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Stoeger M3K 12ga
tsgoutdoors A+(271)
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|Hoschton, GA 30548
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NIB Stoeger M3K 12ga competition semi auto shotgun, 24" barrel, 3 chokes All firearms that are NIB have all the factory accessories included as shipped from the factory. Yes, we will gladly sell to residents of California but it is your responsibility to make sure the item is legal in your state. WE ALSO HAVE A RETAIL STORE AND MOST ITEMS ARE FOR SALE AT SHOP, SO PLEASE LET US KNOW YOU ARE BIDDING BEFORE YOU BID SO THAT THE ITEM CAN BE REMOVED FROM STOCK. We do reserve the right to sell locally and end the auction early without notice. You must contact the seller to resolve any questions or concerns before placing a bid. Call us at 678-261-7599 with any questions you may have. Winner of Auction PAYS SHIPPING AND OPTIONAL INSURANCE (declared value/UPS) UNLESS STATED OTHERWISE. PAYMENT & SHIPPING INFO The winner of the auction must contact us within 24 hours after the end of the auction with payment and FFL info. (678-261-7599). We will need your name, email address, resident address and phone number. If you have any questions please use email to contact us (email@example.com), you will get a faster reply than if you call and leave a voicemail. The flat rate shipping charge listed is basic UPS ground shipping, Alaska and Hawaii will incur a slightly higher charge. Firearms will only be shipped to a dealer (FFL), we prefer an established "store front" FFL holder with normal business hours, however we will ship to any legal FFL. It's just less headaches if you use a retail store. They are in business to do it correctly and shipping is much easier for everyone. It is the purchasers responsibility to obtain an FFL for us to ship too. They can email or fax (877-840-1601) their FFL to us. Payment can be made via US Postal Money Order or with Credit Card. The price reflects a 3% discount for cash/check/money order. Payment is due within 5 days of the auction ending. Negative feedback will be posted on non-payers or slow payers. PLEASE BE SURE TO READ ENTIRE AUCTION DETAILS AND VIEW ALL PICTURES PRIOR TO BIDDING. Gunbroker.com does not allow bid-retractions. If you bid on and win our auction, you will be responsible for paying auction fees should you decide that you made a mistake. Failure to pay for item or auction fees will result in a non-paying-bidder report and negative feedback.This is the only way we get our money back from GunBroker. If Payment and FFL are not done within 5 days after end of auction, we reserve the right to cancel transaction and relist item for sale. We accept credit Visa, MasterCard, & Discover credit cards. Please note that if this is an item that we are shipping directly to you and you wish to pay by credit card, the billing and shipping address must match the credit card address. Final price does reflect a 3% cash discount. Money Order Instructions: We highly recommend USPS postal money orders to pay if you do not wish to use a credit card. They are inexpensive for you and quick verification for us. Our Post Office will verify their origin for us so we can get your gun/item shipped to you. Any other form of Money Order or Certified check has a 10 business day wait period for clearing our bank. Please make checks/money orders out to "TSG Outdoors & Trading Post" . It is very important to use our mailing address at the P.O. BOX 811 and not the shipping address of the store to mail payments to. If you would like to join our mailing list so that you receive special deals when we offer them please email us at the above email address and put MAILING LIST in the subject, or you can go to our website www.tsgoutdoors.com and sign up there, even better, become a fan on Facebook as that is where we will be listing most of our specials. By contacting us you are giving us permission to contact you via email for future sales we may be listing. We are a family owned gun/outdoor store in Northeast Georgia. We will do everything possible to make you happy. We will treat you as we would want to be treated. Please stop in and say hello anytime you are in the area. All Sales are FINAL. All firearm warranties are through the firearm manufacture(s). Georgia sales tax of 7% applies to sales in Georgia. Thank you for viewing our auctions we appreciate your business. Our Mailing address is: P.O. Box 811, Hoschton, GA. 30548. The street address for shipping or over night FEDEX/UPS is 4188 Hwy 53, Hoschton, GA 30548
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|Publication number
|Publication type
|Application number
|Publication date
|Jun 18, 1985
|Filing date
|Sep 4, 1984
|Priority date
|Sep 4, 1984
|Fee status
|Also published as
|Publication number
|James A. Matson
|Original Assignee
|Bristol-Myers Company
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (1), Non-Patent Citations (6), Referenced by (24), Classifications (18), Legal Events (6)
|External Links: USPTO, USPTO Assignment, Espacenet
1. Field of the Invention
This invention relates to a novel antitumor antibiotic and to its production and recovery.
2. Description of the Prior Art
The novel compound of the present invention is related in structure to the antitumor agent, rebeccamycin, disclosed and claimed in co-pending application Ser. No. 461,817 filed Jan. 28, 1983, the entire disclosure of which is hereby incorporated by reference. Rebeccamycin has the formula ##STR1## and is obtained by cultivating Nocardia aerocolonigenes.
Somewhat related in structure to the compound of the present invention is the antitumor agent, staurosporine (also called AM-2282), obtained from fermentation of Streptomyces staurosporeus. Staurosporine is described in J.C.S. Chem. Comm., 1978, Pg. 800-801 and in J. Antibiotics 30(4): 275-282 (1977).
Agnew. Chem. Int. Ed. Engl. 19(6): 459-460 (1980) discloses several indole pigments obtained from the fruiting bodies of the slime mold Arcyria denudata which are structurally related to staurosporine. Certain of the pigments exhibit activity against Bacillus brevis and B. subtilis.
This invention relates to a new antitumor antibiotic designated herein as 4'-deschlororebeccamycin having the structural formula ##STR2## and to the process for the preparation, isolation and purification of 4'-deschlororebeccamycin in substantially pure form.
The antibiotic of the present invention is obtained by fermentation of a 4'-deschlororebeccamycin-producing strain of Nocardia aerocolonigenes, preferably Nocardia aerocolonigenes strain C38,383-RK2 (ATCC 39243) or a mutant thereof, in an aqueous nutrient medium under submerged aerobic conditions until a substantial amount of 4'-deschlororebeccamycin is produced by said microorganism in said culture medium and, optionally, recovering the 4'-deschlororebeccamycin from the culture medium substantially free of co-produced substances.
The compound 4'-deschlororebeccamycin exhibits antimicrobial activity and also activity against experimental animal tumor systems, e.g. P-388 leukemia in mice.
The 4'-deschlororebeccamycin of the present invention is produced by fermentation of a 4'-deschlororebeccamycin-producing strain of Nocardia aerocolonigenes.
An especially preferred 4'-deschlororebeccamycin-producing strain is that disclosed in U.S. application Ser. No. 461,817 filed Jan. 28, 1983 as being the producing organism for rebeccamycin. The present applicant has discovered that during cultivation of this microorganism there is co-produced along with rebeccamycin the 4'-deschlororebeccamycin product of the present invention. This preferred producing microorganism, designated strain C38,383-RK2, was isolated from a soil sample collected in Panama. Cultures of this strain have been deposited in the American Type Culture Collection, Rockville, Maryland, and added to their permanent collection of microorganisms at ATCC 39243.
The results of taxonomic studies performed on strain C38,383-RK2 indicate that the strain is classified as an atyptical species of the genus Nocardia. Based on the characteristics indicated below, strain C38,383-RK2 is believed to belong to the species group of Nocardia aerocolonigenes.
Strain C38,383-RK2 has the following properties:
Strain C38,383-RK2 forms unicellular filamentous cells which develop into substrate and aerial mycelia. Both mycelia are long, well branched and not fragmented into short filaments (0.5 μm in width). Arthrospores are born in the whole of aerial mycelium. These spores are arranged with intercalation of empty hyphae, or formed as a continuous chain. Like the sporulation of Nocardiopsis dassonvillei, (Intl. J. Syst. Bacteriol. 26: 487-493, 1976) the aerial hyphae of strain C38,383 are divided into long segments which subsequently subdivide into spores of irregular size. The chains of intercalary or continuous spores are straight or flexuous in shape. Extremely long spore-chains which contain 50 to 100 spores in a chain are formed along with short or moderate length of chains. The spores are cylindrical in shape, 0.5-0.7�0.7-5 μm in size, and have a smooth surface.
Sclerotia are formed on the aerial mycelium, but sporangia, motile spores and whorls are not observed.
