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Pulaski Furniture Wine Bottle Racks 11-Bottle Wine Cage with Storage Cabinet in Brown Dark Brown Wood DS-2189-304Free Shipping on Over 500K Items!
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You don't have to own a wine cellar just so you can store your favorite bottles at home, thanks to the Magic Chef 6-Bottle Wine Cooler. It can store them at just the right temperature. This black Magic Chef wine cooler comes with a large storage... more
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Marvel 115 V 24" Two Zone Wine Cooler (M24DZBGXL) - Stainless Steel
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Marvel 115 V 24" Two Zone Freestanding Wine Cooler (M24DZBGPL) - Stainless Steel
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Modesto Brown Modern Dry Bar and Wine Cabinet Wholesale Interiors RT209-OCC
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Have an elegant evening with the stylish Prodyne wine cooler that will keep your favorite wine chilled for hours. Fill bottom of cooler with ice & cover with vented ice chamber. 9''T x 4.75''D Cooler is made of durable clear acrylic with double wall... more
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Perlick H50IMSL Perlick 15" Signature Series Indoor/Outdoor Clear Ice Maker - Left Hinge
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Avanti Stainless Steel Freestanding Wine Cooler WCR9000S
Avanti Stainless Steel Freestanding Wine Cooler WCR9000S. Net Capacity: 90 Bottles. Color: Stainless Steel with Glass Door. Defrost System: Auto. Reversible Door: No. Controls: Electronic. Temperature Display: Yes. Pull Out Shelves: Yes. Roll-Out... more
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Avanti Stainless Steel Built In Wine Cooler WCR4600S
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Winsome 94638 Regalia Wine Cabinet
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50 Bottle Compressor Single Zone Wine Cooler
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Wine Rack: Threshold Steel Wine Rack - 8 BottlesSpend $125 Save $20 on Select Home Items
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text:
|Publication number
|Publication type
|Application number
|Publication date
|Apr 3, 1984
|Filing date
|Sep 18, 1980
|Priority date
|Mar 1, 1977
|Publication number
|James P. Davidson, Barnett Rosenberg, Ronald W. Hinz
|Original Assignee
|Research Corporation
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (1), Non-Patent Citations (2), Classifications (12)
|External Links: USPTO, USPTO Assignment, Espacenet
[Pt(II)Ax (OOC)2 --CRR1 ]
This application is a division of application Ser. No. 773,216, filed Mar. 1, 1977 now U.S. Pat. No. 4,258,051 which is a division of application Ser. No. 540,109, filed Jan. 10, 1975 now U.S. Pat. No. 4,053,587.
Although there are many anti-bacterial agents available, very few comounds having in vivo anti-viral activity have been found acceptable to date.
It is an object of the present invention to provide a pharmaceutical composition and a method for treating viral infections in animals.
The present invention comprises a method for treating an animal afflicted with a viral infection comprising adminstering to the animal an effective amount of a platinum coordination compound.
According to a further aspect of the invention, there is provided a pharmaceutical composition in dosage unit form suitable for administration to an animal afflicted with a viral infection comprising a platinum coordination compound and an atoxic pharmaceutically acceptable carrier therefor.
The anti-viral compound useful in the composition and method of the present invention are those having the formula: ##EQU1##
wherein "A" is a monodentate ligand, "B" is a bidentate ligand, m is 0, 2 or 4 and n is 0, 2, 4 or 6.
The monodentate ligands comprising "A" in the above structural formula may be any of those normally associated with platinum in its coordination compounds. For example, "A" may comprise Cl, Br, CN, NO3, NH3, H2 O, OH, OR, OS, etc., wherein R is the residue of an alcohol, preferably, an aliphatic alcohol.
The bidentate ligand (B) in the above structural formula may be any of those normally found in a platinum coordination compound. Suitable bidentate ligands include the aliphatic diamines, e.g., ethylenediamine, propylenediamine, butylenediamine, etc.
Among the preferred compounds are those wherein "A" is Cl, NH3 or mixtures thereof and m is 4 and n is 6. These compounds are conventionally termed chloroplatinumammines. The most preferred chloroplatinumammines are cis-[Pt(II) (NH3)2 Cl2 ] and cis-[Pt(IV) (NH3)2 Cl4 ]. Also preferred are the aquoammine complexes such as cis-[Pt(II) (H2 O)2 NH3)2 ].
Also preferred among the platinum coordination compounds are those having the structural formula:
[Pt(II)AX (OOC)2 --CRR1 ]
cis or trans [Pt(IV)AX (OOC)2 --CRR1)y Lz ]
X=1 or 2;
y=1 or 2;
z=0, 1 or 2,
provided that when y=2, z=0, and when y=1, z is greater than 0;
R and R1 are selected from the group consisting of H, lower alkyl, aryl, aralkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, OH, or combine with the carbon atoms to form a cycloalkyl or cycloalkenyl group and substituted derivatives thereof:
when x=1, A is HR2 N--CHR3 --CHR4 --NR5 H and when x=2, A is H2 NR6 a heterocyclic amine or an amino acid, wherein R2, R3, R4 and R5 are the same or different and are selected from the group consisting of H, CH3, CH2 H5, hydroxy and lower alkoxy, provided that R2 and R5 may also be aryl or aralkyl and each R6 is the same or different and is selected from the group consisting of H, lower alkyl, aryl, aralkyl, hydroxy lower alkyl, hydroxyl- and alkoxyl-amines, alkoxy alkyl amines and heterocyclic substituents including said N as a ring member; all of said alkyl and alkoxy groups being lower alkyl and alkoxy groups.
when z=1, L is a bidentate anionc ligand, and when z=2, L is a monodentate anionic ligand.
