text:
|Número de publicación
|Tipo de publicación
|Número de solicitud
|Fecha de publicación
|25 Dic 2007
|Fecha de presentación
|8 Jun 2005
|Fecha de prioridad
|7 Abr 1998
|También publicado como
|Número de publicación
|Jay S. Walker, James A. Jorasch
|Cesionario original
|Walker Digital, Llc
|Exportar cita
|BiBTeX, EndNote, RefMan
|Citas de patentes (29), Otras citas (1), Citada por (10), Clasificaciones (11), Eventos legales (6)
|Enlaces externos: USPTO, Cesión de USPTO, Espacenet
The present Application is a Continuation of commonly-owned U.S. patent application Ser. No. 10/391,034, entitled "ELECTRONIC AMUSEMENT DEVICE AND METHOD FOR OPERATING A GAME OFFERING CONTINUOUS REELS", filed Mar. 17, 2003, now abandoned which is a Continuation of commonly-owned U.S. patent application Ser. No. 09/578,261, filed May 24, 2000, which issued as U.S. Pat. No. 6,579,178 B1 on Jun. 17, 2003; which is Continuation of commonly-owned U.S. patent application Ser. No. 09/056,489, filed Apr. 7, 1998, which issued as U.S. Pat. No. 6,095,921 on Aug. 1, 2000; all of which are incorporated by reference herein.
The present invention relates an electronic amusement apparatus and more particularly to an electronic amusement apparatus such as a slot machine having continuous reels.
Slot machines are the primary revenue source of most casinos, with machines often earning between fifty and one hundred fifty dollars per day. Because of the profitability of such slot machine use, casinos have begun to market aggressively to both retain existing customers and attract new players—often by offering increasingly high jackpot payouts. Players find higher jackpots more exciting, and will seek out those casinos offering the best rates. Increasing the payouts, however, has a negative impact on the profitability of the machines. In order to maintain a reasonable profit margin for the house in the face of increasing jackpot amounts, casinos were forced to decrease the probability of hitting the top jackpots by reducing the ratio of winning symbols to losing symbols. Although reducing the number of jackpot symbols per reel achieved this end, slot machines were eventually left with very few jackpot symbols per reel. In order to further decrease the probability of hitting the top jackpot, slot machine manufacturers began to increase the number of stops per reel, allowing for less frequent jackpots. More reel stops, however, required physically larger reels and thus larger machines. These larger machines reduced the number of machines that could be fit onto the casino floor, reducing the casino win.
Virtual reel technology, such as the technology disclosed by U.S. Pat. No. 4,448,419 of Telnaes, alleviated some of these problems by providing an electronic reel which operated in combination with the physical reel. Outcomes were determined by the internal electronic reel and then simply displayed by the physical reel. While the physical reel might contain two jackpot symbols and twenty non-jackpot symbols, the virtual reel might have one jackpot symbol and ninety-nine non-jackpot symbols. In this manner, the probability of the reel stopping on a particular symbol such as a lemon was completely determined by the relative frequency of the lemon on the virtual reel—not the physical reel. The benefit of this technology was that the slot machine could now have small physical reels while maintaining an electronic reel with far more reel stops, allowing low frequency of jackpot symbols to support high payouts. The player of such a machine, however, is completely unaware of the virtual reel and tends to assume that the physical reel determines the outcome. He might see an equal number of jackpot symbols and oranges, yet discover that the jackpot symbols "never seem to come up" while the oranges come up frequently. Such an imbalance often leads to the player concluding that the machine is "rigged" to not pay off.
In addition to the misleading probabilities described above, conventional slot machine reels also often fail to provide the player with a satisfying entertainment experience. After seeing the first two reels stop spinning and realizing that there are no longer any possible symbols on the third reel that result in a payout, players are discouraged. Watching the third reel spin is a waste of time when there is no way for a player to win.
Thus, it would be very desirable to provide a slot machine that offers players the ability to play a game of chance having a seemingly endless number of potential outcomes. Such a slot machine would retain a player's interest for longer periods of time, making the game more enjoyable.
An object of the present invention is to provide a slot machine that prevents a player from accurately predicting an outcome until the entire outcome is displayed.
A feature of the present invention is that the disclosed slot machine provides entertainment while the reels are spinning.
An advantage of the present invention is that the disclosed slot machine provides prolonged anticipation regarding the outcome, thus making the game more exciting for players.
In accordance with one aspect of the present invention, a method for operating a gaming device is disclosed. The method includes the step of initiating a paid play. This step is typically performed in response to a user-generated signal such as that generated by the pull of a handle. The method also includes the step of determining an outcome of the paid play.
The method further includes the step of visually displaying the outcome using at least two graphical displays. Each graphical display comprises a visual continuum. The visual continuums may be visual continuums of color, shade, or physical dimension. The outcome is represented by the relative positions of the visual continuums. In addition, the method includes the step of determining a payout based on the outcome.
Alternate embodiments of the present invention, employing overlapping displays and animated displays, are also disclosed. Electronic gaming devices are disclosed for implementing the steps of the described methods.
The above objects, features and advantages as well as other objects, features and advantages are readily apparent from the detailed description when taken in connection with the accompanying drawings.
These and other objects, features and advantages of the invention will be understood from a consideration of the following description of the invention, in which:
Description of the System
In accordance with the present invention there is provided herein a gaming method and apparatus, illustrated by way of a slot machine, for presenting a gaming outcome using at least two visual continuums. As used herein, the term "slot machine" means all gaming machines wherein a paid play generates a random or pseudo-random outcome used to determine a payout which is visually represented to the player.
Referring now to
Slot machine 100 comprises conventional components, with the exception of reels 132, 134, and 136 and the two tables—probability table 127 and a payout table 129 contained in data storage device 104. As will be described in detail below, probability table 127 and payout table 129 function to determine the payout of the slot machine in accordance with the present invention. For purposes of better illustrating the invention, standard components, well known to those skilled in the art, are described only briefly. Although the present embodiment of the invention is described as implemented with physical components, the invention applies equally well to and includes software embodiments such as would be implemented on the Internet and other computer data networks.
Referring again to CPU 102, the device comprises one of many well known processing units, for example a Pentium class CPU manufactured by Intel Corp. Data storage device 104 comprises an appropriate combination of magnetic and optical memory, such as disk drive memory, and semiconductor memory such as random access memory (RAM) and read only memory (ROM). In addition to probability table 127 and payout table 129, data storage device 104 stores appropriate operating system and control software (not shown), functional to operate slot machine 100 in the manner described below. Random number generator 112 comprises one of many well known random or pseudo-random number generators suitable for use in a gaming device. Those of ordinary skill in the art will appreciate that although described as a separate component, random number generator 112 could be embodied in software form and executed by CPU 102. As will be further described below, during game play, data storage device 104 also stores player credit totals and values associated with the outcomes generated.
Coin acceptor 124 is operative to receive one or more coins, and to transmit an appropriate value signal to CPU 102. Hopper controller 122, and hopper 130 connected thereto, are operative under the control of CPU 102 to dispense and output coins to a player. Reel controller 116 is operative to control the spin and outcome displayed by first, second, and third reels 132, 134, 136, respectively, which may be mechanical in nature, or graphically displayed on video display 118. Each of the reels 132, 134, 136 supports a reel strip with indicia as described further below with reference to
Starting controller 108 comprises a player-operated device such as a handle or button for initiating the play of a game. Player tracking device 114 comprises a conventional player interface including a card reader 138 for receiving a player tracking card, a display 142 for communicating alpha/numeric messages to the player, and a keypad 140 for receiving player input such as a player identifier.
Slot network interface 106 comprises a conventional network interface for connecting slot machine 100 to a centrally controlled network consisting of multiple machines, enabling functions further described below.
Referring now to
Continuing with reference to
Referring now to
With reference now to
In another embodiment of probability table 127, random number field 170 and outcome field 172 are combined so that the number generated by random number generator 112 is used directly as outcome 172. Random number generator 112 would be programmed to generate values no less than 0.000and no more than 6.000.
Although random number field 170 and outcome field 172 have been described in reference to a particular embodiment, it should be noted that the fields could be modified to support the alternate outcome forms as described below.
Turning now to
Although presented as separate tables, probability table 127 and payout table 129 may be combined into a single table as will be apparent to those of ordinary skill in the art.
Referring now to
One embodiment of the reel strips of the present invention is shown in
Another reel strip embodiment of the present invention is shown in
Those of ordinary skill in the art will appreciate that there are many more reel strip configurations which may incorporate additive elements. In a playing card embodiment, the values of the cards may be added to achieve a total outcome with card values determined by the rules of blackjack or baccarat. A six, seven, and jack, for example, might result in a player total of twenty-three. This value could then be compared with a house total to determine whether the player had won. Another additive element is geometric symbols in which the number of sides of the symbol represents the outcome total (e.g. a triangle, square, and hexagon would total 3+4+6=13). Players might be paid for achieving a particular number of sides, offering players a simple payout structure that avoids the complexities of conventional payout tables that require more time to understand.