Strain C38,383 is an obligately aerobic actinomycete, and grows well in most agar media. The aerial mycelium is formed abundantly on Czapek's sucrose-nitrate agar, ISP Medium Nos. 2,4,5 and 7, nutrient agar and Bennett's agar, but poorly on glucose-asparagine agar and ISP Medium Nos. 3 and 6. The color of aerial mycelium is white, yellowish white or pale yellow. A yellowish pigment is formed in the substrate mycelium, which diffuses slightly into agar medium. This pigment is not a pH-indicator. Melanoid pigment is not produced. The cultural characteristics are shown in Table 1.
The optimal growth temperature for strain C38,383 ranges from 28� C. to 37� C., and moderate growth is seen at 20� C. and 41� C. No growth is observed at 7� C. and 45� C. Gelatin and starch are decomposed. Tyrosinase reaction is negative. The growth is inhibited in the presence of 8% NaCl, but not by lysozyme at 0.01%. Strain C38,383 utilizes most sugars for growth. The physiological characteristics and utilization of carbohydrates are shown in Tables 2 and 3, respectively.
The amino acid composition in the cell wall was examined according to the methods described by Becker et al. (Appl. Microbial. 13: 236-243, 1965) and Yamaguchi (J. Bacteriol. 89: 441-453, 1965), and the sugar component in the whole cell hydrolyzate was identified according to the procedures outlined by Lechevalier and Lechevalier in Biology of the Actinomycetes and Related Organisms 11: 78-92, 1976. The cell wall of strain C38,383 contains meso-diaminopimelic acid but lacks glycine. Whole cell hydrolyzate shows the presence of glucose, galactose, mannose and rhamnose. The above-mentioned cell wall composition and whole cell sugar components indicate that the strain C38,383 is an actinomycete species of cell wall type IIIC.
Strain C38,383 was compared with eight genera of order Actinomycetales, including Nocardia, Micropolyspora, Microtetraspora, Nocardiopsis, Saccharopolyspora, Pseudonocardia, Actinomadura and Streptoalloteichus, all of which produce spore-chains on the aerial mycelium and contain mesodiiaminopimelic acid in the cell wall. Among these eight genera, the genus Nocardiopsis is most related to strain C38,383 in the spore-chain and spore morphology, but differs from strain C38,383 in the absence of galactose and mannose in the whole cell hydrolyzate.
Gordon et al. (J. Gen. Microbiol. 109: 69-78, 1978) characterized 14 taxa of nocardiae based on the physiological properties and the chemical composition in whole cell hydrolyzate. Strain C38,383 was most similar to Nocardia aerocolonigenes in the amino acid and sugar composition in whole cell hydrolyzate. Therefore, strain C38,383 was compared with the diagnostic physiological properties of N. aerocolonigenes. As shown in Table 4, strain C38,383 was found to be closely related to N. aerocolonigenes but significantly different from Nocardia (Nocardiopsis) dassonvillei. However, all 14 strains of N. aerocolonigenes lack or lose the abilities to form spores and aerial mycelium. Thus, strain C38,383 is considered to be a sporogenic species in the taxon of Nocardia aerocolonigenes.
Strain C38,383 was also found to lose its ability to form aerial mycelium and spores. After five successive transfers, 70% of single isolates lost these abilities. Such property of strain C38,383 seems to be similar to the reported variation of Nocardia aerocolonigenes in the formation of spores and aerial mycelium.
TABLE 1______________________________________Cultural Characteristics of Strain No. C38,383*______________________________________Tryptone-yeast extract G** moderate; floccose, palebroth (ISP No. 1) yellow pellets D noneSucrose-nitrate agar G abundant(Czapek's agar) R strong yellow (84)*** to vivid yellow (82) A moderate, yellowish white (92) to pale yellow (89) D dark grayish yellow (91) to light olive brown (94)Glucose-asparagine agar G poor R white (263) A scant, yellowish white (92) to pale yellow (89) D noneGlycerol-asparagine agar G abundant(ISP No. 5) R brilliant yellow (83) to strong yellow (84) A abundant, pale yellow (89) to light yellow (86) D yellow gray (93) to grayish yellow (90)Inorganic salts-starch agar G abundant(ISP No. 4) R pale yellow (89) to strong yellow (84) A abundant, white (263) to yellowish white (92) D noneTyrosine agar G abundant(ISP No. 7) R brilliant yellow (83) to strong yellow (84) A moderate, pale yellow (89) to light yellow (86) D pale yellow (89)Nutrient agar G abundant R yellowish white (92) to pale yellow (89) A abundant, white (263) D noneYeast extract-malt extract G abundantagar (ISP No. 2) R brilliant orange yellow (67) to strong orange yellow (68) A abundant, yellowish white (92) to pale yellow (89) D dark orange yellow (72) to moderate yellowish brown (77)Oat meal agar G moderate(ISP No. 3) R light yellow (86) to brilliant yellow (83) A scant, yellowish white (92) to pale yellow (89) D noneBennett's agar G abundant R brilliant yellow (83) to strong yellow (84) A abundant, yellowish white (92) to pale yellow D vivid yellow (82)Peptone-yeast extract-iron G moderateagar (ISP No. 6) R pale yellow (89) to light yellow (86) A poor, white (263) to yellowish white (92) D none______________________________________ *observed after incubation at 28� C. for 3 weeks **Abbreviation: G = growth; R = reverse color; A = aerial mycelium; D = diffusible pigment ***Color and number in parenthesis follow the color standard in Kelly, K L. & D. B. Judd: ISCCNBS colorname charts illustrated with Centroid Colors. US Dept. of Comm. Cir. 553, Washington, D.C., No., 1975".
TABLE 2______________________________________Physiological Characteristics of Strain No. C38,383 Method orTest Response Medium used______________________________________Range of tempera- Maximal growth at Bennett's agarture for growth 28� C. to 37� C. Moder- ate growth at 20� C. and 41� C. No growth at 7� C. and 45� C.Gelatin liquefaction Liquefied 1% malt extract, 0.4% yeast ex- tract, 0.4% glu- cose, 20% gelatin.Starch hydrolysis Hydrolyzed Starch agar plateReactions in Not coagulated and Difco skimmedskimmed milk completely peptonized milkFormation of mela- negative Tyrosine agar,noid pigment peptone-yeast extract-iron agar, and tryp- tone-yeast extract brothTyrosinase reaction Negative Arai's method*Nitrate reduction Positive Czapek's su- crose-nitrate broth Positive 0.5% yeast extract, 1% glu- cose, 0.5% KNO3, 0.1% CaCO3.Acid tolerance Growth at pH 5.0. Yeast extract- No growth at pH 4.5. malt extract agarNaCl tolerance Growth at 7% NaCl or Basal medium: 1% less. No Growth at 8% yeast extract, NaCl. 2% soluble starch, 1.5% agar.Lysozyme tolerance Tolerant. Trypticase soy Growth at 0.01% broth plus 1.5% lysozyme. agar.______________________________________ *Arai, T. and Y. Mikami: Chromogenicity of Streptomyces. Appl. Microbiol. 23: 402-406, 1972.
TABLE 3______________________________________Carbohydrate Utilization of Strain No. C38,383______________________________________ Glycerol + D(-)-Arabinose + L(+)-Arabinose + D-Xylose + D-Ribose + L-Rhamnose + D-Glucose + D-Galactose + D-Fructose + D-Mannose + L(-)-Sorbose - Sucrose + Lactose + Melibiose + Trehalose + Raffinose + D(+)-Melezitose - Soluble starch + Cellulose + Dulcitol - Inositol + D-Mannitol + D-Sorbitol - Salicin +______________________________________ observed after incubation at 37� C. for 3 weeks Basal medium: PridhamGottlieb's inorganic medium Abbreviation: +: positive utilization, -: negative utilization
TABLE 4______________________________________Comparison of diagnostic physiological properties amongstrain C38,383, Nocardia aerocolonigenes and Nocardiopsisdassonvillei Nocardia* Nocardiopsis* Strain aerocolonigenes dassonvillei C38,383 (14)** (31)**______________________________________Decomposition ofAdenine - - +Casein + + +Hypoxanthine + + +Tyrosine + + +Urea - + -Xanthine - - +Resistance to:Lysozyme + + -Rifampin - - -Hydrolysis of:Aesculin + + -Hippurate - V +Starch + + +Acid from:Inositol + + -Lactose + + -Melibiose + + -Raffinose + V -Utilization of:Benzoate - - -Citrate + + +Mucate - - -Succinate + + +Tartrate - - -Nitrite from nitrate + V +Survival at 50� C., 8 h - V +______________________________________ +: positive, -: negative, V: 15 to 84% of the strains positive *Data of Gordon et al. (J. Gen. Microbiol. 109: 69-78, 1978) **No. of strains examined
It is to be understood that the present invention is not limited to use of the particular preferred strain C38,383-RK2 described above or to organisms fully answering the above descriptions. It is especially intended to include other 4'-deschlororebeccamycin-producing strains or mutants of the said organism which can be produced by conventional means such as x-radiation, ultraviolet radiation, treatment with nitrogen mustards, phage exposure, and the like.
