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ESMO @ ECC 2013: Phase III FIRE-3 Trial Data Show Most Patients with Wild-Type RAS Metastatic Colorectal Cancer Benefit from First-Line FOLFIRI Plus Cetuximab Treatment
Exclusion of patients with RAS mutations identifies a population which is more likely to benefit from cetuximab.
- Date: 28 Sep 2013
- Topic: Personalised medicine / Gastrointestinal cancers / Anticancer agents & Biologic therapy
Findings from a preplanned analysis by mutational status done on data from the FIRE-3 trial, that expanded KRAS testing as a predictive factor of resistance to more rare NRAS gene and BRAF, confirmed previously reported results that first line treatment with FOLFIRI plus the anti-EGFR (epidermal growth factor receptor) agent cetuximab achieve benefit in term of overall response rate and overall survival in most patients with KRAS wild type (exon 2) metastatic colorectal cancer (mCRC), but the benefit encompass also those with wild type KRAS exon 3/4 and wild type NRAS exon 2/3/4. However, a subgroup of patients with mutated RAS did not show similar benefit and achieved improved progression-free survival following treatment with FOLFIRI plus the anti-VEGF (vascular endothelial growth factor) agent bevacizumab.
Dr. Sebastian Stintzing of the Klinikum Grosshadern, University of Munich in Munich, Germany presented results on Saturday, 29 September during the Gastrointestinal Malignancies/Colorectal Cancer Proffered Papers Session (Abstract E17-7073) at the 17th ECCO – 38th ESMO – 32nd ESTRO European Cancer Congress, which was held in Amsterdam, The Netherlands from the 27 September through the 1 October, 2013. The European Cancer Congresses are organised in joint partnership with ESSO, EACR, EONS and SIOPE to offer multidisciplinary and multi-professional educational opportunities in oncology.
Testing for the RAS mutations
The Fire-3 phase III trial (AIO KRK-0306) was conducted at 150 German and Austrian cancer centres as a head to head comparison of FOLFIRI plus either cetuximab or bevacizumab as first-line treatment in patients with metastatic colorectal cancer (mCRC) who had KRAS wild-type disease. Of 752 enrolled patients, KRAS wild-type tumours were confirmed in 592 patients who were then randomised 1:1 to receive first-line FOLFIRI every two weeks plus either cetuximab at 400 mg/m2 on day 1 followed by 250 mg/m2 weekly (arm A) or bevacizumab at 5 mg/kg every 2 weeks (arm B). The results from this overall study population favoured arm A, with cetuximab patients showing median overall survival (OS) nearly four months longer than in the bevacizumab arm.
The results presented at this Congress were from a preplanned analysis that evaluated the effect of KRAS mutations in exon 3 (codon 59/61), exon 4 (codon 117/146)), NRAS exon 2 (cordons 12/13), exon 3 (cordons 59/61) exon 4 (cordons 117/146)) and BRAF (V600E) on the overall response rate (ORR), progression-free survival (PFS) and OS on treatment arms A and B of the FIRE-3 trial. Mutational analyses were done by pyrosequencing in 592 patients who were wild type for KRAS exon 2. A total of 444 (75%) patients had available tumour tissue; of these, sequencing of all RAS mutations was possible in 396 patients.
Greater benefit was demonstrated with FOLFIRI plus cetuximab in the overall intent to treat population of 592 patients with KRAS wild type disease; ORR was 62.0% and 58.0% in arm A and B, respectively (p = 0.183 [Fisher´s one-sided test]). Median OS was 28.7 months with FOLFIRI/cetuximab versus 25.0 months with FOLFIRI/bevacizumab (logrank p = 0.017). Median PFS was similar in both study arms; 10.0 months in arm A versus 10.3 months in arm B (p = 0.547).
Further analysis showed that 301 patients within the wild type RAS subgroup (wild-type KRAS exon 2/3/4 and NRAS exon 2/3/4) showed greater ORR of 76.0% with FOLFIRI/cetuximab over patients who received FOLFIRI/bevacizumab (ORR = 65.2%; Fischer's one-sided p = 0.026, Fischer's two-sided p = 0.044). The ORR in 40 patients with mutated BRAF (KRAS exon 2 wild-type and BRAF V600E mutant) was 63.2% versus 42.9%, respectively in arms A and B (p = 0.167). However, the ORRs in 55 patients with mutated RAS (KRAS exon 2 wild-type and KRAS exon 3/4 or NRAS exon 2/3/4 mutant) favoured the comparator arm and were 42.9% and 66.7% in the FOLFIRI plus cetuximab or bevacizumab arms, respectively (p = 0.066).
OS was prolonged with FOLFIRI/cetuximab in RAS wild type patients who achieved 33.1 versus 25.9 months (p = 0.010) in arms A and B, respectively; patients with BRAF mutations experienced OS of 12.9 versus 11.0 months (p = 0.448), respectively. The hazard ratio (HR) for adding cetuximab versus bevacizumab for OS in patients with wild type RAS was 0.69 (p = 0.01). Patients with mutated RAS achieved OS of 19.1 months with cetuximab and 20.6 months with bevacizumab (p = 0.622).
