text:
|Publication number
|Publication type
|Application number
|Publication date
|Dec 18, 2001
|Filing date
|Mar 9, 2000
|Priority date
|Apr 6, 1998
|Fee status
|Also published as
|Publication number
|Rachel Decor, Charles Mioskowski, Marc Schmutz, Alain Wagner
|Original Assignee
|Aventis Cropscience Sa
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (3), Non-Patent Citations (2), Classifications (19), Legal Events (5)
|External Links: USPTO, USPTO Assignment, Espacenet
"This is a continuation of application Ser. No. 09/286,406 filed Apr. 5, 1999." Now U.S. Pat. No. 6,068,980.
The present invention relates to a method of transforming cells in which an appropriate quantity of nucleic acid fragments is introduced into the cells. The nucleic acid fragments are introduced in the form of a nucleic acid composition which comprises, in an appropriate vehicle, at least one nucleic acid fragment and at least one compacting agent comprising a nitrogen-containing silicone, useful for compacting the nucleic acid fragments; the compositions comprise aggregates of nucleic acid fragments and silicones according to the invention,
To transform cells by genetic engineering by introducing a nucleic acid fragment foreign to the said cell (or heterologous) by transfection, it is necessary, beforehand, to compact the nucleic acid fragments. This compacting is carried out by means of hyperbranched polyamine compounds such as spermine or polyethylenimines (Garcia Ramirez et al., Biopolymers, vol. 34, 1984, pp. 285-292; WO 97 06833). It is also known to use monomers of silanes to condense DNA for the purpose of its structural study without, however, seeking to transform cells (Fang Y. and Hoh J: "Surface-directed DNA condensation in the absence of soluble multivalent cations" Nucleic acids Research, vol. 26, No. 2, Jan. 15, 1998, pages 588-593).
It is however necessary to find new compacting agents so as to obtain good protection of the nucleic acids and to make it possible to vary the media used for the transfection of cells depending on the applications. The present invention provides a solution to this problem.
The present invention relates to a method of transforming cells in which an appropriate quantity of nucleic acid fragments is introduced into the cells, characterized in that the nucleic acid fragments are introduced in the form of a nucleic acid composition which comprises, in an appropriate vehicle, at least one nucleic acid fragment and at least one compacting agent comprising a nitrogen-containing silicone.
According to the present invention, "nucleic acid fragment" is understood to mean a nucleotide sequence which may be of the DNA or RNA type, preferably of the DNA, in particular double-stranded, type.
Nitrogen-containing silicone is understood to mean according to the invention any compound comprising in its structure at least one silicon atom on which at least one nitrogen-containing hydrocarbon radical comprising at least one nitrogen atom is grafted.
The structure of the nitrogen-containing silicone according to the invention is an oligomer. Oligomer is understood to mean a chain of monomers of at least 2 silanes and less than 30 silanes, advantageously comprising 3 to 20 silanes.
The nitrogen atom in the hydrocarbon radical according to the invention is in the form of a primary, secondary or tertiary amine, preferably a primary amine, optionally in the form of an ammonium salt, or alternatively in the form of functions of the guanidine or amidine type.
Advantageously, the nitrogen-containing hydrocarbon radical according to the invention is an atine-containing hydrocarbon radical comprising at least one amine function as defined above, preferably at least one primary amine function (−NH2).
Hydrocarbon radical is understood to mean according to the invention any radical essentially consisting of carbon and hydrogen atoms, the hydrogens being optionally partly or completely replaced by halogens, and optionally comprising oxygen, nitrogen, sulphur or phosphorus atoms.
Preferably, the hydrocarbon radical is chosen from the alkyl, cycloalkyl and aryl radicals and the polycyclic radicals comprising several aliphatic and/or aromatic rings.
Alkyl radical is understood to mean according to the invention preferably any saturated or unsaturated, linear or branched alkyl radical which is optionally interrupted by one or more oxygen atoms, and in the case of several oxygen atoms the latter are not adjacent, which is optionally interrupted by one or more secondary or tertiary amine, carbonyl, carbonyloxy or oxycarbonyl, carbonate, carbamate or urea functions and the likce, which is optionally sustituted with one or more groups chosen from halogens, hydroxyl or primary, secondary or tertiary amine, or cycloalkyl, aryl or polycyclic radicals. Advantageously, the alkyl radical according to the invention comprises from 1 to 10 carbon atoms, preferably at least three carbon atoms, more preferably from 3 to 5 carbon atoms. Advantageously, the alkyl radical is chosen from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl and pentyl radicals and the various isomers of pentyl
This definition of alkyl radicals also applies to the cycloalkyl radicals according to the invention, it being understood that the rings comprise at least three elements, comprising in particular the cyclopropyl, cyclopentyl, cyclobutyl or cyclohexyl radicals, as well as monosaccharides, in particular pentoses or hexoses such as the derivatives of glucose.
Aryl radical is understood to mean according to the invention any aryl or heteroaryl radical, optionally substituted with one or more radicals chosen from the alkyl, cycloalkyl or polycyclic radicals and/or with one or more groups chosen from halogens, hydroxyl or primary, secondary or tertiary amine.
Preferably, the amine-containing hydrocarbon radical according to the invention is chosen from the 3-aminopropyl or 3-(2-aminoethylamino)propyl radicals.
Among the amine-containing silicones according to the invention are the organic silicones or the derivatives of silica.
The organic silicones according to the invention comprise at least one silicone unit which follows:
in which,
R1 is a nitrogen-containing hydrocarbon radical as defined above,
R2 represents the R1 radical, a hydroxyl radical or a hydrocarbon radical,
R3 represents R2 or the radical of formula
in which R2 is defined above,
x and y, which are identical or different, are 0, 1 or 2, it being understood that the sum x+y is less than or equal to 3.
According to a specific embodiment of the invention, the amine-containing silicone is chosen from the silicones of general formula I or II which follow:
in which,
R1, R2 and R3 are defined above,
R4 represents a hydrogen atom, a hydrocarbon radical or a radical of formula
in which R2 is defined above,
n is at least equal to 1, m is greater than or equal to 0 and p is greater than or equal to 0, on the condition that the sum n+p is greater than or equal to 3.
Preferably, n is between 1 and 10, more preferably between 5 and 9, and m or p are between 0 and 9.
According to a specific embodiment of the invention, in the silicones of general formula I, R2 represents a hydroxyl radical or a hydrocarbon, in particular alkyl, radical, R3 represents a hydroxyl radical and R4 represents a hydrogen atom, n is between 7 and 9 and m is equal to 0.
The silicones according to the invention are prepared according to the customary methods of the state of the art, which are described in particular in Organic Chemistry (vol. 29, Polymer synthese, vol. I, chap. 4, pp. 114-139), by Patai and Rappopor (The chemistry of Silicon Compound, Part 2, pp. 1291-1357), Desachler et al. (Angew. Chem., Int. Ed. Engl., 25, 1986, 236), and in Patent Application JP 9 100 353.
When the amine-containing silicone is a silica derivative, it is advantageously according to the invention a silica support, in the form of particles which are grafted with at least one nitrogen-containing hydrocarbon radical as defined above, Preferably, the particles of silica are nanoparticles having a mean diameter of between 10 and 100 nm, preferably of between 30 and 60 nm, having a specific surface area of about 90 to 100 m2/g. The silica support may be a layer of silica which coats a metallic support; it is advantageously according to the invention a tungsten or gold support. The support is advantageously a particle having a diameter ranging from about 0.5 to 2 μm, preferably of about 1 μm.
The mean diameter of the particles is defined by size and measured by diffraction of light or by visualization under a transmission electron microscope. The measuremnent of the specific surface area is carried out by the BET absorption isotherm.
The particles according to the invention are preferably prepared according to the so-called "St�ber" method by condensation of tetraethoxysilane in ammoniacal aqueous alcoholic medium, followed by a distillation at constant volume of the ammonia and of the alcohol. The water into which the silica particles were transferred is removed by azeotropic distillation in the presence of toluene, followed by heating under vacuum which makes it possible to remove the hydration layers at the surface of the silica.
