While there isn't any opposing perspective for this announcement, it will not function as a booming thesis. Hence, it's crucial that you know strategies to make a very distinct thesis announcement and build up your own debate as quickly as you possibly can. A thesis statement, when it's really a good person, empowers the author decide what arguments and evidence are necessary to produce your own purpose. The reason announcement could possibly be voiced from lots of paragraphs or maybe an whole paragraph.
Both examples are excessively large. You'll find numerous ways to get search materials. This sort of thesis announcement could be particularly helpful if you are getting to be drawing evidence from many of resources. Just because you can find just two kinds of thesis announcements ( persuasive and informative ), you will find two fundamental styles you may utilize.
For extra assist, fully free thesis generators and also manufacturers are offered on the internet. Speaking to a friends during analysis is vital, also I Have discovered that analyzing at a coffee shop as opposed to some library will be a better choice. A thesis is really actually a bit of writing done for a portion of a university diploma with students, dependent on their own research. A "working thesis" is just a thesis that is the right one for you, aiding you to watch wherever your thoughts will be moving.
You can utilize harsher paragraphs within the body of this paper to fortify your place utilizing factual evidence. You will click the case button in most segment to watch a very good instance of a thesis announcement. Your thesis needs to be important so the report can use a structure that's flexible as a way to match from the shoes of their viewers. Composing a great thesis is only one of many most difficult segments of this writing approach, and therefore do not be prepared to perfect it on very first few attempts.
Furthermore, the much more clear you're on your thesis announcement, the easier it really is certainly likely to become for you to compose your draft or prepare your own slides. That will be however a wide breakdown of thesis statements also it ought to be read together with my informative article about ways to compose an effective debut so as to become fully understood. Even though this isn't the ideal thesis statement, the above mentioned instance in position is really to demonstrate how to produce and revise an thesis proposal.
Because there isn't any conflicting view to the statement, it doesn't function as a prosperous thesis. Hence, it's vital that you simply learn strategies to construct a very distinct thesis announcement and build up your argument as quickly as possible. A thesis statement, when it's a good one, enables the author pick what arguments and signs are needed to produce your own purpose. The purpose announcement could be expressed at lots of paragraphs or maybe an whole paragraph.
Finally, you may possibly have spent a lot of time producing your thesis and still not understand whether it's a good one. A thesis is that the effect of an increasingly prolonged believing strategy. Our thesis statement may wish to state one major problem plus yet another key remedy. This extensive thesis announcement conducts the chance of enabling you to move off several tangents.
The reader knows exactly what you mean to go over from the newspaper, exactly what you will argue concerning the matter, and also why it's crucial. You could have a standing at heart, or maybe you just have an total topic you-know you prefer to do the job with. Considering the method that you would really prefer to approach your matter, in different words what sort of promise you prefer to earn, is 1 method to concentrate your thesis onto just one specific facet of your broader matter. Just have a situation around the discipline.
You may possibly have known of something referred to as a thesis. Most significantly, it will offer you a clearer picture of that which you'll love to add in your final thesis. Developing a Thesis just before you compose a thesis statement, it's important to spend some time reading academic articles to collect general background data regarding the problem. It is vital to develop a thesis statement before composing the paper, but such a thesis is usually called a functional thesis and can change together with the contents of the essay .
Whilst the author, you may make use of the thesis announcement for a guide in producing a coherent discussion. Having a tiny amount of exercise, you can write top excellent thesis statements which attract focus to all your papers that are argumentative. It's not simple to create a thesis which accomplishes each of of your own objectives, however it's essential for having a booming essay. What's more, a great thesis is accurate, that means when it is examine it could simply have one particular shot.
Finally, you may possibly have invested a lot of time producing your thesis and not know whether it is a nice person. A thesis would be that the consequence of an elongated thinking approach. Our thesis announcement will desire to state one principal problem and yet one important option. This extensive thesis statement runs the threat of permitting one to move off on several tangents.
You can utilize harsher paragraphs within the human body of the newspaper to fortify your own position utilizing factual signs. You may click the case button at every area to observe a fantastic illustration of a thesis announcement. Your thesis needs to be important so the report may work with a structure which is flexible in order to suit at the footwear of the viewers. Composing a excellent thesis is just one of the toughest sections of the writing approach, and so do not expect you'll perfect it on the very first few tries.
Once you are pleased with the total debate your newspaper makes, come back for your thesis and also see whether it captures exactly what you've argued. Potential as you can't cover all them in 1 newspaper. Be certain your paper reinforces your thesis announcement whatsoever situations. It is unquestionably the most important sentence in your paper!
First, the exact first consideration to bear at heart about a thesis announcement is that it's never put in rock. First, it must be contingent upon a posture carried on an matter rather than restating a truth. Whenever somebody reads your thesis statement, they should have an atmosphere of exactly what the paper is really all about and also that which, if any, slant or debate you've got. A thesis announcement to an argument composition doesn't necessarily deal with a particular audience as it's written to broader audience with all your time and effort to persuade the others to some certain view.
The reader understands exactly what you mean to go over from the newspaper, what you will argue about the topic, and also it's essential. You could already have a standing at heart, or you might just have a overall topic you-know you prefer to operate with. Considering the way you would really prefer to approach your matter, in various phrases what kind of promise you prefer to make, is 1 method to focus your thesis onto just one specific part of one's broader theme. Only take a situation about the discipline.
Since you compose a paper, your primary point can change. If you are experiencing difficulties about the perfect method to select the topic or thesis, cut down everything that comes in your thoughts about a little bit of paper. When a thesis applies a coordinating sentence, including a few parts, it's crucial that each of the pieces are closely related so the focus of the paper isn't diffused. If you're given that the topic, you should trust the type of newspaper which you will need to supply.


text:
Pakistani governor who opposed blasphemy law is…
Pakistani governor who opposed blasphemy law is killed
ISLAMABAD — The governor of Pakistan's most dominant province was shot and killed Tuesday by a bodyguard who authorities said was angry about his opposition to blasphemy laws carrying the death sentence for insulting the Muslim faith.
Punjab Gov. Salman Taseer, regarded as a moderate voice in a country increasingly beset by zealotry, was a close ally of U.S.-backed President Asif Ali Zardari. He is the highest-profile Pakistani political figure to be assassinated since former Prime Minister Benazir Bhutto three years ago, and his death underscores the growing danger in the country to those who challenge the demands of Islamist extremists.
Taseer was riddled by gunshots while walking to his car after an afternoon meal at Kohsar Market, a shopping center in Islamabad popular with Westerners and wealthy Pakistanis. He was shot in the back, said Shaukat Kayani, a doctor at Poly Clinic Hospital.
Initial reports indicated the suspected gunman, a police commando guarding Taseer, unloaded up to 26 rounds from a Kalashnikov automatic rifle. The gunman could have fired that number of rounds in a matter of seconds.
Other guards forced the police commando to the ground, according to police and hospital officials.
"It was one shot first and then a burst," said R.A. Khan, a witness. "I rushed and saw policemen over another police commando, who was lying on the road with his face down."
An intelligence official interrogating the suspect said the commando had been planning the assassination since learning three days ago that he would be deployed with the governor. Police were trying to determine how he was assigned to Taseer's security detail Tuesday and whether he had any help.
Taseer's admirers called the governor a profile in courage in a fight for the soul of Pakistan, which in recent years has increasingly swung away from South Asia's Sufi-influenced moderation to the more fundamentalist approaches to Islam found in some areas of the Middle East.
"Taseer showed himself to be a rare politician, willing to risk his life in espousing an unambiguous position against discrimination and abuse," said Ali Dayan Hasan, senior South Asia researcher for Human Rights Watch.
Cesar Chavez' great-niece 'honored' civil rights leaders' bust part of Biden's Oval Office