Results for PFS by mutational status showed a similar trend; patients with RAS wild type and BRAF mutation obtained slightly more benefit from FOLFIRI/cetuximab treatment than FOLFIRI/bevacizumab. RAS wild types patients had PFS of 10.5 versus 10.4 months (p = 0.627) and PFS in patients with mutated BRAF was 6.3 and 5.7 months (p = 0.626), respectively. The hazard ratio for PFS in wild type RAS patients was 0.94 (p = 0.63). In patients with RAS mutations, the PFS significantly favoured bevacizumab therapy; PFS was 6.1 months in arm A versus 12.2 months in arm B ( = 0.006).
The authors concluded that these data represent the first phase III findings demonstrating the influence of KRAS exon 3,4 and NRAS exon 2,3,4 mutations on the efficacy of first-line treatment with FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab in patients with mCRC and wild type KRAS (exon 2). Furthermore, they point out the impact that these findings may have on daily clinical decisions since subgroups of patients were identified that were most likely to benefit from the treatment.
The authors presented during the Congress an updated analysis with more patients tested for KRAS exon 3/4, NRAS exon 2/3/4 and BRAF V600E.
Clinical trial information: NCT00433927.
Several independent non-randomised retrospective studies, several retrospective analysis of prospective randomised trials and a European consortium study have largely shown that the presence of KRAS activating mutations in exon 2 correlates with primary resistance to anti-EGFR monoclonal antibodies (moAbs) in metastatic colorectal cancer patients (mCRC). As first reported by De Roock et al, other activating RAS mutations can predict poorer outcome of mCRC patients treated both with cetuximab and panitumumab. In line with the results of the PRIME study, the FIRE-3 trial highlights the importance of better selecting the patients who might benefit from anti-EGFR moAbs by considering other RAS mutations. Moreover, the FIRE 3 study is the first randomised multicentre study that compares in a head to head fashion two biologic agents that are active in mCRC.
In particular, the study compared FOLFIRI plus cetuximab to FOLFIRI plus bevacizumab as first-line treatment in patients with mCRC according to the KRAS exon 2 status. In a pre-planned analysis, the effect of mutations in KRAS exon3 (codon 59/61), exon 4 (codon 117/146)), NRAS (exon 2 (codon 12/13), exon 3 (codon 59/61) exon 4 (codon 117/146)) and BRAF (V600E) on overall response rate (ORR), progression free survival (PFS) and overall survival (OS) was evaluated. The ITT population consisted of 592 KRAS exon 2 wild type (WT) patients with its primary endpoint (ORR) not met (62% for cetuximab/FOLFIRI and 58% for bevacizumab/FOLFIRI, p value: 0.183). No difference in PFS was observed but a statistical significant difference in OS was reported with 28.7 months in the cetuximab group as compared to 25.0 months in the bevacizumab group (p value: 0.017)
In 455 out of 592 patients sequencing of all RAS mutations was possible; 65 out of 455 carry an other RAS mutation while 48 out of 455 carry a BRAF mutation. Patients wild type for KRAS exon 2 and other RAS mutations (defined by the authors as RAS WT) showed higher ORR in the FOLFIRI/cetuximab group as compared to FOLFIRI/bevacizumab.(76.0% vs. 65.2%; Fisher´s p (two-sided): 0.044). There was no statistical significant improvement in PFS (10.5 months in the cetuximab arm versus 10.4 months in bevacizumab arm, p value 0.627) while a better OS was observed. In particular RAS WT patients treated with cetuximab reported 33.1 months of OS as compare to 25.9 months observed in the bevacizumab arm (p value 0.010).
In conclusion, the FIRE-3 is the first head to head study that compares cetuximab plus FOLFIRI to bevacizumab plus FOLFIRI in first line treatment of KRAS exon 2 wild type mCRC. When considering the analysis restricted to the KRAS exon 2 population, no benefit in terms of ORR and PFS was observed. On the contrary, a better OS was reported with 3,5 months gain in the cetuximab group as compared to bevacizumab. Furthermore, this is the first data pertaining the influence of KRAS exon 3,4 and NRAS exon 2,3,4 mutations on treatment efficacy of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab in first-line treatment of mCRC patients of a phase III randomised study. The results show that the better identification of other RAS mutations can improve both the ORR and the OS in patients receiving cetuximab as compared to bevacizumab. This highlights the importance for detecting other RAS mutations to better select the group of patients who might benefit from anti-EGFR moAbs. These results may have impact on daily clinical decisions as we are able to define a subgroup of patients most likely to benefit from FOLFIRI plus cetuximab in first-line setting.
*Loredana Vecchione, ESMO spokeperson who was not involved in the study
The authors state the following conflicts of interest: Research sponsored by Merck and Roche; participation on the Advisory board of Merck, Roche, BMS and travel support from Merck, Roche.