In the above structural formulae, R and R1 may comprise lower alkyl, (e.g., methyl, ethyl, n-propyl, isopropyl, n-butyl, etc.); aryl, (e.g., phenyl; lower alkyl-, lower alkenyl-, halo-, nitro-, lower alkoxy-substituted phenyl and naphthyl); aralykyl, (e.g., phenylmethyl (benzyl), 2-(1-napthyl)methyl); alkenyl, (e.g., 4-amino-1-butene, allyl); cycloalkyl, (e.g., cyclopropyl, cyclohexyl, etc.); cycloalkenyl, (e.g., 2-cyclopenten-1-yl, 2-cyclohexen-1-yl); alkoxy, (e.g., methoxy, ethoxy, etc.), and hydroxy. Also suitable are the 1,1-cycloalkylenedicarboxylic acids, (e.g., 1,1-cyclopropanedicarboxylic acid, 1,1-cyclobutane-dicarboxylic acid, etc.) and the 1,1-cycloalkenyldicarboxylic acids, (e.g., 1,1-cyclobutenedicarboxylic acid. etc.)
The malonato compounds of the above structural formula also contain two monodentate ammonia or primary or heterocyclic amine ligands, i.e., when x in the above formula is 2 or one bidentate amine ligand, i.e., when x is 1.
Suitable monodentate amine ligands include lower alkyl amines, (e.g., methyl-, ethyl-, n-propyl-, isopropyl-, n-butyl-amines, etc.), aryl amines, (e.g., aniline), aralkyl amines, (e.g., benzylamine), hydroxy lower alkyl amines, (e.g., ethanolamine, propanolamine, etc.), hydroxylamine, lower alkoxyl amines (e.g., methoxylamine, etc.), alkoxyalkylamines (e.g., methoxymethylamine, etc.), and heterocyclic amines (e.g., pyridine and aziridine). Also included are the amino acids, i.e., R7 --CHNH2 --COOH wherein R7 is H, lower alkyl (e.g., methyl, isopropyl, etc.), hydroxy lower alkyl (e.g., hydroxymethyl, hydroxyethyl, etc.), aralkyl (e.g., benzyl, etc.).
It is to be understood that these coordination compounds may include two identical or different monodentate ligands.
Suitable bidentate amine ligands include the substituted and unsubstituted primary and secondary ethylenediamines. One or both of the carbon atoms of the ethylenediamine may contain substituents such as lower alkyl (e.g., methyl, ethyl), hydroxyl, alkoxy (e.g., methoxy, ethoxy, etc). Secondary ethylenediamines wherein one or more of the amine groups contains substituents such as listed above for the carbon atoms of the primary amine and aryl (e.g., phenyl) and aralkyl, (e.g., benzyl) may also be utilized.
The malonato Pt (IV) coordination compounds may also contain two monodentate or one bidentate anionic ligand where only one malonato ligand is present, i.e., where y=1 in the above formula.
Suitable monodentate anionic ligands include chloride, bromide, iodide, nitrite, hydroxide, nitrate, sulfamate, etc. Among the bidentate anionic ligands which may be present are oxalate, pyrophosphate, dithioxalate.
It is to be understood that the invention includes those coordination compounds containing mixed monodentate anionic ligands.
The preferred malonato compounds are those wherein R and R1 in the above formula are H, methyl or ethyl, i.e., malonatoplatinum, methylmalonatoplatinum and ethylmalonatoplatinum coordination compounds. The most preferred Pt (II) compounds are those malonatoplatinum (II) compounds of the above formula wherein x=1 and R2, R3, R4 and R5 are each H, i.e., malonatoethylenediamine platinum (II), methylmalonatoethylenediamineplatinum (II) and ethylmalonatoethylenediamineplatinum (II); and wherein x=2 and each R6 is H, i.e., malonatodiammineplatinum (II), methylmalonatodiammineplatinum (II) and ethylmalonatodiammineplatinum (II).
The preferred Pt (IV) compounds are those wherein x=2, each R6 is H and y=2, i.e., bismalonato (or bismethylmalonato or bisethylmalonato) diammine platinum (IV); wherein x=1 and R2, R3, R4 and R5 are each H, y=1 or 2, z=2 and L is chloride, bromide, iodide or nitro and each R6 is H.
The malonato compounds may be prepared by one of a variety of well known methods. A general method of preparation of the Pt (II) coordination compounds is as follows: Starting compounds having the formula cis-[Pt a(Hal)2 ] wherein Hal is I, Cl or Br and A is one bidentate or two monodentate amine ligands (prepared by the method of S. C. Dhara, Indian J. Chem., Vol. 8, p. 193 (1970)) are reacted with silver nitrate to form the diaquo complex. The latter is then reacted with the malonate ion to form the coordination compounds of the invention. This method is represented by the following reaction scheme:
cis-[Pt ACl2 ]+2AgNO3 +2H2 O)→cis-[Pt A(H2 O)2 ](NO3)2 +2AgCl
cis-[Pt A(H2 O)2 ](NO3)2 +H2 C--(COO)2 →[Pt A(OOC)2 --CH2 +2NO3 - +2H2 O
wherein A is one bidentate amine ligand or two monodentate amine ligands.