"Turning now to
Referring now to
Referring now to
Central panel 202 houses player tracking device 148 including card reader 138, keypad 140, and display 142 shown set to read "INSERT CARD HERE." To the left of player tracking device 114 is positioned coin acceptor 124 and starting controller 108. In addition, there are four separate display areas which communicate outcome data to the player: reel one display 208, reel two display 210, reel three display 212, and total width display area 214. The value displayed in reel width display 208 indicates the width of reel strip 132 at the point at which it intersects payline 235. The value displayed in total width display 214 is the total width of all three reel strips and indicates the outcome of the slot play, in this case a total width of 2.950 inches, corresponding to a payout of ten coins for each coin wagered.
Lower panel 204 includes a pay table 206 which describes all possible payouts for the slot machine, the details of which were discussed with respect to
With reference now to
Referring now to
Description of the Operation
Referring now to
To enable a game play, a player must first deposit money into the slot machine. This can be accomplished by inserting coins into coin acceptor 124 (step 1002). To initiate a game play, a player operates the starting controller 108 of slot machine 100, in this case by pulling a handle (step 1004). Responsive to the starting of the game, a random number is obtained from random numbers generator 112 (step 1006). It will be understood that this random number can be generated specifically for the game, or may be selected from a series of random numbers being generated on a consistent or periodic basis by random number generator 112. Many methods of generating random numbers are well known in the art.
Subsequent to the generation of a random number for the game play, that random number is used in conjunction with enhanced probability table 127 to identify the record and hence the outcome corresponding to the generated random number (step 1008). For example, the random number 9998 would fall in the range designated by record 187 f, identifying the outcome "3.000-3.499." CPU then instructs reel controller 116 (step 1010) to rotate first reel 132, second reel 134, and third reel 136 and to stop their rotation (step 1012) at a point when the appropriate location is displayed to the player under the payline.
Those of ordinary skill in the art will appreciate that there are many ways in which outcome 172 may be displayed to the player via reels 132, 134, and 136. In one embodiment, random number generator 112 produces a further random number which identifies the precise value within the range identified by outcome field 172 of the appropriate record of enhanced probability table 127. For example, for outcome range "3.000-3.499" CPU 102 may identify a precise value of 3.264 for display to the player. Because this precise value is the total of all three reels, it is first broken into three separate numbers, each number representing a width to be displayed using reels 132, 134, and 136. In one embodiment, the precise number 3.264 is divided by three to obtain three values of 1.088. A further random number then determines an amount to vary the width displayed by the first and third reel (reels 132 and 136) so that each of reels 132, 134, and 136 displays a different value. For example, the number 0.456 may be selected as a varying factor, added to reel 132 and subtracted from reel 136 resulting in widths of 1.544, 1.088, and 0.632 for display on reels 132, 134, and 136 respectively.
The outcome along with the wager value is then used to identify the corresponding payout value from enhanced payout table 129 (step 1014), in this example record 136 f of one coin field 176 for a payout of twenty coins. CPU 102 then directs hopper controller 122 to dispense coins corresponding to the twenty coin payout from hopper 130 at which point slot machine 100 is ready for the initiation of the next game play.
While the best mode for carrying out the invention has been described in detail, those familiar with the art to which the invention relates will recognize various alternative designs and embodiments for practicing the invention. These alternative embodiments are within the scope of the present invention. Accordingly, the scope of the present invention embodies the scope of the claims appended hereto.
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|Universal Entertainment Corporation
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Owner name: IGT, NEVADA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:WALKER DIGITAL, LLC;REEL/FRAME:023180/0629
Effective date: 20090731
Owner name: IGT,NEVADA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:WALKER DIGITAL, LLC;REEL/FRAME:023180/0629
Effective date: 20090731
|27 Jun 2011
|Fee payment
Year of fee payment: 4
|8 Ago 2014
Owner name: IGT, NEVADA
Free format text: LICENSE;ASSIGNORS:WALKER DIGITAL GAMING, LLC;WALKER DIGITAL GAMING HOLDING, LLC;WDG EQUITY, LLC;ANDOTHERS;REEL/FRAME:033501/0023
Effective date: 20090810
|7 Ago 2015
|Maintenance fee reminder mailed
|25 Dic 2015
|Lapse for failure to pay maintenance fees
|16 Feb 2016
|Expired due to failure to pay maintenance fee
Effective date: 20151225


text:
Aberdeen Caledonian Thistle Celtic Dundee Dundee United Hamilton Academical Hearts Kilmarnock Motherwell Ross County St Johnstone
Birmingham City Blackburn Rovers Bolton Wanderers Brentford Brighton & Hove Albion Bristol City Burnley Cardiff City Charlton Athletic Derby County Fulham Huddersfield Town Hull City Ipswich Town Leeds United Middlesbrough MK Dons Nottingham Forest Preston North End Queens Park Rangers Reading Rotherham United Sheffield Wednesday Wolverhampton
Emmanuel Adebayor ready to go
EMMANUEL ADEBAYOR admits he is risking the wrath of Andre Villas-Boas by agreeing to play at the African Nations Cup.
There is a difference between what you say to the press and what you say in private.
Tottenham chief Villas-Boas has always claimed he is happy for Adebayor to take part – but the striker reckons it is a different story behind the scenes.
Adebayor said: "That is what he said to the press, but not what he said to me.
"There is a difference between what you say to the press and what you say in private."
Tottenham will be left with just one recognised striker, Jermain Defoe, in Adebayor's absence, and are scouring the transfer market for cover.
The former Manchester City hitman initially refused to play for Togo after a row over unpaid bonuses and team security.
But he changed his mind after talks with the country's president and could now be away for four weeks.
Adebayor, 28, survived an horrific attack on the Togo team coach by terrorists in Angola in 2010 by hiding under a seat. But three people died, including the assistant coach.
He has been assured by president Faure Gnassingbe that security will be tight in South Africa.

subset: commoncrawl


text:
- Super Sculpey or any baking clay
- Cubcake pan
- Flower cookie cutter about 3.5 or 3.75 inches inches in diameter (I stretched mine out)
- Rolling pin
- Cooking spray
Tuesday, August 14, 2012
Make Lotus Candle Holders in 5 Minutes!
15 comments:
Trish ..I LOVE this .. Me and you both go crazy over garden and candle stuff .. This is an amazing craft .. Fun and cheap .. Great jobReplyDeleteReplies
Awe,thanks Sis...both our homes are filled with candle holders and plants haha-it's never enough!Delete
I really love the idea!!!!! Thank you, it will be useful for me too! :)ReplyDelete
Thanks Cecilia! Glad you like it.Delete
Is there a particular paint you use that it's safe to burn candles on?ReplyDelete
Thanks. What a terrific idea! I plan to make red and green ones as party favors for Christmas. Oh, and silver and gold ones too!
Hey there, any acrylic paint is fine since this holder is not enclosed.-thanks for your comment:)ReplyDelete
- OmRwainaAugust 14, 2012
Thank you , I will make same this soon ..ReplyDeleteReplies
So happy to hear OmRwaina!Delete
- AnonymousAugust 18, 2012
Love this, thanks for sharing!ReplyDelete
Oh my goodness, I love this idea. What a great favor for a wedding. Thanks so much for the idea.ReplyDelete
- AnonymousAugust 21, 2012
Wow. What a wonderful and easy gift idea. Thanks so much for sharing.ReplyDelete
- AnonymousAugust 24, 2012
Do you think these would float?ReplyDelete
Just be careful, as cured Sculpey is flammable. I'd suggest placing a glass votive holder inside as a precaution. :)ReplyDelete
- AnonymousMarch 24, 2015
where did you get the flower cookie cutter from, ive been searching and have had no luck.ReplyDelete
I wish I was this creative. I would have never thought of doing something so crafty and easy.ReplyDelete


text:
"GROVE CITY, PA" Grove City by davecallahan
Grove City Travel Guide: 13 reviews and 23 photos
This quiet college town (Grove City College) used to be a large industrial platform for some heavy steel equipment manufacturing. Some of those 1930s industries still thrive in town. Today, Grove City is synonymous with Mall (Outlet Mall at Grove City) as well as its other activities.
wikipedia info:
8000 people (not sure if that counts the college personnel!!!)