4'-Deschlororebeccamycin may be produced by cultivating a 4'-deschlororebeccamycin-producing strain of Nocardia aerocolonigenes, preferably a strain having the characteristics of Nocardia aerocolonigenes strain C38,383-RK2 (ATCC 39243) or mutant thereof, under submerged aerobic conditions in an aqueous nutrient medium. The organism is grown in a nutrient medium containing an assimilable carbon source, for example, sucrose, lactose, glucose, rhamnose, fructose, mannose, melibiose, glycerol or soluble starch. The nutrient medium should also contain an assimilable nitrogen source such as fish meal, peptone, soybean flour, peanut meal, cottenseed meal or corn steep liquor. Nutrient inorganic salts can also be incorporated in the medium. Such salts may comprise any of the usual salts capable of providing sodium, potassium, ammonium, calcium, phosphate, sulfate, chloride, bromide, nitrate, carbonate or like ions.
Production of 4'-deschlororebeccamycin can be effected at any temperature conducive to satisfactory growth of the organism, e.g. 20�-41� C., and is conveniently carried out at a temperature of about 27� C.
The fermentation may be carried out in flasks or in laboratory or industrial fermentors of various capacities. When tank fermentation is to be used, it is desirable to produce a vegetative inoculum in a nutrient broth by inoculating a small volume of the culture medium with a slant or soil culture or a lyophilized culture of the organism. After obtaining an active inoculum in this manner, it is transferred aseptically to the fermentation tank medium for large scale production of 4'-deschlororebeccamycin. The medium in which the vegetative inoculum is produced can be the same as, or different from, that utilized in the tank as long as it is such that a good growth of the producing organism is obtained.
In general, optimum production of 4'-deschlororebeccamycin is achieved after incubation periods of about seven days.
4'-Deschlororebeccamycin is a minor product of the fermentation and may be recovered from the culture medium and isolated in a substantially pure form according to the multistep procedure described in Example 1 below. Thus, the desired 4'-deschlororebeccamycin is found primarily in the mycelium and recovery from the mycelium may be effected by extraction with an organic solvent such as tetrahydrofuran. After reduction of the extract volume a crude solid containing the desired 4'-deschlororebeccamycin may be obtained. This crude solid may then be subjected to a multistep purification scheme illustrated in the following flow chart:
The physicochemical properties of 4'-deschlororebeccamycin are as follows:
4'-Deschlororebeccamycin is a yellow amorphous solid having a molecular formula of C27 H22 O7 N3 Cl and a molecular weight of 535.8397. It is composed of the elements carbon, hydrogen, oxygen, nitrogen and chlorine. Elemental analysis data is as follows:
Calc'd for C27 H22 O7 N3 Cl.H2 O: C, 58.54; H, 4.37; N, 7.58; Found: C, 53,43; H, 4.29; N, 7.29.
The high resolution mass spectrum of 4'-deschlororebeccamycin was determined with a Kratos MS-50 spectrometer and FAB ionization. The observed mass is as follows:
Calc'd for (M+H)+ ion: 536.1224; Found for (M+H)+ ion: 536.1188.
4'-Deschlororebeccamycin is insoluble in water and soluble in dimethylsulfoxide.
The infrared absorption spectrum of 4'-deschlororebeccamycin when pelleted in KBr exhibits characteristic bands at the following frequencies exhibited in reciprocal centimeters:
3400, 3330, 2930, 1745, 1703, 1575, 1490, 1470, 1458, 1435, 1398, 1380, 1330, 1273, 1238, 1140, 1105, 1083, 1050, 1015, 947, 910, 800, 798, 755, 738, 670, 665, 633.
The ultraviolet absorption spectrum of 4'-deschlororebeccamycin was determined in methanol (0.03462 g/l) under neutral conditions. Observed absorption maxima and absorptivities are as follows:
400 nm (8.6), 315 nm (96.5), 290 nm (107.7), 257 nm (sh), 235 nm (76.3).
A proton magnetic resonance spectrum of 4'-deschlororebeccamycin dissolved in dimethylsulfoxide was determined with a Bruker WM-360 spectrometer operating at 360 MHz and using tetramethylsilane was the internal standard. The observed chemical shifts (δ values), coupling constants (J values in Hz) and pattern descriptions are as follows:
11.81 (s, 1H, N8--H), 11.24 (s, 1H, N5'--H), 9.26 (d, J=7.9, 1H, C1--H or C1'--H), 9.10 (d, J=7.9, 1H, C1--H or C1'--H) 7.77 (d, J=7.9, 1H, C4'--H), 7.63 (m, 2H, C3--H and C3'--H), 7.42 (m, 2H, C2--H and C2'--H), 6.91 (d, J=9.4, 1H, C1"--H), 6.30 (bs, 1H, C6"--OH), 5.25 (d, J=5.7, 1H, C3"--OH), 4.91 (d, J=5.7, 1H, C2"--OH), 4.01 (bs, 2H, C6"--H), 3.90 (d, 1H, C5"--H), 3.67 (t, 1H, C4"--H), 3.62 (s, 3H, C4"--OCH3), 3.53 (m, 1H, C2"--H overlaps with H2 O).
A carbon-13 magnetic resonance spectrum of 4'-deschlororebeccamycin dissolved in dimethylsulfoxide was determined with a Bruker WM-360 spectrometer operating at 22.5 MHz and using tetramethylsilane as the internal standard. The observed chemical shifts (ppm values) and assignments are as follows:
______________________________________Chemical Shift (ppm) Assignment______________________________________170.7 C7170.6 C7'140.7 C4a138.1 C4a'130.4 C5a129.9 C5a'129.4 C3'127.3 C3125.6 C5c124.6 Cl'123.9 Cl122.8 C5c'122.3 C2121.1 C6120.6 C2'119.4 C6'119.1 C5b'117.4 C5b116.4 C4112.1 C4'83.9 Cl"77.6 C3"77.0 C4"76.6 C5"72.1 C2"60.0 OCH358.7 C6"______________________________________
The antibacterial activity of 4'-deschlororebeccamycin was determined against a number of gram-positive and gram-negative organisms by the serial two-fold agar dilution method. The results are shown in Table 5 below in comparison with the activity of rebeccamycin.
TABLE 5______________________________________Antibacterial Activity of 4'-Deschlororebeccamycin Minimum Inhibitory Concentra- tion (MIC) (mcg/ml) 4'-Deschloro-Organism Rebeccamycin rebeccamycin______________________________________S. pneumoniae A9585 >125 32S. pyogenes A9604 >125 32S. faecalis A20688 8 16S. aureus A9537 0.5 2M. luteus A9547 0.5 1S. aureus (Pen-Res) A9606 >250 >250S. coli A15119 >250 >250S. coli A20341-1 >250 >250K. pneumoniae A9664 >250 >250K. pneumoniae A20468 >250 >250E. cloacae A9659 >250 >250E. cloacae A9656 >250 >250P. mirabilis A9900 >250 >250P. vulgaris A21559 >250 >250M. morganii A15153 >250 >250P. rettgeri A22424 >250 >250S. marcescens A20019 >250 >250P. aeruginosa A9843A >250 >250P. aeruginosa A21213 >250 >250List. monocytogenes A15121 32 32List. monocytogenes A20025 32 63______________________________________
4'-Deschlororebeccamycin was also tested against the transplanted mouse leukemia P-388 and the results are shown below in Table 6. The methodology used generally followed the protocols of the National Cancer Institute [Cancer Chemotherapy Rep. Part 3, 3, 1-103 (1972)]. The essential experimental details are given at the bottom of Table 6.