The other coordination compounds employed in the composition and method of the invention may be prepared according to methods well known in the prior art. See for example, Martel and Calvin, CHEMISTRY OF METAL CHELATE COMPOUNDS Prentice-Hall, Incorporated, Englewood Cliffs, New Jersey (1952); Bailar, THE CHEMISTRY OF COORDINATION COMPOUNDS, Reinhold Publishing Company, New York (1956); Dwyer and Mellar, CHELATING AGENTS AND METAL CHELATES, Academic Press, Incorporated, New York (1964); Kauffman, INORGANIC SYNTHESIS, Seven McGraw Hill Book Company Incorporated, New York (1963) and CHEMICAL ABSTRACTS, 44, 5257 g (1950).
The above-described platinum coordination compounds are also described in copending application Ser. Nos. 230,533 (filed Feb. 29, 1972; continuation of application Ser. No. 30,239; filed Apr. 20, 1970) and 260,989 (filed June 8, 1972). It is to be understood that the disclosures of these applications are incorporated herein by reference.
The pharmaceutical compositions of the invention may comprise the above-described platinum coordination compounds in admixture with suitable pharmaceutically acceptable carriers.
Where the composition is adapted for parenteral administration, the platinum coordination compounds may be dissolved or suspended in a suitable carrier liquid such as physiological saline, buffered saline, distilled water, peanut oil, etc. It will be understood that where the composition is intended for intravenous administration, the compounds must be in solution form and that where the compounds are intended for intramuscular or subcutaneous administration they may be in either solution or suspension form.
The platinum coordination compounds are effective against viral infections over a broad range of amounts depending upon the particular platinum coordination compound employed. Obviously, some of these compounds are more effective than others against such types of infections. Generally, however, for parenteral administration, dosages in the range of from about 0.1 to about 100 mg/kg. of body weight of the animal afflicted with the infection are generally effective. The most preferrred dosage range is from about 0.1 to about 10.0 mg/kg. of body weight.
Several of the above-described compounds have evidenced toxicity at the higher dosage levels in the above range. Thus, with respect to some of these compounds, some gastro-intestinal damage, bone-marrow depression or acute renal tabular necrosis may evidence itself at the higher dosage levels. It will be understood that toxicity levels for each compound may be easily determined by established testing methods and the dosages within the above-defined dosage ranges adjusted accordingly.
The following examples are illustrative of the invention:
This example illustrates the inactivation of Rous Sarcoma Virus (BRYAN HIGH TITER STRAIN) with the associated helper virus RAV-1 in chick embryo fibroblast cells obtained from 15-I chickens which have been developed to be particularly sensitive to this virus. The tests set forth herein were done in tissue cultures. A stock suspension of the virus particles of known concentration was diluted and added to petri dishes in which the fibroblast cells had grown. After a predetermined time of incubation, the number of foci per plate was counted. In a second set of tests, the platinum compound, cis-dichlorodiammineplatinum (II), at a concentration of two parts per million was added to the bathing solution of the cells. This concentration was non-toxic to the fibroblast cells. Again, the number of foci were counted. The results are set forth in Table I in four repeat tests.
TABLE I______________________________________Anti-Viral Activity of cis-Dichlorodiammineplatinum (II)Against Rous Sarcoma Virus: Tissue Culture AssayTissue: Chick Embryo Fibroblasts: Line 15-I ChickensConcentration of cis-Pt(II) in treated plates = 2.0 ppm Number of Foci perexperiment PlateNumber Conditions 1 2 3 4 5______________________________________I Control (RSV + RAV-1) 15 20 12 15 16 RSV + RAV-1 + cis-Pt(II) 10 8 5 5 5II Control (RSV + RAV-1) 10 9 9 14 22 RSV + RAV-1 + cis-Pt(II) 5 6 15 16 6III Control (RSV + RAV-1) 17 17 10 15 11 RSV + RAV-1 + cis-Pt(II) 10 9 9 2 0IV Control (RSV + RAV-1) 8 6 15 16 16 RSV + RAV-1 + cis-Pt(II) 1 0 0 7 4______________________________________
Mean number of Foci/Control Plate=13.7
Mean number of Foci/Treated Plate=6.15
% Decrease=˜50%.
It is apparent from the results set forth in Table I that the presence of the platinum coordination compound caused a marked decrease (approximately 50%) in the number of foci per plate. This reflects an inactivation of the Rous virus in a tissue culture system.
The test described herein represents an in vivo test of the platinum coordination compound. Employed as an assay system were 7-8 day old 15-I chickens. All birds were innoculated in the wing web with one half ml stock viral suspension containing 104 Rous Sarcoma Virus particles and associated helper virus, RAV-1. In Table II, the controls in the 4 experiments show that in all chickens employed, the virus caused the development of a Sarcoma tumor at the site of innoculation. There was 100% take of these tumors. In each experiment set forth in Table II, the treated birds were injected simultaneously with 4 mg/kg of cis-dichlorodiammineplatinum (II) in saline solution at the same time and at the same site.
TABLE II______________________________________Anti-Viral Activity of cis-Dichlorodiammineplatinum (II)Against Rous Sarcoma Virus: In Vivo Assay7-8 day old 15-I ChickensAll birds inoculated with 0.5 ml. containing 104 particlesRSV + RAV-1 in the wing web.Treated birds given 4 mg/kg cis-Pt(II) simultaneously in inoculum.Experiment Number ofNumber Conditions Birds Results______________________________________1 Control 6 6 positive Treated 20 4 negative 16 positive2 Control 6 6 positive Treated 20 6 negative 14 positive3 Control 7 7 positive Treated 20 2 negative 18 positive4 Control 6 6 positive Treated 20 3 negative 17 positive______________________________________
The results in Table II show that between 15 and 20% of the birds did not develop a Sarcoma in the wing web. This test indicates the effectiveness of cis-Dichlorodiammineplatinum (II) in causing a marked decrease in the tumor incidence due to the Rous Sarcoma Virus in the chicken in this In Vivo Assay system.
