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Kostenlose Homepage erstellen! - nPage.de
World , Deutsch , Computer , Internet , Webdesign und -entwicklung , Webhosting , Kostenlos , Baukasten
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Changed: 2012-04-06T14:47:06+02:00
Type: ROLE
Name: Hostmaster Of The Day
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Address: Lina-Ammon-Str. 3
PostalCode: D-90471
City: ***rnberg
CountryCode: DE
Phone: +49-9005105298
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text:
I am pretty laid back but always up for an adventure if one comes up. I enjoy traveling; I have been to Spain/Portugal, Holland, Ireland, UK, and a few random tropical islands. I guess during the week I do the normal stuff like go to the gym or bike around. I hate writing these....
Join OkCupid
Find better matches with our advanced
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—% Match
—% Enemy
32 • Amarillo, TX • Man
I'm looking for
- Women
- Ages 23-35
- Near me
- Who are single
- For new friends, long-term dating, short-term dating
My details
- Last online
- Nov 21
- Orientation
- Straight
- Ethnicity
- White
- Status
- Single
- Height
- 6' 0" (1.83m)
- Body Type
- Fit
- Smoking
- No
- Drinking
- Socially
- Drugs
- Never
- Religion
- Christianity
- Education
- University
- Offspring
- Might want kids
- Speaks
- English
My self-summary
Write a little about yourself. Just a paragraph will do.
What I'm doing with my life
Don't overthink this one; tell us what you're doing day-to-day.
I just moved back from Dallas for a new Job. I lived there for about 5 years and also lived in Chicago for a couple of years. I work in the logistics business, keeps me busy!
I'm really good at
Go on, brag a little (or a lot). We won't judge.
Trying to be funny, not getting fired, staying up way to late and going to work late, snowboarding, wake boarding, jet skis, watching Texas Tech football, Rangers, Mavs, Cowboys, bluffing on poker, Calling friends at 3:00 on Friday and setting up a weekend road trip! I'll think of more later.. Please ignore my use of many commas...
Favorite books, movies, shows, music, and food
Help your potential matches find common interests.
Something crime/law related (books). Movies- I love the national lampoons vacation movies, Face Off, Black Hawk Down, Tommy Boy, Knocked up, Top Gun, Spanglish, Superbad, Heat, Goodfellas, It's kind of a funny story, horrible bosses... Shows- Dexter, Modern family, Homeland, Big bang theory, Mad men most of the stuff on the History channel... Music - Rock, Alt Nation on SirusXM channel 36 is great, Country- SirusXM 59. love the old rat pack, some rap, everything really
The six things I could never do without
Think outside the box. Sometimes the little things can say a lot.
1. My parents/family/friends
2. My truck?
3. My stupid iPhone now. Lost it in Europe for 3 weeks and went crazy.
4. Vacation / Holiday
5. Ebay and Amazon.. Spend way too much money
6. Planes.. need them to get around..
**Probably not in that order**
2. My truck?
3. My stupid iPhone now. Lost it in Europe for 3 weeks and went crazy.
4. Vacation / Holiday
5. Ebay and Amazon.. Spend way too much money
6. Planes.. need them to get around..
**Probably not in that order**
I spend a lot of time thinking about
Global warming, lunch, or your next vacation… it's all fair game.
Why we all have to work ridiculous jobs and waste life but I suppose this is the real world.. Don't get me wrong I (like) my job but one day I really want to sail around from port to port and see the world..
On a typical Friday night I am
Netflix and takeout, or getting your party on — how do you let loose?
Usually trying to relax with some friends or traveling somewhere. I am always interested in taking on new hobbies if you have one! I did the Warrior dash and the jailbreak run; they were interesting.
The most private thing I'm willing to admit
I'm an empty essay… fill me out!
On here??
You should message me if
Offer a few tips to help matches win you over.
You want to make a new friend! Just send me a message!
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subset: commoncrawl


text:
Literature: A Murder Is Announced
- 'In an English village, you turn over a stone and have no idea what will crawl out.'
This mystery provides examples of:
- Action Girl: In their backstories, at least. Hinch was an Air Raid Precautions warden during the war, while Emma a.k.a. Julia was in the French resistance.
- Adaptational Heroism: Patrick is generally more likeable in the Joan Hickson adaptation, shown to be worthier of Emma.
- Adaptational Name Change: Mitzi is renamed Hannah in the Joan Hickson adaptation.
- Adaptational Villainy: Edmund Swettenham in the 2005 adaptation is an altogether more bitter and unpleasant boy than in the book, and resentful of his mother's relationship.
- The Bait: Miss Marple talks Mitzi into taking this role; as a result the murderer is caught as she attempts to drown Mitzi in the sink.
- British Stuffiness: Natch.Mrs Easterbrook: Archie... there's going to be a murder.
Col Easterbrook: What time?
Mrs Easterbrook: Six thirty this evening.
Col Easterbrook: Short notice.
- Break the Cutie: The murderer's sympathetic backstory.
- Butch Lesbian: Though never explicitly stated to be one, Miss Hinchcliffe very much fits this trope.
- Dead Person Impersonation: "Letitia" is really the other sister, Charlotte. The real Letitia is long dead. Reasons had to do with inheriting a large sum of money and thinking the fraud couldn't possibly hurt anyone.
- Deadly Deferred Conversation: Miss Murgatroyd realizes "she wasn't there". Miss Hinchcliffe tells her they'll talk about it later—and Murgatroyd is murdered while Hinchcliffe is fetching a dog from the station.
- Did Not Get the Girl: Patrick. Averted in the Joan Hickson adaptation.
- The Ditz: Miss Murgatroyd and Dora Bunner. Mrs Easterbrook plays up to the trope, but is quickly revealed as a shrewd gold-digger using it as a facade.
- Does Not Like Men: Miss Hinchcliffe is convinced from the start that the murderer is a man, "because we all know what dirty pigs men are." She's wrong.
- Funny Foreigner: In what now reads as rather cringeworthy Values Dissonance, Patrick and Julia treat Mitzi, the high-strung Eastern European refugee cook, like one.
- Gold Digger: Inspector Craddock accuses Edmund of being one, but both are playing parts to try to trap the murderer. Julia accuses Patrick of being one also.
- Gossipy Hens: Letitia's neighbours react to the murder advertisement exactly as planned, by showing up at her place at the appointed time and doing a very bad job of hiding their anticipation.
- Hide Your Lesbians: There's a strong subtext between Odd Couple housemates Misses Hinchcliffe and Murgatroyd, but the exact nature of their relationship is not specified. Hinch's vengeful rage at the murderer of Murgatroyd is telling.
- His Name Is...: Poor Miss Murgatroyd. Also a case of Can Not Spit It Out, since she had plenty of time to finish the sentence.
- Kill the Ones You Love: Even though the killer loved one of the victims, she was killed out of fear that she was inadvertently revealing too much about the first murder.
- Lampshade Hanging: The 1985 BBC television adaptation introduces several examples, as follows:
- Last Minute Hookup: Philippa "Pip" and Edmund.
- Last Name Basis: "Hinch" and Murgatroyd.
- Lights Off, Somebody Dies: The one you would least expect.
- Little Old Lady Investigates: Miss Marple is of course the Trope Codifier, but she's also aware about it: "A policeman asking questions is open to the grave of suspicion, but an old lady asking questions is just an old lady asking questions."
- Luke, I Am Your Father: Julia is Philippa's sister.
- Mystery Magnet: When Miss Marple goes to Chipping Cleghorn with the excuse of visiting the vicar's wife, "Bunch" Harmon (who is a distant niece of hers), the vicar remarks, "A man dies in highly suspicious circumstances in Chipping Cleghorn, and suddenly Aunt Jane is coming to stay." Bunch isn't about to argue with him.
- Never One Murder
- Nobody Over 50 Is Gay: Miss Hinchliffe and Miss Murgatroyd, according to a discussion on the Golden Age Mysteries forum.
- Noodle Incident: The police discover something unpleasant about Mrs Easterbrook's past, but as it isn't relevant to the murder they ignore it and we never hear any more details.
- Pet's Homage Name: Rev. Julian Harmon, an Oxford alumnus, named his cat after an Assyrian king.
- Red Herring: The death of Philippa Haymes' husband in a car accident turns out to be completely incidental, and has nothing to do with the main murdet plot.
- The Reveal: A whole chain reaction of them at the Summation Gathering.
- Sarcastic Devotee: Miss Hinchcliffe is rather gruff in her dealings with Miss Murgatroyd, but shows deep affection when pressed.
- Separated at Birth: Philippa and Julia are really long-lost siblings Pip and Emma.
- Screaming Woman: Mitzi, frequently, on very little provocation. Luckily, she's also a brilliant cook.
- Summation Gathering: Subverted with Inspector Craddock's speech; later played straight by Miss Marple.
- Sympathetic Murderer: Downplayed. The murderer is shown as a weak and kindly person who was driven to kill as a result of the consequences of her unwise actions, and who was tired of living a horrible life - but, as Miss Marple points out, others had had it worse and had got back on their feet without having to resort to murder.
- Woobie, Destroyer of Worlds: Charlotte Blacklock
- Yank the Dog's Chain: Letitia's death, preventing Charlotte from enjoying the inheritance that would have, in her eyes, made up for the years of affliction she suffered.
- Younger and Hipper: Hinch and Murgatroyd in the 2005 adaptation.