redpajama_set_name: RedPajamaCommonCrawl


text:
Nickelodeon Greece To Premiere "Make It Pop" On Monday 5th October 2015
Nickelodeon Greece has announced the exciting news on their official website that Nickelodeon Greece will start to premiere and show Nickelodeon's brand-new musical comedy series "Make It Pop" on Monday 5th October 2015 at 9:30pm!
What do an aspiring pop diva, a fashionista and a book worm have in common? Music! "Make It Pop" (20 episodes) is a comedic, music-infused daily strip about three unique girls who come together to start their own K-Pop-inspired band. Randomly selected to room together at the at Mackendrick Prep boarding school, bookish Corki (Erika Tham), fashion-forward Jodi (Louriza Tronco) and social media maven Sun Hi (Megan Lee) meet and bond over music. With the help of fellow classmate and aspiring DJ, Caleb (Dale Whibley), the girls grow from roommates to bandmates when they form their new group, XO-IQ. Can they achieve pop stardom in a school where academics come first and the arts come last? How will these rising stars balance music, grades, relationships and crushes? There's only one way to find out! Get ready for fun, drama, and musical comedy with a K-pop twist and an EDM beat! The series, which features original songs and performances in every episode, is co-created by Thomas W. Lynch and Nick Cannon and produced by DHX Media. Nickelodeon recently ordered a twenty episode second season of "Make It Pop".
Pictured: (L-R) Jodi (Louriza Tronco), Sun Hi (Meghan Lee) and Corki (Erika Tham) in the new live-action series, Make It Pop, coming to Nickelodeon in the 2015-16 season. Photo Credit: Nickelodeon. ©2015 Viacom International, Inc. All Rights Reserved.
To celebrate, Nickelodeon.gr has launched the channels all-new official "Make It Pop" show website, which features information about Nick's brand-new show!
Follow NickALive! on Twitter, Tumblr, Google+, via RSS, on Instagram, and/or Facebook for the latest Nickelodeon Greece and Make It Pop News and Highlights!
Labels: Make It Pop, Nickelodeon Europe, Nickelodeon Greece, Nickelodeon Highlights, Nickelodeon International, Nickelodeon News, Nickelodeon Shows, Official Nickelodeon Websites
Nickelodeon Greece To Premiere More New "ALVINNN!!! And The Chipmunks" Episodes From Sunday 4th October 2015
Nickelodeon Greece has announced the exciting news on their official website that Nickelodeon Greece will start to premiere and show more brand-new episodes of "ALVINNN!!! and the Chipmunks", locally titled "Ο ΑΛΒΙΝΝΝ!!! και η παρέα του", every Sunday at 2:45pm from Sunday 4th October 2015!
Alvin, Simon and Theodore are brothers who tour the world as famous rock stars and still manage to go to school. Completely normal... right? Did I also mention that they're Chipmunks? Along with their best friends, Brittany, Jeanette and Eleanor, also known as The Chipettes, Alvin and his chipmunk brothers cause tons of trouble on and off the stage while their dad, Dave, tries to manage these three rambunctious rodents, while writing all of their hit songs. Alvin, Theodore, and Simon are so different, it's hard to believe that they came from the same litter. With little voices and BIG personalities, there will be no shortage of adventures when these Chipmunks hit the stage!
Follow NickALive! on Twitter, Tumblr, Google+, via RSS, on Instagram, and/or Facebook for the latest Nickelodeon Greece and ALVINNN!!! and the Chipmunks News and Highlights!
Labels: ALVINNN!!! and The Chipmunks, Animation, Nickelodeon Acquisitions, Nickelodeon Europe, Nickelodeon Greece, Nickelodeon Highlights, Nickelodeon International, Nickelodeon News, Official Nickelodeon Websites
Nickelodeon Greece To Premiere More Brand-New "Winx Club" Season 7 Episodes From Sunday 4th October 2015
Nickelodeon Greece has announced the Winx-Tastic news on their official website that Nickelodeon Greece will start to premiere and show more brand-new episodes from the all-new seventh season of the popular animated series "Winx Club" every Sunday at 10:10am from Sunday 4th October 2015!
The seventh season of "Winx Club" carries on with the environmental themes of previous seasons. "Winx Club" series seven carries on the theme of recent Winx releases by carrying a strong environmental message. In this adventure the fairies discover the real importance of the rare Fairy Animals, which they must save from Kalshara, an evil shape-shifter and her clumsy brother, Brafilius. Each Fairy Animal has their own special talent, which is necessary for the balance of the Magic Universe. The theme of endangered animals recurs throughout the series as the Winx establish an Animal Rescue Park on Earth, where they look after vulnerable animals such as pandas and tigers. The girls also undertake missions in the Magic Dimension and Earth to raise public awareness about the animal cause. This builds to their final mission – to discover the ultimate power of the Fairy Animals, which can give control over all the animals of the Magic Universe. The Winx will also be confronted with two new terrible villains.
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Labels: Animation, Nickelodeon Acquisitions, Nickelodeon Europe, Nickelodeon Greece, Nickelodeon Highlights, Nickelodeon International, Nickelodeon News, Nickelodeon Shows, Official Nickelodeon Websites, Winx Club
Nickelodeon Australia And New Zealand To Premiere "One Crazy Cruise" On Friday 9th October 2015
Nickelodeon Australia has announced the exciting news in a post on their official Facebook profile page, Facebook.com/NickelodeonAustralia, that Nickelodeon Australia and New Zealand will premiere the brand-new Nickelodeon Original Movie "One Crazy Cruise" on Friday 9th October 2015 at 6:30pm!:
Labels: Liar Liar Vampire, Nickelodeon Australia And New Zealand, Nickelodeon Highlights, Nickelodeon International, Nickelodeon News, Nickelodeon On Facebook, Nickelodeon TV Movies, One Crazy Cruise
Nickelodeon Australia and New Zealand To Premiere "Every Witch Way" Season 4 On Monday 12th October 2015
Nickelodeon Australia, in a post on their official Facebook profile page, and SKY TV have announced the magical news that Nickelodeon Australia and New Zealand will start to premiere and show brand-new episodes from the all-new epic fourth and final season of "Every Witch Way", beginning with the season opener, "A World Without You", every Monday to Thursday at 6:30pm from Monday 12th October 2015!:
Labels: Every Witch Way, Nickelodeon Australia And New Zealand, Nickelodeon Highlights, Nickelodeon International, Nickelodeon News, Nickelodeon On Facebook, Nickelodeon Shows, Nickelodeon Stars
Nickelodeon Benelux Acquires Rights To "The New Adventures Of Geronimo Stilton" Season Three
The entertainment news website C21Media is reporting the exciting news that Atlantyca Entertainment has pre-sold brand-new episodes of from the upcoming third season of "The New Adventures of Geronimo Stilton" to Nickelodeon Benelux (Nickelodeon Netherlands (Nederland) and Nickelodeon Belgium (België; Flanders)), following Nick Benelux acquiring the broadcast rights to the popular animated series in October 2014!
Image via Animation World Network
"The New Adventures of Geronimo Stilton", a co-production between Atlantyca and French prodco Superprod with Rai in Italy and France Télévisions, follows the story of internationally renowned mouse-journalist Geronimo as he travels across the globe.
Follow NickALive! on Twitter, Tumblr, Google+, via RSS, on Instagram, and/or Facebook for the latest Nickelodeon International News and Highlights!
Labels: Animation, Nickelodeon Acquisitions, Nickelodeon Belgium, Nickelodeon Benelux, Nickelodeon Europe, Nickelodeon International, Nickelodeon Netherlands, Nickelodeon News, The New Adventures of Geronimo Stilton
Nickelodeon South East Asia To Premiere Brand-New "Alvinnn!!! And The Chipmunks" Episodes From Monday 5th October 2015
Get ready for new adventures and a whole lot of trouble!
Nickelodeon South East Asia has announced the exciting news in their latest Facebook cover photo on Facebook.com/nickasia that Nickelodeon South East Asia will start to premiere more brand-new episodes of the hit CG-animated preschool series "Alvinnn!!! and the Chipmunks" every weekday between Monday 5th and Friday 16th October 2015!
Nick SEA will debut each all-new "Alvinnn!!! and the Chipmunks" episode weekdays at 5:30pm on Nickelodeon Philippines (PH) and Nickelodeon Indonesia (WIB) and at 6:30pm on Nickelodeon Singapore (SG) and at 7:30pm on Nickelodeon Philippines (PH) and Nickelodeon Malaysia (MY).
Follow NickALive! on Twitter, Tumblr, Google+, via RSS, on Instagram, and/or Facebook for all the latest Nickelodeon Asia and Alvinnn!!! and the Chipmunks News and Highlights!
Labels: ALVINNN!!! and The Chipmunks, Nickelodeon Acquisitions, Nickelodeon Asia, Nickelodeon Highlights, Nickelodeon International, Nickelodeon News, Nickelodeon On Facebook, Nickelodeon Video Clips
Nickelodeon 4Teen (France) To Premiere "Make It Pop" On Monday 12th October 2015
Nickelodeon France has announced the exciting news in their latest trailer that Nickelodeon 4Teen will start to premiere and show Nickelodeon's brand-new musical comedy series "Make It Pop" on Monday 12th October 2015 at 17:50!:
Ta nouvelle série Make It Pop débarque sur NICKELODEON 4TEEN à partir du lundi 12 octobre !
To celebrate Nickelodeon France debuting "Make It Pop" in October 2015, nickelodeon.fr has launched Nick France's all-new "Make It Pop" show website, which features information about Nick's brand-new show, character bios for Sun Hi, Corki, Jodi and Caleb, exclusive online streaming video clips, including music videos, and a fantastic "es-tu plutôt Corki, Jodi ou Sun Hi?" quiz!
Follow NickALive! on Twitter, Tumblr, Google+, via RSS, on Instagram, and/or Facebook for the latest Nickelodeon France and Make It Pop News and Highlights!
Labels: Make It Pop, Nickelodeon Europe, Nickelodeon France, Nickelodeon Highlights, Nickelodeon International, Nickelodeon News, Nickelodeon Promos, Nickelodeon Shows, Official Nickelodeon Websites
Nickelodeon UK Unveils Four Brand-New "Short Toons" For October 2015
Nickelodeon UK and Ireland has unveiled the latest batch of freshly selected "Short Toons" on their official Nicktoons website and award-winning Nick App!
Covering topics as varied as video games, zombie siblings and port-a-loo-loving Meerkats, twelve developed shorts from the 2013 edition of Nickelodeon's world renowned Global Animated Shorts Programme are currently rolling out on nicktoons.co.uk and Nick App. Four shorts will be available to view at any one time and, on the Nicktoons site, viewers will be able to show their appreciation for the creative work by selecting the "vote" button.
The current shorts available to view are:
Marty's Exotic Animals created by Andrew Friedman:
Marty tries to have Tony, an Amazonian parrot, impress the prettiest girl at school!
Tallie Peer Counselor created by Laura Sreebny
With Tallie Silverman's advice and counsel, you'll be transformed to Prince Charming in no time! Written and directed by Julia Vickerman, animation by PUNY, and music by Adam Deibert and Jarond Gibbs.
Odyssey Squad! created by Ben Adams
There are a lot of situations that distract the Odyssey Squad from their mission!
Wing Dings created by TJ Fuller
What is more fun than a pup in a jar?!
Watch on nicktoons.co.uk and on the Nick App today!
"The Animated Shorts Program aims to discover, mentor and collaborate with exciting new talent in order to develop the best content for Nickelodeon," said Nina Hahn, Senior Vice President, International Production and Development, Nickelodeon. "These shorts all have the potential to be developed into a longer-form series so it is great to be able to share them with UK fans and, through the vote button, get a sense of what is popular with audiences."
The Global Nickelodeon Animated Shorts Program is open to creatives across the world. The 2016 edition of the initiative will launch in January 2016. More information is available at http://nickanimationstudio.com.
Additional source: Cartoon Brew.
Follow NickALive! on Twitter, Tumblr, Google+, via RSS, on Instagram, and/or Facebook for all the latest Nickelodeon UK News and Highlights!
Labels: Nick App, Nickelodeon Animated Shorts Program, Nickelodeon News, Nickelodeon Shorts, Nickelodeon UK News, NickToons (Animation), Official Nickelodeon UK Websites, Short Toons
Mr. Dooves Unveils A Cappella Cover Of "Cardcaptors" Theme Tune
Wind, Rain, Shadow, Wood, Sword, Thunder, Power, Sleep. Cardcaptors of the Clow, Expect the unexpected now!
In their latest addition to their "Saturday Morning A Capella" playlist, YouTube channel Triforcefilms has unveiled an a capella version of the "Cardcaptors" theme tune, which you can watch in the fantastic music video below!:
In the video clip, Mr. Dooves records himself singing and humming 10 different parts (which you can see individually), while the theme song's familiar opening titles plays in the centre of the screen. It's another of those videos you can watch multiple times, yet continue to notice new things!
"Cardcaptors" is the North American version of the popular Japanese anime television series "Cardcaptor Sakura".
"Cardcaptors" follows Sakura, an ordinary girl, in an extraordinary world! A world of magic, mystery and mayhem as she struggles to recapture the legendary Clow Cards, which each have a power all their own.
Sakura can use the cards she's already captured to help her in her quest to capture more - and she's got a little extra help too, in the form of Keroberos - Kero for short - the guardian of the cards. He's always on hand to give advice - whether it's wanted or not!
It's not as simple as it looks, though, because Sakura has competition. The new kid in town, Li, is also collecting the Clow Cards, and he thinks he's a lot better at it than Sakura is. Even so, when Li and Sakura get together, the Clow Cards have nowhere to hide!
"Cardcaptors" aired on Nickelodeon UK in the early noughties.
If you need a refresher, here's the original theme song, in all its nostalgic glory, plus karaoke lyrics below:
Wind, rain, shadow, wood,
Sword, thunder, power, sleep
Cardcaptors of the clow,
Expect the unexpected now
The secrets of the clow
Were all a mystery
But when this mighty book was opened
The powers were set free
Cardcaptors
A mystic adventure
A quest for all time
Each card possesses a power all its own
We've got to find them to bring the power home
Additionally, below are the "Cardcaptor Sakura" opening titles:
Additional source: CLAMP Wiki
Labels: Anime On Nickelodeon, Cardcaptors, Classic Nickelodeon, Classic Nickelodeon UK, Nickelodeon Theme Tunes, Video Clips
Nickelodeon USA To Premiere New "Breadwinners" Episode "Wolf Head Bread"/"Rock N' Roar" On Sunday 25th October 2015
The television news website The Futon Critic is reporting the bread-tastic news that Nickelodeon USA will premiere and show the brand-new "Breadwinners" episode "Wolf Head Bread"/"Rock N' Roar" (#209) on Sunday 25th October 2015 at 11:30am ET/PT, straight after the fourth season premiere of "Teenage Mutant Ninja Turtles" at 11:00am!
It is currently unknown whether Nick USA will continue to premiere all-new episodes of the networks quazy original animated buddy comedy series (Nicktoon) "Breadwinners" every Sunday, or if the premiere is a one-off, for now, to celebrate Halloween.
Original source: ToonZone Forums member kanc.
Follow NickALive! on Twitter, Tumblr, Google+, via RSS, on Instagram, and/or Facebook for the latest Nickelodeon and Breadwinners News and Highlights!
Posted at 10/03/2015 12:36:00 AM
Labels: Breadwinners, Nickelodeon Highlights, Nickelodeon News, Nickelodeon Shows, Nickelodeon USA, NickToons (Animation)
Nickelodeon Greece To Premiere "Make It Pop" On Mo...
Nickelodeon Greece To Premiere More New "ALVINNN!!...
Nickelodeon Greece To Premiere More Brand-New "Win...
Nickelodeon Australia And New Zealand To Premiere ...
Nickelodeon Benelux Acquires Rights To "The New Ad...
Nickelodeon South East Asia To Premiere Brand-New ...
Nickelodeon 4Teen (France) To Premiere "Make It Po...
Nickelodeon UK Unveils Four Brand-New "Short Toons...
Mr. Dooves Unveils A Cappella Cover Of "Cardcaptor...
Nickelodeon USA To Premiere New "Breadwinners" Epi...