A pool of Fowl Pox Virus had been previously prepared and assayed for the number of viral particles by the standard technique. For the tests herein, a glass vial containing a 2 ml frozen aliquot of fowl pox virus from the stock solution was placed in tepid water, allowing the virus suspension to thaw rapidly. The sample was diluted to 0.5�10-3 dilution using sterile distilled water, prechilled to about 2� C., as the diluent. This final solution contained approximately 150 viable virus particles per ml and was maintained at 2� C. in an icewater bath during the course of the experiment.
Freshly embryonated eggs from white leghorn hens were incubated at 37� C. for ten days in a commercial, automatic turning poultry incubator. The eggs were then transferred to a box type incubator requiring hand turning and maintained at 37� C. through the nineteenth day, which was the termination date for the experiment.
On the thirteenth day of embryonation, an artificial air cell was prepared on the chorioallantoic membrane (CAM) of each egg using a standard technique developed by Cunningham.* Shell holes were temporarily sealed with masking tape and all eggs returned to the incubator.
Solutions of cis-diaquodiammineplatinum (II) were prepared in sterile distilled water to contain 0.0195 mg/ml. The solution was stored in the dark between inoculations. 0.1 ml of the virus dilution was inoculated onto the CAM of each egg at the location of the artificial air cell. The time of inoculation was noted. At a selected time interval (0, 1, 2, 4, 6, 8, 10 or 24 hours) following introduction of the pox virus, 0.2 ml of the platinum solution was inoculated onto the CAM in the same site that had previously received the virus. The shell holes were sealed with molten paraffin and the eggs returned to the incubator where they were placed on their sides so that the artificial air cell was uppermost.
A similar number of control eggs received 0.2 ml of sterile distilled water as a substitution for the platinum treatment. Identical time intervals were used following viral inoculation.
Eggs were candled daily for the first two days following the inoculation procedure. Those eggs found dead during this period were considered to have been killed by the technique as opposed to the virus or the platinum coordination compound and were discarded.
On the fifth to sixth day of incubation following infection with the virus, the eggs were opened and the CAM carefully extracted. After two rinses in tap water, the pox lesions present on the membrane were counted. Any necrotic, erosive or ulcerative lesions in the area of the artificial air cell were also noted.
The results of these two sets of experiments are shown in Tables III and IV. In Table III, the time of treatment was extended only to four hours after the virus inoculation.
TABLE III______________________________________Anti-Viral Activity of cis-Diaquodiammineplatinum (II)Against Fowl Fox Virus: In VivoEmbryonated White Leghorn Eggs3.9 micrograms cis-Pt(II)(NH3)2 (H2 O)2 in 0.2 ml.water per eggDelay Time (hours)Between Virus & Pt Pox Lesions/egg Mean Lesions/egg______________________________________0 Virus + Pt 1,0,0,0,0,1,0,3,0 0.56 Virus + H2 O 4,6,20,10,12,8,9,11,0 8.891 Virus + Pt 4,0,0,6,1,1,3,1,0 1.78 Virus + H2 O 11,15,30,8,23,14,18,19 17.252 Virus + Pt 2,1,2,2,1,1,0,1,2,2 1.40 Virus + H2 O 19,18,13,14,5,18,12,8 13.384 Virus + Pt 6,2,2,2,1,2,8,2,3,2 3.00 Virus + H2 O 10,21,24,8,16,8,13,20,25 16.11______________________________________
TABLE IV______________________________________Anti-Viral Activity of cis-Diaquodiammineplatinum (II)Against Fowl Pox Virus: In VivoEmbryonated White Leghorn Eggs3.9 micrograms cis-Pt(II)(NH3)2 (H2 O)2 in 0.2 ml.water per eggDelay time (hours)Between Virus & Pt Pox Lesions/egg Mean Lesions/egg______________________________________0 Virus + Pt 0,0,1,0 0.25Virus + H2 O 7,4,11,13 8.752 Virus + Pt 0,0,1,3,0 0.80Virus + H2 O 20,9,9,12,10 12.004 Virus + Pt 0,1,2,1,0 0.80Virus + H2 O 12,10,23,7 13.006 Virus + Pt 0,4,2,2,4 2.40Virus + H2 O 15,8,2,17,13 11.008 Virus + Pt 0,1,1,3,1 1.20Virus + H2 O 6,30,11,8 13.7510 Virus + Pt 4,5,1,0,7 3.40Virus + H2 O 9,7,6,18 10.0024 Virus + Pt 10,10,9,7,12 9.60Virus + H2 O 9,18,10,18,8 12.60______________________________________
It is apparent from the results of Tables III and IV that the number of pox lesions was greatly decreased by the treatments with the platinum coordination complexes.
The percentage reduction in the number of lesions is a function of the time interval between virus inoculation and platinum compound. The percentage reductions for the experiments in Tables III and IV are shown in Tables V and VI, respectively.