This type of preparation makes it possible to obtain well equilibrated particles (low dispersity of the diameters), free of macro- or micropores (the attaching operations take place exclusively at the surface) and free of contaminations (in particular absence of the salts which are found in precipitated silica).
The silica particles or the layers of silica coating a metallic support are then functionalized by grafting silanes comprising at least one nitrogen-containing hydrocarbon radical described above, in particular covalently.
Many procedures describe the use of alkoxysilanes or of chlorosilanes for functionalizing silica surfaces either in the form of a prehydrolysed mixture or, if the reaction does not take place in a medium which is at least partially aqueous, by reacting with the water in the surface hydration layers.
Another synthesis route described in the literature (Shoji Hara, Akira Dabashi Journal of Chromatography, 186 (1979) 543-552) consists in reacting, in a rigorously anhydrous medium, an alkoxysilane with the surface siloxanes of the nanoparticles previously freed of any adsorbed water. The reaction is carried out for 12 h in toluene at 100� C. and the alcohol formed (ethanol) is removed by azeotropic distillation. The silica is filtered and rinsed with various solvents so as to remove therefrom the excess siloxanes which did not become attached.
Preferably, the functionalization is carried out according to this second type of preparation. The functionalization of the silica may be carried out with various types of alkoxysilanes, preferably with a silane of the following formula:
in which R1 and R2 are defined above and R5 represents an alkoxy radical.
Preferably, R5 represents a methoxy, ethoxy, isopropyloxy, chloride or acetoxy radical.
This functionalization may be carried out in the presence of other silanes for which R1 and/or R2 and/or R5 are different, so as to vary the nitrogen-containing hydrocarbon radical content of the particles obtained. In this case, if nSi—OH is the number of mols of surface silanols and ni the respective number of mole of the various functionalities i added, the reaction is carried out such that:
This mode of preparation makes it possible to control the relative quantity of each function at the surface of the nanoparticles of silica such that for ki, the rate constant for condensation of the compound i, the final molar percentage of a compound 1 at the surface of the nanoparticles will be close to klnl/Skini.
Advantageously, the molar ratio (nitrogen atoms of the nitrogen-containing silicone compound)/(phosphate functions of the nucleic acid fragment) is between 0.1 and 6000, preferably between 1 and 1000.
The appropriate vehicle is an aqueous vehicle, preferably an aqueous solution, which is customary as compacting medium for nucleic acid fragments. It may also comprise additives such as buffers or salts, provided that they do not degrade the nucleic acid fragments and/or destroy the aggregates obtained.
It was observed that the compositions according to the invention exhibited enhanced stability of the DNA fragments, in particular by enhancing the protection of the said fragments against enzymatic degradations, in particular by DNAses.
The present invention also relates to the use of the silicone compounds (organic silicones or silica derivatives) as defined above, for compacting and protecting nucleic acid fragments, in particular for protecting against enzymatic degradations, more especially by DNAses.
The transformation of cells may be carried out by any method known in the state of the art (in particular Jean-Yves Legendre et al., medecine/sciences, 1996; 12; 1334-41),
The cells transformed by the method according to the invention may be animal, plant, bacterial, fungal or yeast cells.
For animal cells, they may be any cell of animal origin, in particular from mammals, especially of human origin, but also insect cells.
For the plant cells, they will be advantageously cells of monocotyledonous or dicotyledonous plants, and more particularly crop plants, intended or otherwise as animal or human food, such as maize, wheat, rapeseed, soya bean, rice, sugar cane, beet, tobacco, cotton and the like. The plant cells transformed may be undifferentiated or differentiated, such as for example protoplast cells or pollen cells. In the latter case, the pollens being rich in DNAses, the transformation will be facilitated by the protection of the nucleic acid fragments by means of the silicone compounds according to the invention.
For the transformation of the plant cells, a series of methods consists in bombarding cells, protoplasts or tissues with particles to which the DNA sequences are fixed. Another series of methods consists in using, as means of transfer into the plant, a chimeric gene inserted into an Agrobacterium tumefaciens Ti or Agrobacterium rhizogenes Ri plasmid.
Other methods may be used, such as microinjection or electroporation or alternatively direct precipitation by means of PEG.
Persons skilled in the art will make the choice of the appropriate method according to the nature of the host organism, in particular of the plant cell or of the plant.
The subject of the present invention is also the plants containing plant cells transformed above, in particular the plants regenerated from the transformed cells. The regeneration is obtained by any appropriate is method which depends on the nature of the species.
For the methods of transforming plant cells and of regenerating plants, there may be mentioned in particular the following patents and patent applications: U.S. Pat. No. 4,459,355, U.S. Pat. No. 4,536,475, U.S. Pat. No. 5,464,763, U.S. Pat. No. 5,177,010, U.S. Pat. No. 5,187,073, EP 267,159, EP 604 662, EP 672 752, U.S. Pat. No. 4,945,050, U.S. Pat. No. 5,036,006, U.S. Pat. No. 5,100,792, U.S. Pat. No. 5,371,014, U.S. Pat. No. 5,478,744, U.S. Pat. No. 5,179,022, U.S. Pat No. 5,565,346, U.S. Pat. No. 5,484,956, U.S. Pat. No. 5,508,468, U.S. Pat. No. 5,538,877, U.S. Pat. No. 5,554,798, U.S. Pat No. 5,489,520, U.S. Pat. No. 5,510,318, U.S. Pat. No. 5,204,253, U.S. Pat. No. 5,405,765, EP 442 174, EP 486 233, EP 486 234, EP 539 563, EP 674 725, WO 91/02071 and WO 95/06128.
Other characteristics of the invention will appear on reading the examples below.
Preparation of the functionalized particles of silica
Nanoparticles were functionalized by a mixture of;
3-aminopropyldimethylethoxysilane 10% trimethylethoxysiloxane 90% or octyltrimethoxysilane 1% 3-aminopropyltrimethoxysilane 1% methyltrimethoxysilane 92%.
In this example, the mixtures are produced as far as possible with the same type of reactive alkoxysilane functions (only monomnethoxy or triethoxy and the like) in order to minimize differences in reactivity.
The nanoparticles, once dried, are handled in flame-sterilizeed glassware, under an inert argon atmosphere. All the organic solvents used are continuously distilled or dried according to the customary methods.
The nanoparticles of silica are suspended by means of ultrasound in toluene in a two-necked flask equipped with a septum, a condenser and under an argon pressure. The alkoxysilane is added in excess using a syringe (2.5�10−3 mol/g dry SiO2).
For the functionalizations with mixtures of alkoxysilanes, the latter are previously mixed in a round-bottomned flask, under argon, containing toluene, and the whole is added using a canula-like tube over the suspension of nanoparticles.
The reaction medium is homogenized using ultrasound for one to two hours and then heated at the reflux temperature of toluene for a minimum of three hours for the compounds carrying three alkoxysilane functions per atom of silicon or for about 12 hours for the compounds containing only one alkoxysilane function per silicon atom.
The medium is then centrifuged at cold temperature (4800 rpm, 3838 G, 4� C.). The supernatant is removed, the pellet is resuspended in toluene (anhydrous) and then centrifuged. The operation is repeated three times. The final pellet is dried under vacuum (appearance; white powder).
The nanoparticles thus obtained can be suspended in the appropriate solvent (including water) for the desired use or the subsequent functionalization steps.
Compaction and protection of the DNA:
Compaction and protection with the functionalized nanoparticles according to the invention
The nanoparticles, at least partially functionalized with 3-aminopropylsilanes, are suspended with the aid of ultrasound in water (filtered on a sterilizing filtration membrane) or in a buffer (Hepes, NaCl, PBS) containing no amines, The sample of nanoparticles is added to a solution of DNA.
If the DNA is added to the suspension of nanoparticles, flocculation is observed due to the aggregation of several nanoparticles around the same DNA strand. Such preparations allow enhanced protection of the DNA against the degradations caused by DNAses compared with the state of the art.