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A great way to make communication more ground-breaking is through creating an open-source web-based forum. And, this is why wave developers are being sought upon as a way to help create and develop more killer applications most especially for Wave.
In fact, it has already begun. The Google Wave Team aims to continue developing more powerful and better extensions for running forums in wave. And, to take it to the next level, the team aspires to incorporate tested features from forums into a robot which in effect can make Google Wave as the ultimate platform for forum-based discussions.
The objective is, improve Wave through incorporating forum which can encourage users to utilize it for other purposes instead of sticking to which is traditional.
And, according to David Crane, an external Wave developer working on the Debatewise Extension, there are three specific areas which need further developing, namely…
(a) Objective: To enable people go hand in hand around a theme of their choice and help find waves of interest. Tasks: Group waves around disciplines.
(b) Objective: To encourage and reward participation in conversations. Tasks: Stir in the levels of participation rates and privileges and the likes.
(c) Objective: To establish mechanisms so people can decide who to invoke or ignore. Tasks: List of all user messages and their classification in the community.
Python, Java and Javascript developers, QA testers and anyone with interest in forum software are invited to join. The project is structured by Debatewise.org, a non-profit debating web site which aims to be the Wikipedia of debate. For those who are interested, contact firstname.lastname@example.com.

subset: commoncrawl


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U.S. Equal Employment
Opportunity Commission
Chemical Company Cognis Unlawfully Fired Employee for Refusing to Waive Charge Rights, Federal Court Holds
URBANA, Ill. – A federal judge has ruled that Cognis Corporation, a German-based part of multinational chemical company BASF, unlawfully retaliated against an employee for refusing to waive his rights to file a discrimination charge, the U.S. Equal Employment Opportunity Commission (EEOC) announced today.
Chief U.S. District Judge Michael P. McCuskey of U.S. District Court for the Central District of Illinois, in an opinion issued May 23, held as a matter of law that Cognis illegally retaliated against the employee. The court said that Cognis fired Steven Whitlow after he revoked his willingness to be bound by a "last-chance" employment agreement because it would have stripped him of his rights to seek relief for discrimination or to file a charge with the EEOC.
In its lawsuit filed Aug. 18, 2010, the EEOC had alleged that Germany-based Cognis retaliated against Whitlow, a longtime employee at its Kankakee, Ill., facility, in violation of Title VII of the Civil Rights Act of 1964 (EEOC v. Cognis Corp., 10-CV-2182, C.D. Ill.). As a condition of his continued employment, Cognis required Whitlow to sign a "last-chance" agreement that prohibited him from filing a discrimination charge with the EEOC – even a charge based on conduct that might occur in the future. Thus, according to EEOC, Cognis conditioned Whitlow's employment on his agreement to give up his right to make any federal complaint of employment discrimination. When Whitlow refused to be bound by that agreement, the company fired him, the court found.
The EEOC's lawsuit also charged that a class of employees who signed similar last-chance agreements was also retaliated against because Cognis forced them to make a choice between termination and signing agreements that stripped them of their right to file charges and seek relief for future discriminatory conduct – or at least deterred them from doing so. At the court's invitation, EEOC filed a summary judgment motion on Jan. 6, 2012, asking the court to resolve all issues in the case in EEOC's favor, leaving the only issue for trial being the question of what damages are due to Whitlow and the class.
In granting the EEOC's motion with regard to Whitlow, the court noted, "It is not often that a plaintiff moves for or is granted summary judgment on a Title VII retaliation claim." Yet the court held that no jury could reasonably conclude that Cognis did not unlawfully retaliate against Whitlow when it fired him, and that Cognis's argument to the contrary "defies simple logic." The only issue now remaining for trial with regard to Whitlow is the amount of damages due to him.
As for the class of employees who signed last-chance agreements but were not terminated as Whitlow was, the court denied EEOC's summary judgment motion, and those claims will now proceed toward trial. The court held that a jury could conclude that Cognis engaged in unlawful anticipatory retaliation against the class when it required those employees to sign agreements waiving their right to file charges of discrimination out of fear that they might seek to exercise that civil right. The court noted that the language of the agreements supported the inference that Cognis acted unlawfully out of just such a fear "because fear of such protected activity seems to be one of the only reasons for placing the retaliatory provision" in the last chance agreements.
"Filing EEOC charges is a fundamental right of American employees, and this agency always stands ready to protect that right," said EEOC's Chicago District Director John Rowe. "This court's opinion should cause employers to remember that seeking to dissuade employees from exercising that right is not only bad policy, it's a violation of federal law which can give rise to very substantial liability."
The EEOC's supervisory trial attorney on the case, Gregory Gochanour of Chicago, added, "We are very pleased with this court's decision, both with regard to Whitlow and to the class. Whitlow is a brave man, willing to risk -- and actually suffer -- termination from a job he held for 19 years, rather than let Cognis strip him of his rights. We expect he will be fairly compensated for his damage attributable to Cognis's unlawful actions. Beyond that, we are highly optimistic that at trial, the jury will find in favor of the other class members and award them just compensation."
In addition to Gochanour and EEOC Regional Attorney John Hendrickson, the EEOC's litigation team included trial attorneys Deborah Hamilton and Brad Fiorito of the Chicago District Office.
Cognis was acquired in December 2010 by BASF, a multinational chemical company. According to company information, BASF Corporation, headquartered in Florham Park, N.J., is the North American affiliate of BASF SE, based in Ludwigshafen, Germany. According to company information, BASF Corp. has about 16,400 employees in North America and had sales of $17.7 billion in 2010.
The EEOC is responsible for enforcing federal laws against employment discrimination. Further information is available at www.eeoc.gov.


text: It has been a while since I published any of the hundreds of mystery photos I have in the huge Overson Photograph Collection. The photos were taken between about 1900 and 1940 in St. Johns, Apache, Arizona by Margaret Godfrey Jarvis Overson. Take a look and see if you recognize anyone.


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Hempel does not have an office in the chosen country. Please contact the office listed below.
Hempel Paints (South Africa) Pty LtdP.O. Box 265415, Three Rivers 1929Shop 3, Head Office BuildingVision 21 Industrial ParkSteel Road, PeacehavenVereeniging, 1939
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July 25, 2017
Alberta, Canada, July 25, 2017: Yanda Canada Ltd., a leading provider of specialized fabrication and installation services and products, was contracted for pressure testing vessels and interconnecting piping at Praxair's newest air separation facility in Alberta. In order to run the tests, 100% oil-free, high pressure air would be needed and Atlas Copco Rental was selected as the preferred provider.
This new facility will provide Oxygen, Nitrogen, Argon, Hydrogen and other common gasses utilizing a 40,000 Hp compressor as its key piece of equipment. Exchangers, interconnecting piping and multiple vessels needed to be tested with ranges from 1,000 to 296,000 cubic feet and at pressures from 15 to 1,700 psi. Yanda Canada's project manager, Rob Hamilton, set up a range of tests needing a variety of air treatment equipment products leading him to call Atlas Copco Rental for an ideal solution.
During the testing, the air treatment equipment would feed into high and low pressure headers with nine lines for testing. Each vessel would contain a different process creating gas that would then be piped directly to the refinery necessitating 100% oil-free, high pressure air. To meet the requirements, Atlas Copco Rental supplied a PTS 1600 oil-free air compressor, a PNS 1250 high pressure oil-free air compressor, a high pressure air dryer, booster and two filter packs.
When high pressure air is needed, boosters are used to significantly increase pressure range. The only problem with using boosters for this job is they use oil to lubricate pistons - increasing the risk of contamination for the end product. It was important to ensure oil-free air to eliminate this risk therefore the Atlas Copco Rental team used a filter pack with the booster to remove up to 99.9% of oil in the air stream. Additionally, a second filter pack was added to catch any containment and provide oil-free air. During the start-up and on-site equipment testing, Praxair used a white cloth swap at the outlet and tested the cloth under black light to find there was no contamination.
The project offered a valuable learning experience for the Atlas Copco Rental Canada team and harbored a great working relationship with Yanda.
Atlas Copco is a world-leading provider of sustainable productivity solutions. The Group serves customers with innovative compressors, vacuum solutions and air treatment systems, construction and mining equipment, power tools and assembly systems. Atlas Copco develops products and services focused on productivity, energy efficiency, safety and ergonomics. The company was founded in 1873, is based in Stockholm, Sweden, and has a global reach spanning more than 180 countries. In 2016, Atlas Copco had revenues of BSEK 101 (BEUR 11) and about 45 000 employees. Learn more at www.atlascopcogroup.com. Specialty Rental is a division within Atlas Copco's Power Technique business area. It serves customers in all industry segments around the world with temporary air, power, flow, steam and nitrogen rental solutions. The specialty rental services are offered under several brands. The divisional headquarters is located in Belgium.
Industrial Rental:
Unit 2 Walderidge Way, Simonside East Industrial Estate,
Newcastle NE34 9PZ
Offshore Rental:
Pearce Avenue, West Pitkerro Ind Est,
Dundee DD5 3SS
24/7 @ 0800 169 6611
+44 1382 778999


text:
Look & Lease Specials
Reserve at College Station
The Reserve is an all-student neighborhood of Colorado-style homes with all the convenience and amenities of a luxury apartment. We have a passion to bring you the best living experience possible and creating a culture that values excellence, service, innovation, and being the best. Join the revolution at The Reserve!