TABLE V______________________________________Percent Reduction in Mean Number of Pox Lesions for DifferentDelay Times Between Virus Inoculum and Pt TreatmentDelay Time % Reduction______________________________________0 93.71 89.72 89.54 81.4______________________________________
TABLE VI______________________________________Percent Reduction in Mean Number of Pox Lesions for DifferentDelay Times Between Virus Inoculum and Pt TreatmentDelay Time % Reduction______________________________________0 97.22 93.34 93.86 78.28 91.310 66.724 23.7______________________________________
The results of the above experiments clearly indicate that the platinum coordination compounds are potent inhibitors of viral infections in an in vivo system even up to 24 hours after the virus infection.
|Cited Patent
|Filing date
|Publication date
|Mar 18, 1977
|Dec 19, 1989
|Title not available
|Cleare et al., Platinum Metal Rev. 17, pp. 2 13, Mar. 8, 1973.
|Cleare et al., Platinum Metal Rev. 17, pp. 2-13, Mar. 8, 1973.
|U.S. Classification
|514/492, 514/188, 514/184
|International Classification
|Cooperative Classification
|European Classification


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El Solito
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TripAdvisor Reviews El Solito Tampico
Travel Blogs from Tampico
Travel day of agony
... Nick was pretty testy. Even more so because we were not seated together.
We both had middle seats. I was in extra room seating 8e. A woman who read on her tablet and a man with a Robert Ludlum book. I mostly slept. It was a smooth flight.
We arrive in Dallas ready for Starbucks. Take the trainto international terminal D. Our seats are again not together. So We delegate. I will grab the coffee and Nick will woothe attendant to giving us seats together. It ...
La Casa Azul
... Leaving La Casa Azul, we headed back towards the metro via the park, which is heavily patrolled by police. We just managed to beat the rush hour and contrived a more efficient route than the one we used on the way. Many metro line changes in DF (Mexico City) require about a kilometre's walk. We got a few bits from the shop and Kori started cooking whilst Ben went out to buy water and some things from the health food shop. He was pleased to run into the charming Fabian on the ...
Day 19 Mexico City
... Ideal Pasteria and it certainly was ideal for bulk-purchase. This place was huge with literally piles of pastries, cakes and sweets of all kind. Customers wander around loading goodies onto pizza-sized plates which are packed into huge boxes. Upstairs was a cake exhibition that we strolled through. Ay carumba - a huge display of wedding, anniversary and birthday cakes, some 6 feet tall, with eight layers or more, the heaviest weighing 110kg. We ...
Today, we are going to Teotihuacan, the most visited archaeological site in Mexico, located about 30 miles northeast of Mexico City. Gibran, a young tour guide with Royal Cars came to pick us up at the hotel. He has a Denali (with DVD player, my kids are in heaven) for the hour drive to the "city of the gods".
We start our adventure driving north. Luckily, we encounter no traffic today. Mexico City is a sprawling metropolis ...
Mexico City - Coyoacan
After about an hour of co-fuffle we managed to get out of the door. We caught the Metro bus to Etiopia and then from there we caugh the Metro train to Coyocan. Coyocan is the art centre of Mexico. The historical buildings were stupendous! They shone brightly in the morning's sun and glistened and gleamed with a twinkle. In the main centre the was a garden made ...
Other places to stay in Tampico
Hotel Mansion Real TampicoSalvador Diaz Miron 106, Tampico | Hotelfrom $66
Mandarin112 Isauro Alfaro Nte., Tampico | Hotelfrom $49
Villa CaprichoBlvd. Costero s/n, Col. Playa Miramar, Tampico | Hotelfrom $82


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351 posts tagged with programming.
Displaying 151 through 200 of 351. Subscribe:
WOW Inside Minecraft
Within Minecraft's blocky world, he has spent about 100 hours so far on a re-creation of Azeroth, the enormous setting of Blizzard's massively multiplayer game, World of Warcraft (WoW). His name is Ramses. Here's an interview he did with Games Beat. You can see his forum posts here. And there are pictures. [more inside]
Too Long; Do Read
The complete story of the collaboration between Asher Vollmer and Greg Wohlwend on Puzzlejuice. [more inside]
Program or be Programmed
Today's formulaic music.
Discover bytebeat. A new genre of algorithmic music has been developed by demoscene coder viznut, a.k.a. PwP. Sharing genes with chiptunes and facilitated by bitwise operators, bytebeats are decidedly non-traditional music created by short, programmatic formulas. Read about computationally minimal art, the aesthetic that spawned bytebeat. Try your hand at composing (some helpful examples). Read an explanation of how the formulas work. A few more pieces.
What's a JavaScript Closure? Ever wonder about some of JavaScript's more advanced and esoteric features? Nathan Whitehead's interactive tutorial explains and walks through each of these concepts one step at a time. At the end of each lesson, you are encouraged to write short snippets of code demonstrating the concepts that you just learned, which are then automatically checked for errors and verified.
Perhaps you're new to JavaScript, or programming in general; CodeAcademy offers similar interactive tutorials that will teach you the basics, and hold your hand along the way. Perhaps you'd rather learn at a more even pace; CodeAcademy's CodeYear will introduce you to one new concept every week throughout 2012. [more inside]
Perhaps you're new to JavaScript, or programming in general; CodeAcademy offers similar interactive tutorials that will teach you the basics, and hold your hand along the way. Perhaps you'd rather learn at a more even pace; CodeAcademy's CodeYear will introduce you to one new concept every week throughout 2012. [more inside]
Code Search is dead. Long live Code Search.
"Google turned off Code Search earlier this week." Google announced Code Search's impending departure last October (to unhappiness). Russ Cox, one of the original authors of Code Search and one of the head Go engineers (previously and previouslier) has published an explanation of how Code Search worked, and enough code that you can run similar queries on your own machine.