Compaction with polyaminosiloxanes
Products Used:
oligoiners of 3-aminopropylsilanetriols in aqueous solution at 40%
oligomers of N-(2-amrinethyl)-3-aminopropylmethylsilane (oil)
products resulting from the polymerization, in the presence of traces of water, of 3-aminopropyltrimethoxysilane in toluene.
To test the absence of compaction in the presence of the monomers:
3-aminopropyltrimethoxysilane (oil)
3-aminopropylmethyldiethoxysilane (oil)
Various plasmids of bacterial origin, supercoiled, of variable length (from 10.2 kb to 3.2 kb) and of various types (Bluescript, Lac-Z, encoding luciferase, β-galactosidase).
2.1 Preparations:
The DNA-polyaminosiloxane complexes were prepared in various media: water (filtered on sterilizing filtration membrane), 75 mM to 150 mM NaCl medium, Hepes buffer medium and CaCl2 medium.
The mixtures were prepared as follows:
The concentrated aqueous solution of polyaminosiloxanes is homogenized using ultrasound. An aliquot of this solution is diluted in half the final volume in buffer and homogenized. The DNA, in solution in the buffer, is added volume for volume to the solution of polyaminosiloxanes. The whole is stirred by means of a vortex. The order of addition of the various components may be modified.
The same procedure was carried out for the control with the monomers which did not give rise to any compaction.
2.2 Effect of Compaction, Protection of the DNA:
During the electron microscopy examination of the mixtures between the DNA and each of the products different figures of compacted DNA are observed, some of which are similar to those obtained in the presence of histones or of known compacting agents such as spermine or polyethylenimines (cf. for example M. Garcia Ramirez, J. A. Subirana, Biopolymers, vol. 34, p. 285-292, 1984).
The figures observed are different in nature depending on the concentration and the product used.
A study of the oligomers of 3-aminopropylsilanetriols clearly showed a dose effect; for increasing (from 0.1 to 6000) (mol of amine function of the polysiloxane)/(mol of phosphate of the DNA) ratios, increasing compaction is observed.
The ethydium bromide (EtBr) exclusion technique made it possible to prove the high capacity of the products to compact DNA.
This compaction makes it possible to protect the DNA from degradations.
Transfection tests were carried out under various conditions and on three types of cell lines (NIH3T3, HeLa and HepG2). Transfection activities are observed.
EXAMPLE of Preparations:
DNA at 10 μg/ml, oligomers of 3-aminopropylailanetriols at 9.1�10−7 mol/ml (that is to say 30 mols of amines per mol of phosphate).
DNA at 10 μg/ml, oligomers of N-(2-aminoethyl)-3-aminopropylmethylsilane at 3�10−8 mol/ml (that is to say one equivalent primary amine per phosphate), 9.1�10−7 mol/ml (30 equivalents primary amines per phosphate) or 3�10−5 mol/ml (1000 equivalents primary amines per phosphate).
These preparations gave a higher expression than the standard polyamine aggregating agents of the state of the art used at 6�10−8 mol/ml.
Transforation of plants
Evaluation of the toxicity is carried out before the trials in vivo. Sixty to seventy mg of cells are transferred into 150-ml flasks containing 10 ml of culture medium and various concentrations of oligomers of N-(2-aminoethyl)-3-aminopropylmethylsilane (0, 1, 2, 4 and 8 mg/l). The cells are collected after 7 days of culture and the fresh weight of the cells is estimated. An increase in the pH (8.1) of the culture medium is observed for concentrations of oligomers of N-(2-aminoethyl)-3-aminopropylmethylsilane of 8 mg/l and inhibition of cell growth is observed, but no toxicity. The molarity of N-(2-aminoethyl)-3-aminopropylmethylsilane for the highest primary amine per phosphate ratio (5333) is 0.16 mM and is equivalent to the polarity of N-(2-aminoethyl)-3-aminopropylmethylsilane in the test of toxicity at 2 mg/l. These results show that the concentrations used for the bombardment are not phytotoxic.
Plant transformation trials were carried out on cells of Arabidopsis (Strain T 87) obtained according to the method described by Axelos (Axelos M. et al., 1992 Plant Physiol. 30 (1), 123-128). The technique used is bombardment (Vain Ph et al., 1993 Plant Cell, Tissue and Organ Culture., 33, 237-246). A transient expression as well as a stable expression (production of calli), equivalent to those obtained with spermidine, are observed.
Examples of preparations or bombardment:
Particles of tungsten (Sylvania Chemicals) M17, having a mean diameter of 1 μm, are sterilized in ethanol at 95% in an amount of 1 g/20 ml. Five hundred μl of particles in suspension are collected, washed 3 times in sterile milli Q water and taken up in 500 μl of water final. The precipitation of DNA around the particles is obtained according to the protocol below. The following mixture is prepared by adding in order: 50 μl of M17 particles, 10 μg of DNA, 50 μl of 2.5 M CaCl2, plus N-(2-aminoethyl)-3-aminopropylmethylsilane so as to obtain the primary amine per phosphate ratios of 167; 667; 1333; 2667 and 5333. After 10 minutes, the mixture thus precipitated is used to carry out 2 shots, −10 μg of DNA are mixed with a solution of 2.5 mg of tungsten particles siliconized with 3-aminopropyltrimethoxysilane in 50 μl of water. After 10 minutes, the mixture thus precipitated is used to carry out 2 shots. A transient expression is observed which is substantially equivalent to that for the preceding complex.
|Cited Patent
|Filing date
|Publication date
|Dec 11, 1991
|Apr 12, 1994
|Zeneca Limited
|Transformation of plant cells
|May 26, 1993
|Dec 8, 1993
|Becton Dickinson and Company
|Chemically synthesized silanes that bind nucleic acids
|Aug 9, 1996
|Feb 27, 1997
|Dendritech, Inc.
|Hyper comb-branched polymer conjugates
|Fang et al. (1998) Nucleic Acids Research 26:588.
|From et al. (1990) Bio/Technology 8:833.
|U.S. Classification
|435/458, 435/459, 435/471, 435/470
|International Classification
|Cooperative Classification
|European Classification
|Jul 30, 2002
|Certificate of correction
|Oct 15, 2002
Owner name: AVENTIS CROPSCIENCE SA, FRANCE
Free format text: CHANGE OF NAME;ASSIGNOR:RHONE-POULENC AGRO;REEL/FRAME:013362/0554
Effective date: 20000127
|Jul 6, 2005
|Maintenance fee reminder mailed
|Dec 19, 2005
|Lapse for failure to pay maintenance fees
|Feb 14, 2006
|Expired due to failure to pay maintenance fee
Effective date: 20051218


text:
Fulton keen to improve 'average' test career
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Peter Fulton believes he's a more versatile player than the last time he played for New Zealand and is desperate to improve his "pretty average" test career.
Fulton was yesterday selected in the Black Caps for the first test against England, starting March 6.
Coach Mike Hesson confirmed he would add to his 10 previous tests, as an opener.
Just who partners him has yet to be decided.
Hesson said this week's New Zealand XI game against England in Queenstown was effectively a trial for openers Hamish Rutherford and Fulton's Canterbury team-mate Tom Latham. He went on to confirm Rutherford had the inside running.
Fulton has two domestic 50-over matches to play for Canterbury before joining New Zealand in Queenstown on Sunday. He said it was hard not to think about playing his first test in more than three years.
"I'm trying not to look too far ahead but it's easier said than done," the 34-year-old said.
Fulton's had his knockers since returning to test contention, with some feeling the Canterbury skipper has had too many chances.
Fulton and domestic coach Gary Stead insist his game has improved since last playing, against Pakistan in December 2009.
"I've always looked at my international career in two parts," Fulton said. "There's the ODI stuff where I played 49 games and compiled a pretty handy record. Then there's the 10 or so tests I played. I never really got going and had a pretty average record.
"I do think my game has changed a bit though and I'm a bit more versatile now. I've scored a few runs this season, some quite quickly and some I've really had to grind out."
Fulton has matured and knows his game better than ever. He plays to his strengths far better than he used to and has learnt not to let his weaknesses cost him his wicket as often.