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Police say a man shot and killed his wife, then turned the gun on himself in their home in Park Forest.
Relatives had heard Tajuanna Davis, 32, and her husband Gerard Jimerson, 33, arguing before shots rang out around 9:30 p.m. Sunday in the 300 block of Todd Street, according to police.
An autopsy conducted today ruled Jimerson's death a suicide and Davis' death a homicide, according to the Cook County medical examiner's office.
Davis and Jimerson were both lying on the floor of their bedroom with gunshot wounds to the head, police said. They were discovered by their daughter, authorities said.
"Based upon early investigation, [the shooting] appears to be a murder-suicide," police said in a release.
The two were pronounced dead at the scene at 1:48 a.m.
The South Suburban Major Crimes Task Force was investigating the deaths with Park Forest Police.
Twitter: @ChicagoBreaking


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Winter fun for everyone!
Tickets and Passes
Season, day, multi-day, lifetime and dog passes are all found here. Kids 17 and under ski free everyday!
The grooming report is updated daily during the winter. You can access the grooming report via this website, by downloading our free Methow Trails smartphone grooming app for mobile devices and the iPad.
Cross-Country Ski Trailheads
The Methow Valley's skiing, scenery, and trails are world class and our extensive trail system provides for 120 miles (200+ kilometers) of skiing in peaceful, freshly groomed and uncrowded conditions. The Nordic ski trail system is divided into four areas, all connected by the Methow Community Trail, which includes a suspension bridge crossing the Methow River, trailheads, and lodges along the way.
Ski Rentals and Lessons
Just a few tips and techniques can take you to a whole new level of skiing! The Methow Valley is a great place to learn how to cross-country ski or build on the skills you already have. The Methow Valley Ski School and the Sun Mountain Ski School offer skate and classic lessons for all ages and abilities with friendly, PSIA-certified instructors. Choose from group lessons (offered daily), or a private lesson for you or your group – you get to pick the time, place and instructor.
Fat Bike
Fat bike on selected ski trails in the Valley! Fat bikes are specially made bicycles that accommodate ultra-wide tires that can be run at very low pressure. The combination of very wide tires and less than ten pounds of pressure allows fat bikes to roll over soft, slippery surfaces like snow. Give it a try! A fat bike day pass ($10) or ski pass is required.
The Methow Valley has endless snowshoe opportunities! Methow Trails hosts family-friendly snowshoe tours every Saturday throughout the winter. Local volunteers lead tours that focus on winter ecology, wildlife and tracks, snow science and more. A ski trail pass or snowshoe trail pass ($5) is required for each person.
Ski Trails For Kids
Kids can learn to cross-country ski almost as soon as they can walk. With the right equipment and a little patience, your whole family can enjoy a day in the tracks together. Methow Trails makes it a little easier for kids to cross-country ski by offering FREE skiing for all kids 17 and under! Don't pass up the chance to introduce this sport to your children.
Ski Trails For Dogs
Methow Trails proudly allows dogs on selected trails in the Methow Valley. It is a program that we have run for years and, despite a dog's inability to talk, anyone who has ever seen a dog out on the ski trails can't deny the joy it brings to these animals. It is contagious. A dog day pass ($10) is required for each dog.
Adaptive Skiing
Whether you have a long-term physical limitation or are recovering from a knee or hip replacement, adaptive nordic skiing can provide you with a great way to get out and enjoy the groomed ski trails with friends and family.


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Newtown victim Charlotte Bacon, 6, loved the color pink
NEWTOWN, Conn. -- Charlotte Bacon loved the color pink.
Her family said they will remember how the 6-year-old with curly, red hair expressed her individuality through her favorite color, according to her obituary.
On Friday, the day she was killed in Sandy Hook Elementary School, Charlotte was wearing an outfit bought specifically for the holidays: a pink dress and boots, her uncle, John Hagen, of Nisswa, Minn., told Newsday.
Charlotte had been begging her mother, JoAnn, to let her wear the outfit to school. Her mother relented on Friday. By the age of 6, it seems, Charlotte had mastered the art of persuasion.
Family members said they would remember Charlotte's beautiful smile and energy for life.
Charlotte loved kicking and throwing punches during weekly taekwando lessons with her father, Joel, and 9-year-old brother, Guy.
"She was going to go some places in this world," Hagen told the newspaper. "This little girl could light up the room for anyone."
Since the age of 2, Charlotte wanted to be to be a veterinarian, according to her obituary.
In her six years of life, she had never come across an animal she didn't like, her family said.
Joel Bacon is a scientist and JoAnn Bacon is a stay-at-home mother who served as her daughter's Girl Scout leader, the Wall Street Journal reported. They have lived in Sandy Hook for four or five years.
Charlotte's grandparents are retired missionaries who moved to Sandy Hook this year to be closer to their grandchildren, according to David Dougherty, of Highlands Ranch, Colo., a former colleague of Dan Bacon, Joel's father.
Charlotte's family said they will remember her as "an extraordinarily gifted 6-year-old who filled her family each day with joy and love."


text:
Alright, it's time for another big cat tutorial! This time I'll be showing you how to draw a jaguar. If you ever get leopards and jaguars mixed up just remember that jaguars have circular groupings of spots and shorter tails. Jaguars are also native to the areas around Central America while leopards are indigenous to Africa and Asia. Let me know in the comments if you want a leopard tutorial as well!
DragoArt members upload artwork and drawing tutorials! They are also allowed to leave comments on tutorials, profiles, etc. Many more features, as well; it's way better than just being a boring guest! Register Now!