Live Coded Demoscene
When Iñigo Quílez isn't hard at work at Pixar, he's active in the demoscene, creating 4KB programs that render incredible procedurally generated scenes. He also writes tutorials on both video and audio synthesis, but arguably the coolest section of his site features live-coding videos of him improvising both audio and video rendering code that will make any experienced programmer feel wholly inadequate.
A knowlege of Java may also be required
print "And now for something completely %s" % 'different'
This month, Python won "Best Programming Language" in the Linux Journal's Reader's Choice Awards 2011. If you're not convinced, Python Facts explains little simple things that make Python great. [more inside]
Phone home
Autism as a job requirement
It's long been thought that there is a high incidence of autism (and autism-related disorders like Asperger's) in IT fields. Now one company is looking to turn that into sales. [more inside]
repl.it is an online environment for interactively exploring programming languages. Supported languages.
When We Were Young
An oldie but a goodie: David Bennabaum on learning how to program and be a sys admin at his high school in his youth.
"Dana is playing Bill Clinton literally breastfeeding puppies—that was our introduction to America."
GQ: Teats Out: An Oral History of the Rise and Fall (and Rise) of "The Dana Carvey Show." "Steve Carell. Stephen Colbert. Louis C.K. Charlie Kaufman. Robert Smigel. Some of comedy's greatest minds got one of their biggest breaks on the short-lived but much-loved "The Dana Carvey Show." Fifteen years later, in this exclusive oral history, the players recount the brief but fertile life of a truly unusual show", all eight episodes of which are available on Hulu. (Previously) [more inside]
A Unique Business Opportunity.
Losing Pockets
When I was watching "children's programming" in the USA circa 1970s I had Romper Room Captain Kangaroo Sesame Street Electric Company Zoom Great Space Coaster Kids Incorporated ... as well as Patches&Pockets (Previously) [more inside]
Video Game Industry Noire
Why developing the acclaimed video game L.A. Noire was a seven year nightmare for its 100+ (uncredited) developers that resulted in an investigation by the International Game Developers Association. [more inside]
"Hey! Over here! I'M OVER HEEERE!"
"I can tell you right now there is no I in A.I., and nor should there be." Veteran game programmer Mike Diskett (Syndicate, Magic Carpet, GTA IV) offers his thoughts on response mechanics, and how fuzzy logic can fail to account for the fog of war.
Hacker Typer - Now you can look like you're doing something important on your computer, like you've always wanted to! (hit hack and just start bashing at your keyboard)
I learned to program...
Hidrodentitis and Halitosis and Hilarious
Embarassing Bodies, your one-stop clinical revulsion shop! Is it painful? And does it ooze? Pus and blood? Yep, that sounds nasty. [warning: NASTY] [more inside]
J programming language
The J programming language is kind of like a super calculator (it's been described as executable mathematical notation). It was developed by Ken Iverson and Roger Hui and is a successor to APL (and there's no need to buy a new keyboard). The language is free and open source, and works on Windows, Mac, and Linux. A series of books and articles on using J are also available to download. To whet your appetite, here's an article on using J to find the eighth ten-digit prime number that appears among the digits of pi.
Emacs Artist Mode
Emacs Artist Mode (screencast) allows you to use the mouse to draw squares, lines, and other shapes in plain text, or even paint. I'm not an emacs user, but I thought this was pretty cool. Even better, you can use an open source Java tool called ditaa to transform ascii text into a full-color graphic. Needless to say, users of other IDEs want this.
For Passionate Thinkers
Forty years of incredible programming from Ontario's public broadcaster now viewable on the Web at The TVO Public Archive. Samples include: Imprint 1993: Leonard Cohen talks about his poetry and music. The Education of Mike McManus 1977: Timothy Leary talks about what freedoms the drug culture wrought and reflects on his own role in bringing about these changes. Talking Film 1980: The Cinema Of John Huston offers anecdotes about Orson Welles, Humphrey Bogart, and Truman Capote. Allan Gregg in Conversation 2007: Carol Off/Alvin Toffler, authors of Bitter Chocolate and Future Shock. [more inside]
static void wake_up_dreamer(struct dreamer_attr *dattr, int level)
Rediscovering WWII's female "computers"
Rediscovering WWII's female "computers". While researching a documentary in Philadelphia, filmmaker LeAnn Erickson came across two women with a story she'd never heard before: thousands of women with advanced mathematical skills employed as "computers", working day and night during WWII to supply soldiers in the field with precise ballistics algorithms. Some of those women also went on to program ENIAC, the first general-purpose computer (previously). Erickson turned their stories into Top Secret Rosies, a documentary released to theaters last year and to DVD this month. One of those programmers, Betty Jean Jennings Bartik, spoke at length to the Computing History Museum in 2008. [youtube, 1:07:19] [via]
Learn to Code
Want to be a coder? Productivity-porn site Lifehacker has posted its 4.5-part "Learn to Code Nightschool Course." [more inside]
Quake: A Look Back
The 'GDC 25' Chronicles: A Quake Aftershock. Shortly after the release of Quake in 1996, former iD employee Michael Abrash gave a talk detailing many of the technical hurdles that had to be resolved in making the game. For its 25th anniversary, GDC has put up video clips of two segments (1 2) as well as audio of the full talk.
"In theory, theory and practice are the same. In practice, they're not."
"There are two ways of constructing a software design. One way is to make it so simple that there are obviously no deficiencies. And the other way is to make it so complicated that there are no obvious deficiencies." - C.A.R. Hoare, from the Top 50 Programming Quotes of All Time.