Fulton, who has scored more than 900 runs in nine first-class matches this season, has changed his priorities when it comes to international cricket.
"Getting selected is great but now I need to work hard, play well and score runs to keep myself in there."
Latham's call from national selection manager Kim Littlejohn came with two surprises.
Latham was first told he would be captaining the New Zealand XI against England instead of the injured Luke Ronchi.
"That was exciting enough," Latham said.
"The news I was in the test team was next. It came as a bit of a shock. I mean, I'm rapt; that's the pinnacle isn't it, test cricket. I've always wanted to play test cricket for New Zealand."
Latham will need to outscore Rutherford in Queenstown this week to strengthen his case and was confident he could handle the switch from the middle order, where he had batted for Canterbury all season.
"I opened for New Zealand A at the start of the summer. There'll be a few tweaks to my game, just to get things a little tighter defensively, but if it's in my areas, I'm still going to try and hit it to the boundary. That's my game."
Hesson has left room for one more bowler in his squad, setting up another trial of sorts in Queenstown, between Mark Gillespie and Neil Wagner.
Martin Guptill (hamstring and thumb), Daniel Vettori (Achilles), Chris Martin (hamstring) and Mitchell McClenaghan (side strain) were unavailable through injury, while James Franklin and Jeetan Patel were dropped.
Patel was omitted in favour of his understudy from the recent South African tour, Auckland's Bruce Martin.
Martin was first called into the New Zealand squad as a teenager to cover for the injured Vettori, 13 years ago.
He was left out and the now-retired Daryl Tuffey debuted in that match.
Martin is now considered the country's top fit tweaker and he's set to finally step into international cricket as a 32-year-old.
Brendon McCullum (c), Trent Boult, Doug Bracewell, Dean Brownlie, Peter Fulton, Tom Latham, Bruce Martin, Hamish Rutherford, Tim Southee, Ross Taylor, B J Watling, Kane Williamson. * plus one to be added.
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When you stay at Isle Bay Resort on Lake Holcombe, you'll experience a multitude of fishing opportunities that will keep you happy throughout your entire stay! The lake is home to many species of fish including muskie, panfish, largemouth bass, smallmouth Bass, northern pike, walleye, sturgeon and catfish. Good luck on catching your trophy fish, or... more
Cast your line into Shawano Lake, a 6215 acre lake that offers excellent fishing for musky, panfish, largemouth bass, and northern pike!... more
Lake Onalaska, 7600 acres, is part of the Mississippi River system. Catfish, sunfish, bluegills, perch, bass, northern, walleyes and white bass are abundant.... more
The Mecan River Fishery Area contains some of the finest trout streams in central Wisconsin. Most of the water is class one brown and rainbow trout streams.... more
Big Swedes Resort
Famous for its 50-inch muskie, Lake Holcombe is also home to a host of trophy walleye, northern pike, and bass. Fish off the dock or find a hot spot exploring the water on a boat. ... more
Nearby Big Green Lake is a unique fishery where you can fish for lake trout, brown trout, white bass and cisco!... more
Doug's Wolf River House
A number of types of fish can be caught in the five lakes in the area, as well as the Wolf River and Fox River that connect them. At Doug's Wolf River House, you'll find all the friendly fishing advice you could ever need!... more
Eagle's Nest Resort
Fishing is a never ending source of recreation you will find when you stay at Eagle's Nest Resort. Cast your line and try to catch anything from bluegill to northern pike, small and largemouth bass all the way to walleye. Whether you're clipping along and fishing from your boat, provided by Eagle's Nest Resort, or braving the cold and wind while... more
Van's Knotty Pine Cottage
Shortly after the ice melts on area lakes, fishermen head to St. Germain for panfishing. Crappies, bluegill and perch are all common in St. Germain's lakes.... more
Fishing abounds from Everts Resort, providing ample opportunity to for you, your family, and friends to all reel in a trophy-worthy fish! Enjoy some of the Upper Midwest's best walleye fishing, as well as world class smallmouth and white bass fishing. You'll even find yourself angling northern pike, catfish, sunfish and crappies! And if you run out... more
On the west shore of the Wolf River overlooking the famous Winneconne bridge, Lang's Landing gives you the perfect opportunity to fish for white bass, walleye, largemouth bass, smallmouth bass, northern pike, and more!... more
Ward's Riverside Cabins
Fishermen of the world, unite! This is the place for you! Bring your boat - Ward's Riverside Cabins has a dock! Cast your lines on your Wisconsin fishing getaway and fry up your Mississippi grouper! You're sure to encounter walleye, muskie, northern pike and bass. It's a wonderful river fishing vacation!... more
Fish the 6215 acres of Shawano Lake for musky, panfish, largemouth bass, northern pike, walleye, and sturgeon!... more


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Miss Dynamite
Hot anime chicks in skimpy outfits... Brutal violence... And PS2! Heaven!
It's Nameless!
Foamy Fanmail
Foamy the squirrel gets a lot of fanmail and he's sick of it!
nice choice in music and great animation
same as the title
very good
could have been longer but awesome choice of music (Rammstein)
That was pretty good,but it'd be better if it was longer
Very good
you did a good animation here, i give you that. But it was too short! Maybe a storyline too?
It's awesome, but with all the wierd tricks it makes it seem more like madness XD


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Did Blue Pup jump the shark with its Windows 8 Metro interface?
When Windows 8 was first released many people were shocked and even horrified by the garish Metro interface. Some even left Windows for Linux or shifted back to Windows 7. Now you can experience some of the...er...magic of the Metro interface in the Blue Pup distro (a Puppy Linux spin), according to LinuxInsider.
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Review: Linux Mint 18 (Sarah)
If you were looking to jump the Ubuntu ship completely, then we recommend taking a look at our recent Review of Fedora 24. It's equally as good as Mint 18 and equally worthy of your consideration. Between Linux Mint 18 and Fedora 24, we reckon it's exciting times in the Linux world. With the exception and onset of the boring world of vanilla Ubuntu releases, Linux feels reinvigorated and fresh once again. Jump on board, because it can only get better from here.
Security Leftovers
GNU News
Leftovers: OSS


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This page contains Cheats for Tales Of Pirates organized by sections for PC. This game has "Role-Playing Massively Multiplayer Online" as genre, made by Moliyo, released on Mar 24, 2008. If you can't find a hint or secret in our list, then please check this page periodically for the latest updates.
- Developer: Moliyo
- Publisher: Igg.com
- Genre: Role-Playing Massively Multiplayer Online
- Release: Mar 24, 2008
- ESRB: Not Set
If you know cheats, secrets, hints, glitches or other level guides for this game that can help others leveling up, then please Submit your Cheats and share your insights and experience with other gamers.
Stuck in this game? Set a specific, clearly defined question and let other gamers answer your question or view answers to previously asked questions. If you think you are an expert then please try to help others with their questions.
How to mining ?? i already bought mining skill book but can not be used because it does not have life skill point. how do i get a life skill that first point?...
Posted on: 12-14-2009
Lost Grimoires: Shard Of Mystery - Gameplay Video
- Jun 24, 2016, Views: 1
Asemblance - Gameplay Video
- Jun 23, 2016, Views: 1
Breached - Gameplay Video
- Jun 23, 2016, Views: 1
1917: The Alien Invasion - Gameplay Video
- Jun 23, 2016, Views: 2
- The Journey: Bob's Story, (PC)
- Deus Ex: Mankind Divided, (PS4)
- Skylanders Battlecast Cards To Life, (AND)
- LEGO Star Wars: The Force Awakens, (PS4)
- Mafia 3, (PS4)
- Forestry 2017 - The Simulation, (XONE)
- MX Vs. ATV Supercross Encore, (XONE)
- Tayutama 2: You're The Only One, (PC)
- Call Of Duty: Infinite Warfare, (PS4)
- Hero Siege: Pocket Edition, (iOS)
- Get 'Em, (iOS)
- Quest To Aztlan, (iOS)
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- Station Manager, (iOS)
- Iron Mission - Classic Arcade Shoot'em Up, (iOS)
- Epic Flail (Noxus Ltd), (iOS)
- 2-bit Cowboy Rides Again, (iOS)
- Dungeons Of Chaos Unity Edition, (iOS)
- Rule With An Iron Fish, (iOS)
- Heroes Of Loot 2, (iOS)
- Fi, Chris And The Apocalypse, (iOS)


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X-POSITION: Bunn Brings "Civil War II" to Marvel's X-Men
Comic Books
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The Buy Pile
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In Your Face Jam
Robot 6
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Although Marvel is heavily focused right now on the various Avengers movies hitting this summer and next, no doubt they're looking for a big franchise to kick off in 2013. Using a green-screen suit, Patrick Willems may just have come up with the answer — The Spot. And he already has a catchy theme song to boot.