98% caucasian, mostly German-Irish heritage
average age is only 27 (pretty young)
average income is $35000 (pretty low)
90% of the residents have at least some college (darn good)
crime is in the lowest ranking (less than 25% of U.S. average)
ZIPCODE is Grove City in Mercer County
41.160, -80.087
Area Code is 724
City Hall is 041-13-57N 080-30-37W
city nickname is "bubble city"
- Pros:Outlet Mall.... big selection
- Cons:Outlet Mall.... drains the wallet
- In a nutshell:OutLet Mall sort of sums it up.....
Reviews (8)
Take $5 and warm up with a bucket of balls on the driving range and practice green. Stop in the pro shop for some extra... more travel advice
as the ad says: "over 140 brand named outlets where customers realize 25%-65% savings over retail everyday" That's... more travel advice
Every October there is the Annual Grove City Fall Fest. It is sort of combination craft show and yard sale with a... more travel advice
Grove City is a pretty safe area to visit. They average less than 1 murder or rape per year. The only prevelant crime... more travel advice
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San Francisco keeps immigrant-protection rules, adds clarifications
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text:
The Red River Valley Park is one of the tourist attractions in Shaanxi Province that is most frequented by thousands of visitors all year round. This has an irresistible enigma which draws a lot of people to go to this place.
The Red River Valley Park covers up to 20 acres. This is found right at the foot of the Taibai Mountain. Because of that, the horizon of this place is absolutely picturesque. For people who would like to take photographs of this scenic destination, they can point their cameras to any section and they would still be able to take postcard-worthy images.
The significance of Red River Valley Park does not end with just its beauty. This is also an important area especially when it comes to preservation of rare species. Although the Red River Valley Park is open for public, the government has implemented proper protection for some of the sections. This applies especially for the specific locations which serve as breeding ground for endangered animals.
Without a doubt, the reason why this has become a dwelling ground even for the rare species is because of the rich environment and impressive maintenance of its natural beauty.
Things To Do
All year round, people flock to the Red River Valley Park to unwind and relax. Usually, tourists take one of the trails to be able to explore the rest of the surroundings. They can follow the designated paths which would lead them to different sections of the area. This will give them an opportunity to really immerse into the beauty that the surroundings has. There are tall trees and a myriad of flower and plants.
Another reason why people go to Red River Valley Park is because this has served as one of the main pathways when going to the top of the Taibai Mountains. Trekkers, mountain climbers and even those who would like to meditate in the mountains would stop by the Red River Valley Park to prepare for their adventure towards the top of the mountain.
There are small commercial establishments which can be found within the Red River Valley Park. These are managed and operated by the locals in order to serve tourists better. For those who are staying within the park, they can find snack bars and other places to stop by for some relaxation. On the other hand, people who plan to go to the top of the mountain can avail the services of locals who are tour guides. Tourists may also find some of their essential needs among the small stores which they could bring with them as they climb up the mountain.
For those who do not have intentions of going to the top of the mountain, staying within the Red River Valley Park is a brilliant idea too. Since it is situated at the foot of Mount Taibai, the climate here is cool and friendly almost all year round. It could get a bit cold during the winter months but this only makes the experience even more pleasurable.
Tourists can choose among the four scenic spots which can be found within Red River Valley Park. There is the Doumu Waterfall which is about 80 meters high. The sight of this is absolutely breath-taking. There is also a gently flowing river. Along the banks are some boats which tourists could hire.
It is also impressive how many historic sites can be seen within Red River Valley Park. Among which are the Lotus Cave, Jinlin Temple, Avalokitesvara Temple, Jade Emperor Tower and Wendong Temple.
Solo Adventure Tips:
Baoji, Shaanxi Province
How to Get There?
Though there are public bus routes which could take passengers close to the park, it is best to take a cab directly to this place.
Ticket Price:
Opening Hours:
8:00 am to 5:00 pm
More Tips:
Autumn and spring months have the best climate in this area.
Autumn and spring months have the best climate in this area.
Information accuracy:
We try to make the information on China Travel accurate when we write/edit it. If you find any outdated information, please inform us.


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i like this a lot very cool
hermoso sueter me encanto es una bellaza sin duda alguna el estampado es lo que mas llama la atencion de todo
Este sweater se ve super fashion y divertido. Perfecto para usae con jeans y botas
so fashionable sweatshirt <3 I love its print also
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|Useful measurements can be made without numbers.
|Measurement should be defined as matching common attributes of things or events.
|The matching operation occurs on an ordinal scale.
|People and animals are successful in measuring aspects of their environments with the help of their senses, not using any instruments.
|Such measurement must be based on internal matching of common aspects of subjective impressions of the physical variables measured. I have called it natural measurement.
|Natural measurement predates the formal physical measurement.
|Numbers are introduced automatically into natural measurement when the behavioral responses are quantized.
|When the numbers of some physical units are introduced, it becomes possible to express the behavioral results of internal matching as functions of associated physical variables.
|There is no fundamental difference between natural measurement and psychophysical matching experiments.
|The problem of coupling numbers to subjective impressions in such experiments has been solved in principle, but work should continue on minimizing biases and variability associated with the coupling.
Bolanowski S. J., Jr. ( 1987). "Contourless stimuli produce binocular brightness summation". Vision Research, 27, 1943-1951.
Collins A. A., & Gescheider G. A. ( 1989). "The measurement of loudness in individual children and adults by absolute magnitude estimation and cross-modality matching". Journal of the Acoustical Society of America, 85, 2012-2021.


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Originally Posted by Avalon®
What's the action required to copy a weapon using Arcane Fusion? Is it supposed to be a free action?
As the description states, it's a free action to create it. I'm going to move the sentence to be the last one.
Also, I added a badass image to represent the class.
A Swordsage's Journal: The Gladiator Arena
[5e] Way of the Four Elements: Remastered
[5e] Army of the Damned: free adventure (lvl 1-5) set in Magic's world of Innistrad
Amazing avatar was made by Ceika!
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Vegreville Country Fair Aug 4-6 – Fun for the Whole Family!!!
Major sponsor of the Vegreville Country Fair is DENNILL'S KUBOTA
With tons to see and do make sure you dont miss the Vegreville Country Fair this summer. Whether it's your child's first ride on the midway, the pounding hooves at the chuckwagon races, a magistic display of horses, or a rousing night of entertainment in the Grandstand, you're sure to have some fun.
August 4 thru 6, 2016
Key Events:
- Parade
- Midway, games, and mouth watering food
- Chuckwagon and Chariot races
- Children's Barnyard Fun
- Tractor Pulls featuring **horse against machine!!!
- Hypnotist Grandstand show
- Horse Show
- Strong man Competitions
- Mini tractor pulls
- Market & trade show
- Grandstand
- Bandshell
- Bingo
- Hall exhibits
- Fireworks
- Beer Gardens
Winner from our video promo contest Kristen Baldwin https://drive.google.com/file/d/0B1Yc3Qzsd4GRenJjZ2MwNFBIQ1E/view


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HSBC New Smartform Update
We would like to inform you that we have updated our Smartform to reflect the requirement of insertion of additional fields related to Sistem Kliring Nasional Next Generation implementation
Notice on Termination of 2x Rewards Point in HSBC Gold Credit Card
With effective from 23 October 2014, the feature of 2x Rewards Point in Groceries, Gasoline, & Online Transaction in HSBC Gold Credit Card will be terminated.
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Hi, I just found this forum, it was recommended to me by someone on the Gear Page, my favorite Musicians forum. I'm new to riding, I started a month ago as recommended by my Doctor as part of a weight loss thing I'm doing. I shopped around for a Bike to fit someone my size, 6'3" 300 pounds and after trying out more then a few, I ended up with a Trek Hybrid.
The first night I went riding I barely made it one mile and felt like I was going to pass out. Out here it's all country roads with hills, so a mile is a work out. Well after a month, I'm up to 6 miles, a few night's a week and I put just over 50 miles on the bike now and I'm really enjoying riding.
I joined the forum to get advice on better riding and ways to work up to going further each week and just all around bike stuff.


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Thought Leadership Video Series
Ricoh's Eric Staples on Clickable Paper
Published on January 10, 2013
Eric Staples, Senior Product Manager at Ricoh, speaks with Cary Sherburne about "Clickable Paper".
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What is the back in time project?
In this project we started in 88 and timetravel till 08, every week is
Welcome to our forums, we are delighted that you've decided to join in our community! If you need
Straight Outta Compton
I came from nothin'
No really, I came from nuttin'
You got here, but you came for nothin'
No really, you
Kanye has released 7 albums in 12 years… Doesn't that make him a contender for that?
