Read more »
Mycobacterium Avium Complex (MAC)...maintenance therapy, azithromycin plus ethambutol are the preferred drugs. The Bottom Line Researchers are developing and testing new drugs and drug combinations that are more effective and have fewer side effects. More novel treatment... Read more »
HIV Testing...(IFA) Window Period Interpretation of Test Results Accuracy of Antibody Tests Anonymous HIV Testing Confidential HIV Testing HIV Name-Based Reporting Partner Notification Orasure Test... Read more »
HIV Testing... What Is HIV Testing? How Do I Get Tested? Who Should Get Tested? When Should I Get Tested? Do Any Tests Work Sooner After Infection? What Read more »
Connect With Others
Rapid Testing
Posted by Anonymous, 1 ReplyAre rapdi tests accurate and dependable? Read more »
Rapid Test Chicago IL
Posted by Anonymous, 1 Reply...Does anyone know locations in Chicago that offer Rapid Tests??? Or is there a website that lists clinics that offer rapid tests? Thanks. Read more »
testing for HIV Aids: urgent pls help!
Posted by Anonymous, 2 Repliesby the way i used a condom but forgot to remove it after the act. then what happened is that it slipped out as i was asleep n rolled on the bed. the fluid must have gotten intach with my penis cuz otherwise i wdnt hav contracted ghonorrea. do you... Read more »
can you get HIV from fingering
Posted by Anonymous, 2 Repliesdo you get aids or HIV from fingering? Read more »
Resource Centers
Guides for People With HIV


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Geek & Cake
Food for Geeks
Geek & Cake
- 305 Pins
The most awesome steampunk cake ever? Artist Kerry Rowe. steampunktendencies
Steampunk Erie, Awesome Steampunk, Steampunk Ll, Steampunk Cake, Things Steampunk
The most awesome steampunk cake ever? Artist Kerry Rowe. steampunktendencies
- The most awesome steampunk cake ever? Artist Kerry...
Elegant Steampunk Wedding Cake
Cake Wrecks - Home
Sweetlake Cakes | Super Mario Brothers Cake
Sweetlake Cakes | verjaardagstaart, taart en bruidstaart Zoetermeer
Steampunk Lighthouse - Cake by Sweet Delights Cakery
Steampunk Lighthouse
STAR WARS Themed Macarons Look Delicious These are definitely the macarons I've been looking for! Semi Sweet Designs created these fantastic Star Wars themed macarons that are a must eat… if I could get my hands on them. I don't eat mararons often, but when I do they are a very delicious treat. Now my mouth is watering, and I'm craving macarons. Thanks a lot, Internet! by Greek Tyrant
STAR WARS Themed Macarons
10004164 Pixel, Geek Cookies, Star Wars Cookies, Semi Sweets, 1 000 4 164 Pixel, Star War Cookies, Cookies I M, Macaron Design, Superb Sweets
STAR WARS Themed Macarons Look Delicious These are definitely the macarons I've been looking for! Semi Sweet Designs created these fantastic Star Wars themed macarons that are a must eat… if I could get my hands on them. I don't eat mararons often, but when I do they are a very delicious treat. Now my mouth is watering, and I'm craving macarons. Thanks a lot, Internet! by Greek Tyrant
Superb sweets.
Stormtrooper Cake tutorial
Star Wars Cakes, Star Wars Fondant Cakes, Cakes Decorated Star Wars, Cupcakes Star Wars, Stars Wars, Star Wars Cupcake, Cake Tutorials, Star Wars Cake Tutorial, Cake Star Wars
Star Wars Storm Trooper Cake Tutorial :D
Con las manos en la cabeza de Stormtroppers
Superman Wedding Cake! by Christopher Garrens
Steel Cake, Married Superman, Christopher Garren Cake, Superman Wedding Cake, Grooms Cake, Wedding Cakes, Groom Cake, Favourite Cake, Superman Cake
Superman Cake or maybe Super Cake
Man of Steel cake
Superman Wedding Cake! by Christopher Garrens cute for a grooms cake
If you marry superman, this will definitely be your cake.
Christopher Garrens Cakes
Star Wars Millennium Falcon Cake
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11 Awesome Tech Geek Birthday Cakes
The Butter End Cakery-Star Wars Millennium Falcon Cake
Millennium Falcon wedding cake created by The Butter End - thebutterend.com
The Millenium Falcon Cake (complete with lights)
Featured Cake Gallery - The Butter End Cakery
Two-tier Star Wars themed birthday cake for twins Ryan & Brendan turning 7 this year. Cake is decorated with hand-cut fondant accents and finished with licensed SW characters.