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MJM is the coolest magic store I found. Their customer services are top and they are all very kind and friendly. Love it, love it!
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A project of People For the American Way dedicated to monitoring and exposing the activities of the right-wing movement. Learn More >
Pat Robertson Threatens 'Full-Scale Exposé' of 'Nasty Group' That 'Misconstrues' His Words
After a week-long break from hosting the 700 Club, Pat Robertson returned to the show today bearing a special message…for us! Robertson introduced the question-and-answer portion of the show with a tirade against a group that he declined to name that monitors his show and posts clips online.
"There are organizations, there is one in particular, which I will not name, but it is set out for one purpose: to embarrass those who are conservative on television. So they take my words and they twist them and distort them," he said.
We have a pretty good idea of who he might be talking about. Robertson specifically referred to our recent post on his response to a question from a woman struggling to preserve her marriage after her husband had an affair. At the time, Robertson's Christian Broadcasting Network released a statement saying that the televangelist's "intent was not to condone infidelity or to cast blame. We regret any misunderstanding."
According to Robertson, by posting his entire answer and quoting him verbatim we were actually misrepresenting his words to make him look bad, but somehow at the same time we were also helping him because he received a letter endorsing his "advice."
After co-host Terry Meeuwsen read the encouraging letter, Robertson boasted about his counseling skills and added, "I am not politically correct, in case you haven't learned; I tell it like it is."
"This organization misconstrues deliberately, they want to do everything they can to make my words and they twist them," Robertson said. "I will not identify the organization but one day we may have a full-scale exposé because it's a nasty group."
Seeing that Robertson already blamed us for 9/11, we are eagerly waiting to see what more he reveals in his "full-scale exposé."
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6/13/16 @ 10:15am


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Motocross Race
4 Wheeler Race 2
4 Wheeler Race 2
Reload Game
Panda Free Games is 100% free. Please help Panda releasing this game on social networks Facebook, Twitter and Google+! Thanks :)
4 Wheeler Race 2
4 Wheeler Race 2
Information about 4 Wheeler Race 2
Game Name: 4 Wheeler Race 2
Description Text » The version number 1 of this game can also be found in the list of games. In this game of motorcycle 4 is a view you stay ahead of your opponent in the final two rounds, collects the turbos to accelerate. It will not be easy.
Type of Game: Shockwave 3D
Tags: pc , shockwave-3d , motocross
Related Categories: PC Games, Shockwave 3D, Motocross Games
Other Games Related »
To Play on: PC Computer Windows and MAC Apple Free and Full: Yes Available for Download: Yes
Can be Played Online: Yes And Offline (without Internet):Yes
Needed to Play:Chrome Browser. Adobe Shockwave (Latest Version) and Shockwave Supplements. Adobe Flash Player (Latest Version).
Click on the image of the game to open the game zone. If the 4 Wheeler Race 2 is available for download, the link/image to download will appear below the gaming zone.
Download available for: PC Computer Windows and MAC Apple
Programs needed to play:
Supplements Shockwave for MAC Apple
Works offline (no Internet connection) after download: Yes
After download, open the file (open with) with Mozilla Firefox. The capabilities of Mozilla Firefox can open this game even without internet, you can play anywhere.Open the Link for the Game Download
Create a new folder on your PC desktop with name PandaFreeGames. Then click in the right button of your mouse over the underlined text above and make "Save link as ..." and save to the new created folder.
After that, enter in the folder PandaFreeGames, click with right mouse button over the saved file and then "open with" and look for Mozilla Firefox browser icon to open the game file, even in offline mode (no internet) the Firefox will be able to open the game on your PC.
If you do not have Mozilla Firefox on your computer, do it the installation by the official website: https://www.mozilla.org/firefox/new/. It is recommended to put the shortcut for Mozilla Firefox on your desktop to be easier to find the Mozilla Firefox icon in the process of "Open With."


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Online operating system, social media mogul? You better believe it.
Facebook's brand new applications bar reminds us of something? A device for world domination, maybe, a handy shortcut to the hoards of applications we all love and cherish, perhaps, but most of all, look at your Windows taskbar, bingo! This pretty obivious observation was hit home even more when Mark Zuckerberg, Facebook founder, suggested that Facebook is aiming to become …Continue Reading


text:
Atoomklok (Gorgy Timing)
van CompuLab, Markus Gömmel
Open iTunes om apps te kopen en te downloaden.
This tool shows you the ultimate precise time of day. To achieve this, it uses a special internet time protocol to fetch the time from an atomic time server.
We are proud to offer version 4 of the Gorgy Timing Atomic Clock. The program is one of the classic applications since the early days of the Apple App Store and has been continually improved based on user feedback.
The Gorgy Timing Atomic Clock shows the precise time of day. To achieve this, it uses a special internet time protocol to fetch the ultimate precise time from cesium atomic clocks available on the internet, or any other time server you like.
The graphical display mimics the clock display of the legendary Gorgy Timing clocks, which are used in professional radio and television studios, and we spent much effort to bring the original feeling of these wickedly expensive clocks to your iPhone.
Version 4 contains the following functions:
* Universal support for all iPhone, iPod touch and iPad devices running iOS 5.1.1 or higher (including iPhone 6, iPhone 6 plus)
* Full support for iOS 8 (multitasking, notifications, etc.), including full 64 bit support
* Alarm function with snooze (touch anywhere on the screen) and 24h alarm off function
* Alarm notification window instead of normal alarm sound, if app is not running or in the background
* Use playlists or a manual picker selection from your own music library as alarm sounds
* The alarm sound is also playing when the device is muted, or the display is switched off, and also works in AirPlay environments
* Customizable time server sources
* Colors: green, red, blue, yellow, white, hidden, with a separate color option for digits, seconds and segments
* Alternative visual display of fractional seconds (1/60th sec. resolution)
* 12/24 hours display
* Optional second tick sound
* Orientation can be changed to landscape mode
* Touching the display lets the buttons and status bar fade out
* Touching the display again will add the current date (in all orientations)
* Disabled screen auto-lock
* Options "sync at startup", "hourly", "daily", or a sync button for manual syncing
* The last known time delta is used when started without sync
* "Night mode", which dims the display using a slider, shows the seconds with only one dot (to prevent a hard brightness switch between second 59 and second 0), switches off the tick sound, and reduces screen updates to save battery
Answers to common questions:
* An application can not set your device's system time, so a time sync between the atomic time and the device time is not possible.
* If you want to wakeup with music, please do not exit the app before going to sleep (which would result in a local notification dialog without music in the morning), but let it run with the display switched off. This application's music alarm, and this is not common, will still work when you switched off the display, even in battery mode. But be aware that running an application all the time, even without display, consumes battery, so please make sure that your iPhone is fully charged before you go to bed, or even better, connect it to your charger.
Wat is er nieuw in versie 4.60
Can you believe, that this is the 34th update of the Atomic Clock app since it started with V1.00?
Here are the changes:
* new option for the second dots ring (default, wave, one-dot, dreamlight)
* new option for hourly or daily time synchronization
* a long press gesture now allows to easily switch between night mode and normal mode
* english is now the fallback language (so the app should no longer start in German, if iOS region settings list is empty)
* clock dots graphics improved
* some internal improvements
Please have a look at the new visual options for the second dots. I think they all look great :)
If you like this app and want to support further development, please rate it 5 star, or even better, write a nice review. I appreciate your support. Please also remember that all reviews and ratings are version dependent, so do not hesitate to resubmit your existing rating or review. Thank you!