Best discography
Best chance to be seen as GOAT in 10 years
Best rap skills
Best lyrics
Best album
and im a product of my community and im a product
Drake has been crashing the boards recently with his new albums, can he be the GOOT?
people gotta stop having their concerts at Le Bataclan fr
starting at Honest
Move That Dope
Covered N Money
Fuck Up Some Commas
Lay Up
Where Ya At
March Madness
and yes i realise theyre all trash but for me its gotta be relapse
Here are some categorys suggestions:
Technical lyrical ability:
I went through this conversation with my niggas back in BX about why didn't Drake mention Weezy instead of the GOAT, Jay-Z. As I told them, this is why Drake didn't mention Weezy:
Drake figures out that a year or two he will be better then Weezy, so when Weezy dies he doesn't have to cry because he is greater than him ( I know what alot of you are thinking [He also said he never cried when Pac died, so is Drake saying he is better than Pac?] not really, maybe he didn't have give two fucks about Pac when he died)
Hov is a fucking god, I know I will cry when Hov dies because then all we have left is one fucking person that could actually give something out to this world; and that's Kendrick Lamar
#Tell me why you think he didn't say Weezy?
#Im Sly tendencies and thank you for taking your time to read this post. Have a nice day.
#Gave you some to think about huh Drake? NOW THINK BITCH LOL!
Well ill throw in my two cents, he has to shout someone industry whos makes a huge profit and is popular, Wayne dosnt have popularity. I dont know why hes saying this, its just kind of stupid,mabey cuz if Jayz likes him he will get promoted or something, i dont know, i find drake to be a little scheming and greedy (just like JayZ and most rappers).
Also i could come up with alot of illuminati conspiracys . I will put one out just for fun, i dont believe in the illuminati. Read this next paragraph with dramatic music in the background
So JayZ is the illuminatis best friend,as we see by all the masonic symbles on his albums. Tupac released killuminati the 7 day theory to influence people to fight against the illuminati, and its working. Drake is an upcomming illuminati member, so hes showing his support to the illuminati by bumping Jayz and putting down tupac so the youth will be following there reighn of masonary untill its to late
someone put thaat^ on youtube, WE NEED TO HAVE THE TRUTH. (sarcasm/)
Drake explained it. He was young when tupac died do he didn't have a grasp on the situation. And why jay instead weezy? Jays a legend weezys not. Weezys impact is minimal compared to jay z
Adonis hit it right on the head. Drake was too young to fully understand the gravity of what happened when Pac died, (though him mentioning Pac is testament to what he meant to hip-hop, notice he didn't say Biggie). Jay-Z however is a living legend who Drake is able to appreciate in his adult life, when Jay dies valleys will be cried.
Could also be seen as a slight swipe at Jay, seeing how his age appears to be the only thing niggas can come up with when theyre dissin'. It might be a way to disguise a punch
because Waynes like 4 years older than Drake. It doesn't make sense to think about a person in the same age group as you dying. Jay on the other hand is 42. He's more than likely gonna die before Wayne or Drake.
Wayne doesn't have popularity? You kiddin' me? You all gotta remember what time it is. This is Wayne's time, and that's real. As much as I don't want to say that, it is the truth. He ran shit this decade that just past, and he's still popular. Just because he gets alot of hate does not mean he still isn't a huge name. Yeah Jay's impact is way bigger than Wayne's, but Wayne will leave a mark.
At Drakes age Jay Z was the man Lil Wayne is just becoming the man recently. Jay is the King to Drakes generation.
So Jay-Z is the GOAT now and Kendrick is the only other one that could be?
Lmao.. oh lawd
doesn't make him a legend. In 30-40 years people are going to remember Jay-Z as a legend. Lil Wayne despite his impact on the present will not go down as someone who will be remembered VIVIDLY in the future.
A few things:
One, regardless of what you think of their respective styles, Drake will never be a better rapper than Wayne. Two, why is Jay the only legend left? Ghost and Rae are so going strong. So are Face, Kool G, and quite a few other GOAT candidates. So why is it gonna be such a sad day when Beyonce is finally single? Three, the Kendrick dick-riding around here is honestly out of control. Also, why does that guy always look like he just woke up from a 20 hour Valium nap?
Maybe drake just had hov in mind on this line
Drake said jay and not wayne because jay is his favourite rapper, he's always liked wayne but jay is his favourite
I stopped reading when you said Jay-Z is the GOAT.
Isn't this line pretty self-explanatory? Why didn't Drake mention Weezy instead of Jay-Z? Maybe because Drake looks up to him more than he looks up to Wheezy
Drake is such an idiot. He didnt even hear the lyrics of Hov's song right. Drake is trying to refer to the song called moment of clarity. Jay Z says "pop died didnt cry didnt know him that well." Drake though HOV said "pac died didnt cry…"What a fucking idiot he cant even listen to songs correctly. Drake fucking sucks.
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Hi, I'm new on this forum.
Just a quick question..... I've got a GT Avalanche 1.0, and I'm wondering what's the best way to shave some weight off the bike?
I've had it for a while and never minded to much, but as I'm using it a lot more now, I think it would be beneficial.
Might be a stupid question..... but just curious...


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Return: (bool) True if the current post is in any of the given categories.
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Key things you need to know aboutDr. Yarbrough:
Dr. Yarbrough's Experience
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- Bon Secours - Mary Immaculate Hospital
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Patients' risk of dying during a hospital stay for heart bypass surgery could be 87.4% lower, on average, at a hospital rated 5 stars compared to a hospital rated 1 star for that procedure. Choosing the right hospital is critical to your health. View Slideshow
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Publications (50)189.12 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: The cystine/glutamate antiporter or system Xc- exchanges cystine for glutamate, thereby supporting intracellular glutathione synthesis and nonvesicular glutamate release. The role of system Xc- in neurological disorders can be dual and remains a matter of debate. One important reason for the contradictory findings that have been reported to date is the use of nonspecific anti-xCT (the specific subunit of system Xc-) antibodies. Often studies rely on the predicted molecular weight of 55.5 kDa to identify xCT on Western blots. However, using brain extracts from xCT knockout (xCT(-/-) ) mice as negative controls, we show that xCT migrates as a 35-kDa protein. Misinterpretation of immunoblots leads to incorrect assessment of antibody specificity and thereby to erroneous data interpretation. Here we have verified the specificity of most commonly used commercial and some in-house-developed anti-xCT antibodies by comparing their immunoreactivity in brain tissue of xCT(+/+) and xCT(-/-) mice by Western blotting and immunohistochemistry. The Western blot screening results demonstrate that antibody specificity not only differs between batches produced by immunizing different rabbits with the same antigen but also between bleedings of the same rabbit. Moreover, distinct immunohistochemical protocols have been tested for all the anti-xCT antibodies that were specific on Western blots in order to obtain a specific immunolabeling. Only one of our in-house-developed antibodies could reveal specific xCT labeling and exclusively on acetone-postfixed cryosections. Using this approach, we observed xCT protein expression throughout the mouse forebrain, including cortex, striatum, hippocampus, midbrain, thalamus, and amygdala, with greatest expression in regions facing the cerebrospinal fluid and meninges. J. Comp. Neurol., 2015. © 2015 Wiley Periodicals, Inc.
Article: MPTP-induced parkinsonism in mice alters striatal and nigral xCT expression but is unaffected by the genetic loss of xCT[Show abstract] [Hide abstract] ABSTRACT: Nigral cell loss in Parkinson's disease (PD) is associated with disturbed glutathione (GSH) and glutamate levels, leading to oxidative stress and excitotoxicity, respectively. System xc- is a plasma membrane antiporter that couples cystine import (amino acid that can be further used for the synthesis of GSH) with glutamate export to the extracellular environment, and can thus affect both oxidative stress and glutamate excitotoxicity. In the current study, we evaluated the involvement of system xc- in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Our results indicate that the expression of xCT (the specific subunit of system xc-) undergoes region-specific changes in MPTP-treated mice, with increased expression in the striatum, and decreased expression in the substantia nigra. Furthermore, mice lacking xCT were equally sensitive to the neurotoxic effects of MPTP compared to wild-type (WT) mice, as they demonstrate similar decreases in striatal dopamine content, striatal tyrosine hydroxylase (TH) expression, nigral TH immunopositive neurons and forelimb grip strength, five weeks after commencing MPTP treatment. Altogether, our data indicate that progressive lesioning with MPTP induces striatal and nigral dysregulation of system xc-. However, loss of system xc- does not affect MPTP-induced nigral dopaminergic neurodegeneration and motor impairment in mice. Copyright © 2015. Published by Elsevier Ireland Ltd.