Tortas Stars Wars, Tortas De Stars Wars, Cake Ideas, Star Wars, Fondant Stars Wars, Wars Theme, Parties Ideas, Birthday Cake, Wars Cake
Tiered Star Wars Cake - Google Search
Two-tier Star Wars themed birthday cake. Cake is decorated with hand-cut fondant accents and finished with licensed SW characters.
Torta de Star wars
Iron Man by ~MaryRiotJane on deviantART
Geek Stuff, Marvel, Comics Book, Art, Man Awesome, Super Heroes, Ironman, Iron Man Suits, Superhero
Iron man One of my favorite super heroes
#IronMan in the clouds. #Marvel
I want the Iron Man suit.
iron man by MaryRiotJane on deviantART
Golden Batman Silhouette - Cake by Kickshaw Cakes ~ Amazing!
Golden Batman Silhouette
It's a Steampunk flavored fairytale by Christopher Garrens
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Amazing wedding cake art
Amazing wedding cake - Steam Punk style
Steam Punk Wedding Cake by Christopher Garren
Top 10 cake designs
Amazing wedding cake by terrie (i don't know who is terrie but she or he did'nt do it ) this cake is from amazing cake by chistopher garen (from orange county from amazing wed cake programe tv!!!!)
Cake Wrecks - Home - 12 Swoon-Worthy Steampunk Sweets
Steampunk Robots Cake
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Machinarium/ robot cake
Steampunk Cake.... MY Birthday Cake!!!
16 Awesome Video Games Cakes
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Amazing cake design!!
Mario Kart 8 Birthday Cake by Irina - Ennas' Cake Design
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Super Mario cake
Cake Central - The world's largest online cake decorating community.
Mario Kart 8 - Icing Smiles, Inc. contacted me a few weeks ago with the request of a cake for a sweet boy, Bryceon! I'd said yes, of course, I was waiting for this opportunity for so long and it was finally here. It was a lot of work, but you know what? it was all worth it! Thanks to God the cakes where finished on time and the best part is that Bryceon was supper happy when he saw his cake and his parents send me an email saying thank you in the most sweet way!
Mario Kart 8 Birthday Cake
Mario Kart 8
attack on titan cake ♥
Cakes Emma Boards, Kyojin Attack, Birthday Parties, Attackontitan, Attack On Titanic Cake, Attack On Titan Cake, Parties Ideas, Animal Cake, There Are Giant Kyojin Into Ji
Cherry's Cakes: Shingeki no Kyojin (Attack on Titan)
not mine. I want to make this attack on titan cake but the fondant would be crazy to make.
Hail Pie-dra
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Captain America Pie
Hail Pie-dra<-- this will never not be funny
This Is The Best Dessert In The Entire Marvel Universe
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Hail Hydra With This Pie-dra
Yoda donut by Dun-Well Doughnuts! #starwars
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Must Eat STAR WARS-Themed Donuts!
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Brooklyn Doughnut Joint Goes All Out For Star Wars Day
Lego Star Wars Millenium Falcon Cake
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Lego Star Wars Millenium Falcon cake with Yoda and Darth Vader duelling.
Lego Star Wars Millenium Falcon
the lord of the rings cake - Cake by alison1966 - CakesDecor
the lord of the rings cake
Minecraft Pig Cake
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A Minecraft pig birthday cake! :-D
Minecraft inspired Piggie Cake ~ This is cool!
Cake decorating - Baking Obsession
Minecraft Pig Cake | Baking Obsession
Pokemon Ball Cake


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Hiv And Loss Of Breath
Here's a taste of what TheBody.com has to offer on this topic:
Ask the Experts
putrid body and breath odor and HIVWhy do i have a really putrid body and breath odor? I was diagnosed with HIV+ in October 2008 and have just started meds a week ago
Response from Keith Henry, M.D.