text:
November 30, 2015
WASHINGTON (AP) - Senate Democrats are deeply divided over whether cuts to popular benefit programs like Medicare and Medicaid should be part of a plan to address the nation's financial problems, raising a big obstacle to an agreement to avoid the fiscal cliff, even if Republicans agree to raise taxes.
Much of the focus during budget negotiations has centered on Republicans in Congress agreeing to higher taxes, though not by raising tax rates. President Barack Obama has said repeatedly that any plan to reduce government borrowing must balance spending cuts with tax increases on the wealthy
But even if GOP lawmakers agree to raise taxes, there is no guarantee Democrats can come up with enough votes in the Senate to cut benefit programs - as Republicans are demanding.
Click Here to access the online Public Inspection File
Viewers with disabilities can get assistance accessing this station's FCC Public Inspection File by contacting the station with the information listed below. Questions or concerns relating to the accessibility of the FCC's online public file system should be directed to the FCC at 888-225-5322, 888-835-5322 (TTY), or email@example.com.


text:
Participate in This Event or find another event
Saturday, October 24, 2015
9 a.m.
Rochester Municipal Park
Pine and Sixth St, Rochester, MI Map it
Already a participant?
Log in here
67 teams and 650 participants have raised $76,883.72
Total above may not reflect all participants, teams, and donations
Making Strides Against Breast Cancer is a celebration of survivorship an occasion to express hope and our shared determination to make this breast cancer's last century.
For more information, please contact firstname.lastname@example.com or call 248-663-3401!
Click on the buttons below for answers to FAQ's!!
You can help finish the fight against breast cancer by raising funds for and walking with American Cancer Society Making Strides of Oakland County. Join more than one million people each year who are helping to end breast cancer.
Making Strides Against Breast Cancer walks are the largest network of breast cancer awareness events in the nation, uniting nearly 300 communities with a shared determination to finish the fight. By signing up, fundraising, and participating in one of our noncompetitive, three- to five-mile walks, you will help us be there for everyone in every community touched by breast cancer. You will help those who are currently dealing with a breast cancer diagnosis, those who may face a diagnosis in the future, and those who may avoid a diagnosis altogether thanks to education and prevention.
Every Making Strides event is an incredible and inspiring opportunity to unite as a community to honor and celebrate breast cancer survivors, raise awareness about the disease, and raise money to help the American Cancer Society save lives from breast cancer by funding groundbreaking breast cancer research, providing free comprehensive information and support, and helping people take steps to reduce their risk of the disease or find it early when it's most treatable.
If your company is interested in sponsorship opporunitites for this event, you can view the 2015 Sponsorship Packet here: https://www.dropbox.com/s/5ojv1ay7uoqtqr9/MSABCSponsorshipOakland.pdf?dl=0
Why your participation matters
Volunteer at our event
View our walk details
Event sponsored by:
Top Participants:
Top Teams:
Top Companies:
Contact Nicole Saco:


text:
Summer Camps
The 2016 summer camp information for 2016 will be available by March, 2016.
Below is a description of last summer's camp offerings.
2015 Preschool Summer Camp Descriptions
All preschool sessions are open to current and incoming preschool students. It is strongly encouraged that kindergartners going into first-grade attend the Elementary Camps. Please use the Registration Form to enroll your child in Summer Camp.
All-Day & Half-Day Preschool, Sessions I - III
The following sessions have an all-day and a half-day option. Both options include lunch. The fee for a two-week All-day camp session is $400 and the fee for the Half-day camp session is $250. The fee is due on the first day of camp.
All-day times are 8:00 am – 5:30 pm.
Half-day times are 8:00 am – 12:30 pm.
Session I: June 1 – 12
Theme: Intro to Montessori (Half-Day)
BMS is offering a camp geared completely toward brand new preschool students. It will be taught by two of our preschool lead teachers in a classroom environment set up specifically to meet the needs of brand new students, with the aim of development of a sense of order, concentration, coordination and independence. This camp will run as a half-day only, with an option to pay the all-day tuition fee and have your child spend the afternoon in the Magnolia classroom.
Teachers: April Waxler & Eve Cusack
Theme: Food & Nutrition (Half-Day or All-Day)
Healthy snacks, simple meal preparation, nutrition and food exploration will be the focus of this camp.
Teacher: Robyn Miller
Theme: Space Camp (All-Day)
Come join us as we blast off into outer space camp! Children will play fun games and sing fun songs about the planets and our universe. We will taste interesting space snacks, make cool art, and have a lot of hands on work experience about the solar system and beyond.
Teacher: Megan Carpenter
Session II: June 15 – June 26
We are only offering one All-Day preschool camp this session.
Theme: Music Camp (All-Day or Half-Day)
Children will participate daily in song plays, musical exploration activities, creative movement, composition, playing instruments, and of course, singing. This camp will be taught by our own BMS elementary music teacher, Amanda Russo, who is also a doctoral candidate in voice performance at IU's Jacobs School of Music and Preschool Lead teacher, Eve Cusack.
Teachers: Amanda Russo & Eve Cusack
Session III: June 29 – July 10
Theme: Art Camp (Half-Day)
In this two week session students will be presented with information about famous artists and several different types of art mediums and styles. Time will be spent learning the elements of design and using them creatively to produce unique masterpieces. Each child will be given the opportunity to compile their own art and place it on display for the art show that will happen toward the end of camp.
Teacher: Molly Pepper
Theme: STEAM Camp (All-Day)
STEAM stands for science, technology, engineering, arts and mathematics. In this camp we will explore these areas in harmony with the Montessori approach of creativity, exploration, classification, and observation. Children will have the opportunity to focus on observational science, experimental science, electricity, design, and math (using a combination of traditional Montessori materials along with weights, measurement, and graphing of information). There will be work available to interest and challenge boys and girls from ages three to six.
Teachers: April Waxler
2015 Elementary Summer Camp Descriptions
All Elementary Summer Camp sessions are open to current and incoming elementary students. It is strongly encouraged that kindergartners going into first-grade attend the Elementary Camps. Please use the Registration Form to enroll your child in Summer Camp.
The fee for a two-week Elementary camp session is $290, due on the first day of camp.
As support for working families with elementary school aged campers, we also provide an aftercare program from 3:15pm to 5:30pm. The fee for a two-week After-care camp session is $70. Your child must be enrolled in a camp during the same session.
Download the 2015 Summer Programs schedule and application form now.
Elementary Session I: June 1st - 12th
Topic: Camp Challenge
Age Group: 6-12 year olds
Time: 8:30 AM-3:30 PM, M-F
Teachers: Emily Miller & David Weigand
In an action packed camp, students will discover their personal best in both group and individual challenges, field games, mind games, logic puzzles and more. Camp Challenge features team building and personal challenges. This camp features something for just about everyone -- a great time to get to know your personal abilities as well as learning how to work as a team.
Elementary Session II: June 15th – June 26th
Topic: Circus Stars Camp
Age Group: 6-12 year olds
Time: 8:30 AM-3:30 PM, M-F
Teacher: Ann Dorwin & Christy True
Long-time circus education specialist is offering a two-week circus camp for students entering first through graduated sixth grade. This camp will introduce students to juggling, plate-spinning, devilstick and diabolo manipulation, object balancing, stilt-walking, clowning and more. Alongside the physical circus skills will be complementary educational works that will allow students to explore a diverse range of subjects such as history, society and culture, language, physics, and economy, all viewed through the lens of the circus. The camp will culminate in a spectacular, full-length circus show, performed by the students for their families and peers.
Elementary Session III: June 29th – July 10th
Topic: Construction Camp
Age Group: 6-12 year olds
Time: 8:30 AM-3:30 PM, M-F
Teacher: Jacob Bailey & Gina Keifer
This is the much requested camp that we have done for years now. Children do a wide variety of building activities. There are many building sets that they use throughout the camp and then there are some one-time make and take projects. There are projects available for gross motor and fine motor development. There will also be an art station always set up. Popular traditions in the camp include, the catapult contest, car racing, cup stacking, tower building (K'nexs), etc. There will be a large amount of legos for use. We will also build some larger scale projects outside. This camp is very child-centered meaning that children can choose what to work on and for how long to work on it. There will not be lengthy lessons about building strategies. The children learn building strategies by practicing.