TABLE 6______________________________________Effect of 4'-Deschlororebeccamycin on P-388 Leukemia Average weight Sur- Dose, IP MST MST change, gm vivorsMaterial mg/kg/inj Days % T/C day 5 day 10______________________________________Rebeccamycin 512 17.0 155 -1.4 6/6 256 15.0 136 -0.3 6/6 128 14.5 132 0.2 6/6 64 15.0 136 0.3 6/6 32 13.0 118 -0.6 6/6 16 15.0 136 -0.8 6/64'-Deschloro- 512 15.5 141 -1.0 4/4rebeccamycin 256 15.0 136 -1.5 4/4 128 17.5 159 -0.6 4/4 64 15.0 136 -0.8 4/4 32 15.5 141 -0.8 4/4 16 18.0 164 -0.9 3/4Control 0.5 ML 11.0 100 0.6 10/10______________________________________ Tumor inoculum: 106 ascites cells, ip Host: CDF1 F mice Treatment: Single injection on day 1 given i.p. Evaluation: MST = median survival time Effect: % T/C = (MST treated/MST control) � 100 Criteria: % T/C >125 considered significant tumor inhibition Control: Saline (0.5 ml) given once daily i.p. for 5 days
As indicated by the antimicrobial and mouse tumor data provided above, 4'-deschlororebeccamycin is useful as an antibiotic and also as an antitumor agent for inhibition of mammalian malignant tumors such as P-388 leukemia.
The invention includes within its scope pharmaceutical compositions containing an effective antimicrobial or tumor-inhibiting amount of 4'-deschlororebeccamycin in combination with an inert pharmaceutically acceptable carrier or diluent. Such compositions may also contain other active antimicrobial or antitumor agents and may be made up in any pharmaceutical form appropriate for the desired route of administration. Examples of such compositions include solid compositions for oral administration such as tablets, capsules, pills, powders and granules, liquid compositions for oral administration such as solutions, suspensions, syrups or elixirs and preparations for parenteral administration such as sterile solutions, suspensions or emulsions. They may also be manufactured in the form of sterile solid compositions which can be dissolved in sterile water, physiological saline or some other sterile injectable medium immediately before use.
For use as an antimicrobial agent, the 4'-deschlororebeccamycin or pharmaceutical composition thereof is administered so that the concentration of active ingredient is greater than the minimum inhibitory concentration for the particular organism being treated. For use as an antitumor agent, optimal dosages and regimens of 4'-deschlororebeccamycin for a given mammalian host can be readily ascertained by those skilled in the art. It will, of course, be appreciated that the actual dose of 4'-deschlororebeccamycin used will vary according to the particular composition formulated, the mode of application and the particular situs, host and disease being treated. Many factors that modify the action of the drug will be taken into account including age, weight, sex, diet, time of administration, route of administration, rate of excretion, condition of the patient, drug combinations, reaction sensitivities and severity of the disease.
The following example is provided for illustrative purposes only and is not intended to limit the scope of the invention, Skellysolve B is a commercially available petroleum solvent (Skelly Oil Co.) comprising isomeric hexanes and having a boiling point of 60�-69� C. Dicalite is diatomaceous earth manufactured by Grefco, Inc. Unless otherwise indicated, all temperatures below are in degrees Centigrade.
Nocardia aerocolonigenes strain C38,383-RK2 (ATCC 39243) was maintained and transferred in test tubes on agar slants of yeast-malt extract agar. This medium consists of 4.0 g glucose, 4.0 g yeast extract, 10 g malt extract and 20 g agar made up to one liter with distilled water. With each transfer the agar slant was incubated for seven days at 27� C. To prepare an inoculum for the production phase, the surface growth from the slant culture was transferred to a 500 ml Erlenmeyer flask containing 100 ml of sterile medium consisting of 30 g glucose, 10 g soy flour, 10 g cottonseed embryo meal and 3 g CaCO3 made up to one liter with distilled water. This vegetative culture was incubated at 27� C. for 48 hours on a Gyrotory tier shaker (Model G53, New Brunswick Scientific Co., Inc.) set at 210 rev/min describing a circle with a 5.1 cm diameter. Four ml of vegetative culture was transferred to a 500 ml Erlenmeyer flask containing 100 ml of sterile production medium consisting of 60 g corn starch, 10 g glucose, 15 g linseed meal, 5.0 g autolyzed yeast, 1.0 g FeSO4.7H2 O, 1.0 g NH4 H2 PO4, 1.0 g (NH4)2 SO4 and 10 g CaCO3 made up to one liter with distilled water. The production culture was incubated at 27� C. on a shaker such as used for the vegetative culture. The agitation rate was set at 250 rev/min. The fermentation was terminated at 168 hours.
The fermentation broth obtained according to Example 1A is filtered using a diatomaceous earth filter aid (the filter aid is admixed with the broth and also used to form a mat). The filtrate is discarded and the mat extracted with tetrahydrofuran (THF) for 30-60 minutes using 0.1-0.2 volumes based on the original broth volume (the THF preferably contains 0.025% butylated hydroxytoluenes as preservative). The THF extract is filtered and the insolubles discarded. The filtrate is concentrated in vacuo until almost all the THF is removed. Inert filter aid is then admixed with the concentrate and the resulting mixture is filtered on a mat of inert filter aid. Air is sucked through the mat for four hours or more to dry the mat as much as possible.
The mat obtained as described above is then extracted for about 30 minutes with enough THF to get a good slurry. The extract is filtered and the mat discarded. The filtrate is concentrated by boiling at one atmosphere. Hot methanol is simultaneously added as the volume becomes low. After crystallization of yellow solids begins, the mixture is boiled gently until bumping becomes a problem. The reaction mixture is then allowed to cool and is chilled to 5�-8� C. The solid product is filtered, rinsed with cold methanol and dried. This material containing the desired 4'-deschlororebeccamycin is used in the following separation procedure.
Crude solids from Example 1B (336.3 g) were suspended and partially dissolved in 2.51 of 2 parts chloroform: 1 part methanol and transferred to a 61 round bottom flask. Approximately 1 kg of filter aid (Dicalite) was mixed into the suspension. The mixture was diluted with approximately 1.51 of Skellysolve B. The resultant slurry was concentrated to a powder in vacuo in a rotatory evaporator. This powder was slurried in 61 of Skellysolve B and packed into a 12 cm o.d.�90 cm flash chromatography column. A bed was formed with pressurized flow (N2 --5.7 psi). The packed column was eluted with pressurized flow with the following elutropic series: 9 liters of Skellysolve B (3 liters fresh+6 liters packing solvent); 13 liters of toluene; 12 liters of methylene chloride; 12 liters of ethyl acetate; 18 liters of tetrahydrofuran; and 7 liters of methanol. The toluene eluant was evaporated to dryness in vacuo in a rotatory evaporator to yield 5.15 g of solid designated residue A.
A Glenco Series 3500 Universal LC column (2.67 cm i.d.�75 cm) was packed with 80 g Woelm silica gel (0.063-0.200 mm) in chloroform. Residue A was dissolved in 40 ml of chloroform and pumped directly onto the column. Elution commenced with an initial isocratic rinse of 500 ml chloroform. Elution continued with a 41 linear gradient of chloroform to 5 parts methanol in 95 parts chloroform collecting twenty 200 ml fractions. Fractions 13 to 16 were judged nearly homogeneous. These were pooled and evaporated to dryness to yield 663 mg of residue B.
The Glenco column (2.67 cm i.d.�75 cm) was packed with Baker Bonded Phase Octadecyl silica gel (C-18) in methanol. The column was equilibrated with approximately 2.5 bed volumes of eluant: 3 parts acetonitrile, 3 parts methanol and 4 parts 0.1M ammonium acetate. Residue B in 3 ml of dimethysulfoxide was drawn into the sample loop and pumped onto the column with eluant. Elution commenced while monitoring the eluant at 280 nm. After an initial 2 liter forerun, forty 50 ml fractions were collected. Based on the UV chromatogram, fractions 9 to 32 were pooled. The composite was extracted with 2 liters of chloroform. The lower phase was separated and concentrated to dryness in vacuo in a rotatory evaporator. The residue was partially dissolved in 50 ml of chloroform with sonication. The suspension was added to 1 liter of Skellysolve B with rapid stirring. The resultant precipitate was collected by filtration to yield 606 mg of 4'-deschlororebeccamycin.