Consumers of fruits and vegetables are frequently exposed to small amounts of hormonally active pesticides, some of them sharing a common mode of action such as the activation of the human estrogen receptor α (hERα) or β (hERβ). Therefore, it is of particular importance to evaluate risks emanating from chemical mixtures, in which the individual pesticides are present at human-relevant concentrations, below their corresponding maximum residue levels. Binary and ternary iso-effective mixtures of estrogenic pesticides at effect concentrations eliciting a 1 or 10% effect in the presence or absence of 17β-estradiol were tested experimentally at the hERα in the yeast-based estrogen screen (YES) assay as well as in the human U2-OS cell-based ERα chemical-activated luciferase gene expression (ERα CALUX) assay and at the hERβ in the ERβ CALUX assay. The outcome was then compared to predictions calculated by means of concentration addition. In most cases, additive effects were observed with the tested combinations in all three test systems, an observation that supports the need to expand the risk assessment of pesticides and consider cumulative risk assessment. An additional testing of mixture effects at the hERβ showed that most test substances being active at the hERα could also elicit additive effects at the hERβ, but the hERβ was less sensitive. In conclusion, effects of the same ligands at the hERα and the hERβ could influence the estrogenic outcome under physiological conditions.
Copyright: © 2016 Seeger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was financially supported by the Federal Institute for Risk Assessment in Berlin, Germany (grant FK.3 1329-484 6433898). PS received the funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Many substances used as crop protection products possess hormonal activity, which may influence human health by imitating or disrupting endogenous hormones . Exposure is barely avoidable considering the widespread occurrence in conventionally grown fruits, vegetables and other crops. Up to 2013 there were about 800 substances with known hormonal activity ; their total number still remains unknown, since many substances have not been tested for that type of activity . Nowadays, high-throughput bioassays for screening purposes, which are suited to evaluate the potential of pesticides with endocrine activity, are needed. Besides the identification of effects emanating from single substances there is scientific evidence that chemical mixtures of substances sharing the same mode of action elicit predominately additive effects in vitro as well as in vivo [3–6]. Pesticide residues of substances acting in a similar way on the same cellular targets are found in/on one food sample caused by simultaneous application of various pesticides, by cross-contamination due to common storage or by application of pesticide formulations containing mixtures of pesticides sharing the same mode of action . The individual residues are usually present in low concentrations, mostly below their individual maximum residue levels, but have been shown to act additively, thereby eliciting remarkable effects, even when applied in combination with the individual compounds at concentrations below their individual No Observed Adverse Effect Levels (NOAELs) [4,5,8]. A recent cumulative risk assessment approach considers evaluating pesticides in mixtures, grouped by organ-specific toxicity, in addition to evaluating individual substances . The tested pesticides (pirimicarb, propamocarb, fenhexamid, fludioxonil, chlorpyrifos, fenarimol) were selected based on their occurrence as residues listed in the 2013 European Union report on pesticide residues in food  and their estrogenic activity known from the literature [1,11–14]. We included pesticides frequently used, like fenhexamid and fludioxonil, as well as 2,4'-DDT and 4,4'-DDT, which were banned a number of years ago and are not detected in plant-derived foodstuffs anymore , but are well-characterized estrogenic substances. Therefore, they were used to test whether the test systems are suited to detect compounds capable of activating the hERα and hERβ, but were not included in the mixture studies, since their occurrence in plant-derived foodstuffs, even in low concentrations, is unlikely. Unfortunately, data on human exposure to hormonally active pesticides is rarely available [15,16]. In this context, an analysis by Kortenkamp et al.  showed that anti-androgenic environmental contaminants are present in human serum in picomolar to nanomolar concentrations. At such concentration levels one would not expect a significant effect by individual chemicals, but mixtures of substances being present at low concentrations and sharing the same mode of action could influence the human endocrine system [4,5,8].
We investigated the effects of single pesticides (pirimicarb, propamocarb, fenhexamid, fludioxonil, chlorpyrifos, fenarimol, 2,4'-DDT and 4,4'-DDT) as well as selected binary and ternary mixtures of them at low effect concentrations in a β-galactosidase reporter gene assay, the broadly used Yeast-based Estrogen Screen (YES) assay, as well as in the human U2-OS cell-based ERα chemical-activated luciferase gene expression (ERα CALUX) assay. Full concentration-response curves were evaluated for the mathematical modeling, but the assessment of additivity was restricted to low effect concentrations (EC01 and EC10) in the range of human-relevant concentrations. Furthermore, the substances were screened in combination with a saturating concentration of 17β-estradiol (E2) to test for an E2 potentiating or an anti-estrogenic activity in the YES assay, and the anti-estrogenic substances were also tested for anti-estrogenic activity in the ERα CALUX assay.
Most studies have analyzed the mixture effects of pesticides at the hERα, while only a few reports have dealt with the effects of individual pesticides on the human estrogen receptor β (hERβ) and to our knowledge no study has investigated pesticide mixture effects at the hERβ. While the hERα frequently occurs in tissues related to reproductive activity (uterus, mammary gland), the hERβ is more widely distributed, and the ligand binding domains of the two isoforms slightly differ (59% homology) (reviewed by Gustafsson ), thereby indicating differing effects of the substances at the receptor isoforms. Since the hERβ is mostly regarded as a negative regulator of the hERα  and the risk emanating from an estrogenic substance depends on its activity at both receptor subtypes, we additionally investigated the effects of the individual test substances as well as combinations of them on the hERβ in the ERβ CALUX assay.
The well-known concept of concentration addition (CA), based on the work of Loewe and Muischnek , was used for the prediction of the outcome of the mixture experiments, supposing that additive effects of the pesticides occurred at the hERα and hERβ level.
The aim of this study was to evaluate the suitability of the established YES assay and the more recent ERα CALUX assay to identify estrogenic or anti-estrogenic effects at the hERα and to investigate mixture effects of estrogenic pesticides at low concentrations via CA. Additionally, the effects of the pesticides and mixtures at the hERβ, mostly acting as a counterpart of the hERα in vivo , were analyzed. The data generated for pesticide residue mixtures at the level of the hERα and hERβ support the assumption of additive effects of pesticides sharing the same mode of action, again emphasizing the importance of a cumulative risk assessment of pesticides.
17ß-estradiol (E2; CAS# 521-18-6; ≥ 98% purity), 17α-methyltestosterone (CAS# 58-18-4; 99.5% purity), 2,4'-dichlorodiphenyltrichloroethane (2,4'-DDT CAS# 789-02-6; 99.5% purity), 4,4'- dichlorodiphenyltrichloroethane (4,4'-DDT CAS# 50-29-3; 99.8% purity), 4-hydroxytamoxifen (4-HT; CAS# 68047-06-3; ≥ 98% purity), chlorpyrifos (CAS# 2921-88-2; 99,7% purity), corticosterone (CAS# 50-22-6; ≥ 98.5% purity), fenarimol (CAS# 60168-88-9; 99.9% purity), fenhexamid (CAS# 126833-17-8; 99,7% purity), fludioxonil (CAS# 131341-86-1; 99.9% purity), ICI 182,780 (ICI; CAS# 129453-61-8; > 98% purity), pirimicarb (CAS# 23103-98-2; 98.5% purity), propamocarb (CAS# 24579-73-5; 99.3% purity), resveratrol (CAS# 501-36-0, ≥ 99% purity), and tamoxifen (CAS# 10540-29-1; ≥99% purity) were purchased from Sigma Aldrich (Schnelldorf, Germany). By dissolving the chemicals in dimethyl sulfoxide (DMSO; CAS# 67-68-5; ≥ 99.5% purity; Carl Roth, Karlsruhe, Germany), dilution series were stored at -20°C in glass vials freeze-thawed for each experiment or batched in polypropylene vials and only thawed once.
The YES assay developed by Routledge and Sumpter  was used as described by Kolle et al.  with slight modifications: The maximal concentration of DMSO in the medium was 3% v/v and the E2 concentrations ranged from 0.01 pM to 10 nM. Each pesticide and pesticide mixture was tested in quadruplicate in at least five experiments. To asses anti-estrogenic, estrogenic or potentiating effects in combination with E2, the substances were initially tested with and without a saturating concentration of E2 (1 nM) in increasing concentrations. 4-HT at a concentration of 1 μM combined with 1 nM E2 was used as anti-estrogenic control in a complete concentration-response curve in each plate.
A cytotoxic effect was defined as a decrease in optical density of the cell suspension at 690 nm by more than 30% when compared to the solvent control , and such concentrations were excluded from the tests.
Substances that could not be fully solubilized in the YES assay were tested in a cell-free control plate, and the turbidity, as a benchmark for insolubility, was measured at a wavelength of 690 nm. This was necessary to distinguish between a real growth induction of the yeast cells by the tested substance and an artifact resulting from the insolubility of the compound at higher concentrations, since in both cases an increase of turbidity in the cell-containing assay would be observed. It should be taken into account that an increased turbidity could also mask cytotoxicity.
The ERα and ERβ CALUX assay were performed to evaluate the effect of the test substances on the hERα and hERβ as described by van der Burg et al.  with slight modifications. The pesticides were tested in three independent experiments, individually and as mixtures, in triplicates in 96-well plates. DMSO was used as solvent and was present in the test medium at a maximal concentration of 0.2% v/v. Solvent controls were included in each plate. Controls were selected based on the Organisation for Economic Co-operation and Development (OECD) Test Guideline 455 . A full dose-response curve for E2 was included in one 96-well plate per experiment (E2 concentration range: 0.1 pM to 0.1 nM in the ERα CALUX assay, 0.3 pM to 30 nM in the ERβ CALUX assay). The same plate also contained 3 μM 17α-methyltestosterone as additional estrogenic control as well as 10 nM corticosterone as negative control. On each subsequent plate per experiment a middle concentration of E2 (3 pM in the ERα CALUX assay, 0.1 nM in the ERβ CALUX assay) and a high concentration of E2 (0.1 nM in the ERα CALUX assay, 30 nM in the ERβ CALUX assay) were tested, and the effects were compared to the respective controls on the first plate. A prescreen, in which all test substances were tested for estrogenicity between 0.01 μM and 60 μM, was performed. The three highest test substance concentrations and controls were checked for their ability to affect cell membrane integrity by quantification of the lactate dehydrogenase leakage (LDH) with the CytoTox-ONE™ Homogeneous Membrane Integrity Assay (Promega, Madison, WI, USA), which was performed as recommended by the manufacturer. Those test substance concentrations leading to a decline of the effect after a maximum was reached as well as those leading to insolubility were excluded from further experiments.
In the case of anti-estrogenicity assessment in the ERα CALUX assay, test substances that showed an anti-estrogenic activity in the YES assay, fenhexamid and fludioxonil, were tested in combination with 3 pM E2 (~ EC50). One plate per experiment included a full dose-response curve of the competitive hERα antagonist tamoxifen (3 nM to 10 μM), 1 nM 4-HT as additional anti-estrogenic control and 10 μM resveratrol as negative control, all also combined with 3 pM E2.