text:
Severe fires around Ft. Collins are causing the ride organizers to evaluate an alternate finish. They will announce the change on Wednesday. Two options mentioned include finish in Boulder or end the ride in Estes Park.
Ride the Rockies final day ride would utilize resources required for dealing with the fire.


text:
Jolt Cola
Jolt Energy
BevNET Review
Last Updated: 5/31/2001 6:09 PM
Nothing really needs to be said about this beverage. All the sugar and twice the caffeine. It doesn't really taste all that special, but it is a classic beverage. We never really could understand why they put all that caffeine in it. A semi-superior cola.
Product Type
Carbonated Soft Drink: Regular
Nutritional Info
Nutritional information is not available for this product.
Ingredients are not available for this product.


text:
The lack of progress on the debt ceiling negotiations has raised serious concerns that an agreement will not be reached before the August 2nd deadline. How have the negotiations gotten so derailed?
In a recent interview on Radio Boston, Professor Robert Bordone, director of the Harvard Negotiation and Mediation Clinical Program, suggested that one of the biggest obstacles in these negotiations is that they are not being conducted in a closed door environment, where trust could be built and maintained. By speaking out in the media so often, both parties have heightened tensions and made compromise more difficult. "The more they go to the public and embarrass each other, the more they raise the stakes for each of them in the next political election cycle," says Bordone.
Similarly, Professor Dan Shapiro, author of Beyond Reason and faculty affiliate of the Program on Negotiation, noted recently that the negotiation has been framed as a "war," in which only one side can win. This framing has made the negotiation more difficult. "There's very little listening, very little learning — mutual learning — very little cross-group communication, very little creative thinking."
As the negotiations head into the final hours, perhaps tactics will shift. "Often times a looming deadline does help parties reach an agreement," Bordone noted in an interview with CNN. "But whether or not there is a good outcome, this process could have been less painful."
Related Posts
- Negotiation Master Class Fall 2015 Program Guide
- Sally Soprano: Role-Play Simulation
- Nantucket's Never-Ending Negotiations: Harvard Negotiation and Mediation Clinical Program (HNMCP) Students Shape How Town and Unions Work Together
- "Confronting Evil: Interdisciplinary Perspectives" Conference to be held at Harvard
- Roger D. Fisher, 1922-2012
Choosing to Help