Further details of the above isolation procedure are set forth below:
The following components were used to construct an analytical HPLC system: Waters Associates Model 6000A Solvent Delivery System pump; Varian Varichrom Model VUV-10 uv/vis Detector set at 254 nm 0.1 O.D.; Fisher Recordal Series 5000 Recorder; Waters Associates Model U6K injector; Altex Spherisorb ODS (10μ) column (4.6 mm i.d.�25 cm). The components were connected with 316 stainless steel tubing (1.6 mm o.d.-0.23 mm i.d.). The eluant of 4 parts acetonitrile, 3 parts methanol, and 3 parts 0.1M ammonium acetate was pumped at 2 ml/min for all analysis. Occasionally, a Hewlett Packard 1040A HPLC Detector System was substituted for the Varian Varichrom VUV-10 Detector.
TLC was carried out on Analtech precoated Silica Gel GHLF plates (2.5 cm�10 cm 0.25 mm thick layers). The plates were developed in glass cylinders (6.4 cm diameter by 15 cm high) purchased from Whatman, Inc. The tanks were charged with 10 ml of 5 parts methanol-95 parts chloroform and allowed to equilibrate prior to introducing the plate. The developed, air dried plates were visualized with 254 nm and 366 nm ultraviolet light using either a Chromato-VUE model CC-20 light box (Ultra-Violet Products Inc.) or a model UVSL-58 hand held mineral light lamp (Ultra-Violet Products Inc.).
The following components were used to construct a medium pressure liquid chromatography system: Fluid Metering, Inc. Model RP-SY 2CSC FMI Lab Pump; Fluid Metering Inc. Model PD-60-LF FMI Pulse Dampener; a 15 ml sample loop constructed of polypropylene tubing (3.0 mm o.d.�1.5 mm i.d.) wrapped around a cardboard tube (8.65 cm o.d.); Glenco Series 3500 Universal LC column (2.67 cm i.d.�75 cm); Instrumentation Specialties Co. Model UA-5 Absorbance/Fluorescence Monitor with a Type 6 optical unit; Instrumentation Specialties Co. Model 590 Flow Interrupter Value; and an Instrumentation Specialties Co. Model 328 Fraction Collector. The components were connected with polypropylene and Teflon tubing (3.0 mm o.d.�1.5 mm i.d.) and Glenco multifit connectors and valves in the order listed.
The Glenco series 3500 Universal LC column was slurry packed with the defined absorbent in the designated solvent using standard techniques. The void between the settled bed and tube top was filled with standard Ottawa sand. Eluant was pumped at a maximum rate which would not exceed 60 psi back pressure (approximately 20 ml/min).
A Glenco gradient elution apparatus consisting of two chambers of equal diameter, height and volume connected in tandem with a Teflon valve was used for gradient elutions. One chamber served as a mixing chamber and one as a static reservoir. The less polar solvent, chloroform, was initially held in the mixing chamber. The more polar solvent 5 parts methanol in 95 parts chloroform, was held in the static chamber. Teflon coated magnetic stirring bars (1.0�3.7 cm) were placed in both chambers and driven by Thomas Model 15 Magne-matic stirrers. Eluant was pumped from the mixing chamber to the medium pressure hplc system through polypropylene tubing (1.5 mm i.d.�3.0 mm o.d.). As eluant was removed from the mixing chamber, the solvent in the static reservoir was allowed to freely replace it, thus creating a linear gradient of eluant.
|Cited Patent
|Filing date
|Publication date
|Jan 27, 1984
|Aug 8, 1984
|Bristol-Myers Company
|Rebeccamycin and process for its preparation
|Angew. Chem. Int. Ed. Engl. , 19, (6), Indole Pigments from the Fruiting Bodies of the Slime Mold Arcyria denudata, W. Steglich et al., pp. 459 460, 1980.
|Angew. Chem. Int. Ed. Engl., 19, (6), Indole Pigments from the Fruiting Bodies of the Slime Mold Arcyria denudata, W. Steglich et al., pp. 459-460, 1980.
|J. Antibiotics , 30, (4), A New Alkaloid AM 2282 of Steptomyces Origin Taxonomy, Fermentation, Isolation and Preliminary Characterization, S. Omura et al., pp. 275 282, 1977.
|J. Antibiotics, 30, (4), A New Alkaloid AM-2282 of Steptomyces Origin Taxonomy, Fermentation, Isolation and Preliminary Characterization, S. Omura et al., pp. 275-282, 1977.
|J. C. S. Chem. Comm. , X Ray Crystal Structure of Staurosporing: A New Alkaloid from a Streptomyces Strain, A. Furusaki et al., pp. 800 801, 1978.
|J. C. S. Chem. Comm., X-Ray Crystal Structure of Staurosporing: A New Alkaloid from a Streptomyces Strain, A. Furusaki et al., pp. 800-801, 1978.
|Citing Patent
|Filing date
|Publication date
|Mar 18, 1985
|Jan 28, 1986
|Bristol-Myers Company
|Process for preparing 4'-deschlororebeccamycin
|Sep 17, 1984
|May 10, 1988
|Schering Corporation
|Antibiotic, antitumor compounds and their use
|Apr 11, 1986
|Aug 16, 1988
|Eli Lilly And Company
|Antibiotic A42125 and process for its production
|Mar 9, 1987
|Sep 26, 1989
|Eli Lilly And Company
|Pure culture of antibiotic A42125-producing strains of Nocardia aerocolonigenes
|Mar 20, 1987
|Jun 19, 1990
|Kyowa Hakko Kogyo Co., Ltd.
|UCN-01 and process for production thereof
|Sep 23, 1991
|Oct 27, 1992
|Bristol-Myers Squibb Company
|May 18, 1993
|Jul 5, 1994
|Bristol-Myers Squibb Co.
|Antitumor antibiotic BMY-41219
|Mar 19, 1993
|Aug 20, 1996
|Burroughs Wellcome Co.
|Further indole derivatives with antiviral activity
|Jun 2, 1994
|Jul 21, 1998
|Taisho Pharmaceutical Co., Ltd.
|Human-derived tumor cell growth inhibitors
|May 31, 1995
|Jan 19, 1999
|Banyu Pharmaceutical Co., Ltd.
|Gene encoding glycosyltransferase and its uses
|May 31, 1995
|Jun 5, 2001
|Banyu Pharmaceutical Co, Ltd
|Gene encoding glycosyltransferase and its uses
|Mar 16, 1987
|Sep 23, 1987
|Kyowa Hakko Kogyo Co., Ltd.
|Polycyclic condensed amino sugar derivatives with anti-tumor and anti-bacterial activity, produced by streptomyces
|Mar 16, 1987
|Nov 25, 1987
|Kyowa Hakko Kogyo Co., Ltd.
|Polycyclic condensed amino sugar derivatives with anti-tumor and anti-bacterial activity, produced by streptomyces
|Apr 9, 1987
|Oct 14, 1987
|Eli Lilly And Company
|Antibiotic A42125 and process for its production
|Apr 9, 1987
|Sep 7, 1988
|Eli Lilly And Company
|Antibiotic a42125 and process for its production
|Nov 20, 1987
|Jun 1, 1988
|Bristol-Myers Squibb Company
|Rebeccamycin analogs
|Nov 20, 1987
|Aug 29, 1990
|Bristol-Myers Squibb Company
|Rebeccamycin analogs
|Mar 22, 1990
|Sep 26, 1990
|Bristol-Myers Squibb Company
|BMY-41950 antitumor antibiotic
|Mar 22, 1990
|Jan 16, 1991
|Bristol-Myers Squibb Company
|Bmy-41950 antitumor antibiotic
|Mar 5, 1991
|Sep 11, 1991
|Bristol-Myers Squibb Company
|Rebeccamycin analog and pharmaceutical composition containing it
|Dec 14, 1993
|Jun 22, 1994
|Banyu Pharmaceutical Co., Ltd.
|Process for preparation of indolopyrrolocarbazole derivatives
|Dec 14, 1993
|Apr 19, 1995
|Banyu Pharma Co Ltd
|Process for preparation of indolopyrrolocarbazole derivatives.
|May 31, 1995
|Dec 21, 1995
|Banyu Pharmaceutical Co., Ltd.