text:
Make social videos in an instant: use custom templates to tell the right story for your business.
Post jobs, find pros, and collaborate commission-free in our professional marketplace.
Get your team aligned with all the tools you need on one secure, reliable video platform.
Browse and buy exceptional, royalty-free stock clips, handpicked by the best.
Cub Studio
See more at 100Frames.com
100 Frames is a brand new collaboration between Animator and Director - Fraser Davidson, Actor and Writer - Dan Jones and Producer - Matthew Harvey. We work together with a small team of colleagues, including Simon Tibbs and Morgan Samuel.
With over 20 years experience in the entertainment industry, the trio aim to create an exciting forum in which to combine animation, comedy and art. The unique quality to our site is to attract like-minded people who want to create and showcase their craft.
Applying the moniker - '100 frames', there are only a few simple rules to what the content on our site can be. Firstly, each creation must be no more than 100 frames of animation. Secondly, it must be funny. Thirdly and most importantly, it must be artistic and beautiful.
We hope you enjoy.
Fraser, Dan & Matthew


text:
Fairview Health Services is seeking Neonatal Nurse Practitioners to join our Neonatal Nurse Practitioner team. NICU locations include: University of Minnesota Masonic Children's Hospital, Fairview Southdale Hospital, Fairview Ridges Hospital, Maple Grove Hospital and North Memorial Hospital.
SIGN-ON BONUSES being offered to both NEW and EXPERIENCED NNP's.
The NNP is a member of the health care team who works in collaboration with licensed physicians to provide comprehensive health care services to NICU patients and families. The NNP will engage in independent decision making about health care needs; managing the care of NICU patients hospitalized with complex acute health problems. Diagnose, prescribe medications and interventions, order and interpret laboratory and diagnostic tests, coordinate the interdisciplinary health care team, plan and coordinate patients' discharge, rehabilitation, home health care and follow-up; ensuring continuity of care within the hospital setting. The NNP will also perform procedures within their scope and realm of their collaboration agreement with their physician partner.
With 22 lakes in the city limits alone, Minneapolis combines a lush green environment with cosmopolitan sophistication. Music, theater and world-class art, history and culture museums thrive here alongside abundant sports and recreation opportunities. Sidewalk dining, abundant shopping, educational excellence and economic vitality combine to make Minneapolis an attractive city in which to live and work.
Contact information:
email@example.com 800-842-6469
EEO/AA Employer


text:
Balls Stick Together
The Balls are on fire.
The Balls are on fire. In an intensely fierce game at the end of November, the RISD basketball team won over its top rival: Cooper Union. The win was doubly sweet as it's the first time in the history of the two clubs that RISD has triumphed over the New York-based squad.
"The crowd's reaction was explosive," remembers Byron Olson 12 IL, the athletic coordinator who oversees the Balls. "Fans jumped out of their seats to rush the court. Everyone was cheering and hugging."
But the coup was far from a shutout. In the first half of the game, RISD was down a disheartening 16 points. The turning point came in the second half when Connor Griffith 15 FAV narrowed in on Cooper Union's lead by sinking a series of well-executed shots. RaMell Ross MFA 14 PH – a newcomer to the team who played NCAA basketball for Georgetown University – helped close the gap by fouling out the opposing team's best player.
"The running joke is that RaMell Ross is actually 7,000-feet-tall," Olson says with a smirk. "He's a powerhouse of a player. The Cooper Union coach was not happy to see him step onto the court."
After Ross netted his freethrow shots with ease, the Balls continued to edge out Cooper Union by making smart, skillful plays. When the final buzzer went off, the scoreboard flashed 63-57. "It great to see history in the making," notes Olson. "It was truly a team effort."
According to the Balls, the rivalry between the two teams is heated. "Our truest rival may be Pratt [Institute]," notes Olson. "But no team is more of a threat on this campus than Cooper Union. Maybe it's because – until now – they've been whooping us for the last 10 years. It felt so satisfying to finally beat them."
Game commentators Timothy Plummer 16 GD and Adam Blake 16 AP provide some courtside ball busting of their own. Microphones in hand, the cheeky sophomores deliver hilarious recaps of the game peppered with astute pop-culture references and playful comments about teammates' physical attributes.
"I know absolutely nothing about basketball, which is precisely why they asked me to commentate. But we are experts at hyping up the home crowd," notes Blake. "Sometimes I like to make lewd comments about the other team – usually while blasting the Spice Girls."
The team has a storied history. Originally founded in the 1970s, the Balls had disbanded by the time Joe Gebbia 05 ID/GD (now a RISD trustee and co-founder of the popular lodging company Airbnb) got to RISD. But the avid basketball player knew that there was plenty of interest – if precious little time – among the student body, so he worked with what is now the Center for Student Involvement to get a new team off the ground. During a recent visit to New York, current team captain John Bai 14 ID sat down with the start-up entrepreneur to discuss the future of the Balls. The meeting proved to be so inspiring that the industrial design senior now plans to start an on-campus campaign to call for the evolving Campus Master Plan to include a basketball court.
As it stands now, players walk up College Hill every Tuesday night to practice at the nearby Wheeler Gym (owned by the private K-12 Wheeler School). Players are getting fit and fine tuning their technique in preparation of the first-ever Art School Invitational, a tournament hosted by RISD, Mass Art, Cooper Union and The New School. The Balls are confident that their camaraderie will take them all the way.
"I think this season will be our best yet," notes Plummer. "To borrow a phrase from the court, when the heat is on, the Balls stick together."
-Abigail Crocker


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Diadora Sportswear for Women
The Diadora women's wear range includes a wide choice of sportswear for women, designed and produced to guarantee maximum comfort, with the best technology. From windproof jackets to breathable sweatshirts, including gilets and tracksuits, Diadora's girlswear has everything you need to play sport in any weather, without compromising on style. Be captivated by all the exclusive details on our T-shirts, tank tops, polo shirts and sweaters. Match them up with soft running leggings or a pair of technical shorts. Thanks to the meticulous workmanship and perfect aerodynamics of our garments, designed to follow the contours of the female body, feeling dynamic and fashionable will no longer be just a dream. And if you want even more choice, remember that you can always visit the Women's Footwear and Accessories sections of our online shop for a totally sporty and trendy look.