Recensies van klanten
😃😃Altijd op tijd🕑🕒
Wat een prachtige en accurate app
Thank you
Deze app is wel 10 sterren waard
Server weg?
Deze app synchroniseert niet meer. Jammer.
- € 1,99
- Categorie: Diensten
- Bijgewerkt: 13-09-2015
- Versie: 4.60
- Grootte: 5.9 MB
- Talen: Nederlands, Duits, Engels, Frans, Japans, Pools, Spaans
- Ontwikkelaar: CompuLab
- © 2008-2016, CompuLab
Compatibiliteit: Vereist iOS 5.1.1 of nieuwer. Compatibel met iPhone, iPad en iPod touch.


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All Photos
Posted on
NTNA pre challenge 2 entry
by KateyLaurenson
Posted on Jun 24, 2016
61 Views | 2 Likes 1 Comment
Red White And Blue Nails
by Valleybabe
106 Views | 2 Likes 0 Comments
Neon pink sugarnails
by Fanzis_com
126 Views | 3 Likes 0 Comments
Marilyn Monroe Inspired
by Denisebourne22
Posted on Jun 29, 2016
5 Views | 1 Like 0 Comments
Nails by Jekeia aka Jade
by JHines
112 Views | 2 Likes 0 Comments
NAILS Magazine is the professional's choice. We feature the latest in Technique, Style, Business, and Health issues to help nail techs and salon owners do their jobs better and make money!
See our most recent issueSubscribe to NAILS Magazine hereNAILS Magazine Nail ArtNail Art Gallery Magazine


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Slightly cooler weekend; big shift next week
Orange County begins the summer with highs reaching toward the mid 80s, easing back just a few degrees for the weekend, the National Weather Service says.
But inland highs could hit the low 90s by the end of next week.
A double dose of low-pressure air moving inland should keep a lid on temperatures through Monday. Then high pressure is expected to expand in our direction from the east, and the heat is on.
Morning clouds were patchy Friday and mostly hugging the coast, with fog possible in places. The day should turn out to be mostly sunny and 79 to 84 inland, 71 on the coast.
Saturday also should see some low clouds and fog opening into mostly sunny skies. Inland highs should be 77 to 82, 70 on the coast.
Sunday and Monday end up partly cloudy after some clouds and fog in the morning. Inland highs tick down into the 75 to 80-range for Sunday, knocking off about a degree for Monday.
Coastal highs stay around 69 both days, and Tuesday as well.
Inland highs, meanwhile, bump back up about a degree Tuesday as areas of low clouds and fog give way once again to mostly sunny skies.
Wednesday could see highs of 84 to 89 as high pressure takes over. Otherwise it's the usual drill: some low clouds and fog yielding to mostly sunny skies.
Thursday should see only partly cloudy skies in the morning before turning mostly sunny.
That's when Orange County highs are expected to hit the gas: 88 to 93 inland, 79 on the coast.
It won't be as impressive as valleys farther inland, which could soar past the century mark, or the lower deserts to the east, which could see 115 or more, the Weather Service says.
Share your weather photos:
Send your recent, Orange County weather photos to email@example.com along with your name, home city, when and where the picture was taken and what it shows.
We publish many reader photos online and in print.
Text OCRQUAKE to 56654 to get free quake news alerts.
Text OCRSCIENCE to 56654 to get free science news alerts.
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Throwback Thursday! MailOnline exclusively reveals Kardashian pal Jonathan Cheban's yearbook photos... and how he morphed from a geek with a mullet to the most famous BFF on the planet
He is always by Kim Kardashian's side: where she goes, he normally follows - usually accompanying her on a private jet or at the very least in First Class.
PR Jonathan Cheban, 41, has been the one constant in the reality queen's life - and their friendship has lasted longer than most of her relationships.
For a pair both obsessed with image and 'selfies', this is the first fascinating glimpse of Jonathan as a fresh-faced high school student - and proves he's come a long way from his school days in Fort Lee, New Jersey (well, at least he's got rid of the mullet).
Scroll down for video
Senior: Jonathan Cheban teams his mullet with a black bow tie for his final yearbook shot at Fort Lee High School in New Jersey, where he graduated in 1991
He's still got the bangs: Jonathan Cheban has only slightly grown out his bangs, seen here in his final Senior year of high school
Sweet: Jonathan Cheban as a Sophmore - on the left - in 1989 - and a junior in 1990 - on the right
Born in February 1973 to Russian parents, Mikhail, a diamond dealer who died in 2011, and Galina, 66, who works as a real estate agent with Sotheby's, Cheban was an only child.
And his yearbook photos from Fort Lee High School show that even from a young age the young PR guru was image conscious, appearing in his final Senior picture wearing a black bow tie and dapper black tuxedo - even though his hair would undoubtedly make him cringe now.
His most prominent mention in the 1991 yearbook, the year he graduated, is in a section called 'Chill Out!' about the 'expressive slang' used by students.
Sporting a flowing mullet, Cheban is photographed staring off camera with his bottom lip slightly open as if he is a posing like model.
Next to him is the caption: 'Jon Cheban VEGGES OUT'.
And despite his later rise to someone firmly fixed in the public eye, Cheban seems not to have been involved in life at Fort Lee High School very much at all.
He was not voted the most sociable student, nor was he a member of any sports clubs - only pictured at Greek Club and cooking in a home economics class.
He was also not involved in the school newspaper or the production of the yearbook, even if his later career would move him in media circles.
However, Cheban's former classmates said that he was a 'normal kid' who was quiet and studied hard and was on the Honor Roll.
Former classmate Cindy Mavronasios admits she was shocked when she saw him on TV, appearing on Keeping Up With The Kardashians, where most Kardashian fans would have first caught sight of Cheban.
She said: 'I was watching the Kardashian show on TV - I don't care much for Kim Kardashian as I don't find her interesting - and he came on with her.
'I recognized him straight away. I thought to myself: 'Good for you'.
Bestie selfie time! Kim posted this photo, taken by Jonathan from their seats on a swing at a Jersey shore fair
Some good old fashioned fun: Kim and Jonathan followed in the footsteps of where the Jersey Shore gang filmed their TV show
From fresh-faced freshman - Jonathan Cheban in 1988 on left - to Kim Kardashian's BFF, last month, on right
She added that Cheban 'never caused any trouble' and that he did not hang around outside of school with his friends at all, instead preferring to go home, saying: 'I am surprised he ended up doing what he did. I could have seen him becoming a doctor, he was smart'.
Instead, after graduating with a communications degree from Hofstra University in 1995, Cheban immersed himself in the New York party scene and embarked on a career in PR that would see him eventually launch his own firm, CommandPR, to which he remains a consultant after selling off his share of the company last year.
He is believed to have known Scott Disick, the boyfriend of Kim Kardashian's older sister Kourtney, since childhood.
Indeed, in a 2004 interview with the New York Observer, he mused: 'It's really weird, because I do have a lot of friends who are famous, but I always knew them way before.
'I mean, back in the day when Ozzy would play Madison Square Garden, I was sneaking Kelly and Jack into Suite 16. And I've been friends with Paris and Nicky (Hilton) since they were kids.'
Greek club: Jonathan Cheban was rocking his mullet as he joined his classmates for Greek Club
Crafty: Jonathan Cheban shows off his cooking skills as rustles up something to eat for home economics class
A bit more chic: A far cry from Jonathan Cheban's school days in New Jersey as he joins Kim Kardashian on the Jersey Shore last month
From having one of the first viewings of Baby North West and attending Kim's wedding to Kanye West in Florence in May, Cheban remains the star's trusted confidant.
And the friendship seems to have worked both ways as Cheban scooped his own reality show with E! - The Spin Crowd - after his appearances on Keeping Up With The Kardashians.