|Gene coding for glycosyltransferase and use thereof
|Apr 19, 2004
|Nov 4, 2004
|Lonza Ag
|Process for the recovery of staurosporine from a fermentation broth
|U.S. Classification
|514/43, 536/28.8, 435/85, 536/27.1, 536/27.12
|International Classification
|Cooperative Classification
|European Classification
|Oct 29, 1984
Owner name: BRISTOL-MYERS COMPANY 345 PARK AVE., NEW YORK, NY
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:MATSON, JAMES A.;REEL/FRAME:004319/0939
Effective date: 19840829
|Dec 5, 1988
|Fee payment
Year of fee payment: 4
|Sep 24, 1992
|Fee payment
Year of fee payment: 8
|Jan 21, 1997
|Maintenance fee reminder mailed
|Jun 15, 1997
|Lapse for failure to pay maintenance fees
|Aug 26, 1997
|Expired due to failure to pay maintenance fee
Effective date: 19970518


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Small (5%)
high risk
* Always check the full terms & conditions on the betting website Switch Odds type: percentage / example / decimal
Stats for the Epsilon and gB as they've appeared on Tipify
Two Spanish sides facing off here in a game that could be interesting. Gbots have looked good lately, completely demolishing NR yesterday, even taking the first map 16-0. They have a lot of firepower in Mixwell, who must be one of the best Spanish players. I know as well that gB are at the moment preparing for a LAN, and are bootcamping, so I hope they use this match as a serious game and not just practice.
The ex-Espilon boys have more experience in their roster, and perhaps overall more individual skill, especially in players such as Alex and Musamban1 but they seem to be in a big slump right now and overall their performances are weak. Their best map is Cache, but they even struggled on that map against Tricked, and will need to be on point today. Perhaps beating their fellow countrymen will inspire them to raise their game.
With how both sides played recently, and with this being a BO2, the most logical bet is to go on the one more likely to take both maps, and in current form this would have to be gB. I would suggest going LOW on them as long as the odds don't move about 70%. Otherwise I'd probably SKIP as this game could potentially be a really close one.
My odds for this match: Epsilon 35:65 gB
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What is JotForm?
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FormsCentral Exporter: Import/update new responses recieved since last importAsked by dcullen339 on May 28, 2015 at 11:17 AM
The above email describes an additional option when using the FormsCentral Import Page.
However when I got back from vacation and went to that link, instead of what was described, I got a download for an executable. When I ran that executable (FormsCentral Exporter by JofForm) and choose 'select which forms to input' I stopped at the next screen because the button says "import to JotForm". But I only want to import new responses (as advertised in the email).
I did a search for "formscentral exporter site:jotform.com" but found no (obvious) help page on your web site.
Can you provide some clarity here please.
JotForm Support
We have removed the login option in the website and added the executable file for that purpose. I'm downloading the app now and will get back to you.
JotForm Support
I'm stuck at login. If you do not have the option to update forms with new responses, you can choose to re-import everything. That shouldn't take long.
If you are not sure and feel unsafe, you can create a new account and import the forms there. If the process went through fine, we can move the forms to your original account.
That's a step backwards. I specifically do not want to reimport the forms! All I want are the new responses.
Because JotForms is not 100% identical to FormsCentral I've had to do some minor tweaks (that don't affect the answer fields). So re-importing the forms just overwrites my tweaks.
When will this be fixed?
JotForm Support
I'm sorry for it then. Anyways, I was able to login now and indeed, the option to just update the submissions is missing in the app. I'm not yet sure of the reason, but this thread is now submitted to our developers for further view. Maybe that option is not possible anymore, probably because of Adobe Terms and/or Adobe disallow that process. We'll know.
JotForm Support
We added that option to our TODO list and a fellow developer os already working on it. It will be live next week. I will let you know when it happens. Thanks for your feedback.
I would also like to import only the new responses. Is this change updated yet? Thank you.
JotForm Support
We did the hard work about importing new responses, it will be live tomorrow. Thanks for your patience.
I re-downloaded the importer today and it still did not recognize that I have had a previous import.
JotForm Support
Sorry for the late response, we just released "import response" options. Please re-download the app and you should see an option named "Update previous imported forms" on bottom left after Adobe login.
Thanks for your patience.
Will this override the forms I have redesigned since importing? I want ONLY the new responses, not the forms themselves. Thanks.
JotForm Support
The main usage of the option to is to update the responses so I don't think it will override the forms. You may consider trying it with a single form so to make sure.
Could you kindly provide the ID of the form that you were attempting to import the new responses so that i can check it against the importation queue.
It was this form: https://secure.jotformpro.com/form/50845757692974
Could you by any chance also know the Form-Central ID/URL of the form you were importing the new responses form, It will enable me to restart the queue for only the new responses as the one I've found seems to belong to responses already in the form provided.
Thank you
This is the Adobe URL: https://adobeformscentral.com/?f=OtdY1B4yJjAzlwOiPqYlLA
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Hi, I would assume that you are a different person from the one who originally opened this thread. To better assist our users, we advise them to open their own thread. In this case, I went ahead and opened one for you, please refer to this link: http://www.jotform.com/answers/589020. We will address it shortly.
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Tales from the Squeezed Middle(93 Posts)
Article in today's Weekend FT.It does look as if the Durham couple in the article below (see a forthcoming R4 programme mentioned at the end) are being a bit foolish. Their daughter with her Cambridge degree can pay back her student debt during her life. No need to sell their home when they have 2 other children too.
"First Person: Caroline Beck
As told to Rosie Millard
The struggling freelance writer says she can see the abyss
Wed always thought of this house as being our pension. It was derelict when we bought it 14 years ago, we have done everything ourselves; the painting, the flooring, the garden But we need that money now. I cant think of any alternative but to sell.
Roisin, our eldest daughter, has been offered a place at Cambridge university. I cant bear the thought of her being saddled with huge debts, so we will sell up and live in rented accommodation.
I am a freelance writer, my partner is a wine merchant. Lots of people here in County Durham architects, graphic designers, photographers are going through the same thing. We all used to be OK. Some of them now have no work. I am still working but I can always see the abyss, my toes are reaching over the edge.
Six years ago both the children played the piano, one went swimming and my eldest daughter had singing lessons. They dont have any lessons any more. Its my youngest daughter Eves birthday next week. She hasnt asked us for anything. We wont give her a party because this week we had three catastrophic bills: the exhaust fell off my car yesterday; our oven blew up at the beginning of the week; and, last month, the lights in the kitchen fused.
IN FT Magazine
The Inventory Felicity Kendal
My father, the good Nazi
A hire truth
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We look at our finances every day to find out where the money is coming from. For the last two weeks of each month we live off a lot of lentils and chickpeas.
I make my own bread because it saves me £10 a week. I make all my own cakes because if the girls take a slice of it to school, they wont spend £2 on a muffin. So much of my time is devoted to domesticity. And I find that boring.
For six months I have not been out of this jumper. I wash it. I put it on the radiator. And then I wear it the next morning because its the warmest thing I possess. We all have one pair of jeans, and we do the same thing. We also save by not having the heating on much.
We used to take really flash holidays. But when we went to Europe last year, we stayed in hostels. We would have breakfast in the morning, then we wouldnt eat again until the evening.
Recently I had a voucher for £7 off my weekly shop. I gave it to the shop assistant at the till and she told me it was out of date. Although the date on the voucher said it was in date, the scanner was saying it wasnt. So, I am standing there with my shopping my kids are saying Oh Mum! There are people standing behind me, but I dont care: I want this £7 off, because £7 off is £7 off. I never would have done that eight years ago. I would have thought: Oh that is a crazy woman in the supermarket. I dug my heels in, and, in the end, it got knocked off.
I went to university in the early 1980s when we were told that our generation of young women could have it all. And I did think we could have it all. I thought I could have a career. I thought I could have children. I thought I could have a cleaner and go out occasionally. When I was 21, if somebody had fast-forwarded my life and said Thats what you will be doing, I would have said: No, no, no. Thats my mothers generation, I will not be doing that.
It wont bother me not owning a house.
What bothers me is getting us all through the next decade, so we can get our children to a point where they are self-sustaining. Right now that seems a long way off. We are not living in a Victorian novel. We are healthy, we are happy, we are together. But I cant see an end to it. I dont know how they are going to ever afford to buy a house. They are going to be living in rented accommodation for the rest of their lives.