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Dangerous Drug Use Falling In Western WorldIt may not seem like it, what with all the horror stories regularly meted out by the media, but the Western world is seeing a steady decline in the use of dangerous drugs. With the exception of heroin, which (for various reasons, which we'll go into a little later) is increasing its hold on the USA, more and more people are turning down the allure of drugs in favor of more regulated, less harmful entertainment.
Belgium quits coal power with Langerlo plant closureIt is the end of an era for a dirty fuel that accounted for 27% of the country's electricity generation in 1994.
CO2 Emissions Flatline in 2014, Even as Global Economy GrowsA key stumbling block in the effort to combat global warming has been the intimate link between greenhouse gas emissions and economic growth. When times are good and industries are thriving, global energy use traditionally increases and energy-related carbon dioxide emissions also go up.
EPA proposes cutting carbon dioxide emissions from coal plants 30% by 2030The Environmental Protection Agency proposed a regulation Monday that would cut carbon dioxide emissions from existing coal plants by up to to 30 percent by 2030 compared with 2005 levels, taking aim at one of the nation's leading sources of greenhouse gases.
U.N. Court Orders Japan to Halt Antarctic WhalingThe decision to ban Japan's annual whaling drive off Antarctica, handed down by the United Nations' highest court on Monday, is a hard-won victory for conservationists who have long argued that Tokyo's whaling research is a cover for commercial whaling.
The World Becomes What You TeachZoe's TEDx talk "The World Becomes What You Teach" asks: What if schooling prepared us to solve the most pressing challenges of our time, for ourselves, other people, animals and the earth? What if we educated a generation of "solutionaries"?
To tackle pollution, China to drop pursuit of growth at all costsChina will steer local governments away from the pursuit of economic growth at all costs and beef up their powers to punish polluters as part of a campaign to reverse the damage done by three decades of unchecked expansion.
California is first state to ban lead in hunting ammoIn a move to protect wildlife and the environment, California on Friday became the first state to ban lead in hunting ammunition.
Limits Approved for Genetically Modified Crops in Kauai, HawaiiLegislators on the island of Kauai in Hawaii have approved a bill that would restrict the use of pesticides by companies developing genetically modified crops there.
Environmentalists win U.S. court fight to protect whales from Navy sonarA federal judge in California has sided with environmental groups in their lawsuit against the U.S. government over Navy training exercises off the West Coast involving sonar that they say harms endangered whales, dolphins and other protected marine mammals.
New York City Air Quality Cleanest in DecadesAhh, smell that New York City air. No, seriously, go ahead. Mayor Michael Bloomberg on Thursday said the city's air quality has hit its highest levels in 50 years, a development officials say has led to fewer deaths and hospitalizations.
Europe's key animals 'making a comeback'Some of Europe's key animals have made a comeback over the past 50 years, a report suggests.
A Vaccine For HIV? Clinical Trial SuccessfulA vaccine to prevent HIV has aced clinical testing, according to Canadian researchers.
Nepal sees tiger population go up by 63% since 2009The number of wild tigers living in Nepal has increased by 63% to 198 since 2009, a government survey has shown.
Pope Francis: Gay People 'Should Not Be Judged'He told reporters people should not be marginalised because of their sexual orientation - but he reaffirmed the Church's position that homosexual acts are a sin and said its opposition to gay marriage was clear.
Canada's crime rate lowest since 1972Canada's police services are once again reporting fewer crimes, a continuing trend that has cut the national crime rate to its lowest level since 1972.
Obama to launch major initiative to curb wildlife traffickingBarack Obama launched a new initiative against wildlife trafficking on Monday, using his executive authority to take action against an illegal trade that is fuelling rebel wars and now threatens the survival of elephants and rhinoceroses.
South Korean airlines ban shark fin as cargoSouth Korea's two largest airlines, Korean Air and Asiana, said Thursday they had both decided to ban shark fin from their cargo flights as part of a growing global campaign against the Asian delicacy.
City of Vancouver proclaims country's first Meatless MondayVancouver has become the first city in Canada to embrace 'Meatless Monday,' encouraging residents to forego meat for one day a week for the sake of the planet and their health.
EU to ban pesticides in bee scareThe European Commission will restrict the use of pesticides linked to bee deaths by researchers, despite a split among EU states on the issue.
'Most Earth-like' planets discoveredThe search for a far-off twin of Earth has turned up two of the most intriguing candidates yet.
New Zealand legalises same-sex marriageNew Zealand's parliament has legalised same-sex marriage, the first country in the Asia-Pacific region to do so.
New law to protect Puerto Rico leatherback turtlesPuerto Rico has introduced a new law protecting a swathe of the island's coast that has become a major nesting site for the world's largest turtle, the leatherback.
U.N. overwhelmingly approves global arms trade treatyThe 193-nation U.N. General Assembly on Tuesday overwhelmingly approved the first treaty on the global arms trade, which seeks to regulate the $70 billion business in conventional arms and keep weapons out of the hands of human rights abusers.
Safer vaccine created without virusBritish scientists have developed a "holy grail" vaccine for foot-and-mouth disease that is safer and more resilient than current vaccines, according to an article published in the journal PLOS Pathogens on Wednesday.
China, world's largest emitter of greenhouse gasses, will tax carbonChina's Ministry of Finance has announced that the country will levy a tax on carbon emissions, reports Xinhua.
New wind power cheaper than coal or gas in AustraliaElectricity supplied from a new wind farm is cheaper than that from a new gas or coal-fired power plant in Australia, reports a new analysis published by Bloomberg New Energy Finance.
Lenses found to 'cure colour-blindness'Scientists say they have invented spectacle lenses that cure red-green colour blindness, which affects some women and one in every 10 men.
Gorillas to Be Protected with New Congo National ParkThe Republic of Congo has declared a new national park that conservationists hope with protect a core population of western lowland gorillas, a critically endangered species, as well as other threatened species, the Wildlife Conservation Society announced.
From the brink of extinction: elephant seals stage remarkable comebackIn the 19th century the Northern Pacific Elephant was thought to be extinct until a small population was discovered on an island of Baja California in 1892. Since then, the species has staged a remarkable comeback which was greatly accelerated by protective measures adopted by the U.S. and Mexican governments.
Nations agree on legally binding mercury rulesMore than 140 countries have agreed on a set of legally binding measures to curb mercury pollution, at UN talks.
Six million turn out for global garbage clean-upMore than six million volunteers from 96 countries collected an unprecedented 100,000 tonnes of garbage last year as part of a global, web-driven clean-up campaign, cyber-environmentalists said Friday.
Totally blind mice get sight backTotally blind mice have had their sight restored by injections of light-sensing cells into the eye, UK researchers report.
Obama triples area of protected California coastlineOn Friday President Obama announced the government would add almost 3,000 square miles of California coastline to the National Marine Sanctuary system, reports the Sierra Club.
Asahi's auto glass blocks UV, filters out IR raysAs prolonged exposure to sunlight increasingly becomes a health hazard, causing skin problems and even cancer, automakers have started to incorporate glass that blocks harmful ultraviolet light.
Swiss Parliament Passes Plastic Bag BanSwitzerland's Parliament has approved a motion banning single-use plastic shopping bags. Both houses of the Swiss Parliament Thursday voted to forbid the distribution of the plastic bags. The next step is for the government to implement the ban.
Earth's nearest solar neighborhood has a habitable planetThe nearest single Sun-like star to the Earth hosts five planets - one of which is in the "habitable zone" where liquid water can exist, astronomers say.
Obama 'backs assault weapons ban'US President Barack Obama wants to reinstate an assault weapons ban in the wake of the mass killings in Newtown, Connecticut, his spokesman says.
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The great news network is a news site that reports only positive news stories. Positive news inspires and motivates people to do their part to make a better world. That is why we exist.
The great news network is a news site that reports only positive news stories. Positive news inspires and motivates people to do their part to make a better world. That is why we exist.
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FRISCO, Texas -- It's a new year, and that means it's time once again for FC Dallas' fourth annual Cocktails & Cleats season kickoff event. But this isn't the same C&C from years' past; we've revamped the entire event to make the party bigger and better so we can get the 2014 season started right!
Join us on Thursday, March 6 from 7-10pm at F.I.G. (1807 Ross Ave. Dallas, TX 75201), our brand new downtown location, for Cocktails & Cleats 2014!
For the first time ever, admission to Cocktails & Cleats will be FREE and open to the public (21 and up only), and it will be your first chance to see the brand new 2014 FC Dallas home kit presented by AdvoCare. The FC Dallas Foundation will be accepting $10 donations that will be used to purchase soccer balls for children in Brazil during this summer's World Cup.
The event will also be your first chance to meet the full 2014 FC Dallas squad and it'll still feature a silent auction benefiting the FC Dallas Foundation. Guests will enjoy complimentary food and drinks while listening to a live DJ and mingling with their favorite FC Dallas players.
So mark your calendars now and don't miss out on this one-of-a-kind event to kick off the 2014 FC Dallas season!