Teen Mathletes Do Battle at Algorithm Olympics
In today's example of kids smarter than you and I, Wired follows the exploits of two teens competing at the International Olympiad in Informatics.
brains = [ brain1, brain2, brain3 ]
Diceman at the dollar store
Real world implementation of the buy-bot from xkcd. Follow it on Twitter!
Geometry, Surfaces, Curves, Polyhedra
Geometry, Surfaces, Curves, Polyhedra (many of which are beautiful) l Google Earth Fractals l fractals and chaos. [more inside]
(define this 'awesome)
Probably one of the 5 best amateur animated music videos about Lisp you'll see today. [more inside]
Programmers Who Defined The Technology Industry: Where Are They Now?
The Demoscene is alive and kicking
The latest thing they're doing with Commodore 64s - Cubase 64 [more inside]
Quite possibly the strangest programming language you'll see today
Pictorial Janus (SLYT)
Quantum Chess!
"Computers can search all possible outcomes of all possible moves in conventional chess and beat even top human players, so Akl wanted to make the computation more difficult." The result? Quantum chess! [via]
Programming cats
"Have you ever wondered how many cats you would have if you started with just one female and left it alone with males for 5 years?" via Forrst
Introducing: Lady Java. (Follow-up to the almost SFW "Java 4-Ever".) [more inside]
wink bloop twitch tsch
WordPress, Thesis and the GPL
Who gets to make money off WordPress? Dust-up brewing in the world of WordPress as theme author Chris Pearson and WordPress head honcho Matt Mullenweg battle out the question: Is a theme a 'derivative work'? [more inside]
Making web apps for the Iphone
Building iPhone Apps with HTML, CSS, and JavaScript
Jonathan Stark's book is online in its entirety, with a Creative Commons license. Kind of cool.
Jonathan Stark's book is online in its entirety, with a Creative Commons license. Kind of cool.
Hypercard for phones?
Could App Inventor, Google's new easy development software for Android, be Hypercard for phones?
Internet Relay Programming
Internet Relay Chat (IRC) has been around since 1988, and discussed several times on metafilter. It has been used as a communication medium, a news source, and now, as a programming language.
"Dad? Why do we always use .net?"
Java 4-Ever (safe for work apart from that one bit) - an amusing language centric film trailer made to promote the Scandinavian JavaZone conference.
if (ourChildren.learning == true)
Why Johnny can't code - David Brin asks how to get kids hooked on programming.
The first Global Hackathon organized by Random Hacks of Kindness has begun. Satellite-linked hackers are attending events in Washington DC, Sydney, Nairobi, Jakarta, and Sao Paulo. Some of the projects being coded right now: Near-Realtime UAV (unmanned aerial vehicle) image processing; BushFire Connect Project; Person finder [more inside]
If you watch this and say, "Someone has too much time on his hands," I hate you.
HELLO WORLD (SLYT) "Lego felt tip 110" printer connected to an Apple Mac. This is not a kit you can buy and does not use mindstorms. I designed/built/coded it all from scratch including analog motor electronics, sensors and printer driver, the USB interface uses a "wiring" board.


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This company is a personal management firm that provides children to modeling agencies, casting directors and commercial producers for commercial modeling assignments. Ad kids, Inc. is not a modeling or talent agency, but rather a company that manages children as an option for parents who do not wish to freelance.
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Registration takes less than 1 minute.
Norfolk Southern Corp. will modify its Triple Crown Services (TCS) subsidiary to focus on the transport of auto parts, while other business will shift to the railroad's intermodal network.
The U.S. Government Accountability Office said in a report issued Friday CPFA requirements have increased the overall cost of shipping food aid by an average of 23 percent from April 2011 through fiscal year 2014.
The forwarder will transport Toyota Material Handling Group's new line of racking systems from suppliers to the company's customer sites across Europe.
No sighting of lifeboat yet as multiple aircraft and ships search the area for TOTE Maritime Puerto Rico ship and crew.
Rep. Stephen Fincher, R-Tenn., introduced a bill that would restore Ex-Im Bank's operations and include various reforms, but will require a "discharge process" to reach the House floor for a vote.
The company's minority investment in e-commerce specialist Ally Commerce Inc. is more about research than revenues, according to Rimas Kapeskas, head of UPS's strategic enterprise fund.


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Fall is for planting! The cooler weather and almost nightly rain makes a perfect environment for getting some new plants into the garden. All of our trees, shrubs, and perennials are now 25% off! Stop by and see how beautiful fall can be!Our homegrown mums are starting to stretch their beautiful petals too, just $5.99 for a great splash of color!
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Gift certificates are always available, in any denomination. Perfect gifts for the gardeners in your life! Stop in to the Garden Shop or call to order one today!