text:
Are you Se-Jung Lee?Claim your profile
Publications (21)63.66 Total impact
Article: Interleukin-5 enhances the migration and invasion of bladder cancer cells via ERK1/2-mediated MMP-9/NF-κB/AP-1 pathway: Involvement of the p21WAF1 expression[Show abstract] [Hide abstract]
ABSTRACT: Inflammatory cytokines may be a critical component of epithelial cancer progression. We examined the role of interleukin (IL)-5 in the migration of bladder cancer cells. The expression of IL-5 and its receptor IL-5Rα was enhanced in patients with muscle invasive bladder cancers (MIBC), and then it was detected in bladder cancer cell lines 5637 and T-24. IL-5 increased migration and MMP-9 expression via activation of transcription factors NF-κB and AP-1, and induced activation of ERK1/2 and Jak-Stat signaling in both cells. Treatment with ERK1/2 inhibitor U0126 significantly inhibited induction of migration, MMP-9 expression, and activation of NF-κB and AP-1 in IL-5-treated cells. However, none of the Jak inhibitors affected the IL-5-induced migration of bladder cancer cells. Moreover, gene knockdown for IL-5Rα, using siRNA transfection, suppressed migration, ERK1/2 activation, MMP-9 expression, as well as the binding activation of NF-κB and AP-1 in IL-5-treated bladder cancer cells. Similar results were observed in βc siRNA (si-βc) transfected cells. Unexpectedly, IL-5 treatment resulted in significant induction of p21WAF1 in both cell lines. The p21WAF1-specific small interfering RNA inhibited IL-5-induced cell migration, ERK activity, MMP-9 expression, and activation of NF-κB and AP-1 in bladder cancer cells. The effects of IL-5-induced cell responses were confirmed by transfection of IL-5 gene, which demonstrated that p21WAF1 participates in the induction of cell migration, leading to an increase in ERK1/2-mediated MMP-9 expression through activation of NF-κB and AP-1 in IL-5-treated bladder cancer cells. These unexpected results provide a theoretical basis for the therapeutic targeting of IL-5 in bladder cancer.Cellular Signalling 06/2013; 25(10). DOI:10.1016/j.cellsig.2013.06.004 · 4.32 Impact Factor
Article: Suppressive effects of an ethanol extract of Gleditsia sinensis thorns on human SNU-5 gastric cancer cells[Show abstract] [Hide abstract]
ABSTRACT: The thorns of Gleditsia sinensis are a traditional Oriental medicine used for the treatment of swelling, suppuration, carbuncle and skin diseases. In the present study, we identified a novel molecular mechanism by which an ethanol extract of Gleditsia sinensis thorns (EEGS) inhibits the growth of the SNU-5 human gastric cancer cell line. EEGS treatment inhibited cell growth and was associated with G1 phase cell cycle arrest at a concentration of 400 µg/ml (IC50) in SNU-5 cells. Treatment with EEGS also stimulated p21WAF1 expression, which significantly decreased the expression of cyclins and cyclin-dependent kinases (CDKs). Further study suggested that p38 MAP kinase pathways may be involved in the inhibition of cell proliferation through p21WAF1‑dependent G1 phase cell cycle arrest in EEGS-treated cells. In addition, NF-κB and AP-1 transcription factor binding sites were identified as the cis-elements for tumor necrosis factor-α (TNF-α)-induced matrix metalloproteinase-9 (MMP-9) expression in SNU-5 cells, as determined by gel-shift assay. Treatment of cells with EEGS suppressed MMP-9 expression induced by TNF-α via a decrease in the binding activity of both NF-κB and AP-1 motifs. These data demonstrate that EEGS-mediated inhibition of cell growth appears to involve the activation of p38 MAP kinase, subsequently leading to the induction of p21WAF1 and the downregulation of cyclin D1/CDK4 and cyclin E/CDK2 complexes. Moreover, EEGS strongly inhibited TNF-α-induced MMP-9 expression by impeding the DNA binding activity of NF-κB and AP-1. Overall, these results provide a potential mechanism for EEGS in the treatment of gastric cancer.Oncology Reports 02/2013; 29(4). DOI:10.3892/or.2013.2271 · 2.30 Impact Factor
Article: Interleukin-20 Promotes Migration of Bladder Cancer Cells through Extracellular Signal-regulated Kinase (ERK)-mediated MMP-9 Protein Expression Leading to Nuclear Factor (NF- B) Activation by Inducing the Up-regulation of p21WAF1 Protein Expression[Show abstract] [Hide abstract]
ABSTRACT: The role of inflammatory cytokine interleukin-20 (IL-20) has not yet been studied in cancer biology. Here, we demonstrated up-regulation of both IL-20 and IL-20R1 in muscle invasive bladder cancer (MIBC) patients. The expressions of IL-20 and IL-20R1 were observed in bladder cancer 5637 and T-24 cells. We found that IL-20 significantly increased the expression of matrix metalloproteinase (MMP)-9 via binding activity of NF-κB and AP-1 in bladder cancer cells and stimulated the activation of ERK1/2, JNK, p38MAPK, and Jak-Stat signaling. Among the pathways examined, only ERK1/2 inhibitor U0126 significantly inhibited IL-20-induced migration and invasion. Moreover, siRNA knockdown of IL-20R1 suppressed migration, invasion, ERK1/2 activation, and NF-κB-mediated MMP-9 expression induced by IL-20. Unexpectedly, cell cycle inhibitor p21WAF1 was induced by IL-20 treatment without altering cell cycle progression. Blockade of p21WAF1 function by siRNA reversed migration, invasion, activation of ERK signaling, MMP-9 expression, and activation of NF-κB in IL-20-treated cells. In addition, IL-20 induced the activation of IKK, the degradation and phosphorylation of IκBa, and NF-κB p65 nuclear translocation, which was regulated by ERK1/2. IL-20 stimulated the recruitment of p65 to the MMP-9 promoter region. Finally, the IL-20-induced migration and invasion of cells was confirmed by IL-20 gene transfection and by addition of anti-IL-20 antibody. This is the first report that p21WAF1 is involved in ERK1/2-mediated MMP-9 expression via increased binding activity of NF-κB, which resulted in the induction of migration in IL-20/IL-20R1 dyad-induced bladder cancer cells. These unexpected results might provide a critical new target for the treatment of bladder cancer.Journal of Biological Chemistry 12/2012; 288(8). DOI:10.1074/jbc.M112.410233 · 4.57 Impact Factor
Article: Identification of Pro-Inflammatory Cytokines Associated with Muscle Invasive Bladder Cancer; The Roles of IL-5, IL-20, and IL-28A[Show abstract] [Hide abstract]
ABSTRACT: We used gene expression profiling to identify inflammatory cytokines that correlate with bladder cancer development. Gene expression profiles of the tissue samples were investigated using cDNA microarrays that contained 103 non-muscle invasive bladder cancers (NMIBC), 62 muscle invasive bladder cancers (MIBC), 58 samples of histologically normal-looking surrounding tissues, and 10 normal, healthy subjects who served as the control cohort for comparison. We grouped the data-sets according to biological characterizations and focused on immune response genes with at least 2-fold differential expression in MIBC vs. controls. The experimental data-set identified 36 immune-related genes that were significantly altered in MIBC samples. In addition, 10 genes were up-regulated and 26 genes were down-regulated in MIBC samples compared with the normal tissues. Among the 10 up-regulated molecules examined, the capacity for both wound-healing migration and invasion was enhanced in response to IL-5, IL-20, and IL-28A in bladder cancer cell lines (253J and EJ cells), compared with untreated cells. The expression levels of IL-5, IL-20, and IL-28A were increased in patients with MIBC. All 3 cytokines and their receptors were produced in bladder cancer cell lines, as determined by real-time PCR, immunoblot analysis and confocal immunofluorescence. Up-regulation of MMP-2 and MMP-9 was found after IL-5, IL-20, and IL-28A stimulation in both cell types. Moreover, an EMSA assay showed that treatment with IL-5, IL-20, and IL-28A induced activation of the transcription factors NF-κB and AP-1 that regulate the MMP-9 promoter. Finally, activation of MAPK and Jak-Stat signaling was observed after the addition of IL-5, IL-20, and IL-28A to bladder cancer cells. This study suggests the presence of specific inflammatory cytokine (IL-5, IL-20, and IL-28A)-mediated association in bladder cancer development. All 3 cytokines may be important new molecular targets for the modulation of migration and invasion in bladder cancer.PLoS ONE 09/2012; 7(9):e40267. DOI:10.1371/journal.pone.0040267 · 3.23 Impact Factor
Article: Role of the p38 MAPK signaling pathway in mediating interleukin-28A-induced migration of UMUC-3 cells[Show abstract] [Hide abstract]
ABSTRACT: Although interleukin-28A (IL-28A) is believed to have an antiviral effect, its role in tumor migration requires further examination. The present study was intended to verify the effect of IL-28A on the migration of UMUC-3 bladder cancer cells. IL-28A and its receptor IL-28AR1 mRNA were detected in UMUC-3 cells. Although exogenous IL-28A showed no effect on cell proliferation, a wound-healing migration assay showed that the migration of UMUC-3 cells was induced by IL-28A. Furthermore, treatment of the cells with IL-28A significantly promoted MMP-9 expression via binding activities of NF-κB and AP-1. IL-28A also induced the activation of p38 MAPK and Jak2-Stat2 signaling. Using the p38 MAPK inhibitor SB203580 and the dominant-negative plasmid DN-p38, we found evidence that the inhibition of p38 MAPK signaling suppressed the effects of IL-28A including wound-healing migration and MMP-9 expression by activation of NF-κB and AP-1 binding in UMUC-3 cells. However, Jak-2 inhibition by AG490 did not affect IL-28A-induced migration of UMUC-3 cells. Collectively, we suggest for the first time that the p38 MAPK pathway mediates IL-28A-induced cell migration through MMP-9 expression by activating NF-κB and AP-1 binding motifs.International Journal of Molecular Medicine 07/2012; 30(4). DOI:10.3892/ijmm.2012.1064 · 2.09 Impact Factor
Article: Interleukin-28A triggers wound healing migration of bladder cancer cells via NF-κB-mediated MMP-9 expression inducing the MAPK pathway[Show abstract] [Hide abstract]
ABSTRACT: Interleukin (IL)-28A, also called IFN-λ2, is a member of the classIIcytokine family and has demonstrated anti-proliferative and anti-viral signals. The present study demonstrated migration inducement of IL-28A-treated bladder cancer cells - a novel function. RNA microarray analysis showed an enhanced expression of IL-28A and its receptor IL-28AR1 in muscle invasive urothelial carcinoma in a human bladder. Strong expression of IL-28A and IL-28AR1 was detected in bladder cancer tissues and cell lines (5637, T-24, and HT1376 cells), as determined by real-time PCR and immunoblot analysis. IL-28A treatment induced migration of bladder cancer cells, independent of the cell growth. IL-28AR1-specific small interfering RNA (si-IL-28AR1) inhibited the induction of migration in IL-28A-treated cells. IL-28A treatment stimulated the expression of matrix metalloproteinases-9 (MMP-9) via activation of transcription factor NF-κB. Gene knockdown for MMP-9 and the p65 subunit of NF-κB, using siRNA transfection, suppressed wound healing migration in IL-28A-treated bladder cancer cells. Also, treatment with IL-28A induced activation of mitogen-activated protein kinase (MAPK) in bladder cancer cells. MAPK function blockage by a MAPK-specific inhibitor showed that MAPK phosphorylation is required for IL-28A-induced MMP-9 expression through activation of NF-κB. The transient transfection of bladder cancer cells with ERK1/2 knock down (si-ERK1/2) and dominant negative p38 (DNp38) suppressed IL-28A-induced migration. IL-28A-induced induction of MMP-9 expression, MAPK activation, and DNA binding activity of NF-κB was abolished in the presence of IL-28A neutralizing antibody or by transfection of si-IL-28AR1. These results show that IL-28A/IL-28AR1 dyad-induced wound healing migration requires NF-κB-mediated MMP-9 expression by MAPK activation.Cellular Signalling 04/2012; 24(9):1734-42. DOI:10.1016/j.cellsig.2012.04.013 · 4.32 Impact Factor
Article: Gleditsia sinensis Thorn Extract Inhibits Proliferation and TNF-α-Induced MMP-9 Expression in Vascular Smooth Muscle Cells[Show abstract] [Hide abstract]