The raw optical density values obtained at 690 nm in the YES assay were subtracted as background from the values obtained at 540 nm and thereafter the corresponding solvent control values were also subtracted. All data points were normalized to the effect of 1 nM E2 (~ EC100), and mean values were generated in the YES assay. The data from the ERα and ERβ CALUX assays were evaluated in a similar manner: Solvent controls were subtracted from the raw luminescence values and all mean values were normalized to 0.1 nM E2 (~ EC100) in the ERα CALUX assay and 30 nM (~ EC100) in the ERβ CALUX assay, with one exception: When fludioxonil and fenhexamid were tested for anti-estrogenic effects in the ERα CALUX assay, the values were normalized to 3 pM E2.
Normalized concentration-response data from the YES, ERα and ERβ CALUX assays were analyzed by nonlinear regression after the x-axis with the test substance concentrations was log-transformed. The best-fit approach established by Scholze et al.  was used with few modifications: The regression model selection was performed using the Akaike Information Criterion with a correction for finite sample sizes, whereby logit, probit, Weibull, generalized logit I and II, as well as Aranda-Ordanz were the applicable models, while the 95% confidence intervals (CIs) were determined by application of the bootstrap method with 1,000 bootstrap simulations. All mathematical/statistical analyses were performed using R version 3.1.2 (R Foundation for Statistical Computing, Vienna, Austria).
Fixed mixtures ratios were calculated to be iso-effective , i.e. in proportion to their individual concentration that caused a 1 or 10% effect, as calculated from the concentration-response curve of the individual compounds (effect concentrations EC01 and EC10, as listed in Table 1 for the corresponding test systems). The calculated mixture ratios are listed in the S1 Table. CA was applied as described by Rajapakse et al. . A worked out example of the mixture ratio calculation, production of the mixtures and interpretation of the data can be found in S1 File.
Table 1. EC01 and EC10 values of the single substances in the corresponding test systems.
The hERα was trans-activated concentration-dependently by E2 in the YES assay (Fig 1A) and the ERα CALUX assay (Fig 1B). The maximally induced hERα activity was reached at 1 nM E2 in the YES assay and at 0.1 nM in the ERα CALUX assay, while the EC50 values were 0.16 nM and 4.9 pM, respectively. Trans-activation of the hERβ in the ERβ CALUX assay (Fig 1C) was at its maximum at 30 nM E2 with an EC50 of 0.21 nM.
Fig 1. E2 in the YES, ERα CALUX and ERβ CALUX assays.
Regression models with the indicated EC50 concentrations and the 95% confidence bands for E2 in the (A) YES, (B) ERα CALUX and (C) ERβ CALUX assays.
All tested pesticides showed estrogenic activity with full concentration-response curves in the YES and ERα CALUX assays with the exception of pirimicarb, which was negative in both assays, and propamocarb, which was only active in the ERα CALUX assay (Fig 2A and 2B, Table 1, S2 and S3 Tables). Most substances were in the effect range of E2 in the YES assay, except for fenarimol with a maximum of 2.69 normalized to the effect of 1 nM E2 (Fig 2A and S2 Table). Fenarimol (maximum of 1.17) also exceeded the effect of 0.1 nM E2 in the ERα CALUX assays, as did fenhexamid (maximum of 1.37) and 2,4'-DDT (maximum of 1.23) (Fig 2B and S3 Table). Fenarimol, chlorpyrifos and 2,4'-DDT enhanced the effect of 1 nM E2 in the YES assay to a maximum of 4.36, 1.84 and 1.22, respectively (Fig 3A, S5 Table).
Fig 2. Regression models of the test substances.
Regression models of the test substances in the (A) YES, (B) ERα CALUX and (C) ERβ CALUX assays. Substances not eliciting an effect are not shown.
Fig 3. Regression models of the test substances applied in combination with E2.
Regression models of the test substances in the (A) YES (with 1 nM E2) and the (B) ERα CALUX assay (with 3 pM E2). Substances not eliciting an effect are not shown.
Fenhexamid and fludioxonil showed concentration-dependent anti-estrogenic effects when combined with 1 nM E2 in the YES assay (Fig 3A, S5 Table). The two above-mentioned compounds were also tested in combination with 3 pM E2 in the ERα CALUX assay, but in both cases an anti-estrogenic effect was not observed (Fig 3B, S6 Table).
In the ERβ CALUX propamocarb, fenarimol, fludioxonil, fenhexamid, 4,4'-DDT and 2,4'-DDT showed a dose-dependent estrogenic activity at the hERβ (Fig 2C, Table 1, S4 Table).
The concentrations of the test substances to be tested were limited depending on their solubility. A decreased solubility led to an increase of turbidity/optical density measured at 690 nm in the yeast-based assay or was determined by microscopic examination in the CALUX assays. Concentrations leading to insolubility were excluded in the CALUX assays, but not in the YES assay. In the CALUX assays it was possible to generate full concentration-response curves at lower concentrations. It should be pointed out that fenarimol and chlorpyrifos only showed reporter gene activity in the YES assay when applied in concentrations leading to insolubility; nevertheless, these were tested in the YES assay (100 μM fenarimol, 100–1000 μM chlorpyrifos, 100–500 μM fludioxonil, 100 μM fenhexamid, 50–500 μM 2,4'- and 4,4'-DDT). Cytotoxicity, measured by performing the LDH leakage assay, was not observed in the case of the U2-OS cells (data not shown). A decrease of turbidity in the YES assay was assumed to be equivalent to an inhibition of yeast cell growth. Fenhexamid decreased turbidity in the YES assay by more than 30% in comparison to the solvent control at concentrations ≥ 500 μM and the concentrations were therefore excluded (data not shown).
Iso-effective combinations of different estrogenic pesticides resulted in a concentration-dependent increase of reporter gene activity in the YES assay (S1 Fig), the ERα CALUX assay (S2 Fig) as well as in the ERβ CALUX assay (S3 Fig). In the case of the ERα CALUX assay, 95% CIs of the EC01 and EC10 were very narrow (Table 2); therefore, deviations from additivity were identified, mostly towards subadditivity (seven out of twelve predicted EC01/EC10 values were below the experimentally observed 95% CIs. Five out of ten comparisons between the experimental and the predicted data sets showed slight synergism in the YES assay, the predictions being higher than the experimentally obtained 95% CIs; the others were clearly additive (Table 3). The predicted values for the EC01 and EC10 mostly correlated with the 95% CIs of the experiments in the ERβ CALUX assay (Table 4).
Table 2. Regression model parameters of the mixtures in the ERα CALUX assay and comparison of the observed and predicted EC01 and EC10 values.
Table 3. Regression model parameters of the mixtures in the YES assay and comparison of the observed and predicted EC01/10values.
Table 4. Regression model parameters of the mixtures in the ERβ CALUX assay and comparison of the observed and predicted EC01 and EC10 values.
In the present study mostly additive effects of pesticide mixtures at low effect concentrations in the YES, the ERα CALUX as well as the ERβ CALUX assays were observed. The predicted EC01/10 values not lying in the range of the 95% CIs of the experiments in the ERα CALUX (Table 2) can be explained by the fact that the 95% CIs were very narrow. The concentrations of the prediction are maximally 1.32-fold higher or 0.45-fold lower than the experimentally obtained data (Table 2), which does not represent a biologically relevant deviation from additivity. Those findings underpin the applicability of CA to predict mixture effects of pesticides sharing a common mode of action in the human cell-based ERα CALUX and ERβ CALUX assays as well as in the yeast-based YES assay. This additive behavior of estrogenic substances was previously shown in studies with hERα reporter gene bioassays  as well as in a MCF-7 proliferation assay  and in vivo in the immature mouse uterotrophic assay . To our knowledge, this is the first study that has evaluated mixture effects of pesticides at the hERα and hERβ. Since the hERβ may acts as counterpart of the hERα, it could be of great relevance for the risk assessment process not to limit the analysis to the mixture effects of low concentrations of pesticides to the hERα level, since most hERα ligands also bind to the hERβ, which is also valid for the test substances in this study. The extent of the estrogenic effect in the different tissues largely depends on their hERα:hERβ ratio (reviewed by Böttner et al. ). In the present study, it has been shown that the pesticides did not elicit the same maximal response at the hERβ as compared to the effects at the hERα (e.g. Fig 2), but the potencies of the substances to elicit a 1 or 10% effect (Table 1, EC01 and EC10 in comparison in the corresponding test systems) are in the same order of magnitude when compared to the ECs in the ERα CALUX. These results, in turn, lead to the conclusion that most pesticides tested at low concentrations as well as their mixtures induce stronger effects at the hERα when directly compared to those at the hERβ, but the same substances elicit estrogenic effects in an additive manner at the hERβ. Additive effects of pesticides at the hERα activating the corresponding receptors should be considered in a cumulative risk assessment, and it is an important finding that the substances eliciting additive effects at the hERα in most cases also influence the hERβ additively, albeit with a lower efficacy.
There was a high level of concordance between the ERα CALUX and the YES assay regarding the identification of estrogenic effects of single substances. With the exception of pirimicarb and propamocarb, all tested pesticides trans-activated the hERα in both test systems. Pirimicarb was negative in both bioassays. There were certain differences in the identification of estrogenic and anti-estrogenic activity in the selected reporter gene assays: Propamocarb was identified as an estrogenic compound with an effect at the hERα in the ERα CALUX assay but not in the YES assay. Both substances were applied alone in the YES and in the ERα CALUX assay and in combination with a saturating concentration of 1 nM E2 in the YES assay. As known from the scientific literature, pirimicarb [11,27] and propamocarb  did not stimulate the proliferation of MCF-7 cells in the E-Screen with or without E2, but they induced a stronger effect in a β-galactosidase and luciferase-based transactivation assay performed with MCF-7 BOS cells, when added in combination with a saturating concentration of E2 . In this case, it was suggested that the substances could influence the interaction of E2 or cofactors with the estrogen receptor or the binding of the ligand-receptor-complex to its response element . Bonefeld-Jorgensen et al.  also showed that propamocarb did not elicit an effect alone and in combination with an E2 concentration at the EC50 level in a stably transfected reporter gene assay based on MVLN cells and speculated that propamocarb might interact with the reporter vector and/or internal standard vector in the MCF-7 BOS cell-based assay used in the study of Andersen et al. , therefore leading to an artifact. Pirimicarb was negative in both reporter gene assays used in this study, even when combined with 1 nM E2 (saturating effect) in the YES assay. Interestingly, propamocarb, which did not induce any effects in the YES assay, was able to elicit concentration-dependent effects in the ERα and ERβ CALUX assays when applied alone. As far as we know, there is no in vivo data concerning the estrogenic activity of these two substances, and it is not possible to assess their estrogenicity based on the outcome of the above-mentioned studies, but it is most likely that the described potentiation the E2 effect in the transiently transfected MCF-7 BOS cell assay used in the study of Andersen et al.  depends on a particular interaction in this assay. An alternative explanation for the positive outcome in the CALUX assays could be that propamocarb is unable to cross the yeast cell wall or that it could be metabolized to compounds with a certain estrogenicity in the U2-OS cells used in the CALUX assays. Although U2-OS cells do not express any cytochrome P450 enzymes, they possess a certain enzymatic capacity, as shown in a proteomic analysis by Niforou et al. , which could impact the estrogenicity of propamocarb in the ERα CALUX assay, but not in the YES assay.