At the end of the day its a house. Its a house that we have done up and we love and we have been really happy here. But it is just a house."
Tales from the Squeezed Middle, by Rosie Millard, will be broadcast on Radio 4 on Monday May 6.
Message withdrawn at poster's request.
alpine they can say all they like that they will bring proceedings against debtors overseas. But how do they know where you have gone? You are supposed to inform them. But we all know the UK govt cant even tell if failed asylum seekers are still in the country! Most of NZs outstanding loans are to debtors overseas. So far they have prosecuted 20 odd people living in Australia only. We started the loan scheme in 1992 fyi.
By the way, some calculations said 2/3 of debtors won't repay their loans over their lifetime. It is quite a shocking number really.
semua, I agree. I have listened to half of it and trhey do not really provoke any sympathy at all and things they seem to take for granted or did in their more better off past seem extravagent so you are almost pleased they are getting their come uppance and they are reaping what they sowed as one man gave up wellpaid work (so of course he has no money) and a few women stopped work to have children and then the husband's job went so again they took that risk. Their moaning about having to do cleaning as it's boring is fun to hear.
Xenia please stop using the royal 'we' when talking about money.
Message withdrawn at poster's request.
I will certainly listen to it as it is on my list of things to catch up with. They sound like moaners and are suffering the consequences of their choices (as presumably Ms Millard has done - having to send her children to state schools because she chose to be a journalist not something better paid).
I agree there are lots of reasons not to pay the tuition fees. I suspect I may be in the rare category where it is worth paying them however. If my girls earn £50k - £70k in their mid 20s and their brothers are likely to it is highly likely all 5 children will be paying this 9% tax. Given the fees are less than the school fees I already easily pay (due to my wise career choice etc... laughing as I type) and I can also fund their first flat/house deposits I think that is a case where it is worth my paying for the youngest when their time comes.
You should be proud of her.
There is a huge focus on results in education, but what I want as well, is kids who can wait for a bus patiently, who can solve problems for themselves and not blame others, who can eat a range of food including fish and veg, who dont need "things" to prop up their self esteem, who can budget, and who are essentially nice, interesting, curious and thoughtful.
I would also like them to have an island so I can go and visit, but am hoping Xenia will invite me instead....
I did not hear the broadcast but having your parents sell their home so you can study in London without a loan or without having to take a p/t job does not seem particularly appealing.
Do I take it that you didn't hear the broadcast Xenia? It was right up your street. Basically, they had arsty-fartsy careers that didn't pay enough to amply provide for their DC. They did muse at one stage about whether they should have 'gone into insurance' but decided that if they had their time again then they would still prefer the type of life they had.
Hard to feel sorry for them really
but I am a meanie. DD was only entitled to the absolute minimum student loan and had very little assistance off us (no cash, but things like a Big Shop at the beginning of term). She has financed the shortfall herself, though it undoubtedly helped to have a working Gap Year before she went. It's amazing how cheaply you can live when you have to - she can have a barnstorming night out for £5 apparently!
I am very proud of her; she has proved that she can budget, and survive on a limited amount of money. I have no worries about her appearing in the media in 20 years' time bemoaning the price of muffins.
The colleague who worked in Norway is English. (Though I do know another from my PhD class that is working in the Scandanavia). It will take forever for the UK govt to work out a bilateral agreeement with all the EU countries. And probably will never happen if we leave the EU.
Haven't read the entire thread but only the first page.
First, agree with the poster saying the family needs to read the MSE. It's not worth paying for the degree upfront.
Second, learn a leaf from kiwis. We've been paying for university fees since the 90s. The govt has no power on repayment when you are overseas. It's only recently the govt strike up a pact to recover student loan payments from australia. They aren't recovering anything from debtors in the UK yet. They will never get a cent back from those moved to the US. Many of my classmates now work in the US. (I have PhD in engineering. Most of my PhD classmates are in California). A colleague of mine told me he never paid either when he worked in Norway.
Have a look at these pages on the Money Saving Expert website.
Don't pay their tuition! They can get a loan for that. All their peers will get a loan for it too.
If they don't get a good job then they will pay off the loan very slowly, if at all.
We won't be able to afford to pay the tuition for our children but I am of the thinking that if they have a loan they will be more motivated to get a good job. We will of course help financially where we can and our home will always be their home for as long as they need it.
Nearly everybody will be in the same boat. These silly stories just don't wash. People just think what idiots.
Forgot to add - (c) living beyond their means. And yes, having lots of children or a big mortgage is a lifestyle choice!
Alpinemeadow - if their earnings have fallen then either (a) the amounts that their offspring are entitled to in the form of maintenance loans / grants / uni bursaries will rise in accordance, or (b) their income hasn't dropped below the ~£60k that means you get the minimum loan.
If it is the latter, then they are just part of the idiot middle class that does not realise that shopping in Waitrose, going on foreign holidays and going for meals out are not necessities. Anyone who claims that they cannot find £3-4000 a year from an income of £60k for their offspring is either (a) lying or (b) selfish in prioritising their material wants over the material / educational needs of their offspring.
This does all stem from the fact that they clearly do not understand the student finance system (and gahhhh - half my working life seems to be spent explaining SF, so I would quite like to speak to these parents personally) so half this discussion is irrelevant to the people in the story in the OP, though still relevant to others.
It was similar in my day - full grants but not if your parents had a certain amount of money. My parents chose to make up the money to the full grant but plenty of parents did not which caused huge problems in the early 80s for children of less generous parents.
I think we are saying the suggestion is students need £7500 for rent and food etc. The rent seems to be about £3500 in many places. What they spend on travel and the like varies and some spend more than others. Just because all your peers may think certainly luxuries are necessities does not mean you need to have the same views. There are a lot of spoilt children out there and one of the best things children can get out of university is poverty and having to make do and walk not take the bus.
It's way, way older than that mummytime. And to add to your reply, the Bodleian is currently having a shiny new £78m extension built.
I'm not quite sure what your library point is about in any event, but it doesn't seem especially valid
Also, university cost rises do not equate with brighter people going. Fees equate with wealth, not brains. The wealthy are not necessarily the most brainy. The concept of money=brain is a fallacy of this bling obsessed century.
More scholarships need to be created at the top universities which genuinely cover maintenance costs rather than a nod to books and stationary.
Magdalene college Oxford is a wonderful place. I was there at a classical dance concert the other day and the auditorium was superb, with John Piper tapestries all round the foyer.
xenia the only person saying students need to find 3k a year is you.
I would say more like £5k a year and more for London.
Message withdrawn at poster's request.
Bloody bonkers. They clearly have no idea of the student loan system, and their children will probably be much better off in the long term inheriting the house (assuming no protracted care home stays, obviously) than having no student debt.
I get the distinct impression that they have always had quite a nice lifestyle, and there is no mention of redundancy / work drying up. So, if we assume that their income has no dropped substantially (and this is borne out by the lack of mention of any grants or bursaries, though they may just be that clueless) then by making the sort of cost savings that the rest of us do (holidays in hostels / no holidays at all, turning down the heating etc.) then they could quite easily make up the difference between the c. £4000 minimum loan and the c. £7500 you need to live off.
But then again, some people have no idea really - my (very well paid) landlord referred not long ago to a household income of £25,000 being a "pittance". I struggled to keep a straight face.
I did mean the Bodelian, actually. And obviously Magdalen's must have been pretty modern, because my old college one is about 400 years old.
mummytime sorry to contradict but Magdalen is doing exactly that (the library thing). The plague pit uncovered during excavations for the new library has only just, after several months, been covered up. They found old wigs from a barber's shop there too. And they had to identify whether or not any skeletons were Jewish because that had an impact on whether or not they could be moved. It's fascinating actually.
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Tweets by @LordstownLocal
Community NewsLetter Aug 2017
Lordstown Schools currently receives nearly $1.6 million dollars in Tangible Personal Property tax reimbursements from the State of Ohio. Current law phases the entire amount over time costing our schools much needed dollars at a district that receives much less from the State of Ohio than the average school in Ohio. While Lordstown Schools provided testimony to Ohio House Committees and Ohio Senate Committees advocating for a solution to this issue that would benefit Lordstown Schools the legislature needs to hear from all stakeholders: school staff, school families, area businesses and the Lordstown Community.