ABSTRACT: The thorns of Gleditsia sinensis, which are extensively used as a medicinal herb in Asian countries, have been reported to exert various pharmacological effects. However, the anti-atherogenic effect of Gleditsia sinensis thorns has never been investigated. In the present study, we investigated the role and effect of the ethanol extract of Gleditsia sinensis thorns (EEGS) on cultured vascular smooth muscle cells (VSMC). Treatment of VSMC with EEGS led to a significant decrease in cell growth by arresting cells in the G2/M-phase of the cell cycle, which was associated with up-regulated p21WAF1 levels and suppression of G2/M cell cycle regulators, cyclinB1, Cdc2 and Cdc25c. In addition, EEGS treatment led to the induction of extracellular signal-regulated kinase1/2 (ERK1/2), p38 MAPK, and JNK (c-Jun N-terminal kinases) activation. EEGS-induced p21WAF1 expression was blocked by treatment with the p38 MAPK-specific inhibitor SB203580. SB203580 also markedly recovered the inhibition of cell growth and decrease in cell cycle proteins in EEGS-treated VSMC. Moreover, EEGS inhibited matrix metalloproteinase-9 (MMP-9) expression induced by tumor necrosis factor-α (TNF-α) in VSMC. Finally, an electrophoresis mobility shift assay demonstrated that EEGS suppressed expression of transcription factor, nuclear factor kappaB (NF-κB) and activator protein-1 (AP-1), which are essential cis-elements for the MMP-9 promoter in TNF-α-treated VSMC. These results demonstrate that EEGS exerts a potent inhibitory effect on cell proliferation and MMP-9 expression in VSMC. These unexpected novel findings represent theoretical data for the preventive and therapeutic use of EEGS for the treatment of atherosclerosis disease.The American Journal of Chinese Medicine 01/2012; 40(2):373-86. DOI:10.1142/S0192415X12500292 · 2.76 Impact Factor
Article: Inhibitory effect of esculetin on migration, invasion and matrix metalloproteinase-9 expression in TNF-α-induced vascular smooth muscle cells[Show abstract] [Hide abstract]
ABSTRACT: Esculetin, a potent non-competitive inhibitor of lipoxygenase, has been shown to inhibit vascular smooth muscle cell (VSMC) proliferation. However, the effect of esculetin on the matrix metalloproteinase-9 (MMP-9) regulation responsible for cell migration and invasion has not been previously investigated. The results of the present study showed the esculetin (12.5-25 µg/ml) induced the inhibition of migration and invasion in tumor necrosis factor-α (TNF-α)-treated VSMC, as demonstrated by a matrigel invasion assay and wound healing analysis. However, esculetin did not affect cell viability in TNF-α-treated VSMC under 0-25 µg/ml concentration conditions. In addition, both zymographic and immunoblot experiments showed that esculetin suppressed the TNF-α-induced expression of MMP-9 in VSMC in a dose-dependent manner. Furthermore, the treatment of cells with esculetin decreased the activity of the TNF-α-induced MMP-9 promoter, which was driven by a luciferase reporter. Finally, esculetin reduced the binding activities of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), which are cis-elements present in the promoter of the MMP-9 gene, in TNF-α-treated VSMC. Taken together, these results demonstrated that esculetin decreased the migration and invasion of cells by suppressing MMP-9 expression, which subsequently reduced the binding activities of NF-κB and AP-1 in TNF-α-treated VSMC. These novel findings provide basic information for effective therapeutic treatment with esculetin for atherosclerotic disease.Molecular Medicine Reports 03/2011; 4(2):337-41. DOI:10.3892/mmr.2011.420 · 1.55 Impact Factor
Article: Gleditsia sinensis thorn extract inhibits human colon cancer cells: The role of ERK1/2, G2/M-phase cell cycle arrest and p53 expression[Show abstract] [Hide abstract]
ABSTRACT: The thorns of Gleditsia sinensis are used as a medicinal herb in China and Korea. However, the mechanisms responsible for the antitumor effects of the water extract of Gleditsia sinensis thorns (WEGS) remain unknown. HCT116 cells treated with the WEGS at a dose of 800 μg/mL (IC₅₀) showed a significant decrease in cell growth and an increase in cell cycle arrest during the G2/M-phase. G2/M-phase arrest was correlated with increased p53 levels and down-regulation of the check-point proteins, cyclinB1, Cdc2 and Cdc25c. In addition, treatment with WEGS induced phosphorylation of extracellular signal-regulated kinase (ERK), p38 MAP kinase and JNK (c-Jun N-terminal kinases). Moreover, inhibition of ERK by treatment of cells with the ERK-specific inhibitor PD98059 blocked WEGS-mediated p53 expression. Similarly, blockage of ERK function in the WEGS-treated cells reversed cell-growth inhibition and decreased cell cycle proteins. Finally, in vivo WEGS treatment significantly inhibited the growth of HCT116 tumor cell xenografts in nude mice with no negative side effects, including loss of body weight. These results describe the molecular mechanisms whereby the WEGS might inhibit proliferation of colon cancer both in vitro and in vivo, suggesting that WEGS has potential as an anticancer agent for the treatment of malignancies.Phytotherapy Research 12/2010; 24(12):1870-6. DOI:10.1002/ptr.3214 · 2.66 Impact Factor
Article: Decursin inhibits growth of human bladder and colon cancer cells via apoptosis, G1-phase cell cycle arrest and extracellular signal-regulated kinase activation[Show abstract] [Hide abstract]
ABSTRACT: Decursin, a pyranocoumarin isolated from the Korean Angelica gigas root, has demonstrated anti-cancer properties. In the present study, we found that decursin inhibited cell viability in cultured human urinary bladder cancer 235J cells and colon cancer HCT116 cells. The inhibited proliferation was due to apoptotic induction, because both cells treated with decursin dose-dependently showed a sub-G1 phase accumulation and an increased cytoplasmic DNA-histone complex. Cell death caused by decursin was also associated with the down-regulation of anti-apoptotic factor Bcl-2 and the up-regulation of pro-apoptotic molecules cytochrome c, caspase 3 and Bax. Treatment of both types of cancer cells with decursin resulted in G1-phase cell cycle arrest, as revealed by FACS analyses. In addition, decursin increased protein levels of p21WAF1 with a decrease in cyclins and cyclin dependent kinases (CDKs). Furthermore, decursin induced the activation of extracellular signal-regulated kinases (ERK) in both cancer cell lines, with the notable exceptions of c-Jun N-terminal kinase (JNK) and p38 mitogen activated protein (MAP) kinase. Finally, pretreatment with ERK-specific inhibitor PD98059 reversed decursin-induced p21WAF1 expression and decursin-inhibited cell growth. Thus, these findings suggest that decursin has potential therapeutic efficacy for the treatment of bladder and colon cancer.International Journal of Molecular Medicine 04/2010; 25(4):635-41. DOI:10.3892/ijmm-00000386 · 2.09 Impact Factor
Article: Inhibitory effects of the ethanol extract of Gleditsia sinensis thorns on human colon cancer HCT116 cells in vitro and in vivo.[Show abstract] [Hide abstract]
ABSTRACT: The thorns of Gleditsia sinensis have traditionally been used in the treatment of several diseases, which includes their use as anti-tumor agents, but there has been no scientific evidence of this anti-tumor effect. However, the present study has identified a novel mechanism for the anti-tumor effect of Gleditsia sinensis thorns in the treatment of colon cancer. Treatment with the ethanol extract of Gleditsia sinensis thorns (EEGS) resulted in significant growth inhibition together with G2/M-phase cell cycle arrest at a dose of 600 microg/ml (IC50) in HCT116 cells. In addition, treatment with EEGS induced p27 expression and down-regulated expression of cyclins and cyclin-dependent kinases. Moreover, EEGS treatment induced phosphorylation of extracellular signal-regulated kinases (ERK), p38 MAP kinase and JNK (c-Jun N-terminal kinases). Among the pathways examined, only PD98059 (ERK-specific inhibitor) abolished EEGS-dependent p27 expression. Similarly, suppression of ERK function reversed EEGS-mediated cell proliferation inhibition and decreased cell cycle proteins. In addition, tumor necrosis factor-alpha (TNF-alpha)-induced matrix metalloproteinase-9 (MMP-9) expression was inhibited by EEGS treatment via decreased transcriptional activity of both activator protein-1 (AP-1) and nuclear factor-kappaB. Finally, EEGS treatment significantly reduced tumor sizes in HCT116 cell-xenografted tumor tissues, which was associated with the changed levels of ERK phosphorylation, p27 and MMP-9 expression. Overall, these results have identified a novel molecular mechanism for EEGS in the treatment of colon cancer and might provide a theoretical basis for the potential therapeutic use of EEGS in the treatment of malignancies.Oncology Reports 12/2009; 22(6):1505-12. · 2.30 Impact Factor
Article: Cordycepin causes p21WAF1-mediated G2/M cell-cycle arrest by regulating c-Jun N-terminal kinase activation in human bladder cancer cells[Show abstract] [Hide abstract]
ABSTRACT: Cordycepin (3'-deoxyadenosine), a bioactive compound of Cordyceps militaris, has many pharmacological activities. The present study reveals novel molecular mechanisms for the anti-tumor effects of cordycepin in two different bladder cancer cell lines, 5637 and T-24 cells. Cordycepin treatment, at a dose of 200 microM (IC(50)) during cell-cycle progression resulted in significant and dose-dependent growth inhibition, which was largely due to G2/M-phase arrest, and resulted in an up-regulation of p21WAF1 expression, independent of the p53 pathway. Moreover, treatment with cordycepin-induced phosphorylation of JNK (c-Jun N-terminal kinases). Blockade of JNK function using SP6001259 (JNK-specific inhibitor) and small interfering RNA (si-JNK1) rescued cordycepin-dependent p21WAF1 expression, inhibited cell growth, and decreased cell cycle proteins. These results suggest that cordycepin could be an effective treatment for bladder cancer.Archives of Biochemistry and Biophysics 10/2009; 490(2):103-9. DOI:10.1016/j.abb.2009.09.001 · 3.02 Impact Factor
Article: c-Jun N-terminal kinase 1 is required for cordycepin-mediated induction of G2/M cell-cycle arrest via p21WAF1 expression in human colon cancer cells[Show abstract] [Hide abstract]
ABSTRACT: Cordycepin (3'-deoxyadenosine) has many anti-cancer properties. However, neither its molecular mechanism nor its molecular targets are well understood. In the present study, we investigated novel molecular mechanisms for the anti-tumor effects of cordycepin in human colon cancer HCT116 cells. After treatment of cells with cordycepin, dose-dependent cell growth inhibition was observed at an IC(50) value of 200muM. Cordycepin treatment resulted in G2/M-phase cell-cycle arrest, which was associated with increased p21WAF1 levels and reduced amounts of cyclin B1, Cdc2, and Cdc25c in a p53-independent pathway. Moreover, cordycepin treatment induced activation of JNK (c-Jun N-terminal kinases). Pretreatment with SP600125, a JNK-specific inhibitor, abrogated cordycepin-mediated p21WAF1 expression, cell growth inhibition, and reduced cell-cycle proteins. Furthermore, JNK1 inhibition by small interfering RNA (siRNA) produced similar results: suppression of cordycepin-induced p21WAF1 expression, decreased cell growth, and reduced cell-cycle proteins. Together, these results suggest a critical role for JNK1 activation in cordycepin-induced inhibition of cell growth and G2/M-phase arrest in human colon cancer cells.Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 10/2009; 48(1):277-83. DOI:10.1016/j.fct.2009.09.042 · 2.90 Impact Factor
Article: Lee SJ, Kim WJ, Moon SK. TNF-alpha regulates vascular smooth muscle cell responses in genetic hypertension[Show abstract] [Hide abstract]