University of Minnesota, School of Medicine...New body odor has not been an issue with the vast majority of persons with either HIV infection or on treatment. I thorough history and physical (including oral/nose/sinus exams) focusing particularly on intake Read more »
Pneumonia, weight loss, shortness of breatheMy mom is 44 years old and was recently diagnosed with HIV two weeks ago which was January 2011. ... Read more »
breathing difficultysince i started taking trimune drogs i have experience breathing difficulty, my breath is short i... Read more »
Researchers Develop Breath-Monitoring Device to Monitor Treatment Adherence Among HIV-Positive People... Researchers at the University of Florida and Xhale have developed a breath-monitoring device that can detect whether people living with HIV/AIDS adhere to their treatment regimens, ANI/Thaindian News Read more »
Lactic Acidosis and HIV/AIDS...lactic acidosis include: Persistent nausea, vomiting, and abdominal pain Unexplained tiredness Shortness of breath Rapid breathing Enlarged or tender liver Cold or blue hands and feet Abnormal heart beat ... Read more »
Women, Depression and HIV/AIDS...preparations used for depression that include St. Johns wort should not be taken with some HIV medications. Meditation, massage, yoga, breathing, and relaxation exercises are all alternative therapies that may help you feel better. Acupuncture... Read more »
Women, Anemia and HIV/AIDS...it goes unnoticed. Symptoms usually increase as anemia gets worse. Symptoms include: Severe fatigue (tiredness) Difficulty breathing Rapid heart rate Pale skin Decreased pinkness of the lips, gums, lining of the eyelids, nail beds, and... Read more »
Connect With Others
ARS - Heartrate and difficulty breathing
Posted by Anonymous, 1 Reply...Is there any suggestion that an increased heartrate and difficulty breathing in the evening/night are symptoms of ARS? Read more »
Posted by johnson39595...Does tongue tasting weird or feeling cold breathing in have to do with hiv? I am worried so much. Read more »
Can't breath...
Posted by Anonymous, 1 Reply...cell count, white blood cells, platlets, etc... to see why she is so tired... It was at 5pm and it's now almost 10pm! I can't breath! UGH I just know something is wrong! I guess I just have to start acting like she has it and get ready for... Read more »
Can I breathe easy now?
Posted by Anonymous, 2 Replies...negative approx. 8 weeks or so after what would have been his last "exposure". Therefore, since he is negative at 8 weeks, can I breathe a sigh of relief that I am also negative?? Is 8 weeks "good enough"?? *As I said, I will still probably get... Read more »
Resource Centers
Guides for People With HIV


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The general manager of the Alouettes believes he has a 50/50 shot of signing defensive-end Michael Sam — the first openly gay football player — before the Canadian Football League team goes to training camp at the end of May. "The CFL is cut out perfectly for his style," Jim Popp told the Montreal Gazette in a telephone […]
In one graceful motion, Pierre-Alexandre Parenteau picked up a pass in front of the Canadiens net and made a hairpin turn toward centre ice. He gathered speed as he entered the neutral zone, attempting to circumvent New Jersey Devils winger Tuomo Ruutu. Parenteau then briefly lost control of the puck, leaning forward to reel it […]
It is March 4, 1981, and Guy Lafleur is standing at the Canadiens' bench, waving his gloved hand to thank the Montreal Forum crowd for its standing ovation. Lafleur has just earned his 1,000th NHL point, scoring his 21st goal of the season 54 seconds into the third period on assists from Keith Acton and Larry Robinson, […]
Canadiens GM Marc Bergevin was eating his Wheaties early in San Jose on Monday, trading a 2015 second-round draft pick and a conditional fifth-round pick to the Edmonton Oilers for defenceman Jeff Petry.
Considering the two heart transplants and a heart attack that nearly killed him, the fact Erik Compton has even earned a spot on golf's toughest circuit is worthy of celebration.
Following several massive free-agent deals and blockbuster trades, there are plenty of compelling storylines heading into baseball's first spring training since Rob Manfred took over as commissioner in January.
What do the Leafs and a fine wine have in common? They both spend a lot of time in the cellar, cost too much and are only enjoyed on select occasions.
Just over a year ago, nobody in Quebec seemed to know who Dale Weise was. Now, he's a household name.
Claude Ruel coached the Canadiens from 1968 to 1971 — winning the Stanley Cup in 1969 — and again from 1979 to 1981.
The Canadiens' winning streak ended at five games as they dropped a 3-2 decision to the Arizona Coyotes Sunday afternoon at the Bell Centre.
Andrey Pedan's right hook hit Jarred Tinordi with such impact that it briefly disconnected the big defenceman from reality and sent him plummeting face-first to the ice.
"I'm not the bad guy anymore," Duclair told reporters after practice Tuesday. "It's motivating, you're playing in front of your hometown. This is a special tournament for me and I'm excited to get going."
"I'm not the bad guy anymore," Duclair told reporters after practice Tuesday. "It's motivating, you're playing in front of your hometown. This is a special tournament for me and I'm excited to get going."