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Sennheiser - Sennheiser CX 200 Street II
"Everybody knows Sennheiser. They are doing great job at delivering good sound for all prices. I am doing this review with price factor in thought. First of all it is suprisingly detailed sounding headphone for me. I mean i am not audiophile or i didnt try much of audiophile gear but, they can race easily with px 100ii in terms of detail in my opinion. It have a signature that bass is forward..." --Gonomon
Sennheiser OMX 90 Style Series Clip-On Earphone with Volume Control
"The build quality of these earphones are perfect: from the very first time you hold a pair of these in your hands you know that they won't fall apart any time soon. But this build quality leads to some issues: the housing is pretty heavy and this can make the use of these clip-on styled headphones pretty uncomfortable for some people. Noise canceling isn't really good but keep in mind that this..." --Maniello
Sennheiser IE 8 In-Ear Headphones
" This is my first top tier IEM. I own it quite a long period of time. I am very happy with the SQ.... Anyway here is my review after 5 days of usage =) ( i left it in seller website) Честно говоря звук сразу после распаковки был ужасен :) Но я знал что динамическим затычкам надо время что бы 'раскрытся'. Так и произошло. Буквально через 5 часов они зазвучали значительно лучше...." --Vladimir_F1
Compact Monitors Stage 2
Top class dual driver InEar with exceptional dynamic and sound. Two drivers (one for the low/mid frequencies and one for the high frequencies) in each earpiece will give you an extraordinary performance with crystal clear high frequencies combined with tight and precise bass Due to the specially selected drivers this InEar creates a headroom at the low end that usually would not be...
Compact Monitors Stage 3
Studio sound meets In Ear - ...enter the next Stage! Extremely precise and linear sound - three drivers and a crossover with parts of absolutely close tolerance makes the Stage 3 sound perfectly balanced No matter where – stage, studio or for your portable player: Stage 3 will make you get addicted to sound...!
Sennheiser IE800
"After reading glowing reviews of both of these in ear monitors I was still unable to decide which one would be right for me so I bought both, first the Shure and a few weeks later the Sennheiser. I already own the JH Audio 16 Pro, Ultimate Ears Triple.fi 10 Pro, HiFi Man HE-500, Sennheiser HD 650, Shure SRH940 among others. My music files are all in FLAC format and I play them through an..." --Art inTampa
Sennheiser MX 660 Black Earbuds with Volume Control and Cable Winder (Black)
The Sennheiser MX 660 earbuds are high quality earphones with Sennheiser's innovative "Basswind" system for superior, bass-driven stereo sound experience. They are ideal for use with all MP3, CD, DVD players and portable gaming systems as well as feature a volume control integrated in the cable and a cable winder for convenient cable length adjustment.
Sennheiser IE 8 Earphones
Rediscover your music collection and tailor it to your aural tastes with a tunable bass frequency response. The customized sonic signature is complemented by a unique fit thanks to the included ear adapters. This fit isolates the user from their environment, offering passive noise attenuation and the best sound experience. The IE 8 stores quickly and safely in the included carrying case.
Sennheiser IE80
"Anyone aspiring to be an audiophile would have heard the name of these IEMs, they are one of the very best around and only a few are in the same league as this one. The IE80 was released a few years ago, following the IE8 which was for a long time, the best that Sennheiser had to offer in this regard. Lets cut the introduction short. This review is not an Audiophile perspective. Its just my..." --jnxr
Sennheiser CX 485 Premium Earbuds
The CX 485 delivers the musical experience and comfort that only Sennheiser can. Using the type of transducers usually reserved for headphones costing 3x as much, the CX 485 has the detail and response you require to re-discover your music all over again. With a painstakingly crafted ergonomic design, the CX 485 fits into smaller ears for a snug yet comfortable fit you dreamed of.The unique...


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Digging Deep
Sometimes life requires us to dig in and put in extra effort - to live for God in ways that we've never done before, and trust in Him for things we never thought would happen. The 'bigger' parts of faith seem more relevant to things like mission trips or taking on a new role at church. But, some of the things that take 'all your might' might look different at second glance. Take a look at Galatians 5:22-23 - the Fruits of the Spirit verses. They're a big part of faith by anyone's measure: becoming more like Jesus. And if you're like us, you'll know they don't come easy. Putting His will first can take as much attention, energy, and prayer as the biggest mission trips, but it's life-changing and so thoroughly worth it.
What do we mean? It takes a lot of effort to be gentle in that situation where you'd rather let anger boil over. Wrestling our human tendencies is tiring like that. It can take a lot of effort to exercise self-control.
To bring any action before God when we're feeling weak can take all of our might. But it's so important. When we act out of love (which is the best motive we can have, according to Corinthians 13:2), and ask God to bless our efforts, we're not pointlessly exhausting ourselves in order to 'be good'. We're being changed by Him in a permanent, enriching way.
So what now? Sing a worship song out loud to God. Voicing your faith to yourself helps to build you up on the inside.
Soulfood : Ex 1-3, John 1:29-42, Ps 63, Prov 25:26-28


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Front Fastening Bras
Easy fasten bras that close at the front
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Why not read our informative blog post 'All You Need To Know About Front Fastening Bras' to find out a bit more about these wonderfully versatile bras
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My Nonprofit Reviews
Ana C.
Review for Artserve Michigan Inc, Wixom, MI, USA
I have partnered with ArtServe Michigan since it was first formed. Most recently I partnered with them in my role as Michigan Department of Education Arts Education Specialist - a role from which I have recently retired. It is a pleasure to comment on the importance of ArtServe Michigan to the cultural well-being of our state. From the annual student workshops with international caliber clinicians, to the daily updates on arts advocacy issues, I have relied on ArtServe Michigan's to be there as the state's voice on arts advocacy. They have been successful in reducing competitiveness across arts and arts education organizations creating a collaborative environment in which the State Department of Education, the State Arts Council and the Michigan Youth Arts Association have been able to create an arts education agenda for the state. ArtServe also provided direct service to public schools in Detroit without dedicated arts educators through a Comic Book Literacy project in which students produced their own comics and teachers received the professional development needed to continue the work in their schools without additional assistance. A non-profit I am president of has also participated in the Michigan Cultural Data Project. The face to face and webinar support has been invaluable to a small non-profit managing its resources.