ABSTRACT: Cellular and molecular events in vascular smooth muscle cells (VSMC) from Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were investigated. SHR-derived VSMC showed increased proliferative capacity and MAP kinase levels in comparison with WKY-derived VSMC. Flow cytometry analysis revealed that progression from G1 to S phase was faster in SHR-derived VSMC in response to tumor necrosis factor-alpha (TNF-alpha) as compared with cells from WKY. The G1 cell cycle-associated proteins such as cyclin D1, cyclin E, CDK2 and CDK4, and kinase activities associated with CDK2 and CDK4, were increased in SHR-derived VSMC. In addition, CDK inhibitor p21 was elevated in SHR-derived cells. Matrix metalloproteinase-9 (MMP-9) expression and migration were also increased in response to TNF-alpha in SHR-derived cells. This increase was characterized by the up-regulation of MMP-9, which was transcriptionally regulated at the AP-1 and NF-kappaB sites in the MMP-9 promoter. These results suggest that the hypertensive-associated increase in VSMC proliferative capacity, G1 to S-phase cell-cycle progress and MMP-9 expression may play a role in vascular remodeling in hypertension.International immunopharmacology 04/2009; 9(7-8):837-43. DOI:10.1016/j.intimp.2009.03.010 · 2.47 Impact Factor
Article: Inhibitory effects of the aqueous extract of Magnolia officinalis on the responses of human urinary bladder cancer 5637 cells in vitro and mouse urinary bladder tumors induced by N -Butyl- N -(4-hydroxybutyl) nitrosamine in vivo[Show abstract] [Hide abstract]
ABSTRACT: This study investigated the anticancer activity of Magnolia officinalis on urinary bladder cancer in vitro and in vivo, and elucidated the mechanism of its activity. An aqueous extract of M. officinalis inhibited cell viability and DNA synthesis in cultured human urinary bladder cancer 5637 cells. Inhibition of proliferation was the result of apoptotic induction, because FACS analyses of 5637 cells treated with M. officinalis showed a sub-G1 phase accumulation. M. officinalis extract also increased cytoplasmic DNA-histone complex dose-dependently. These inhibitory effects were associated with the upregulation of proapoptotic molecules Bax, cytochrome c and caspase 3. Treatment of 5637 cells with M. officinalis extract suppressed the expression of matrix metalloproteinase 2 (MMP-2) and MMP-9, as revealed by zymographic and immunoblot analyses. When M. officinalis extract was given to mice simultaneously with the carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine, which induces urinary bladder tumors, the size of the induced tumors was smaller. Finally, histological data indicated that the histological grade of carcinoma and the depth of invasion were dramatically decreased by treatment with M. officinalis extract in mice with N-butyl-N-(4-hydroxybutyl) nitrosamine-induced urinary bladder tumors. In conclusion, the findings showed that M. officinalis extract exhibited potential chemopreventive activity against urinary bladder tumor in vitro and in vivo.Phytotherapy Research 01/2009; 23(1):20-7. DOI:10.1002/ptr.2413 · 2.66 Impact Factor
Article: Signaling pathway for TNF-α-induced MMP-9 expression: Mediation through p38 MAP kinase, and inhibition by anti-cancer molecule magnolol in human urinary bladder cancer 5637 cells[Show abstract] [Hide abstract]
ABSTRACT: We investigated the molecular mechanisms involved in the expression of matrix metalloproteinase-9 (MMP-9) and the inhibition of MMP expression by magnolol in 5637 human urinary bladder cancer cells. Tumor necrosis factor-alpha (TNF-alpha) stimulated the secretion of MMP-9 in 5637 cells, as shown by zymography and promoter assay. The transcription factor nuclear factor kappaB (NF-kappaB) binding site was identified by gel-shift assay to be a cis-element for TNF-alpha activation of the MMP-9 promoter. Our results also demonstrated that TNF-alpha stimulates MMP-9 expression via the p38 MAP kinase signaling pathway in 5637 cells. Moreover, p38 MAP kinase-mediated MMP-9 gene regulation in response to TNF-alpha is involved in the NF-kappaB response element in 5637 cells. In addition, magnolol inhibited TNF-alpha-induced expression of the MMP-9, as determined by zymography and immunoblot, in 5637 cells. The TNF-alpha-induced invasion and migration of cells was inhibited by magnolol, as assessed by a modified boyden chamber and wound-healing assays, respectively. Finally, magnolol blocked MMP-9 expression, at least in part, by decreasing the binding of transcription factor NF-kappaB to DNA. In conclusion, TNF-alpha induced MMP-9 expression in 5637 cells by activating the transcription factor NF-kappaB, which is involved in the p38 MAP kinase-mediated control of MMP-9 regulation. Magnolol inhibited MMP-9 expression through the transcription factor NF-kappaB in TNF-alpha-induced 5637 cells.International Immunopharmacology 10/2008; 8(13-14):1821-6. DOI:10.1016/j.intimp.2008.08.018 · 2.47 Impact Factor
Article: Magnolol elicits activation of the extracellular signal-regulated kinase pathway by inducing p27KIP1-mediated G2/M-phase cell cycle arrest in human urinary bladder cancer 5637 cells[Show abstract] [Hide abstract]
ABSTRACT: Magnolol has been reported to play a role in antitumor activity. However, the relevant pathway integrating cell cycle regulation and signaling pathways involved in growth inhibition in cancer cells remains to be identified. In the present study, magnolol treatment of these cells resulted in significant dose-dependent growth inhibition together with apoptosis, G1- and G2/M-phase cell cycle arrest at a 60 microM (IC50) dose in 5637 bladder cancer cells. In addition, magnolol treatment strongly induced p27KIP1 expression, and down-regulated expression of cyclin-dependent kinases (CDKs) and cyclins. Moreover, treatment with magnolol-induced phosphorylation of ERK, p38 MAP kinase, and JNK. Among the pathway inhibitors examined, only PD98059, an ERK-specific inhibitor, blocked magnolol-dependent p27KIP1 expression. Blockade of ERK function consistently reversed magnolol-mediated inhibition of cell proliferation and decreased G2/M cell cycle proteins, but not G1 cell cycle proteins. Furthermore, magnolol treatment increased both Ras and Raf activation. Transfection of cells with dominant negative Ras (RasN17) and Raf (RafS621A) mutant genes suppressed magnolol-induced ERK activity and p27KIP1 expression. Finally, the magnolol-induced reduction in cell proliferation and G2/M cell cycle proteins was also abolished in the presence of RasN17 and RafS621A mutant genes. These data demonstrate that the Ras/Raf/ERK pathway participates in p27KIP1 induction, leading to a decrease in the levels of cyclin B1/Cdc2 complexes and magnolol-dependent inhibition of cell growth. Overall, these novel findings concerning the molecular mechanisms of magnolol in 5637 bladder cancer cells provide a theoretical basis for therapeutic treatment of malignancies.Biochemical pharmacology 07/2008; 75(12):2289-300. DOI:10.1016/j.bcp.2008.03.022 · 5.01 Impact Factor
Article: Activation of matrix metalloproteinase-9 by TNF-α in human urinary bladder cancer HT1376 cells: The role of MAP kinase signaling pathways[Show abstract] [Hide abstract]
ABSTRACT: The expression of matrix metalloproteinase-9 (MMP-9) has been implicated in tumor invasion and metastasis. In this study, the factors and signaling pathways that are involved in the regulation of the MMP-9 expression were examined in urinary bladder cancer HT1376 cells. Tumor necrosis factor-alpha (TNF-alpha) stimulated the secretion of MMP-9 in HT1376 cells, as shown by zymography and immunoblot analysis. At the level of transcription, TNF-alpha also stimulated 5'-flanking promoter activity of MMP-9. Transcription factor NF-kappaB, AP-1 and Sp-1 binding sites were identified by a gel shift assay to be cis-elements for TNF-alpha activation of the MMP-9 promoter. TNF-alpha activates multiple signaling pathways in HT1376 cells, including the extracellular signal-regulated kinase (ERK1/2), p38 MAP kinase and JNK pathways. Chemical inhibitors, which specifically inhibit each of these TNF-alpha-activated pathways, were used to examine the signaling pathways involved in TNF-alpha-mediated MMP-9 expression. The ERK1/2 inhibitor, U0126 and the p38 MAP kinase inhibitor, SB203580, significantly down-regulated TNF-alpha-induced MMP-9 expression and promoter activity. The transactivation of TNF-alpha-stimulated NF-kappaB, AP-1 and Sp-1 were inhibited by U0126 and SB203580 treatment. In conclusion, the findings of the present study indicate that TNF-alpha induces MMP-9 expression in HT1376 cells by activating transcription factors, which are involved in the ERK1/2- and p38 MAP kinase-mediated control of MMP-9 regulation, namely, NF-kappaB, AP-1 and Sp-1.Oncology Reports 05/2008; 19(4):1007-13. DOI:10.3892/or.19.4.1007 · 2.30 Impact Factor
Article: Sanguinarine-induced G(1)-phase arrest of the cell cycle results from increased p27KIP1 expression mediated via activation of the Ras/ERK signaling pathway in vascular smooth muscle cells[Show abstract] [Hide abstract]
ABSTRACT: The present study identified a novel mechanism for the effects of sanguinarine in vascular smooth muscle cells (VSMC). Sanguinarine treatment of VSMC resulted in significant growth inhibition as a result of G1-phase cell-cycle arrest mediated by induction of p27KIP1 expression, and resulted in a down-regulation of the expression of cyclins and CDKs in VSMC. Moreover, sanguinarine-induced inhibition of cell growth appeared to be linked to activation of Ras/ERK through p27KIP1-mediated G1-phase cell-cycle arrest. Overall, the unexpected effects of sanguinarine treatment in VSMC provide a theoretical basis for clinical use of therapeutic agents in the treatment of atherosclerosis.Archives of Biochemistry and Biophysics 04/2008; 471(2):224-31. DOI:10.1016/j.abb.2008.01.008 · 3.02 Impact Factor
Article: Requirement for Ras/Raf/ERK pathway in naringin-induced G1 -cell-cycle arrest via p21WAF1 expression[Show abstract] [Hide abstract]
ABSTRACT: Naringin, an active flavonoid found in citrus fruit extracts, has pharmacological utility. The present study identified a novel mechanism of the anticancer effects of naringin in urinary bladder cancer cells. Naringin treatment resulted in significant dose-dependent growth inhibition together with G(1)-phase cell-cycle arrest at a dose of 100 microM (the half maximal inhibitory concentration) in 5637 cells. In addition, naringin treatment strongly induced p21WAF1 expression, independent of the p53 pathway, and downregulated expression of cyclins and cyclin dependent kinases (CDKs). Moreover, treatment with naringin induced phosphorylation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase and c-Jun N-terminal kinase. Among the pathways examined, only PD98059, an ERK-specific inhibitor, blocked naringin-dependent p21WAF1 expression. Consistently, blockade of ERK function reversed naringin-mediated inhibition of cell proliferation and decreased cell-cycle proteins. Furthermore, naringin treatment increased both Ras and Raf activation. Transfection of cells with dominant-negative Ras (RasN17) and Raf (RafS621A) mutant genes suppressed naringin-induced ERK activity and p21WAF1 expression. Finally, the naringin-induced reduction in cell proliferation and cell-cycle proteins also was abolished in the presence of RasN17 and RafS621A mutant genes. These data demonstrate that the Ras/Raf/ERK pathway participates in p21WAF1 induction, subsequently leading to a decrease in the levels of cyclin D1/CDK4 and cyclin E-CDK2 complexes and naringin-dependent inhibition of cell growth. Overall, these unexpected findings concerning the molecular mechanisms of naringin in 5637 cancer cells provide a theoretical basis for the therapeutic use of flavonoids to treat malignancies.Carcinogenesis 03/2008; 29(9):1701-9. DOI:10.1093/carcin/bgn055 · 5.33 Impact Factor
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Chung-Ang University
Sŏul, Seoul, South Korea
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Chungbuk National University
Chinsen, Chungcheongbuk-do, South Korea
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Vanish Valley's 3rd album Queen of the Concert is out now!! Vinyl is now available - you can get it right here.
We had a blast playing Make Music Pasadena Festival - check out the pics here.
Big thanks for the write-ups in Americana UK and Slug Magazine and Buzz Bands LA.