We detected an anti-estrogenic activity of fenhexamid and fludioxonil when applied in combination with E2 in the YES assay (Fig 3A), which could not be confirmed in the ERα CALUX assay (Fig 3B). Fenhexamid and fludioxonil led to an inhibition of the E2 effect in the YES assay by 79 and 44%, which is in line with a study by Mertl et al.  on food contact materials: Some of these substances showed an anti-estrogenic effect in the YES assay, but not in the ERα CALUX assay. Teng et al.  reported an increase of miR-21 expression in breast cancer cells and an inhibition of E2-induced cell proliferation in MCF-7 cells when applying fenhexamid and fludioxonil, which are associated with downstream anti-estrogenic effects.
Supramaximal estrogenic effects of substances eliciting higher putative effects than E2 itself were observed (Fig 2A and 2B, S2 and S3 Tables) and were also shown to act additively as a mixture in the YES assay (S9 Table, Figure C and D in S1 Fig). As shown in the Supplemental Material section, those supramaximal effects are receptor-dependent, mostly occur at high concentrations not relevant for the risk assessment of pesticide residues at low concentrations and are most likely to be a post-transcriptional artifact in hERα reporter gene bioassays [32–34] and do not deviate from the assumption of additivity, consequently not influencing the results of the present mixture study. Furthermore, fenarimol and chlorpyrifos were tested in a MCF-7 proliferation assay by Vinggaard et al.  without exceeding the effect of E2, thereby underlining that the biological relevance of the supramaximal effects in the YES assay is questionable.
To our knowledge, this is the first study to test mixtures of pesticides for additive effects not only at the hERα but also at the hERβ level. Most pesticides being active at the hERα were also active at the hERβ, and additive effects were observed when applied as mixtures. Although the pesticide mixtures were less efficient at the hERβ, one should analyze their effects at both receptor subtypes, since after an exposure one would expect that the compounds interact with both receptors in humans, the receptor subtype ratio influencing the estrogenic outcome. Additive effects of the tested pesticides at the hERα were mostly observed in the YES assay as well as in the ERα CALUX assay, an observation that supports the assumption of additivity of pesticides sharing a mode of action. The used in vitro assays are suitable for the identification of estrogenic effects at the hERα and hERβ level and, moreover, for the hazard identification step in the risk assessment process. The shown additive effects implicate that pesticide mixtures sharing a mode of action should be taken into account, besides a single substance assessment, in a cumulative risk assessment approach.
S1 Fig. Regression models for mixtures in the YES assay.
Red line, regression models of the mixture experiments with 95% confidence belts; blue line, CA model prediction; (A) EC01 and (B) EC10 mixture of fludioxonil and fenhexamid; (C) EC101 and (D) EC110 mixture of chlorpyrifos, fenarimol and 1 nM E2; (E) EC01 and (F) EC10 mixture of chlorpyrifos, fludioxonil and fenhexamid.
S2 Fig. Regression models for mixtures in the ERα CALUX assay.
Red line, regression models of the mixture experiments with 95% confidence belts; blue line, CA model prediction; (A) EC01 and (B) EC10 mixture of fludioxonil and fenhexamid; (C) EC101 and (D) EC110 mixture of propamocarb, fludioxonil and fenhexamid; (E) EC01 and (F) EC10 mixture of chlorpyrifos, fludioxonil and fenhexamid.
S3 Fig. Regression models for mixtures in the ERβ CALUX assay.
Red line, regression models of the mixture experiments with 95% confidence belts; blue line, CA model prediction; (A) EC01 and (B) EC10 mixture of fludioxonil and fenhexamid; (C) EC101 and (D) EC110 mixture of propamocarb, fludioxonil and fenhexamid.
S4 Fig. Regression models of pesticides applied together with competitive inhibitors of the hERα.
Regression models with 95% confidence bands; dashed end of the regression model line stands for concentrations at which the turbidity of the yeast suspension was reduced; S4A–S4F Fig show experiments in the YES assay with (A) 1 mM chlorpyrifos applied together with 1 nM E2 and increasing concentrations of 4-hydroxytamoxifen; (B) 1 mM chlorpyrifos applied together with 1 nM E2 and increasing concentrations of ICI 184,780; (C) 100 μM fenarimol applied together with 1 nM E2 and increasing concentrations of 4-hydroxytamoxifen; (D) 100 μM fenarimol applied together with 1 nM E2 and increasing concentrations of ICI 184,780; (E) 100 μM fenarimol applied together with increasing concentrations of 4-hydroxytamoxifen; (F) 100 μM fenarimol applied together with increasing concentrations of ICI 184,780; (G) 60 μM fenhexamid applied together with increasing concentrations of tamoxifen were tested in the ERα CALUX assay.
for an iso-effective binary mixture of fludioxonil and fenhexamid in the ERα CALUX assay, based on their individual EC10 values.
S1 Table. Mixture components and ratios.
Iso-effective mixtures based on EC01/EC10 or EC101/EC110 values of the single compounds.
S2 Table. Regression models of single substances in the YES assay.
RM, the selected regression model; , the estimated model parameters; , set 0; , the mean of the highest effect observed in the assay, corresponding to the effect induced by 1 nM E2.
S3 Table. Regression models of single substances in the ERα CALUX assay.
RM, the selected regression model; , the estimated model parameters; , set 0; , the mean of the highest effect observed in the assay, corresponding to the effect induced by 0.1 nM E2.
S4 Table. Regression models of single substances in the ERβ CALUX assay.
RM, the selected regression model; , the estimated model parameters; , set 0; , the mean of the highest effect observed in the assay, corresponding to the effect induced by 30 nM E2.
S5 Table. Estrogenic effects of single substances in the YES assay when combined with 1 nM E2.
RM, the selected regression model; glogitII, generalized logit II; , , the estimated model parameters; , set 1 if the effect is enhanced by the test compound in comparison to 1 nM E2 or the smallest mean value if the substance inhibits the effect of E2; , the mean of the highest effect observed in the assay, corresponding to the effect induced by 1 nM E2 or set to 1 if the substance inhibits the effect of E2; EC101/EC110, the effect concentration needed to elicit a 101% or 110% effect of 1 nM E2; [CI], the approximate 95% confidence interval.
S6 Table. Regression models of single substances in the ERα CALUX assay when combined with 3 pM E2.
RM, the selected regression model; , , the estimated model parameters; , set 1; , the mean of the highest effect observed in the assay, corresponding to the effect induced by 3 pM E2.
S7 Table. Combination of pesticides with competitive hERα inhibitors in the YES assayRM, the selected regression model; glogitI, generalized logit I; , , the estimated model parameters; , the mean of the highest anti-estrogenic effect observed in the assay, corresponding to the effect induced by 1 nM E2; , the mean of the highest effect observed in the assay, corresponding to the effect induced by 1 nM E2.
S8 Table. Combination of pesticides with competitive hERα inhibitors in the ERα CALUX assayRM, the selected regression model; , , the estimated model parameters; , the mean of the highest anti-estrogenic effect observed in the assay, corresponding to the effect induced by 0.1 nM E2; , the mean of the highest effect observed in the assay, corresponding to the effect induced by 0.1 nM E2.
S9 Table. Mixtures of pesticides with supramaximal effects in the YES assayRM, the selected regression model, glogitI, generalized logit I; , , , the estimated model parameters, , set 1; , the mean of the highest effect gained in the assay; EC101/EC110, the effect concentration needed to elicit a 101or 110% effect of 1 nM E2; [CI], the approximate 95% confidence interval.
This study was financially supported by the Federal Institute for Risk Assessment in Berlin, Germany (grant FK.3 1329–484 6433898).
Conceived and designed the experiments: BS PS. Performed the experiments: BS. Analyzed the data: BS PS. Contributed reagents/materials/analysis tools: FK BNB PS. Wrote the paper: BS PS.
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text:
The Darkest Cyberpunk Worlds In Japanese Video Games
Gergo Vas
Filed to:show us
Kotaku EastEast is your slice of Asian internet culture, bringing you the latest talking points from Japan, Korea, China and beyond. Tune in every morning from 4am to 8am.
Cyberpunk was a big deal in the 80s and in the 90s. Writers like Philip K. Dick and William Gibson, movies like Blade Runner, and anime such as Akira heavily influenced video games. The result was games with a dark, dystopian future, high technology and low life.
We've gathered Japanese games from this era to see how the cyberpunk setting created masterpieces and made all of them looking absolutely badass.
Heavily influenced by Western adventure games and cult science fiction movies, Hideo Kojima's early creation is one of the best cyberpunk video games out there. We play as Gillian Seed, and we have to hunt down robotic beings, who disguise themselves as humans.
Osman (Cannon-Dancer)
Mitchell's 1996 side-scrolling arcade game has a really strange and unique Middle Eastern setting with cyberpunk elements.
While the anime is a cult classic, there's a reason why only a fan English translation exists for Taito's 1988 Akira video game.
Now You Too Can Play the Terrible Akira Video Game!
In 1988, Taito released Akira, cash-in on the hugely-popular animated film of the same name. Just…
Side-scroller, originally released for the... wait for it... Sharp X68000 in Japan, but it got ports later on. Our main weapon is a lightsaber, and with all the anime and cyberpunk elements, the overall game is totally badass.
Einhänder
In Squaresoft's scrolling shoot 'em up, we control a fighter craft during a war between Earth and the Moon in the near future.
Policenauts
Released on multiple platforms during the 90s, the follow-up to Snatcher is a similar, brilliant graphic adventure game filled with minor action sequences.
The Megami Tensei series
The Megami Tensei games always had a wicked combination of paranormal and cyberpunk themes. The screens are from the upcoming 3DS title, Shin Megami Tensei IV.
In the PlayStation adaptation of the original GitS anime, we control a nameless member of Section 9 in a Fuchikoma tank throughout 12 missions.
The Metal Gear series
Besides cyborgs, the complex storyline of the Metal Gear universe always contained a lot of philosophical and ethical questions heavily influenced by cyberpunk.
The near future chapter in Live-A-Live
We have to visit different time periods in this Japan-only Super Famicom game from Squaresoft. One of these periods takes place in the near future, where our protagonist is called Akira, for some reason.
The Screamer
A really old JRPG for the PC-88, released in 1985 in Japan. The Screamer is a mixture of horror, post-apocalyptic future and cyberpunk.
Hagane
The 1994 SNES action game Hagane is a really hard side scroller, without the possibility of saving. It is about two rivaling ninja clans using advanced cyber-technology in the near future.
These games all have a superb atmosphere, but there obviously are many more. What are your favorite Japanese games with a cyberpunk feel? Put them up in the comments below with visual support!
sources: Rockandrollstrikesback, merlin196, pixelpolygonsandpie, Vysethedetermined2, ASVG, Metal Gear Wiki, HardcoreGaming101, JenaPlissken86