- [Show abstract] [Hide abstract] ABSTRACT: The cystine/glutamate transporter, designated as system xc-, is important for maintaining intracellular glutathione levels and extracellular redox balance. The substrate-specific component of system xc-, xCT, is strongly induced by various stimuli, including oxidative stress, whereas it is constitutively expressed only in specific brain regions and immune tissues such as thymus and spleen. While cystine and glutamate are the well-established substrates of system xc- and the knockout of xCT leads to alterations of extracellular redox balance, nothing is known about other potential substrates. We thus performed a comparative metabolite analysis of tissues from xCT-deficient and wild-type mice using capillary electrophoresis time-of-flight mass spectrometry. Although most of the analysed metabolites did not show significant alterations between xCT-deficient and wild-type mice, cystathionine emerged to be absent specifically in thymus and spleen of xCT-deficient mice. No expression of either cystathionine β-synthase or cystathionine γ-lyase was observed in thymus and spleen of mice. In embryonic fibroblasts derived from wild-type embryos, cystine uptake was significantly inhibited by cystathionine in a concentration-dependent manner. Wild-type cells showed an intracellular accumulation of cystathionine when incubated in cystathionine-containing buffer, which concomitantly stimulated an increased release of glutamate into the extracellular space. By contrast, none of these effects could be observed in xCT-deficient cells. Remarkably, unlike knockout cells, wild-type cells could be rescued from cystine deprivation-induced cell death by cystathionine supplementation. We thus conclude that cystathionine is a novel physiological substrate of system xc-, and that the accumulation of cystathionine in immune tissues is exclusively mediated by system xc-. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
Article: Absence of system xc- in mice decreases anxiety and depressive-like behavior without affecting sensorimotor function or spatial vision[Show abstract] [Hide abstract] ABSTRACT: There is considerable preclinical and clinical evidence indicating that abnormal changes in glutamatergic signaling underlie the development of mood disorders. Astrocytic glutamate dysfunction, in particular, has been recently linked with the pathogenesis and treatment of mood disorders, including anxiety and depression. System xc- is a glial cystine/glutamate antiporter that is responsible for nonvesicular glutamate release in various regions of the brain. Although system xc- is involved in glutamate signal transduction, its possible role in mediating anxiety or depressive-like behaviors is currently unknown. In the present study, we phenotyped adult and aged system xc- deficient mice in a battery of tests for anxiety and depressive-like behavior (open field, light/dark test, elevated plus maze, novelty suppressed feeding, forced swim test, tail suspension test). Concomitantly, we evaluated the sensorimotor function of system xc- deficient mice, using motor and sensorimotor based tests (rotarod, adhesive removal test, nest building test). Finally, due to the presence and potential functional relevance of system xc- in the eye, we investigated the visual acuity of system xc- deficient mice (optomotor test). Our results indicate that loss of system xc- does not affect motor or sensorimotor function, in either adult or aged mice, in any of the paradigms investigated. Similarly, loss of system xc- does not affect basic visual acuity, in either adult or aged mice. On the other hand, in the open field and light/dark tests, and forced swim and tail suspension tests respectively, we could observe significant anxiolytic and antidepressive-like effects in system xc- deficient mice that in certain cases (light/dark, forced swim) were age-dependent. These findings indicate that, under physiological conditions, nonvesicular glutamate release via system xc- mediates aspects of higher brain function related to anxiety and depression, but does not influence sensorimotor function or spatial vision. As such, modulation of system xc- might constitute the basis of innovative interventions in mood disorders.
Article: Evaluation of oocyte quality and ovarian function in aged female cystine-glutamate transporter gene-deficient mice
Article: Enhanced expression of cystine/glutamate transporter in the lung caused by the oxidative-stress-inducing agent paraquat[Show abstract] [Hide abstract] ABSTRACT: In mammalian cultured cells, the activity of a cystine/glutamate transporter, designated System x(c)(-), has been shown to be essential for maintaining intracellular glutathione levels and the extracellular cystine/cysteine redox balance. The substrate-specific subunit of this transporter, xCT, is strongly induced by various stimuli, including oxidative stress, which suggests that xCT is one of the adaptive cellular defense systems against these types of stress. Embryonic fibroblasts from xCT-deficient mice fail to survive unless a cysteine precursor, N-acetylcysteine, is present. However, it is unclear whether xCT has similar functions in vivo because xCT-deficient mice are apparently normal. In this study, we investigated the phenotypes of the xCT-deficient mice under paraquat-induced oxidative stress. At a paraquat dose of 45mg/kg, the survival rate of the xCT-deficient mice was significantly lower than that of the wild-type mice. Under this condition, total glutathione [the reduced form of glutathione (GSH)+the oxidized form of GSH (GSSG)] levels in the lungs of the xCT-deficient mice were lower than those in the lungs of the wild-type mice. Histopathological examinations showed that paraquat administration worsened the alveolar structures of the xCT-deficient mice compared with the wild-type mice. After paraquat treatment, obvious 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2- nonenal reactivities were detected in the lung of the xCT-deficient mice. Although xCT expression was slightly detectable in the lungs of the normal wild-type mice, paraquat administration induced xCT mRNA expression in the lung. Constitutive expression of xCT mRNA was detected in alveolar macrophages isolated from the pulmonary lavage fluid of the wild-type mice, and paraquat administration strongly enhanced xCT mRNA expression in these cells. GSH levels in bronchoalveolar lavage fluid were significantly higher in the paraquat-treated wild-type mice than in the paraquat-treated xCT-deficient mice. These results suggest that xCT contributes to the maintenance of glutathione levels in lungs and the glutathione redox state as a protective system against paraquat toxicity in vivo.
- [Show abstract] [Hide abstract] ABSTRACT: The Mouse Multiple Tissue Metabolome Database (MMMDB) provides comprehensive and quantitative metabolomic information for multiple tissues from single mice. Manually curated databases that integrate literature-based individual metabolite information have been available so far. However, data sets on the absolute concentration of a single metabolite integrated from multiple resources are often difficult to be used when different metabolomic studies are compared because the relative balance of the multiple metabolite concentrations in the metabolic pathways as a snapshot of a dynamic system is more important than the absolute concentration of a single metabolite. We developed MMMDB by performing non-targeted analyses of cerebra, cerebella, thymus, spleen, lung, liver, kidney, heart, pancreas, testis and plasma using capillary electrophoresis time-of-flight mass spectrometry and detected 428 non-redundant features from which 219 metabolites were successfully identified. Quantified concentrations of the individual metabolites and the corresponding processed raw data; for example, the electropherograms and mass spectra with their annotations, such as isotope and fragment information, are stored in the database. MMMDB is designed to normalize users' data, which can be submitted online and used to visualize overlaid electropherograms. Thus, MMMDB allows newly measured data to be compared with the other data in the database. MMMDB is available at: http://mmmdb.iab.keio.ac.jp.
Article: Anti-Diabetic Effects of a Kaempferol Glycoside-Rich Fraction from Unripe Soybean (Edamame, Glycine max L. Merrill. 'Jindai') Leaves on KK- A y Mice[Show abstract] [Hide abstract] ABSTRACT: The anti-diabetic effects of a kaempferol glycoside-rich fraction (KG) prepared from leaves of unripe Jindai soybean (Edamame) and kaempferol, an aglycone of kaempferol glycoside, were determined in genetically type 2 diabetic KK-A(y) mice. The hemoglobin A(₁c) level was decreased and tended to be decreased by respectively feeding KG and kaempferol (K). The area under the curve (AUC) in the oral glucose tolerance test (OGTT) tended to be decreased by feeding K and KG. The liver triglyceride level and fatty acid synthase activity were both decreased in the mice fed with KG and K when compared to those parameters in the control mice. These results suggest that KG and K would be useful to improve the diabetes condition. The major flavonoids in KG were identified as kaempferol 3-O-β-D-glucopyranosyl(1→2)-O-[α-L-rhamnopyranosyl(1→6)]-β-D-galactopyranoside, kaempferol 3-O-β-D-glucopyranosyl(1→2)-O-[α-L-rhamnopyranosyl(1→6)]-β-D-glucopyranoside, kaempferol 3-O-β-D-(2-O-β-D-glucopyranosyl) galactopyranoside and kaempferol 3-O-β-D-(2,6-di-O-α-L-rhamnopyranosyl) galactopyronoside, suggesting that these compounds or some of them may be concerned with mitigation of diabetes.