You can help in one of two ways. Attached is a document titled TPP letters. This document has letters addressed to all thirty-three Ohio Senators. Also attached are the contacts for all of the senators. You can print and mail these directly to the senate offices or print and drop them off at Lordstown Schools on Friday, May 19th or Monday, May 22nd. You can also come by the school and pick up copies and return them signed to the school by 2:00 PM on Monday, May 22nd.
Members of the Class of 2017, whom have completed their classes, will be heading to the statehouse on Tuesday, May 23rd. These students will be delivering the signed letters directly to the offices of the Ohio Senators. Thank you for helping us advocate for fiscal fairness.
Open Enrollment Applications are now available at either building or the Superintendent's office from 8:00 am to 3:00 pm, Monday thru Friday. All applications along with required documentation are due by April 30, 2017. Please see below for policy information and applications.
Registration for both Kindergarten and Preschool will be held on Thursday, March 23. Please call (330) 824-2572 to schedule an appointment. Items to bring are: Child's Original Birth Certificate, Original Social Security Card, Immunization Record, Proof of Residency and Custody Papers if applicable.
Madilyn Hickman, a 6th grade student, was the winner of the annual Spelling Bee held at the Elementary School. Reagan Roberts, a 5th grade student, was the Runner Up. Congratulations to all participants as well!!!!
Please join us for the 2017National Honor Society Induction CeremonyJanuary 27th 9:30 amHigh School Auditorium
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Gorgiano Studios – About us
Painting Holidays Italy – Gorgiano Art Studios are run by husband and wife team Caroline and Andrea.
We moved to Camerino from Bethnal Green in the East End of London, about 8 years ago. We already knew what we wanted to do. I know my way around an easel and Andrea is pretty handy with a frying pan. It is a great privilege to be do something which uses both our skills.
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Contact Details
We are Caroline Crawford and Andrea Silvestri
our address is Tenuta Gorgiano, Localita Gorgiano 2, Camerino (MC) 62032, Italia
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Moira, Australia, 2016
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Wish I had done this course before I did the others, I wouldn't have needed to search further afield.
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my progress has been so much more than I had hoped for.
Anna, Australia 2015
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(he said other things but I feel this should be immortalised!)
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Valentine's Day is one of my favorite classroom holidays. I love promoting kindness even more than usual this month through the class party, read alouds, and discussions. In addition to promoting kindness the month of February, I love having my students complete Valentine's Day themed activities. Today I want to share some of my favorite Valentine's Day activities for upper elementary students, many of which are completely free to download.
Valentine's Day Math Activities
This huge set of math centers is always a hit with my students. The variety of skills in the pack allows me to easily differentiate and review lots of skills during the month of February. All the different candy and chocolate graphics are super appealing to the students, even the boys! The centers shown above are from my 5th grade set, but I also have a set dedicated specifically to 4th grade standards. Click here to see them both!
This FREE Valentine's Day Math center is a perfect quick center for your students to complete. Equivalent fractions are always a skill that my students can use a refresher on and this center can be used all the way from 3rd grade up to 5th. Click here or on the image to grab your free copy.
As much as I love using math centers, I also love some engaging (and skill based) no prep printables for homework and independent work. My Valentine's Day printables are a perfect fit for my needs; they are themed and include engaging graphics that students love to color. Click here to see these sets in my store.
I have recently discovered my love for Sweethearts candy. I am lucky enough to be able to use candy in my classroom, so I put together this quick printable for some Sweetheart themed math practice. Give each student the printable and an individual box of sweethearts (or a handful or small baggy from a larger bag if you don't want to go the individual route) and let them practice some math skills while enjoying some sweet treats. Click here to download the printable.
Valentine's Day Literacy Activities
My students are a huge fans of themed holiday reading materials, and these Valentine's Day reading passages with activities are no exception. I use these to mix up our regular reading homework routine, and sometimes even as a literacy center. To read more about what I give for reading homework, click here.
The best part about these sets is that they include three passages: one fiction text, one informational text, and one poem. Each text includes several text dependent printables, so one passage can be used over the course of an entire week with a different printable each day. This is a perfect way to sneak some more close reading practice into your reading homework. To see this reading resource in my TpT store, click here.
In my opinion, Valentine's Day is the prefect time to review idioms because of all the idioms about hearts in the English language. This FREE set of three interactive notebook templates is perfect for themed idiom review. The students identify, define, and use idioms in a sentence in these templates. Print these on red colored paper (or pink and purple) to make them even more themed. Grab your free set of templates here or on the image above.
Valentine's Day Party Letter and Class List
A couple of years ago, I shared a similar image to the image above on my Instagram and I got a lot of comments from people who wanted the template I used. So, I made it editable, and I am including it in this post. The fonts, graphics, and some of the text is not editable (due to copyrights and terms of use); however you can type in your class party date and your students' names. You will need powerpoint to edit this file. Grab it by clicking here or on the image above.
Those are just a few of my favorite Valentine's Day activities that are perfect for upper elementary students. What are your favorite activities for Valentine's Day?
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Bhubaneswar: After the end of the fifth round Thursday, three players were leading the field with five points in The Telegraph Schools Chess Championship, Bhubaneswar leg, being played in Gymnasium-cum-Indoor Hall, Sahid Nagar.
Three players were closely following the leaders on 4.5 points.
On the top board Kiran Manisha of Aurovinda School, playing black against Anwesha Upadhyay of Stewart School (Bhubaneswar), opted for the Sicilian Scheveningen Variation and got an advantage in the opening which she turned into a win in the middle game.
On the second board Swayams Mishra of Stewart School (Cuttack) faced the Modern Defence employed by Chinmayee Misra of Saraswati Sisu Vidya Mandir. Chinmayee got the exchange in the 23rd move but was unable to get any advantage.
On the other hand, Swayams played very actively and slipped in an unstoppable passed pawn for which Chinmayee had to give up a rook. Ultimately, Chinmoyee resigned on the 49th move.
The 15th seed Novneet of Kendriya Vidyalaya No 1 (Bhubaneswar) continued to create upsets, this time defeating sixth seed Sambhabi Patnaik of Blessed Sacrament HS, Puri.
Sambhabi went for the Sicilain Defence and obtained an equal position. She made a fatal move in the middle game and resigned on the 46th move.
There were two major upsets in the fourth round. Third seed Aurovind Khuntia (3) lost to 14th seed Anwesha Upadhyay (4) in a Queens Gambit Declined game. In another encounter, 15th seed Novneet (4) beat fourth seed Thompson Sahoo in a Caro Kann Defence, Classical Variation.
FIFTH ROUND: Anwesha Upadhyay (4) lost to Kiran Manisha Mohanty (5); Swayams Mishra (5) bt Chinmoyee Mishra (4); Sambhabi Patnaik (4) lost to Navneet (5); Sourav Mohapatra (4.5) drew Debashish Das (4.5); Utkal Ranjan Sahoo (3.5) lost to Khitendra Prateem Dalai (4.5).
FOURTH ROUND: Kiran Manisha Mohanty (4) bt Saket Sagar Dash (3); Pratik Barik (3) lost to Swayams Mishra (4); Aurovind Khuntia (3) lost to Anwesha Upadhyay (4); Novneet (4) beat Thompson Sahoo (3); Bharat Bhushan Mohanty (3) lost to Debashish Das (4).


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Why aren't all questions appearing on report?Asked by gsobeautiful on June 18, 2014 at 04:35 PM
I have created a new evaluation form, and have received one submission. However, when I create a new report, only 2 of the questions are generated on the report. As an additional point of information, all questions were answered on the submission (there were no questions skipped).
JotForm Support
I cloned your form to test it and the submissions I receive seem to match up with your questions.
You can check which fields will be in the report by going to the "Setup and Embed" tab while editing your form. Then click on "Email Alerts", select the alert you wish to view, then all of the fields that will be included in that report will be listed.
You can add more by clicking on the form fields on the far right. If this does not help please let us know and we will be happy to assist you further.
Thank you for using Jotform!
Thank you for your response! Yes, I'm getting all fields included in the submission reports. However, when creating a Report (i.e., bar graphs, pie charts, etc.), only 2 of the questions appear on the report.
Please disregard -- I have determined how to create a full report by adding fields. Thank you!
JotForm Support
Sorry I misunderstood your question. I am very glad you found the solution anyway. Please let us know if there is anything else we can assist you with and we will be happy to help.
Thank you for using Jotform!