Buongiorno miei amata amici! As I was preparing last night's supper consisting of Sweet Basil & Cheese Manicotti (as pictured), it occurred to me that I have not shared a few simple tips when baking pasta dishes.
First, you do NOT have to precook your pasta by boiling it first. In fact, boiling it first makes it more difficult to work with and it loses the al dente texture by the time if completes baking, turning your hard work to mush in the mouth. Just one more reason I was disappointed when I made lasagna in our slow cooker/crock pot.
Whether constructing lasagna or manicotti, I simply use the dehydrated noodles from the store just as they are when layering or filling. You have two options, you can either just allow the pasta to derive its tenderness from the fillings or layers or you can add about 1 cup of water to every 2 cups of pasta sauce. I add water, then cover it with foil while baking, until the last 10 minutes when I am browning the cheese on top. An additional 15 minutes in the oven ensures the pasta is done to al dente perfection.
Also when filling manicotti or cannoli noodles, you can actually put the mixture into a pastry bag or ziploc baggie with the end snipped off and squeeze them full of cheese, meat, or cream.
Further, baked pasta dishes can be prepared a day or two before baking. How do you think Nonna always had lasagna baking for lunch on Sunday's family gatherings right after church?
Another thing, I almost always have left overs of the raw cheese center from manicotti and I put it in a ziploc freezer bag, label it, stick it in the freezer, and save it to add to a future lasagna.
For a cheese topping, if you want it to show more of the pasta and sauce, be sure to use a fine grate on the cheese and sprinkle lightly. My family consists of cheese lusters, so I use the large grate and smother it. However, I do use the fine grate for garlic cheese bread.
One last thing, always spray your pan with olive oil to make the release and clean up of your scrumptious meals a snap.