Article: Loss of System xFormula Does Not Induce Oxidative Stress But Decreases Extracellular Glutamate in Hippocampus and Influences Spatial Working Memory and Limbic Seizure Susceptibility[Show abstract] [Hide abstract] ABSTRACT: System x(c)- exchanges intracellular glutamate for extracellular cystine, giving it a potential role in intracellular glutathione synthesis and nonvesicular glutamate release. We report that mice lacking the specific xCT subunit of system x(c)- (xCT(-/-)) do not have a lower hippocampal glutathione content, increased oxidative stress or brain atrophy, nor exacerbated spatial reference memory deficits with aging. Together these results indicate that loss of system x(c)- does not induce oxidative stress in vivo. Young xCT(-/-) mice did however display a spatial working memory deficit. Interestingly, we observed significantly lower extracellular hippocampal glutamate concentrations in xCT(-/-) mice compared to wild-type littermates. Moreover, intrahippocampal perfusion with system x(c)- inhibitors lowered extracellular glutamate, whereas the system x(c)- activator N-acetylcysteine elevated extracellular glutamate in the rat hippocampus. This indicates that system x(c)- may be an interesting target for pathologies associated with excessive extracellular glutamate release in the hippocampus. Correspondingly, xCT deletion in mice elevated the threshold for limbic seizures and abolished the proconvulsive effects of N-acetylcysteine. These novel findings sustain that system x(c)-) is an important source of extracellular glutamate in the hippocampus. System x(c)(-) is required for optimal spatial working memory, but its inactivation is clearly beneficial to decrease susceptibility for limbic epileptic seizures.
Article: The oxidative stress-inducible cystine/glutamate antiporter, system x c-: Cystine supplier and beyond[Show abstract] [Hide abstract] ABSTRACT: The oxidative stress-inducible cystine/glutamate exchange system, system x (c) (-) , transports one molecule of cystine, the oxidized form of cysteine, into cells and thereby releases one molecule of glutamate into the extracellular space. It consists of two protein components, the 4F2 heavy chain, necessary for membrane location of the heterodimer, and the xCT protein, responsible for transport activity. Previously, system x (c) (-) has been regarded to be a mere supplier of cysteine to cells for the synthesis of proteins and the antioxidant glutathione (GSH). In that sense, oxygen, electrophilic agents, and bacterial lipopolysaccharide trigger xCT expression to accommodate with increased oxidative stress by stimulating GSH biosynthesis. However, emerging evidence established that system x (c) (-) may act on its own as a GSH-independent redox system by sustaining a redox cycle over the plasma membrane. Hallmarks of this cycle are cystine uptake, intracellular reduction to cysteine and secretion of the surplus of cysteine into the extracellular space. Consequently, increased levels of extracellular cysteine provide a reducing microenvironment required for proper cell signaling and communication, e.g. as already shown for the mechanism of T cell activation. By contrast, the enhanced release of glutamate in exchange with cystine may trigger neurodegeneration due to glutamate-induced cytotoxic processes. This review aims to provide a comprehensive picture from the early days of system x (c) (-) research up to now.
- [Show abstract] [Hide abstract] ABSTRACT: The polyphenol fraction of Actinidia arguta (AP) inhibited α-glucosidase activity in vitro. The oral administration of AP with maltose and starch suppressed postprandial hyperglycemia associated with the intake of the respective sugars by rats. The area under the curve (AUC) of blood glucose in the oral glucose tolerance test (OGTT) of type 2 diabetic KK-A y mice, fed AP for 6 weeks, significantly decreased when compared with that of the control group. The fraction containing isoquercitrin and hyperoside, which was prepared from AP, showed a stronger inhibitory activity for maltase. The blood glucose levels in OGTT of KK-A y mice fed isoquercitrin for 4 weeks tended to be lower at 60 min after the administration of glucose. These results suggested that AP has antidiabetic effects, and isoquercitrin, a component of AP, may be useful in preventing type 2 diabetes mellitus. A decrease in the G6Pase activity and increase in the ACO or CPT activities in the liver of KK-A y mice fed AP or isoquercitrin suggested that the suppression of gluconeogenesis and the enhancement of β-oxidation of lipids, as well as the inhibition of maltase by AP and isoquercitrin, might also be related to their anti-diabetic effects.
Article: Dopaminergic neurons of system xFormula-deficient mice are highly protected against 6-hydroxydopamine-induced toxicity[Show abstract] [Hide abstract] ABSTRACT: Malfunctioning of system x(c)(-), responsible for exchanging intracellular glutamate for extracellular cystine, can cause oxidative stress and excitotoxicity, both important phenomena in the pathogenesis of Parkinson's disease (PD). We used mice lacking xCT (xCT(-/-) mice), the specific subunit of system x(c)(-), to investigate the involvement of this antiporter in PD. Although cystine that is imported via system x(c)(-) is reduced to cysteine, the rate-limiting substrate in the synthesis of glutathione, deletion of xCT did not result in decreased glutathione levels in striatum. Accordingly, no signs of increased oxidative stress could be observed in striatum or substantia nigra of xCT(-/-) mice. In sharp contrast to expectations, xCT(-/-) mice were less susceptible to 6-hydroxydopamine (6-OHDA)-induced neurodegeneration in the substantia nigra pars compacta compared to their age-matched wild-type littermates. This reduced sensitivity to a PD-inducing toxin might be related to the decrease of 70% in striatal extracellular glutamate levels that was observed in mice lacking xCT. The current data point toward system x(c)(-) as a possible target for the development of new pharmacotherapies for the treatment of PD and emphasize the need to continue the search for specific ligands for system x(c)(-).
- [Show abstract] [Hide abstract] ABSTRACT: GSH is the major antioxidant and detoxifier of xenobiotics in mammalian cells. A strong decrease of intracellular GSH has been frequently linked to pathological conditions like ischemia/reperfusion injury and degenerative diseases including diabetes, atherosclerosis, and neurodegeneration. Although GSH is essential for survival, the deleterious effects of GSH deficiency can often be compensated by thiol-containing antioxidants. Using three genetically defined cellular systems, we show here that forced expression of xCT, the substrate-specific subunit of the cystine/glutamate antiporter, in gamma-glutamylcysteine synthetase knock-out cells rescues GSH deficiency by increasing cellular cystine uptake, leading to augmented intracellular and surprisingly high extracellular cysteine levels. Moreover, we provide evidence that under GSH deprivation, the cytosolic thioredoxin/thioredoxin reductase system plays an essential role for the cells to deal with the excess amount of intracellular cystine. Our studies provide first evidence that GSH deficiency can be rescued by an intrinsic genetic mechanism to be considered when designing therapeutic rationales targeting specific redox enzymes to combat diseases linked to GSH deprivation.
- [Show abstract] [Hide abstract] ABSTRACT: This study examined the question of whether deficiency of xCT, a cystine-transporter gene, exacerbates ischemia-reperfusion-induced acute renal failure (ARF). Two weeks after the right nephrectomy of male mice at 16-18weeks of age, the left renal vessels were clamped for 45min to induce renal ischemia. After (24h) induction of ischemia, xCT(-/-) mice had elevated concentrations of blood urea nitrogen and creatinine indicative of ARF, while in xCT(+/-) and xCT(+/+) mice, these parameters did not differ from the sham-operated mice. Immunohistochemical analyses of kidneys using antibodies against the oxidative stress markers revealed stronger staining in xCT(-/-) mice compared with xCT(+/+) mice. Induction of xCT mRNA in the kidneys of xCT(+/+) mice was demonstrated using reverse transcriptase (RT)-PCR analysis and was further confirmed using quantitative RT-PCR. These data provide the first in vivo evidence that xCT is induced by oxidative stress and helps prevent ischemia-reperfusion injury to kidneys.
Article: Transforming growth factor-β 1 elicits Nrf2-mediated antioxidant responses in aortic smooth muscle cells[Show abstract] [Hide abstract] ABSTRACT: The anti-inflammatory properties of transforming growth factor-beta(1) (TGF-beta(1)) account for its protection against atherosclerotic plaque rupture. This study investigates whether activation of the Nrf2 (nuclear factor erythroid 2 [NF-E2]-related factor 2) transcription pathway is involved in TGF-beta(1) mediated induction of the antioxidant enzyme heme oxygenase-1 (HO-1) in smooth muscle cells (SMC). Human aortic smooth muscle cells (HAoSMC) or wild-type and Nrf2-deficient mouse (MAoSMC) aortic SMC were treated with TGF-beta(1) (2.5-10 ng/ml, 0-24 hrs). We report the first evidence that TGF-beta(1) induces Nrf2 mediated HO-1 expression and antioxidant response element activity, which was paralleled by enhanced superoxide production and expression of the NAD(P)H oxidase subunit p22(phox). TGF-beta(1) failed to induce HO-1 expression in MAoSMC derived from Nrf2-deficient mice, and HO-1 induction by TGF-beta(1) in HAoSMC was attenuated by inhibition of extracellular signal regulated kinase or c-jun-N-terminal kinase but not p38 mitogen activated protein kinase. Inhibition of NAD(P)H oxidase or scavenging of superoxide diminished HO-1 induction in response to TGF-beta(1). The oxidative stress agents glucose oxidase (GOx) and diethylmaleate enhanced TGF-beta(1) generation and HO-1 expression in HAoSMC, while antagonism of TGF-beta(1) signalling by adenoviral Smad7 overexpression attenuated their induction of HO-1. Pre-treatment of HAoSMC with TGF-beta(1) reduced nuclear translocation of the pro-apoptotic mediator p53 elicited by GOx. Our findings demonstrate that Nrf2 is a new target of TGF-beta(1) signalling in the vasculature which may contribute to the atheroprotective properties attributed to this growth factor.