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Does this sound good?
So tonight I am planning on making chicken roll-ups stuffed with provolone and asparagus. We have an extra avocado (the others are for the Super Bowl--we're making guac). I wondered if what I'm making would be good with an avocado-cream sauce. Thoughts?
I have not tried avocados...but I hope you get everything to work out for your meal....
I think it sounds good, I didn't use to like avocados but lately they have grown on me.
I've never tried avocado. The chicken roll ups sound yummy though!
An avacado cream sauce sounds like it would be good on chicken or fish!


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A promiscuous woman who appears to have changed her ways backslides when her boyfriend is away on an extended business trip. On his return there is a shock in store for her. Emeka Enyiocha, Ernest Asuzu, Robert Peters.


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National Parks
National Parks in NSW
NSW is home to some of the most diverse natural terrain in Australia. With close to 900 national parks, featuring sub-tropical rainforests, pristine marine parks, outback landscapes, mountain ranges and UNESCO World Heritage-listed reserves there is a world of natural wonder to experience.
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Key places to go
There are many extraordinary features that make NSW's National Parks truly remarkable, from the vast and shimmering estuary of The Great Lakes, which hold more water than Sydney Harbour, to the highest mountain in mainland Australia, Mount Kosciuszko in Kosciuszko National Park.
With more than 850 protected parks, forests and reserves, this vast range of habitat covers more than 7 million hectares and has been internationally recognised for its unique beauty and importance.
Dorrigo National Park in the state's north is part of the Gondwana Rainforest Reserves of Australia, selected as a World Heritage sites for exceptional biodiversity or rarity. Dorrigo National Park, also known for it's crystal waterfalls, is home to a wide variety of birds, such as the wompoo fruit-dove and the regent bowerbird. Capertee National Park, about 50km north of Lithgow, is also a well known bird watching spot, and a breeding and feeding site for the nationally endangered regent honeyeater, a distinctive black-and-yellow bird with a sturdy, curved bill.
Other great parks include Mutawintji National Park, with its ancient Aboriginal rock art and engravings. The world's oldest known ceremonial burial site can meanwhile be found in the ancient landscapes of Mungo National Park.
By contrast, Rainforest Way provides a rolling series of drives through World Heritage-listed rainforests and national parks in northern NSW. Enjoy the tranquillity of scenic loop roads, stopping for a walk through forests dappled with sunlight or an invigorating swim in a creek fed by waterfalls.
National parks around Nimbin in NSW's far north, including Nightcap National Park and Mebbin National Park, also enjoy high rainfall and spectacular waterfalls.
Bushwalking and hiking are at optimum in NSW, from the diverse trails of The Blue Mountains National Park, featuring the stunning Three Sisters, to t he equally dramatic rainforests and waterfalls of the Gibraltar-Washpool World Heritage walk . This walk connects the Gibraltar Range National Park and Washpool National Park .
The stunning vistas from Jamberoo Lookout in the Buderoo National Park offer fantastic vistas of NSW coastline, while further north the Royal National Park, Australia's oldest national park, offers short and long walks through a variety of terrains and settings, from lush bushland to rugged cliffs to pristine coastline.
Further down the NSW South Coast, Jervis Bay remains a hidden treasure. Its beautiful beaches include Hyams Beach , which has the whitest sand in the world, according to Guinness World Records.
Situated near Eden, the Ben Boyd National Park stretches across 45 km of coastline. You're sure to find the perfect place for whale watching along the way. Following several kilometres of scenic coastline, the gentle Light to Light Walk from Green Cape Lighthouse to Pulpit Rock is a popular whale watching location and also offers expansive ocean views. Head through coastal heath toward Pulpit Rock and savour great northerly vistas.
National Parks also provide protection for a vast number of flora and fauna in New South Wales, as well as areas of geological, cultural and historical significance. Preservation of and public access to these areas allows the enjoyment and exploration of all New South Wales has to offer.
Royal National Park
The World Heritage listed Royal National Park is just an hour's drive from both Sydney and Wollongong and is one of the the world's oldest national parks. It is ideal for hiking, cycling, surfing, swimming and whale watching.
Dorrigo National Park
An hour's drive from Coffs Harbour and part of the Gondwana Rainforests World Heritage Area, ancient Dorrigo National Park contains a range of forest types, including lush rainforests, and protects a huge variety of animals and birds.
Warrumbungle National Park
Home of the striking Breadknife rock formation, Warrumbungle National Park is located near Coonabarabran. At night, the park offers perfect conditions for stargazing, by day, it's a great spot for camping, hiking and birdwatching.
The Pilliga Forest
The Pilliga Forest, west of Dubbo, is the largest semi-arid woodland in NSW. With a landscape as eerie as it is intriguing, there are many scenic walking tracks, forest drives and bird watching routes to explore.
Blue Mountains National Park
With magnificent views, iconic rock formations and heritage tracks and lookouts, it's easy to see why the Blue Mountains National Park is one of NSW best known parks, and less than 2 hours drive from Sydney.
Mungo National Park
Part of the Willandra Lakes Region World Heritage Area, the stark and striking landscape of Mungo National Park is famous for the discovery of a rare archaeological find - the oldest human skeleton in Australia.
Swimming safety information
NSW has a wide range of wonderful swimming options from beaches, ocean pools, harbourside pools, lakes, rivers or swimming holes at the bottom of waterfalls. However to ensure maximum safety and enjoyment, swimmers should follow this general advice:
Look for patrolled beaches (this is where lifesavers are on duty you will see red and yellow flags that indicate this). You should always swim between the red and yellow flags as they mark the safest place to swim.
Never swim alone at night, or under the influence of alcohol, or directly after a meal.
Always check water depth before diving in as rocks or trees could be submerged and never run and dive into the water from the beach.
Check for signs regarding advice on water conditions at your chosen swimming spot and at any natural swimming hole. Always proceed with caution as surfaces could be slippery and water conditions may not be immediately apparent; particularly if the areas has recently experienced heavy rainfalls or flooding.