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Bungard (, ) ist ein Dorf in der Region Siebenbürgen in Rumänien.

Lage

Bungard ist das südöstliche Nachbardorf von Hermannstadt und ist verwaltungsmäßig Teil der Gemeinde Șelimbăr (Schellenberg), drei Kilometer außerhalb des Gemeindezentrums gelegen.

Zwischen Bungard und Șelimbăr verläuft seit 2010 die Autobahn A1, die hier zugleich die Stadtumfahrung von Hermannstadt ist. Parallel zur Autobahntrasse verläuft eine Eisenbahnstrecke der CFR.

Geschichte
Bungard ist eine jener siebenbürgischen Ortschaften, die von bulgarischen Bogumilen gegründet wurden. Die bulgarische Bevölkerung assimilierte sich im Lauf der Jahrhunderte an die rumänische Mehrheitsbevölkerung.

Sehenswürdigkeiten
 Orthodoxe Dorfkirche Adormirea Maicii Domnului (1690)

Persönlichkeiten
 Martin Samuel Möckesch (1813–1890), Theologe und Schriftsteller, war Pfarrer in Baumgarten

Weblinks und Quellen

 Bürgermeisteramt Schellenberg
 Kreisrat Sibiu
 Private Homepage mit Informationen zu den Bogumilen in Siebenbürgen

Șelimbăr

redpajama_set_name: RedPajamaWikipedia


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The mission of the Nebraska Lottery is to generate proceeds for good causes as determined by the voters and the Legislature, while providing quality entertainment options to Nebraskans.
In November of 1992, 63 percent of Nebraska voters approved a constitutional amendment authorizing the creation of a state lottery. The Nebraska Lottery was created by LB 138, passed by the Nebraska Legislature on February 24, 1993. When the Nebraska Lottery began, it was the 37th lottery in the United States.
The Nebraska Lottery sells $1, $2, $5, $10 and $20 Scratch tickets, and offers Lotto games such as 2by2. Pick 5, Pick 3, MyDaY, Mega Millions, Lucky For Life, and Powerball. Scratch ticket sales began on September 11, 1993, and Lotto ticket sales began on July 21, 1994.
Amendment 4 passed by Nebraska voters in November of 2004 established the following distribution formula: Education as directed by the Legislature (44.5 percent) - currently distributed to the Nebraska Education Improvement Fund; Nebraska Environmental Trust Fund (44.5 percent); Nebraska State Fair (10 percent); and the Compulsive Gamblers Assistance Fund (1 percent, plus the first $500,000 in fund proceeds each fiscal year).
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Holderness Media has released version 1.4.7 of its Echo Pad multi-fx processor for iOS.
Echo Pad 1.4.7 adds two new delay effects, Oil Can Delay and Multi-tap.
Echo Pad is a realtime Multi-FX processor compatible with Audiobus including: Tape Echo, Oil Can Delay, Multi-Tap, Stereo Delay, Shimmer Delay, Smooth Filter, Decimator, Flanger, Distortion, Loopers and more. Effects are controlled by a large multi-touch pad on your iPad, iPhone and iPod touch device.
New effect Multi-Tap Delay, a stereo multi-tap delay with cross-feedback.
New effect Oil Can Delay, inspired by vintage oil can reverb/echo units.
Adjustable buffer size from 64 to 1024 samples.
Option to enable/disable input light animation.
Global preferences now saved (background audio, audio buffer size setting, hardware input setting, input light animation on/off).
Echo Pad costs $3.99 USD.


Chuffed to make it in amongst such illustrious company! It's this sort of thing which makes it all worthwhile, and why I keep on keeping on. Thanks man, without people like you the musical world would be a dull and uninspiring place.


text:
Knajpa je kiosek zbudovaný v nadmořské výšce 996 metrů v Jizerských horách na severu České republiky. Jeho provozovatel a posléze i majitel, jímž je Jan Špecián, zde nabízí turistům občerstvení při jejich lyžařských či pěších nebo cyklistických túrách. Špecián v kiosku podniká od počátku 21. století a pocestným nabízí jídlo či pití, které sem denně dováží, nebo si v zimě mohou lyžaři na roztopených kamnech usušit své oděvy.

V kiosku je jedno zároveň z míst, kde je v případě nouze k dispozici defibrilátor (AED).

Odkazy

Reference

Externí odkazy

Horské chaty a hotely v Jizerských horách
Stavby v Hejnicích


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› A point of view on Emerging technologies
A point of view on Emerging technologies
Technology is becoming more and more prevalent across industries. "Disruptive Tech" has become a buzzword that many are becoming familiar with as they go about trying to understand what a specific technology is, how it may impact their business, and see how it can be exploited for growth or at the very least, help them remain relevant.
Marco J. Vassallo
Partner, Emerging Technologies
KPMG in Malta
Also on home.kpmg
Disruptive technologies often elicit polarizing opinions when they start making headway towards mainstream adoption, with current trending examples including Artificial Intelligence (AI) and Distributed Ledger Technologies (DLT). Even though they have not been around for the same amount of time, 2018 put the spotlight firmly on them thanks to the way governments, organisations and even people started to discuss them. Some opinions are positive to the extent that they are quasi-utopian, while others are negative and often rooted in misconceptions about the technology. Ultimately however, this is all a natural part of technologies that have such a disruptive potential and it is up to those who understand them to educate others and help separate the myth from fact.
After all, the internet was itself engrossed in similar debates in the early 90s, but over the past 25 years we started relying on it because of the numerous benefits that increasingly came about.
Not all technologies are equally disruptive in the same wide scale as AI and DLTs. This can make adoption somewhat easier as there are far lower risks with the potential of high reward nevertheless. The Internet-of-Things is one such case, boosted by the fact that associated advantages are easier to comprehend thanks to the prevalence of the internet and digital devices, with cost and investment commitment required often being cited as the key inhibiting factor. Robotic Process Automation (RPA) is another emerging technology that is rather simple in concept, as it is intended to fully automate repetitive and well documented tasks which every organisation invariably has. What truly sets RPAs apart in making it ideal for adoption however, is that the return on investment can be seen in a short space of time, and with the shortage in workforce being something a lot of businesses are facing locally, exploiting this technology becomes a no-brainer!
While everything points towards DLTs and AI still being the main talking points throughout 2019, it is important to look at technologies as nothing more than tools to provide efficient solutions to very existing and real problems.
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Maybe being an awkward teen who struggles to apply makeup and achieve a look that gets people out of their seats was a hard task 20 years ago, but today, with all the makeup channels and tutorials going around, it's pretty easy to pick up on a couple of tricks. And with the growing wide-spread of makeup, we offer you this cosmetic label presentation mockup that enables you to bring any brand to life.
Provided by Graphic Pear, the high-resolution mockup showcases 2 scenes, one on a light background and the other on a dark background. It can be downloaded with a couple of clicks, but that isn't even the best part yet. The PSD mockup is free for personal use, so once you edit it through the smart object layers, you can include it in any cosmetics related project.


Every journey is a quest of sorts but, as we leave the familiar behind, what are we looking for?
Perhaps it is the enticing prospect of the unknown. Perhaps we are in search of the simple pleasures of immersing ourselves, however briefly, in another way of life. Perhaps we just want a break from the monotony of the daily grind, where the act of leaving is more important than the destination. Perhaps it's all of the above.
Whatever the reason, when we return home we do so with a greater understanding of the world around us and with an insatiable need to see – and feel – more of it. And, whether we realize it or not, we also gain a greater understanding of ourselves along the way.
As we accumulate more and more journeys to look back on, we recall the enthralling cities and the intoxicating views. But we know it was the chance encounters, the wrong turns, and the obstacles – often self-inflicted – that defined the experience.
The awe-inspiring has us reaching for our cameras. The unexpected can change our lives.
On a gloriously sunny day in late November, we were driving east along the southern route of Iceland's ring road.
After stopping for lunch in Vík, we chose to enjoy the unseasonably pleasant weather by taking a quick stroll along the town's adjacent beach before continuing our journey.
The Atlantic Ocean was lapping gently at the beach as it advanced towards its high tide mark. The sun, which at that time of year seems to run on a rail just a few feet above the horizon, was already casting long shadows. It was a beautiful scene.
The black sand at Vík – and what turned out to be some significant footprints.
As we returned to our car, I had the vague sense that something was missing. As nonchalantly as I could, I checked all of my pockets (there are a lot in a multi-layered winter coat). It wasn't there. I had lost the car key.
It was a standard car key with a dull, silver-colored business end and a black rubber head – with the rental car company's clear plastic tag attached.
To summarize, I had dropped an almost entirely black key somewhere on a black sand beach that we'd been walking around for half an hour. And the tide was coming in.
Apologizing profusely and repeatedly to my traveling companions, we set off in different directions, trying to retrace our meandering steps, heads pointed downwards. Some of those heads may have been uttering words unfit for mixed company.
As panic descended, the "needle in a haystack" analogy mocked me. But it was worse than that.
That parallel would only be accurate if the needle in question were hay-colored and the haystack itself were positioned on a shoreline close to an advancing ocean that was shortly going to wash it away. Maybe it already had.
I felt distraught; that I had let everyone down. I could not see beyond the feeling that, in one single act of carelessness, I had ruined the entire trip for everyone. Consequently, my initial contributions to the activities of the search party were somewhat less than effective.
Seeing my anxiety, my wife, Sarah, added some much needed calm and focus to the situation.
Even if we don't find the key, she said, even if it has already been washed out into the ocean, there are other solutions. Yes, our plans for the day will change. So what? We can call for a replacement key. We can stay here overnight if we need to. This is not the disaster you think it is. We will sort it out.
Returning my attention to the search, after around 30 minutes and with my eyes beginning to see a car key shape in every grain of black sand, I stumbled across the actual car key. I will never forget the relief.
For the remainder of our trip, every time I left the car, I placed the key on its own in an inside zipped pocket. Three other people watched me do it. Every time.
As I thought back on the incident and Sarah's timely counsel, her perspective was reflected in the people around us.
Icelanders are a wonderfully optimistic and resilient group of people, with a gritty determination built on enduring long, harsh, almost perpetually dark winters.
If climatic injustice were not enough, less than ten years ago the country stared into the abyss of economic disaster precipitated by the global financial crisis. Iceland was on its knees – and on its own.
Their journey from the brink of catastrophe to becoming a leading global travel destination is one of the world's most remarkable transformations. That kind of thing cannot happen without massive quantities of optimism and resilience.
It is hardly surprising, therefore, that the country's unofficial motto is "Þetta reddast" – which roughly translates as, "it will sort itself out in the end".
As if chance were wielding a great, bold underlining pen, later that same evening we arrived at Jökulsárlón.
It is a glorious place to end any day. From the icebergs floating silently in the lagoon to the fragments that wash up on to the nearby beach, the scene is always breathtaking.
Before we departed, I looked across at Sarah. She was lying with our friend, Jane, on one of the larger blocks of freshly-stranded ice. They were giggling like schoolgirls.
The memory of the earlier frantic search faded as I laughed along. With a huge sigh, I realized that I had found more than a black key on a black sand beach today. I had found a new perspective and with it, a new understanding that, even if our plans take a wrong turn, the path we follow may just lead us to where we need to be.
Had I known the expression at the time, I would have said to myself, "Þetta reddast".
Maybe I'll get a t-shirt made.