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I can't seem to find the filter for an image update.
Right now I have the code below, which works great until someone clicks on an image in the editor and updates it. Then it throws the height and width back in. Is there a filter I can use to stop this? I've tried several to no avail.
add_filter( 'post_thumbnail_html', 'remove_thumbnail_dimensions', 10 );
add_filter( 'image_send_to_editor', 'remove_thumbnail_dimensions', 10 );
function remove_thumbnail_dimensions( $html ) {
$html = preg_replace( '/(width|height)=\"\d*\"\s/', "", $html );
return $html;


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U.S. actor Will Smith says he turned down the chance to play the title character in Quentin Tarantino's "Django Unchained" because the role wasn't the lead.
The pre-American Civil War film was a Best Picture Oscar nominee, with Jamie Foxx playing the title character, a former slave on a journey to reunite with his wife.
Writer-director Tarantino earned the Best Original Screenplay Oscar, while Foxx's co-star Christoph Waltz won the Best Supporting Actor Oscar for his role of Django's gun-slinging partner.
"Django wasn't the lead, so it was like: 'I need to be the lead. The other character was the lead,'" Smith told EW.com.
"I was like, 'No, Quentin, please, I need to kill the bad guy!'"
Smith said he liked the way the film ultimately turned out, however.
"I thought it was brilliant," he told EW.com. "Just not for me."


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VirtuBox offers digital solutions like VirtuPaper, VirtuKiosk, VirtuVision, VirtuNav, VirtuQuery, VirtuTab. These Cloud based Software as a Service (SaaS) for Mobile devices are quick and easy to launch in days and costs less than a coffee a day, Explore and implement all possibilities VirtuBox platform offers users of your App on both iOS and Android Platforms.
White Labeled App published under your own name and brand tuned to your own target audience. Easy to search, navigate, share products, services with your team members, friends, family through images, videos, etc.
Access, control and edit content, images, videos, orders, queries etc. through mobile devices in real time on the go. View detailed analytics.
Fast, easy, and cost effective. Easy to share on social media, email, SMS etc. using share feature. QR code enabled for detailed analytics on every product to reach broader audience.
Real time data available on user's behaviour and pattern. Analytics on data, product view, enquiry and order and much more by users with timestamp and geolocation.