Article: Anti-diabetic effects of pumpkin and its components, trigonelline and nicotinic acid, on Goto-Kakizaki rats.[Show abstract] [Hide abstract] ABSTRACT: The effects of a pumpkin paste concentrate and its components on oral glucose tolerance and serum lipid levels were determined in non-obese type 2 diabetic Goto-Kakizaki (GK) rats. In the oral glucose tolerance test, the pumpkin paste concentrate-fed group maintained a lower glucose level than the control group between 15 and 60 min. The compounds considered to be effective in improving glucose tolerance and contained in the methanol extract of the pumpkin in relatively abundant amounts were isolated and identified as trigonelline (TRG) and nicotinic acid (NA).Feeding a diet containing TRG and NA respectively improved and tended to improve glucose tolerance. The insulin level increased after 15 min in the TRG-fed GK rats and then gradually decreased over the next 120 min. In contrast, a gradual increase was seen in the insulin level over 120 min in the control GK rats not fed with TRG, suggesting that TRG could improve the insulin resistance. The serum and liver triglyceride (TG) levels in the TRG- and NA-fed GK rats were lower than those in the control GK rats. Lower activity of liver fatty acid synthase (FAS), and higher activity of liver carnitine palmitoyl transferase (CPT) and glucokinase (GLK) in the TRG- and NA-fed GK rats than in the control GK rats were observed. This suggests that the regulation of these enzyme activities by TRG and NA was closely related to the suppression of both TG accumulation and the progression of diabetes.
Article: AntiDiabetic Effects of Pumpkin and Its Components, Trigonelline and Nicotinic Acid, on Goto-Kakizaki Rats[Show abstract] [Hide abstract] ABSTRACT: The effects of a pumpkin paste concentrate and its components on oral glucose tolerance and serum lipid levels were determined in non-obese type 2 diabetic Goto-Kakizaki (GK) rats. In the oral glucose tolerance test, the pumpkin paste concentrate-red group maintained a lower glucose level than the control group between 15 and 60 min. The compounds considered to be effective in improving glucose tolerance and contained in the methanol extract of the pumpkin in relatively abundant amounts were isolated and identified as trigonelline (TRG) and nicotinic acid (NA). Feeding a diet containing TRG and NA respectively improved and tended to improve glucose tolerance. The insulin level increased after 15 min in the TRG-fed GK rats and then gradually decreased over the next 120 min. In contrast, a gradual increase was seen in the insulin level over 120 min in the control GK rats not fed with TRG, suggesting that TRG could improve the insulin resistance. The serum and liver triglyceride (TG) levels in the TRG- and NA-fed GK rats were lower than those in the control GK rats. Lower activity of liver fatty acid synthase (FAS), and higher activity of liver carnitine palmitoyl transferase (CPT) and glucokinase (GLK) in the TRG- and NA-fed GK rats than in the control GK rats were observed. This suggests that the regulation of these enzyme activities by TRG and NA was closely related to the suppression of both TG accumulation and the progression of diabetes.
Article: Transforming Growth Factorbeta-1 elicits Nrf2-mediated antioxidant responses in aortic smooth muscle cells.[Show abstract] [Hide abstract] ABSTRACT: The anti-inflammatory properties of transforming growth factorbeta-1 (TGFbeta-1) account for its protection against atherosclerotic plaque rupture. This study investigates whether activation of the Nrf2 transcription pathway is involved in TGFbeta-1 mediated induction of the antioxidant enzyme heme oxygenase-1 (HO-1) in smooth muscle cells (SMC). Human (HAoSMC) or wild-type and Nrf2 deficient mouse (MAoSMC) aortic SMC were treated with TGFbeta-1 (2.5-10 ng/ml, 0-24 h). We report the first evidence that TGFbeta-1 induces Nrf2 mediated HO-1 expression and antioxidant response element activity, which was paralleled by enhanced superoxide production and expression of the NAD(P)H oxidase subunit p22(phox). TGFbeta-1 failed to induce HO-1 expression in MAoSMC derived from Nrf2 deficient mice, and HO-1 induction by TGFbeta-1 in HAoSMC was attenuated by inhibition of extracellular signal regulated kinase or c-jun-N-terminal kinase but not p38 mitogen activated protein kinase. Inhibition of NAD(P)H oxidase or scavenging of superoxide diminished HO-1 induction in response to TGFbeta-1. The oxidative stress agents glucose oxidase and diethylmaleate enhanced TGFbeta-1 generation and HO-1 expression in HAoSMC, while antagonism of TGF(-1 signalling by adenoviral Smad7 overexpression attenuated their induction of HO-1. Pretreatment of HAoSMC with TGF(-1 reduced nuclear translocation of the pro-apoptotic mediator p53 elicited by glucose oxidase. Our findings demonstrate that Nrf2 is a new target of TGFbeta-1 signalling in the vasculature which may contribute to the atheroprotective properties attributed to this growth factor.
- [Show abstract] [Hide abstract] ABSTRACT: Altered glutamate signaling is associated with Parkinson's disease. To study the involvement of the cystine/glutamate antiporter in the pathogenesis of Parkinson's disease, we developed new polyclonal antibodies recognizing xCT, the specific subunit of this antiporter. The striatal xCT protein expression level was investigated in a hemi-Parkinson rat model, using semiquantitative western blotting. We observed time-dependent changes after a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway with increased expression levels in the deafferented striatum after 3 weeks. Twelve weeks postlesion, expression levels returned to normal. These data suggest, for the first time, an involvement of the cystine/glutamate antiporter in determining the aberrant glutamate neurotransmission in the striatum of a parkinsonian brain.
Article: Deficiency of the cystine-transporter gene, xCT, does not exacerbate the deleterious phenotypic consequences of SOD1 knockout in mice[Show abstract] [Hide abstract] ABSTRACT: Because glutathione scavenges reactive oxygen species (ROS) and also donates electrons to antioxidative systems, it may compensate for the oxidative stress caused by SOD1 deficiency. The cystine/glutamate transporter, which consists of two proteins, xCT and 4F2hc, has been designated system x c−. This transporter system plays a role in the maintenance of glutathione levels in mammalian cells. In the present study, we created SOD1 −/−; xCT −/− double-knockout mice by intercrossing xCT-knockout and SOD1-knockout animals. We determined if the double-knockout mice express the phenotypic characteristics unique to SOD1 −/− mice—increased oxidative stress and the production of autoantibodies against erythrocytes. We also compared the phenotype of the double-knockout mice with those of the single-knockout and wild-type mice. Although two major antioxidative systems were found to be defective in the SOD1 −/−; xCT −/− mice, relative to the SOD1 −/− mice, no functional deficits were observed. Based on these results, it appears that defects in system x c− do not exacerbate the phenotypic consequences of SOD1 deficiency in postnatal mice under ordinary breeding conditions.
Top Journals
Niigata University
Niahi-niigata, Niigata, Japan
- Department of Medical Technology
Iwate UniversityMorioka, Iwate, Japan


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Liverpool Message Board
A Yahoo! User Nov 13, 2006 11:06 Flag
Rafa must go !
It's now 10 straight defeats away to Arsenal, ManU and Chelsea.
I've been a loyal supporter for over 20 years now through thick and thin, mainly thin ( although a Spurs fan said to me that 95% of clubs would kill to have the success we've had since the turn of the century) and in all that time I can never remember such a miserable run.
At this stage I don't think there's any shame in just mass defending away from home for a couple of games just to get a clean sheet or 2 at least and maybe even nick a goal on the break and then hopefully the confidence will return.
Rafa's run out of excuses for the shite we've had to endure this season, it's time to do the talking on the pitch.
I just wanted to comment on a couple of statements made in previous posts.
Firstly, until today we'd only conceded 1 goal from a set-piece which is better than anyone else, including Chelsea, so I don't think that can be blamed.
Secondly, I don't think Rafa can be blamed every time his name is linked to Spain or Italy, I mean didn't he sign a new contract in the summer ? I don't think his commitment can be doubted and besides if he leaves Liverpool in a mess then his stock will surely fall. With regard to Ged, he inherited an already established title-winning team, and Ive read a couple of reports in the broadsheets( the Guardian & Times I think ) that said the team are performing in spite of him not because.
I hope from now on we see a bit more heart, balls and pride in wearing the Red shirt. Stevie needs to stop sulking and get on with the job he's paid for, after all what kind of example is he setting for the rest of the players. It seems that individual mistakes are costing us as well as a general malaise when we leave Anfield.