But the short-lived show about his PR firm and day to day life was canceled in 2010 after one season.
Now, he's working on the gadget to help you take the perfect selfie - a subject on which he and Kim, of course, are the experts.
By her side: Jonathan Cheban accompanied Kim Kardashian to MailOnline's party on board a yacht on June 18 during the Cannes Lions Festival
ANOTHER selfie: Jonathan Cheban and Kim pose for a picture in Paris before her wedding to Kanye West in May
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Ship Equip announced a contract with Varada Marine to install its SEVSAT (Ship Equip VSAT) maritime broadband solution on the company's entire fleet of Offshore Supply Vessels.
Varada Marine, a company with its head office in Kristiansand, Norway, has announced an extensive new building program at ABG Shipyard Ltd in India. Deliveries of SEVSAT systems will commence in step with the new building program, with the first system already delivered to the yard.
Ship Equip Sales Manager Sindre Alnes, who negotiated the contract, said that "Varada Marine will have a worldwide connection plan based on the Ku-band SEVSAT product with initially 128Kbps/128Kbps speeds and four telephone lines, including a prepaid Crew Calling setup on selected lines."
Varada Marine Technical Director and COO Kjell Eivind Karlsen said, "In particular, good coverage in Brazil was a requirement of great importance, along with well-established worldwide coverage and a global service organization."
Maritime Today
The Maritime Industry's original and most viewed E-News Service
Norwegian marine geophysical company PGS has extended its non-exclusive service agreement with Radio Holland for navigation and communication services onboard nine seismic vessels in its global fleet.
Four new fast ferries, owned and managed by Manly Ferries and operating in the busy waters of Sydney Harbour, will use Simrad technology for safe navigation.
One of Maersk Line's innovations turns the reefer container into a digitally connected device!
"At Maersk Line, we're always looking for ways to improve cargo care on behalf of our customers.
Stena Line's ferry passengers are set to experience new levels of communication services following a upgrade to the VSAT connectivity on board, says Marlink, who


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We are recruiting an engineering director to play a key leadership role in building our next-gen Big Data predictive analytics platform & products with a focus on B2B marketing/sales. The person will join a group filled with talented people, including many with background from5/3/2016 San Mateo, CA Save This Job
UIEvolution is an early leader in IoT platforms with over 100 million devices running UIEvolution software including connected TVs, digital signs and connected cars. UIE designs intuitive, technology-transparent connected experiences by integrating connectivity, data and5/3/2016 Kirkland, WA Save This Job
Sales Washington DC, United States Apply Send Jobvite The Federal Sales Director / Account Executive will define the Federal market strategy, business plan and sales strategy within a DOD, Civilian and / or IC assigned market. They will lead a team of MapR internal resources6/20/2016 Washington, DC Save This Job
Global Services - San Diego, CA - Full Time JOB DESCRIPTION: Verimatrix is a high-growth software company that operates at the leading edge of the pay-TV industry, protecting movies and television from piracy, and our customers from theft of service. We are currently deployed at6/16/2016 San Diego, CA Save This Job
Product Management Denver, CO, United States Product Operations management is the administration of business practices to create the highest level of efficiency possible within an organization. Unlike Program/Project Management, which supports the business through executing5/15/2016 Denver, CO Save This Job
at Boingo (View all jobs) Los Angeles, CA Boingo Wireless ? one of the Best Places to Work in Los Angeles! ? LA Business Journal, 2015 Senior Software Engineer, R&D The Research and Development Engineer will primarily be involved in utilizing Research, development and testing6/20/2016 Los Angeles, CA Save This Job
Job description The Medical Director will work closely with peers around the company: Provide clinical subject matter expertise during customer engagements with sales, account management and customer implementation Act as a resource and participant with the Engineering and5/24/2016 Minneapolis, MN Save This Job
Menlo Park, CA (HQ) Delphix is the market leader in Data as a Service, which helps enterprises accelerate application projects by 50%, including ERP rollouts, custom development, and migrations to private and public clouds. Delphix provides its DaaS Platform as on-premises or5/18/2016 Menlo Park, CA Save This Job
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AVAILABLE LOCATIONS: MID-ATLANTIC AREA Position Overview Reporting directly to the Vice President of Sales and Marketing, the Business Development Director will have full responsibility for selling all of Security Innovation?s products and services into existing and prospective5/1/2016 Wilmington, MA Save This Job
NEW YORKBUSINESS DEVELOPMENTFULL-TIME APPLY FOR THIS JOB About Foursquare Since our inception in 2009, Foursquare has been a leading force in changing how location information enriches our real-world and digital lives. As a location intelligence company, Foursquare is comprised5/1/2016 New York, NY Save This Job
Type Full-time Company Anark Corporation provides powerful enterprise software and solutions to manufacturing organizations that need to cost-effectively utilize their 3D CAD data and manufacturing information for numerous down-stream applications, including: 3D Manufacturing4/25/2016 Boulder, CO Save This Job
Full-Time ? San Francisco Slack is looking for an engineering manager to help lead the Backend Services engineering team. This team is responsible for the real-time network services that make Slack feel like Slack. This person will report to the Director of Service Engineering6/6/2016 San Francisco, CA Save This Job
Engineering San Jose, California Description Principal Software Engineer ID #2016-93 Roles and Responsibilities: We are looking for a principal software engineer with strong experience in developing enterprise software products and solutions for deployment in public,5/29/2016 San Jose, CA Save This Job
REMOTE - USPRODUCTFULL-TIME APPLY FOR THIS JOB Job Purpose: We?re looking for a bright, creative, and self-motivated individual to take on an active role in the product management activities for our Procure-to-Pay product line. This is a key position within the Products5/24/2016 Oakland, CA Save This Job
Engineering Salt Lake City, UT Apply Now Send Jobvite Venafi, the Immune System for the Internet, is the leading market cybersecurity company in Next-Generation Trust Protection (NGTP). Venafi delivered the first trust protection platform to secure cryptographic keys and6/28/2016 Salt Lake City, UT Save This Job
Location: North Carolina Job Description: Own I manage the KBI corporate Validation Master Plan for all computer systems. Manage the execution and documentation of the corporate CSV Program . This includes management of life cycle of process from protocol, corporate alignment ,6/28/2016 Durham, NC Save This Job
at Boingo (View all jobs) Los Angeles, CA Boingo Wireless ? one of the Best Places to Work in Los Angeles! ? LA Business Journal, 2015 Software Engineer Entrepreneurial-Minded Senior Software Engineer Wanted: Boingo Wireless offers a ?buffet for technologist?! Choose from a6/20/2016 Los Angeles, CA Save This Job
"Responsible for defining, locating developing, negotiating and closing OEM business relationships within the IT Security, IT Operations and Cloud Service Provider vendor communities." Job Duties: ? Define OEM go-to-market plan, aligned with corporate goals, by researching OEM6/13/2016 Boston, MA Save This Job
Los Angeles, CA Boingo Wireless ? one of the Best Places to Work in Los Angeles! ? LA Business Journal, 2015 Software Engineer Entrepreneurial-Minded Senior Software Engineer Wanted: Boingo Wireless offers a ?buffet for technologist?! Choose from a smorgasbord of tools &5/21/2016 Los Angeles, CA Save This Job


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I thoroughly agree with John Florez's column on Aug. 10 ("Make the education elephant dance"). He said if we want to make the right changes in our educational system, we should get answers from the students, parents and tax payers, not the so called professionals who have brought us to our current predicament.
This same philosophy could also be used for the Post Office and any failing enterprise. IBM made a complete turn-around in their business focus when they listened to the brightest minds in their own company. Straight thinking individuals who have no other motive than to solve current problems would readily agree that unions are destroying our cities and states, the post office and our educational system because their highest priority is to win contracts with special rights and privileges for their members over doing what is in the best interest of the businesses or organizations they serve.