Monday, Oct. 20 A new temporary Nuns' Island bridge opens to traffic. Home daycare workers throughout the province go on a one-day strike. Hearings begin on Quebec's controversial health care reform bill. The Quebec government inaugurates a new segment of Highway 5 in the Gatineau region. Westmount's Eugenie Bouchard is one of the Top 8 […]
The Habs will face face a difficult task as they confront a Detroit team that is one of the stingiest in the NHL on defence
Lighthearted goalie speaks of the many photo days he's been part of, playing a kids' game with teammate Max Pacioretty and being watched sleeping by actor Jay Baruchel for a team TV spot.
There's only one spot in play on the Canadiens' fourth line and three men compete for it almost every night.
As Milan Lucic went into his third-period meltdown against the Canadiens Thursday, it hit me. There was Lucic, the dynamite having blown up in his face, his whiskers singed, looking for all the world like Wile E. Coyote after he has failed, for the 999th consecutive time, to corral the Road Runner. As Lucic went […]
Canadiens forward Max Pacioretty's leadership qualities are clear this season in his offensive and defensive work on the ice and in his efforts in the community, his charitable work making a difference for many.
The Alouettes aren't out of the woods yet. While they've won six of their last seven games and technically sit first in the East Division, they've yet to secure a playoff berth.


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Register now for free, or sign in with any of these services:
Status: Closed
Know more about this business than we do? Cool! Please submit any corrections or missing details you may have.Help us make it right
Will be opening in Red Bank, New Jersey, the first week of September 2014. Birravino will be located at 183 Riverside Avenue in Red Bank in an open, Industrial-era inspired space.
Birravino is a new restaurant concept created by Vic Rallo, host of Eat! Drink! Italy! on Create TV. Over the past 10 years, Vic has been fortunate enough to travel to Italy more than 20 times, discovering the...
In the Rallo family, cooking isn't merely about food, it's a way of life. Victor Sr. and Jr. have spent the majority of their lives perfecting the art of fine cuisine. The Rallo's time tested recipes are showcased regularly at the Original Basil T's. Their famous Pizza Napolitana, authentic Italian, and original recipes are a feast for the body and soul.
The Original Basil T's is all about...
The Original Basil T's is Red Bank's finest Brewpub and eatery, and a life long labor of love of the Rallo family. Everything is homemade, from their sauces and dressings, mozzarella cheeses, and their fine selection of beer.
Be the first NJ.com user to add photos or videos of Basil T's
A real Italian table at this popular restaurant in Red Bank.
Red Bank's 'popular' brewpub is known for its 'sociable' atmosphere...
Always have an excellent meal there, never disappoints!!! Service is great too!
Most amazing service and food!! Tried half of the menu and loved it all.
Discover Birravino, a new way of meeting, eating and drinking Italian.
The Original Basil T's is all about tradition. Everything is homemade, from the sauces and dressings to the mozzarella cheese, as well as the spectacular desserts and award winning beers. Come and enjoy truly unequaled culinary delights that only generations of dedication can produce. To the Rallo family, the Original Basil T's is much more than a restaurant. . .it is life itself.


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OP Member
Thanks Meter: 9
32 posts
Join Date:Joined: Dec 2013
I just put it in a flashable zip for Galaxy Tab 8 users.
Use CWM or any CWM based recovery to flash these.
And refer to this thread if you're unsure.
Preview is here
I made a boot logo to match the boot animation:
It's in the attachments.
]I take no responsibility if this breaks your device, use it at your own risk.
Last edited by yoozer08; 9th June 2014 at 02:19 PM. Reason: Formatting, precautions.


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Error-need help
Tried to go to the web site of the funeral home,and got this
Quick time error---then plug in error---an error occured inside a plug-in contained on this page
How can I correct/delet this
I checked and yes I have Quick time listed in programs
I have XP and used internet explorer to search for web site.
PS-Computer said something about Apple???Tried to install it-but got same error
I might look in my Internet Explorer Manage Add-Ons... and try to remove the QuickTime if it shows there & then go to Control Panels Add/Remove programs , and uninstall it.
Then go back to the site and it should offer to install it.. if the page really uses it.
Or you can reinstall Quicktime for windows from apple computers from here....
Here is a link that might be useful: http://www.apple.com/quicktime/download/
Were you trying to access some form of audio or video that is hosted on the funeral home web site? If yes, can you download the item and play it with whatever software is appropriate?
If this is not what you were trying to do, then it wouldn't surprise me if the error was generated by an ad not being loaded properly by the funeral home web site. Unless you are having other similar problems, I'm not sure its worth the effort of dealing with it. The following is just an opinion: until the day comes that I want an Apple computer, no Apple software will ever be on my Windows computer. That includes iTunes and especially Quicktime. YMMV.