So, like sendmarcanemail, I too am writing off this season. I think realistically the best we can hope for is 3rd unless the others suffer major meltdowns.
Another cup would be nice, preferably old big ears.
Anyway it could always be worse, we could be Everton fans.
YNWASort: Newest | Oldest | Most Replied Expand all replies
I totally agree, he has had his days now. Bring back loyal player back as Mananger I suggest Phil Thompson, what an assistant manager in Houllier absence, won all three cups and had a shout at Premiership title race till Houllier came back. Why do Liverpool go for foreign coaches when the country has good English coaches
- 1 Reply to rttt
...and Glenn Roader looked like manager of the year at the end of last season didn't he?? don't be so fucking reactionary --- try supporting the manager and live in the real world --- unless you have a sugar daddy building an EPL winning team takes time --- how many years did it take Fergie??? this isn't championship manager!!!
I totally agree, he has had his days now. Bring back loyal player back as Mananger I suggest Phil Thompson, what an assistant manager in Houllier absence, won all three cups and had a shout at Premiership title race till Houllier came back. Why do Liverpool go for foreign coaches when the country has good English coaches
- 1 Reply to rttt
A Yahoo! User Nov 14, 2006 06:40 Flag
I'd still like to see John Toshack at Pool in some capacity or maybe Steve Heighway as a future manager.
But we need to stick with RAFA, all other alternatives mean yet more 'rebuilding '.
Managers on a roundabout never work.
We are still going to finish 4th, we have got all the top clubs out of the way and will now start to go on a run which will bring our confidence back in time for a Euro cup/ league cup / big ears treble.
To be fair to the Bluenoses on this thread dixiedunc made a good and obvious point - we're proclaiming CL 2005 as the start of the 'Rafalution' then win last season's FA Cup with an extremely high points total and clean sheet record and now you're saying he should go???
I know you're Red thru & thru but we need what is missing in the modern game and that is patience. It's impatience that makes managers look abroad for the short-term option and not blood their Academy players; impatience that results in a high turnover of managers when all they want is to be allowed to do the job and be left alone, and impatience that makes teams sack in haste and repent in leisure.
I'm as disappointed as the rest of the Reds on this thread that we've not managed to get our season off to a winning start away from home. We need to look at what we did last season and follow from that. We've got near enough the same players from last year and have added players for cover so we should be looking to improve the situation. We need consistency and that starts with leaving Rafa alone to work his magic through the rest of the squad.
We are by no means the finished article but please remember, we have added the Champions League, FA Cup, Super Cup and a Charity Shield while being the unfinished article!
- 1 Reply to Imran
A Yahoo! User Nov 13, 2006 22:13 Flag
Rafa will leave at the end of the season and probably move to a big club in spain or italy. Liverpool will probably finish the top 6 in the league and win no cups.
As for Rafa's replacement - there can only be one man. Martin O'Neill. He can bring back the British toughness to this Liverpool team and make them once again a hard team to beat in the League week in week out.
One things for sure - Mr. O'Neill would play Gerrard every week in the centre and built to team around our best player and captain. I mean Bolo Zenden is surely not the answer?
Rafa has done well for us, but i dont think we can win the league with him. Mind you, if Villa finish above us in the league this year - why would Mr. O'Neill want to leave?!
A Yahoo! User Nov 13, 2006 20:18 Flag
For Christs sake sack Rafa you have to be f**king joking mate! Champions League winner in his first year, FA Cup winner and highest Premier League total last year, 6 finals in 2 years, 4 of which have been won - Jesus Christ!
You do realise as well that we are only 4 points from 3rd place.
Just who are you going to get in by the way?
A Yahoo! User Nov 13, 2006 20:07 Flag
You have a really short memory, how long ago was it that you were going on about the rafaloution, and 1 night in may!
now you are calling for his head! typical.
yes thats it --- get rid of the manager and go through 10 more years of transition --- wait I have an idea -- how about sticking with the manager giving him a fair crack of the whip and try and let him build a dynasty -- what did SAF win in his first 6 years???
he's not a miracle worker and has already won us 2 major trophies -- yes we were crap yesterday and the decision to play
Zenden still baffles... but who do you want to manage the team?? I honestly think Rafa is the best man for the job -- but it's clear that he wanted some different players but the money isn't there and has had to wheel and deal -- Pennant (for example) was def. not 1st choice....
- 2 Replies to Jinder
A Yahoo! User Nov 14, 2006 02:19 Flag
jk80jk did you actually read my first post, the headline is just to get your attention, I never said he must go.
What I've actually said is that his commitment can't be doubted as he signed an extension to his current deal in the summer, it's not his fault he's constantly linked to jobs abroad. And why should he have to come out in the press every couple of months to reiterate his position and give the media what they want. As usual it's just tabloid shite trying to sell the muck they print
I do stand by my earlier statement that he can't keep trotting out the same old crap excuses about our pathetic away form, when clearly nothing's changed. Time to give Agger a bit more pitch time as despite have some very good games for us, Sami is not consistent enough anymore and clearly anyone with pace is going to get past him.
We should give him 'til the end of his contract and see where the land lies then.
I just don't agree with the blind faithers who think it's an affront to dare criticise the team, especially when they are clearly deserving of it.
A Yahoo! User Nov 13, 2006 20:10 Flag
you spent 6 million on pennant, so if he aint 1st choice you should worry about your transfer policy, having said that, I agree with what you say about rafa beneathus
A Yahoo! User Nov 13, 2006 18:49 Flag
Were is our team spirit. I think we should judge rafa at end of season as he turned them round the last 2 we need to win 6 or 7 prem games in a row to get back into it. We have the players but we dont have the balance. The scum at the top will drop points. Chelsea may not drop points but we should be moving onwards on hoping for 3rd or 4th we probaly played all of our hardest away games so if you look at our fixtures theres not 1 were we cant win but we must inprove.
There was no link up play at all between midfield and the forwards to negative for my liking get garcia and pennant from the start they might be frustraiting at times but they look to go forward everytime.
Zenden poor, Our worst player, Get shot in jan please rafa
- 1 Reply to A Yahoo! User
no-one seems to be talking about our defence!! Hyypia seems to blow hot and cold - good some weeks shite the next. Maybe we need to rotate him (sorry "rest himn") from the big games where he looks slow and our whole defence very very Leaky!!
Until we get this right we can't build the confidence to attack or break away and nick a goal - which offsides permitting we did twice yesterday.
A Yahoo! User Nov 13, 2006 12:36 Flag
Good post mate, agree with pretty much everything you've said.
I didn't realise we had such a bad record against the big boys, things have never so bad even under Souness, Evans or Houllier, with regard to the top teams that is.
Again, our title callenge is over so by November, let's hope the new lads bed in sooner rather than later and we can challenge for some of the cups.
Rafa seems to have gone backwards this season after our good away form last season, what's he doing ?
For the love of God let's hope they turn the corner soon.
- 1 Reply to A Yahoo! User
meijermagic, as a Liverpool fan we all feel very disappointed with the team's performance this season, especially so much was expected from the players and they were showing so much promises.
But to start doubting Rafa is a bit too far. When new players come in there is a gelling period, some take longer. Look at ManU when they started rebuilding their team 3 years ago, they won bugger all for 2 seasons.
I am prepared to wait for as long as it takes for Rafa to transform our team into a title winning team. Of course it hurts to know that we lost 10 in a row to ManU, Arsenal and Chelsea, but that it part of the pain we have to go through in the rebuilding process. I have faith in Rafa and Gerrard, they will lead us round the corner. YNWA


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Chamber's vision for 2015
By PATTI KIDWELL Hyde Park Chamber of Commerce President The year 2015 has many exciting things in store for the city of Chicago as well as Hyde Park. The economy is showing some signs of life, the stock markets are on the rise and I hear and see more optimism from our local business owners.(…)


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I love the way this feels on my face. The only question I have still is is it making me break out. I started getting little tiny bumps on my face a few days after using. I stopped for a couple of day and the bumps went away. Jusy started using it again so we will see if it was just a coincidence or if it was the product.3
This is a perfectly fine moisturizer. I like it, and am very happy with the generous sample size. I am quite content to use this until the sample is finished. However, I will not be purchasing this at this price point. For $94, I don't want a perfectly fine moisturizer, I want the most wonderful moisturizer I've ever used. This doesn't seem any different from any other moisturizer.4
I do plan to purchase this....but it's still in it's trial stage at the moment. Using this one for just a week isn't enough, so i'm definitely going to use it for one more week before deciding if i want to purchase this product.
I love the texture and the smell is okay. But my face feels a bit happier with it being used! So one more week to see if the results are what i've been looking for. Good find girls!