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ISAF Sailing World Cup Mallorca – Burton's form guide
by Rob Kothe, Sail-World.com on 1 Apr 2014
Tom Burton - ISAF Sailing World Cup Miami 2014 ISAF Sailing World Cup Miami
ISAF Sailing World Cup Mallorca – Australian Tom Burton spent most of the last year as the top ranked Laser sailor in the world. He had been Tom Slingsby's training partner leading into the London 2012 Olympics and it seemed that much of Slingsby's Gold Medal speed rubbed off on the younger Tom.
Burton has currently slipped to World ranked number two behind Croatian Tonci Stipanovic, but not for long if the young Aussie has his way.
'We have a big Australian contingent here in Palma. We have got seven guys here so it is pretty good even just training. It is nice to be able to go by ourselves and still have a decent group and still a reasonable size. But we like to test ourselves against the Europeans.
'And of course the guy we have to get round at the moment is Robert Scheidt, who has won nine Laser World titles in his early years and Croatian Tonci Stipanovic, who is currently ranked World number one ahead of me. Tonci is getting much more consistent, he won in Miami, Scheidt, who was second there, has the titles and amazing experience and is obviously the most dangerous. Then there Nick Thompson, who was third in Miami ahead of me.
'There a lot of good guys here. Just looking down the entry list there are heaps of guys that can win races.
'But I am keen to climb back to top. This season I will be spending more time in the Laser and just be enjoying it and just be keen to go sailing every day which is where I am at the moment.
'Last year I had a few detours with the Youth America's Cup and other things so just spending more time in the Laser is building my consistency.
'Naturally with my body and body weight it suits me better in the light but being from Australia probably helps me more in the breeze because the Europeans are better in the light. I think we have a bit more advantage in the breeze.
'I think this week I would like it to be windy. It doesn't really matter. I think the best thing for me is if we get a bit of everything and that will set me up really well.
'I think if the whole Australian squad sails well this week then we could all be going really well. Matt Wearn's going really well, he is sixth in the world. Ash Brunning, currently seventh, and Ryan Palk, 16th, are going well too and the younger guys as well. I think they could be winning races as well. Most races I think there will be an Aussie near the front of the fleet anyway.'
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G Data AntiVirus Internet Security 2006
Works well, comprehensive
Nothing new here
We're already half way through the year and still updates of antivirus software are coming through the door. It's always good to see internet tools being supported and updated but G Data has arrived a little late on the market that is already saturated with tools that help detect spyware, adware and other virus checking sweeps, along with the ubiquitous firewall and popup protection.
This may all sound a little down beat but unless such a package has anything new to offer, there are far better known brands to choose from. So, sceptically we loaded up the software hoping to be surprised. What we got was an easy install, with about 20MB of memory needed for all the apps, before running updates. You'll need to reboot the system but once you have, you'll find the tool populated in your taskbar.
The main system itself consists of five windows that deal with different aspects. By default you'll find yourself on the AntiVirus page, with the other sections being Firewall, AntiSpam, WebFilter and KidSafe.
Taking a different approach to most companies, you'll find that G Data has opted for not one antivirus tool but two, both of which are third-party. So, you'll find BitDefender running along Kapersky tools, which can be a little resource sapping, especially if you're running a budget or older machine. Fortunately, you can choose to switch one off when needs be, which sort of defeats the object.
The Firewall is neat and quite comprehensive. Working exactly the same way as other packages, when a new request comes through you'll get a message asking whether you wish to accept it or not. However, you can easily find which sites and programs are allowed from the menu, as well as a list of sites that have recently been blocked.
WebFilter is used to stop popups and other annoying banners that seem to proliferate on the web. However, if you're running Firefox you'll find this is already a built-in feature and even IE has a plug-in, so in many respects this is the weakest tool here.
The KidSafe feature is a parental lock that allows you to set filters when using specific Windows user accounts. This way, you can create a wall-garden approach to the Internet for your kids but still have full access under your own account. There's support for different types of filters for both Internet Explorer as well as Firefox, which is a nice touch and at least admits that we're not all still using IE.
Considering it's arrived half-way through the year, G Data hasn't done too bad a job creating an internet security suite to suit the average home user. Sure, it offers little that isn't already out there but at £40 (inc. VAT) it's as good a package as you'll need. If you've already got such a suite we wouldn't recommend switching, you're not missing out, but if you're looking for your first package, there is enough here to at least consider it.
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Judge sanctions Jehovah's Witnesses
Imposes $4000-a-day penalty for not producing documents in sex-abuse case
Dorian Hargrove 4:30 p.m., June 24
This is the main sculpture in the center of Nikki de Saint Phalle's Queen Califia's Magical Circle sculpture garden in Escondido. It's a great place to take kids.
Photo by Mango
Posted November 4, 2010
Dorian Hargrove 4:30 p.m., June 24
Garrett Harris 4 p.m., June 24
Jeff Smith 3:30 p.m., June 24
Matt Potter 2:35 p.m., June 24
Walter Mencken 2 p.m., June 24
Various Authors 1:04 p.m., June 24
Matthew Lickona 11 a.m., June 24
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Yesterday, after a 12-year legal battle, India's Supreme Court upheld Section 377 of the constitution, an old British law that criminalizes sodomy. Here are some poignant social media reactions from the Indian public.
In 2009, Delhi's High Court struck down Section 377 of the Indian constitution, an anti-sodomy law from when India was under British rule.
On Dec. 11, 2013, India's Supreme Court reinstated it, thereby recriminalizing same-sex intercourse in India.
Some Indians have taken to social media to express their outrage at and disappointment in the ruling:
wrote posters after a long time... Protest against #Sec377 @ Kolkata... @sarkar_swati— anirban biswas (@anirvanas)
anirban biswas
wrote posters after a long time… Protest against #Sec377 @ Kolkata… @sarkar_swati
/ Via
RT @Ananthaforu: #LGBT protest against #SupremeCourt on #Sec377 in #Bangalore @dna pic— Eshita (@Eshita_12)
RT @Ananthaforu: #LGBT protest against #SupremeCourt on #Sec377 in #Bangalore @dna pic
/ Via
6. Some people are coming out as "criminals."
18. Some brands have responded to the verdict…
19. As have celebrities.
@ibnlive just came back from Bangalore protest.Chants of We Want Justice, Repeal #Sec377, filled the air— Gaylaxy (@GaylaxyMagazine)
@ibnlive just came back from Bangalore protest.Chants of We Want Justice, Repeal #Sec377, filled the air
/ Via
24. To put things in perspective:
In a statement, the coalition fighting Section 377 said:
The decision by overturning the historic Delhi High Court judgment which recognized that Lesbian, Gay, Bisexual, Transgender (LGBT) persons are full citizens of India, attempts to stem the tide of history. By overturning the Naz Foundation judgment, the Supreme Court has, in one fell stroke again reduced LGBT persons to the status of what the Delhi High Court memorably called 'unapprehended felons'…
We proclaim that inspite of the judgment of the Supreme Court, the only way the LGBT movement will go is forward and the arc of history though long will turn towards justice. We pledge to continue this struggle with redoubled vigour till such time that Section 377 is consigned to where it belongs – the dustbins of history.
More information about the ruling here.
- Ex-London mayor Boris Johnson has dramatically ruled himself out of the race to be the next Conservative UK prime minister.
- The three suicide bombers behind Istanbul's airport attack were from Russia, Uzbekistan, and Kyrgyzstan, Turkish officials say.
- Ready for the U.S. presidential election in November? It's #TurnUpToVote week at BuzzFeed and you can register here 🇺🇸


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Interactive sequential key system to input characters on small keypads
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United States Patent #7561072
This invention discloses an interactive sequential system to input letters of the English alphabet and of many world languages, numbers, punctuation marks and many other symbols on keypads with few buttons. The invention includes a device for receiving input characters from a user, having a keypad with a plurality of keys arranged in rows and columns forming a keypad array; a display screen showing a plurality of character sets arranged in rows and columns forming a character set onscreen array wherein each element in the character set array is mapped to each element in the keypad array; and a processor for receiving a selection of one of the plurality of keys on the keypad to designate a character set by its corresponding location coordinate as mapped on the keypad array. Sequential key selection drills down through nested arrays.
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