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Viewers of Game of Thrones were rewarded in a recent episode with a highly anticipated meeting of two of the show's biggest characters, Jon Snow and Daenerys Targaryen.
But while fan theories flood the internet over the pair's relationship, local viewers may also have had that fuzzy feeling of familiarity during the episode.
During the epic culmination of seven years of plot and character development, a new Northern Ireland filming location was seen on screens around the globe: the cliffs of Fairhead.
Known as Northern Ireland's tallest cliff face, the impressive and iconic Fairhead rises 600 feet above sea level near Ballycastle.
Highly regarded as an outstanding rock-climbing location, it's believed to be the biggest expanse of climbable rock in Britain or Ireland.
HBO filmed parts of Season 7 at Fairhead, forming the backdrop for much of Episode 3, "The Queen's Justice", which saw Jon Snow finally meet Daenerys and her dragons at Dragonstone, and reunite with Tyrion Lannister.
It adds to the list of stunning Game of Thrones filming locations which are publicly accessible across Northern Ireland.
A series of new walking routes are part of the visitor experience at Fairhead, where hardy walkers can enjoy breathtakingly beautiful views from the top to Ballycastle, Murlough Bay, Rathlin Island and the Scottish isles.
The challenging route – which requires good walking boots, a map and caution near the cliff edge (particularly in bad weather) - gives walkers a sense of how fire, ice and volcanic activity shaped the unique formation of the headland some 60 million years ago.
Walkers have a number of route choices, with loops from 1.5 to 3.4 miles. Whichever walk you choose to do, take time to read the hidden interpretation information at some of the waymarkers pointing out important sites of historic and geological interest along the way.
There are early housing settlement villages, known as clachans, to be discovered. The area was once an important industrial site for coal mining and the kelp industry.
And just like Westeros, it's steeped in mystic mythology. Legend has it the Children of Lir were put under an evil spell, transforming them into swans to spend 900 years in exile from humanity in the Sea of Moyle. You might say they got off easy compared to some of the Stark children…
Wild goats roam the rocks beneath the clifftops, as you wind along the rugged coastline. After a gradual climb, views of Ballycastle and Rathlin island will open up, offering an almost bird's eye view of the lighthouses and rocky shores. The Hebridean islands of Islay, Jura and the Mull of Kintyre on the Scottish mainland echo of the ancient kingdoms of Dal Riata (Dalriada) and the Rithe Innse Gall (The Lords of the Isles).
These Gaelic kings controlled this sea kingdom for hundreds of years, later becoming Lords of the North Coast and Glens of Antrim. Their dynasty was known as The Mac Donnell Clan but unlike Jon Snow they never tried to claim the title of "King in the North".
Other Game of Thrones filming locations nearby include Larrybane, which became Renly Baratheon's camp in the "Stormlands". It's where Brienne of Tarth was granted her wish to be named to Renly's Kingsguard.
Murlough Bay, a hidden gem, was transformed into "Slavers Bay" in Season 5. It's where slavers captured Tyrion Lannister and Ser Jorah Mormont – and is accessible by foot via a steep winding path.
And further along the Causeway Coast lies one of the show's most recognisable filming locations, Ballintoy Harbour. It has become synonymous with Pyke and the Iron Islands and was first used for these scenes in Season 2 Episode 2: The Night Lands.
Judith Webb, Tourism NI's Experience Development Officer, said: "Game of Thrones is the biggest TV show in the world and it has been transformative for Northern Ireland as a screen tourism destination.
"There is an international hunger to access the filming locations, providing a huge tourism opportunity for Northern Ireland. But it also gives locals a new reason to get out and explore our beautiful landscape - the filming locations provide a unique itinerary for the ultimate Northern Ireland staycation."
To navigate your way around the accessible filming locations from the show, download the Game of Thrones® Filming Locations Northern Ireland app, available for Apple and Android at DiscoverNorthernIreland.com/GameofThrones. Here you can also view Game of Thrones experiences around Northern Ireland and the Fairhead walking routes, opened by Heart of the Glens Landscape Partnership Scheme.


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Scientific Explorer Electric Motor Mini Lab
Please check your favorite toy retailer for availability. Prices may vary.
Electric Motor Mini Lab
Product Description
Kids will love learning out to make their own electric motor! Let kids explore the basics of electro-magnetics with this fun science kit from Scientific Explorer®. This kit lets kids build their own working motor, install it in a mini-boat, and cruise their boat around in water! This science kit is a great educational gift for kids 8 and older.
Electric Motor Kit includes:
- Spool of wire
- Propeller
- Boat
- Motor base
- Rear spaces
- Front spacer
- Spacer ring
- Spacer cap
- Battery holder
- 2 magnets
- Sandpaper
- Compass needle
- Motor shaft
- 3 battery contacts
- 3 armature contacts
- 2 brushes
- 10 armature plates
- 16-page instruction manual
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SinCity87 - PornHub [Chicago Unsigned Artist]
From The Upcoming mixtape "Pay2Play" SinCity87
releases his first offering...
Directed By @SeussLeroy
For Bookings Email email@example.com and follow @sincity87
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Governor Whitmer supports allowing undocumented (illegal) immigrants drivers license privileges.
Making this a Michigan state-wide option could pose problems (withstanding and beyond Trump).
For example, how many laws would an undocumented immigrant have to break or ignore to present to the Secretary of the State to acquire a drivers license (last I checked you need very specific documents)?
What will the adaptations be to allow the illegals licensing process (documentation) not available for US citizens?
And how does this advance Detroiters? How would auto insurance be impacted? How would liability be addressed in the case of accidents.


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Make yourself comfortable–pull on a self–designed hoodie that's all YOU, any way you zip it. Just create a sweatshirt or hoodie with the photo, image or even saying of your choice, and when you slip it on, you'll feel the ultimate in cozy. Soft, snuggling fleece on the inside and customized zip hoodie on the out make this quite possibly the most comfortable sweatshirt known to man, woman or child. And when you add your own style a la our CafePress Product Designer, you create a custom, no minimum order sweatshirt that speaks your very own warm & toasty language.
Want to share that language with others? Design away! You can create customizable sweaters for all your friends and family–no minimum order required! Warm, comfy, and one–of–a–kind hoodies and sweatshirts–what's not to love?


text: It is said that The Holy Family visited Glastonbury in Somerset when Jesus was a boy and that is the theme of this song written by Alan Bell a few years ago. It is one of our most requested numbers and we had the pleasure of performing it on Harry Secombe's 'Highway' programme recently. (1990)


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Using and Understanding the NE1 Counter
Posted by on 08 November 2011 10:29 AM
The NE1 web builder includes a simple, but effective web counter to enable a webmaster to keep track of hits to a particular page on their site. It is important to note here that the Bronze, Silver, and Gold hosting packages all contain much more sophisticated counters and statiscal analyzers for a more in depth study of your site's stats. However, the NE1 counter is a good way to get a quick overview of your busiest pages and your monthly traffic.
NOTE: The numbers in the columns may not always add up correctly as they are figuring totals based on hits since the last "reset."
The easiest method for accessing the counter is to log in to the webmaster page. The counter icon is at the upper right corner of a set of icons:
Once the counter is accessed, it is easy to see simple hit stats for the site's individual pages. Pressing the 'Reset' button will set all numbers back to zero.


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Safety through optimal suspension tuning! Progressive winding of the fork springs ensures optimal performance for road and track use. At low compression, they offer maximum convenience due to the finest response (low breakaway torque). At the same time, if compressed further, the springs enable tight and precise driving for best traction properties and drift protection. For the right damper tuning to the fork springs the recommended Wilbers fork oil should be used - the viscosity may vary from the one used originally.
For our Swiss customers:
Please note that due to road traffic legislation of Switzerland subsequently a valid authorization certificate must be issued by one of our Swiss Stores.
For our Swiss customers:
Please note, that due to the Swiss traffic regulation you'll need a valid allowance certificate which will be issued by our Swiss shop assistants and will NOT be delivered with the article.