text: I work at a nursery and go to Palomar college part time, studying design and working on a toy design degree. I'm super girly but I also like to go on adventures and I'm not afraid to get messy. I like baking and painting and I like wearing dresses and working on my garden and reading. I hate roller coasters. I love playing guitar.


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Priced at a really affordable $205 without contract, the Mi 4i sports good looks and pretty great specs for its low cost.


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Battlefield 4 Official Website Launched, Teases First Screenshot Offers Exclusive Dog tag for BF 3
|3 years ago
|class of '04 - away - #1
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DICE and EA Games have launched the official website for Battlefield 4, effectively announcing the game as something more official than hearsay from second-hand sources.
The website invites interested players to sign up for an Origin account to help unlock details about the game. Those who already have accounts are urged to log in. It's designed so anyone interested in the game will have to pitch in as a part of a concentrated social effort to bring the game to light.
As an incentive to Battlefield 3 players, anyone who logs in prior to the game's full reveal will earn an "I Was There" in-game dog tag for use in BF3.
Logging in reveals what appears to be a screenshot of the game, which depicts a pair of Bradley IFVs followed by an M1A2 Abrams main battle tank in the rain. There's a city behind them that's been widely rumored to be located in China, although it's impossible to confirm whether that's actually the case.
A first look at Battlefield 4's gameplay will be revealed on March 27. Although release details have yet to be revealed, the game is widely anticipated to be announced for the PC and next-gen platforms including Sony's recently announced PlayStation 4 and Microsoft's successor to the Xbox 360which everyone is tentatively referring to as the Xbox 720.
We've created a Battlefield 4 wallpaper for all you hardcore fans who can't wait for the March 27 announcement.
BF 4 1080p Wallpaper
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BF 4 720p Wallpaper
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Source -Battlefield 4 Official Website Launched, Teases First Screenshot
|Props given to Da Ill One
|hot topic (03-20-2013)


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In the last decade, the synergistic interaction of neurosurgeons, engineers, and neuroscientists, combined with new technologies, has enabled scientists to study the awake, behaving human brain directly. These developments allow cognitive processes to be characterized at unprecedented resolution: single neuron activity. Direct observation of the human brain has already led to major insights into such aspects of brain function as perception, language, sleep, learning, memory, action, imagery, volition, and consciousness.
The idea that a specific brain circuit constitutes the emotional brain (and its corollary, that cognition resides elsewhere) shaped thinking about emotion and the brain for many years. Recent behavioral, neuropsychological, neuroanatomy, and neuroimaging research, however, suggests that emotion interacts with cognition in the brain. In this book, Luiz Pessoa moves beyond the debate over functional specialization, describing the many ways that emotion and cognition interact and are integrated in the brain.
This volume offers a comprehensive overview of the latest neuroscientific approaches to the scientific study of creativity. In chapters that progress logically from neurobiological fundamentals to systems neuroscience and neuroimaging, leading scholars describe the latest theoretical, genetic, structural, clinical, functional, and applied research on the neural bases of creativity. The treatment is both broad and in depth, offering a range of neuroscientific perspectives with detailed coverage by experts in each area.
This book explores the relationships between language, music, and the brain by pursuing four key themes and the crosstalk among them: song and dance as a bridge between music and language; multiple levels of structure from brain to behavior to culture; the semantics of internal and external worlds and the role of emotion; and the evolution and development of language. The book offers specially commissioned expositions of current research accessible both to experts across disciplines and to non-experts.
How do we make decisions? Conventional decision theory tells us only which behavioral choices we ought to make if we follow certain axioms. In real life, however, our choices are governed by cognitive mechanisms shaped over evolutionary time through the process of natural selection. Evolution has created strong biases in how and when we process information, and it is these evolved cognitive building blocks—from signal detection and memory to individual and social learning—that provide the foundation for our choices.
Cognitive neuroscientists increasingly claim that brain images generated by new brain imaging technologies reflect, correlate, or represent cognitive processes. In this book, William Uttal warns against these claims, arguing that, despite its utility in anatomic and physiological applications, brain imaging research has not provided consistent evidence for correlation with cognition.
We form individual memories by a process known as consolidation: the conversion of immediate and fleeting bits of information into a stable and accessible representation of facts and events. These memories provide a version of the past that helps us navigate the present and is critical to individual identity. In this book, Thomas Anastasio, Kristen Ann Ehrenberger, Patrick Watson, and Wenyi Zhang propose that social groups form collective memories by analogous processes.
This volume offers a range of perspectives on a simple problem: How does the brain choose efficiently and adaptively among options to ensure coherent, goal-directed behavior? The contributors, from fields as varied as anatomy, psychology, learning theory, neuroimaging, neurophysiology, behavioral economics, and computational modeling, present an overview of key approaches in the study of cognitive control and decision making.
Patients with Parkinson's disease (PD) suffer most visibly with such motor deficits as tremor and rigidity and less obviously with a range of nonmotor symptoms, including autonomic dysfunction, mood disorders, and cognitive impairment. The neuropsychiatric disturbances of PD can be as disabling as its motor disorders; but they have only recently begun to be studied intensively by clinicians and scientists.
In recent decades, empathy research has blossomed into a vibrant and multidisciplinary field of study. The social neuroscience approach to the subject is premised on the idea that studying empathy at multiple levels (biological, cognitive, and social) will lead to a more comprehensive understanding of how other people's thoughts and feelings can affect our own thoughts, feelings, and behavior.
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