New for Fall Maclaren has introduced 4 new messenger and diaper bags. Stylishly designed so they can be used after your little one has moved on from diapers, the new collection features sophisticated designs that are spacious enough to hold all of your baby's essentials, while leaving room for mom's necessities. Each bag also includes a removable, wipeable changing mat which is must-have for moms on the go!
Also new for the family gear company is a beautiful heart glider. Designed by David Netto, this comfy chair also provides ergonomic support for late night feeds and afternoon cuddle sessions. With its carefully selected combo of premium materials and fabrication techniques, the Heart Glider rocks, swivels, and (best of all) gently glides like no other.
Parents who need more storage will love the new Universal Insulated Pannier. Designed to fit most umbrella fold strollers, this side of the buggy storage is fully insulated to keep drinks and snacks cool, with a removable bottle divider.
I am partial to the denim bag too. I am trying to get away from a plain black diaper bag but still want something that is not too flashy.
The Scarlett Field bag is beautiful!
I like the canvas park bag.
The Rose Camo Smart Set is my favorite-very pretty!
I like the canvas diaper tote!
I have a new baby on the way this April, so I'm in big need of a diaper bag!
The rose camo smart set is cute!
My favorite is the Scarlet Field Bag.


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19 Nov From aerospace engineering to language industry legislation
Posted at 12:49h in Continuing Education, Interpreters, Interpreting, Language Associations, Leadership, Mentoring, Odds & Ends, Professional Development, Recent Posts, The Profession by Observer Editor 0 Comments
Editor's note: This week's post will have a special focus. NAJIT is sponsoring the upcoming 4th International Virtual conference organized by Linguist Education Online. If you can sign up, please do so!
This year, NAJIT is partnering with Linguist Education Online (LEO) to support LEO's 4th International Virtual conference that will be hosted on December 2-3. One of the main speakers at LEO's conferences is Dr. Bill Rivers, who is a part of an acclaimed panel "What the Future Holds." Bill is the founding Chair of ASTM Technical Committee F43, Language Services and Products, and chairs the U.S. Technical Advisory Group to ISO Technical Committee 232, Education and Learning Services. He serves as a member of the America's Languages Working Group of the American Academy of Arts and Sciences and is an honorary member of the Association of Language Companies.
Before establishing WP Rivers & Associates, Bills served for eight years as the Executive Director of the Joint National Committee for Languages – National Council for Languages and International Studies, leaving a legacy of significant legislative and policy accomplishments, including the establishment of the Congressional Caucus on America's Languages, and the passage of the World Languages Advancement and Readiness Program, among many others. We asked Bill some questions about his background and career and about what the future holds for the language industry.
Q: How did you start in the language industry?
By happenstance – I was in my dorm room at the University of Maryland in 1989, and the phone rang out in the hallway (there was one phone for all twenty-five rooms, in the middle of the hall). "Rivers – It's for you!" So, I go out and pick up the receiver, and I hear "Are you Bill Rivers?" "Yes." "And you are an aerospace engineering major?" "Yes." "And you speak Russian?" "Um, who is this?" It turns out it was a professor of mine, Walter Melnik, and he asked me to come to his office the next morning at 8 a.m. I was a bit confused – I was carrying a solid B in his course on hypersonics – but I showed up the next morning in his office.
As it turned out, he had been contacted by colleagues of his at the NASA Goddard Spaceflight Center, which is about five miles east of the University of Maryland. They were looking for a "Russian translator," as a delegation from the Soviet Space Research Institute – the Soviet equivalent of NASA – would be visiting in a couple of weeks. Professor Melnik gave me a number to call, and I did. It was for the Russian émigré owner of a small language services company, who interviewed me briefly and then told me to show up in a couple of weeks at NASA Goddard. This was the height of "glasnost" and "perestroika," and there was a number of joint satellite projects, and I was about to get plunged into the middle of one.
I did, and I was handed a microphone and told to "translate the speeches" of the directors of NASA and the Soviet Space Research Institute. I had no idea what I was doing – although I knew that I was interpreting, not translating. The Soviet director spoke at a reasonable pace, and paused every couple of sentences, while the NASA director droned on and on. One of them at least was familiar with working with an interpreter. I ended up doing chuchotage at lunch and dinner, consecutive in working meetings of engineers and scientists. After a full day – no breaks – I was handed a sheaf of yellow legal loose-leaf paper – half in handwritten Russian, and the other half in English, and I was asked if I could bring a clean version of the draft treaty for this satellite project to the meetings the next morning. So, I wrote out two versions in longhand, caught a couple of hours of sleep, and handed them in. Again, I had no idea that there were professions called "interpreter" and "translator," nor that there was any training for them, so I was easily exploited.
As it turns out, my invoice was never paid – the check bounced, and the agency skipped town, leaving no forwarding address. As green and raw as I was, I guess I did okay, because I was asked back several times (and paid, thankfully). When I recounted my story to one of my Russian professors, Dick Brecht, who was teaching a class on translation that year, he said "Bill, you're an idiot." This did not come as news, nor was it the first or last time I would hear that. He told me: "Go join the American Translators Association and learn something." I'm still working on the second half of that instruction.
I worked as a freelance interpreter, translator, and terminologist, and later as a staff translator at an academic publishing and exchange organization for about seven years, while eventually earning a Ph.D. in Russian, and then working as an academic researcher and administrator, a researcher and operational leader in the Intelligence Community as a contractor, and finally, for the last ten years, as a language lobbyist.
Q: What does WP Rivers & Associates do?
My company provides government-relations and strategic-management consulting to the language industry.
Q: How did you establish the company? What was most challenging in starting a business?
In May of 2020, I decided to step away from the Joint National Committee on Languages, a non-profit umbrella advocacy organization for the language enterprise in the U.S., and start my own company. Making that decision was the hardest part – with two kids at home, a mortgage, and all that – but once I got started, things moved quickly. I'm very happy in what I do, and the clients are fantastic.
Q: You speak French and Russian. Why did you choose to master these, not so easy languages?
Since I heard some Québécois French at home before I started school, it never occurred to me that it would be hard. I started learning French formally in kindergarten. I added Russian in high school, and by the time I started Russian I thought it was pretty easy – but that's a common effect of being bilingual – learning additional languages isn't as challenging as the second language. I took both French and Russian through college and chose to double major in Russian and aerospace engineering. When I graduated, I had offers to go to graduate school in both subjects and a job offer as an engineer. My undergraduate Russian advisor, Dr. Don Hitchcock, told me that I should do what I like best, so I picked Russian linguistics.
Since then, I've added Spanish, German, and Irish to the mix, through self-study and a week at the Concordia Language Villages for Spanish.
Q: What do you like the most about your work?
The language industry is an amazingly dynamic, lively place – it's always changing, we're part of every sector of the global economy, and what we do matters to the common wealth – we make lives better, we make the world a safer place, we advance the global economy by our work.
Q: What are your favorite books or movies?
Favorite movies – Atanarjuat, almost anything by David Lean (except Ryan's Daughter!), Gran Torino, Men in Black I & II. Pretty random.
Books – Doctor Zhivago, Master and Margarita (both are better in the original Russian); Ron Chernow's biography of Ulysses S. Grant, Guns and Steel by Jared Diamond.
Q: How do you stay motivated? Any tips on being successful and goal-oriented, especially during such trying times as these?
The motivation part is easier – I enjoy my work and the people with whom I interact. The language industry is full of super smart, interesting people. As to success, a strong tendency to be stubborn in pursuit of one's goals helps.
Q: You have been an integral part of LEO's conferences from the beginning. What do you like the most about our conferences, and what can be improved?
That's very kind of you! I like the depth of knowledge and the diversity of presenters and subjects. I don't know what we could do to improve the conference – as much as I would like to see people in person, it's LEO, and that online part makes it very accessible to a broad audience.
Q: Your panel will be talking about the future at LEO's 4th International Virtual Conference. Can you give us a glimpse of what to expect from this panel and the future?
Well, I can only speak to my part of the panel – I expect smart and interesting and thought-provoking things from my colleagues, but I've no idea exactly what they will say. For my part, I think we will see a much more gradual evolution of the "new normal" than we might have predicted at the 3rd International Virtual Conference. We still have a long way to go before there's a stable situation in regard to COVID-19, and that will impact global travel, the hospitality sector, and more. It's also clear that we may well end up paying more for expertise, as the "great resignation" continues apace. Finally, virtual remote interpreting is here to stay, and that has pluses and minuses. On the plus side, language access for all kinds of services and events is now much more accessible than it was two years ago. On the minus side, we're seeing clients asking for reduced minimums and rates, based on the virtual nature of interpreting, which is nuts – the same expertise is doing the same work, just not on site.
Dr. Bill Rivers is the immediate past and founding Chair of ASTM Technical Committee F43, Language Services and Products, and chairs the U.S. Technical Advisory Group to ISO Technical Committee 232, Education and Learning Services. He serves as a member of the America's Languages Working Group of the American Academy of Arts and Sciences and is an honorary member of the Association of Language Companies, as well as a recipient of the ALC Bill Graeper Award in 2019. Before establishing WP Rivers & Associates, Dr. Rivers served for eight years as the Executive Director of the Joint National Committee for Languages – National Council for Languages and International Studies, leaving a legacy of significant legislative and policy accomplishments, including the establishment of the Congressional Caucus on America's Languages, and the passage of the World Languages Advancement and Readiness Program, among many others. Contact: bill@wpriversassociates.com
Main and body photos courtesy of Linguist Education Online.
accidental starts, advocacy, Business, exploitation, formative experiences, French, glastnost, Goddard, golden opportunity, journey, legislation, open doors, Opportunities, perestroika, Russian, self-employment, the profession, visibility


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Ayrton
by / Aug 13, 2020
One of the Greatest
Let us celebrate the amazing life of Ayrton Senna.
Ayrton, the racing driver, needs no introduction. King of Pole Position, King of Rain, without a doubt, one of the greatest racers that ever lived. So many of today's F1 fans can establish a direct connection between their first love for the sport and the Brazilian. Many still wake up at odd hours to see distant races in the hope of getting a glimpse of what F1 was back then, the end of an era when man was still greater than machine and F1 driving was a pure experience.
More than a Legend
Ayrton, the man, is beloved the world over for his honesty and passion for the sport and life. A silent humanitarian who invested most of his fortune in the fight for social equality in Brazil, imposing only one condition - total secrecy (no, we're not crying, you're crying!). In a country that worships football like religion and footballers like gods, Senna is not only the most beloved sportsman to ever come out of Brazil - he's the most precious person, the immortal embodiment of all that's good about Brazil.
How lucky we are to have met you!
See the tribute socks


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