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Problem: Solve 122 = 40*n - 118 for n.
And the answer is... | 6 | 8 | Flan2021 | math_dataset/algebra__linear_1d:1.0.0 | zs_opt |
The critic consesnsus is: Reese Witherspoon is charming enough, but the road to Alabama is well-traveled.. What reviews supported this critic consensus? | 1. Melanie eventually slugs the Yankee. Too bad the former Murphy Brown doesn't pop Reese back.
2. Never rises above the level of TV sitcom mediocrity.
3. Using her blond, blue-eyed pout to full advantage, Witherspoon is just as likable as a Southern belle as she was as a California sorority girl in Legally Blonde.
4. A horrifyingly predictable romantic comedy that, unlike Legally Blonde, can't coast even partially on the formidable charm of suddenly-a-star Reese Witherspoon.
5. Reese Witherspoon stars in a startlingly well-written and enjoyable romantic comedy full of laughs and finely crafted characters.
6. The battle of the country spouse versus the city spouse - either way, Reese is the winner. Cute movie.
7. Director Andy Tennant works straight out of the romantic-comedy playbook, right down to the big kiss in the fake rainstorm.
8. If one defines a 'movie star' as an actress/actor whose presence can carry, even elevate, a mediocre movie, Reese Witherspoon is definitely a movie star. Despite the predictable plot and cliche stereotypes, her irresistable charisma makes it frothy and am
9. Every time you look, Sweet Home Alabama is taking another bummer of a wrong turn.
10. About the best that can be said about Sweet Home Alabama is that it will make a good airplane movie -- it's bland, mostly inoffensive, and predictable enough that you can nap through large sections and not get lost. | 8 | Flan2021 | opinion_abstracts_rotten_tomatoes | zs_opt |
Read this: The people of Somerset are mentioned in the Anglo-Saxon Chronicle's entry for AD 845, in the inflected form "Sumursætum", and the county is recorded in the entry for 1015 using the same name. The archaic name Somersetshire was mentioned in the Chronicle's entry for 878. Although "Somersetshire" was in common use as an alternative name for the county, it went out of fashion in the late 19th century, and is no longer used possibly due to the adoption of "Somerset" as the county's official name after the establishment of the county council in 1889. As with other counties not ending in "shire," the suffix was superfluous, as there was no need to differentiate between the county and a town within it.
What archaic name was mentioned in 878
What is the answer? (If it cannot be answered, return "unanswerable") | The archaic name Somersetshire was mentioned in the Chronicle's entry for 878 | 7 | Flan2021 | squad/v2.0:3.0.0 | zs_opt |
Write the next sentence in this paragraph:
How to identify spiders by region
Identify green lynx spiders by their green coloration and their large size; they also often have pink spots on their bodies.
Notice the eye pattern of jumping spiders.
They have 3 rows of eyes and the front row of eyes is very prominent, giving them an almost comical appearance.
Options are:
[1]. Recognize flying spiders by color, so as to make more sense to you : Flying black spike-black silos-black striped dark black tiger-like spiders standing next to haunted haunted homes. Know the characteristics of flying spiders : See above.
[2]. Look for a hungry-looking eyes, and put their location at the front of the figures. Look for a large snake, which can be any size, though often devalued by its size.
[3]. To distinguish from the insects, you'll need to look at the wings and legs and identify them : They have grey webbing, the initial color of a hawk. They have black, brown, black arterial stripes, and large eye structures, like wings and heads.
[4]. Look for both the green lynx and the jumping spider in areas where there is heavy vegetation. Learn to recognize the garden spider by these characteristics : A white cross mark on the abdomen-this distinctive marking is the reason the european garden spider is also called the cross spider. | [4]. | 4 | Flan2021 | hellaswag:1.1.0 | zs_opt |
What's an example of a movie review? | Distortion is a disturbing, haunting film, about life imitating art and art reflecting life. Haim Bouzaglo, the director of the film, plays the role of Haim Bouzaglo, artistically blocked and sexually impotent playwright, who finds inspiration in his suspicions about the subject of his girl friend's documentary. As an Arab suicide bomber, disguised in skullcap and American t-shirt, wanders through the landscape in search of his target and his nerves, Haim transcribes his girl friend's life as she films her documentary and incorporates himself and his actors' lives during rehearsals. But the bomber has already struck and Haim has left the restaurant just minutes earlier. Despite the manipulation of time and space, the story is crystal clear, comprehensive and absorbing, a brilliant commentary on the "distortion" of everyday Israeli life, where the political is intertwined with the personal, where everyone lives "on the edge," and people never know whether they are playing leading roles in their own lives or are merely dispensable bit players in someone else's dramatic narrative.
Bouzaglo plays with this notion of everyone being an actor in someone else's production brilliantly. We are always voyeurs, seeing what the fictional director sees illicitly but also what the "real" director chooses to reveal. To remind us that these glimpses are violations of privacy, Bouzaglo takes us into the bathroom and the bedroom (sometimes the bedroom is the street and rooftop), and repeatedly frames his views within TV, video, or security screens. Actors play the role of actors who represent the "real" characters played by actors. Of course, each of the actors is the star of his or her own production, only dimly aware of their diminished roles in their fellow actor's personal films. The detective hired by the playwright becomes a character in the play. The actor hired to play the role of the detective seeks out the detective for "tips" on how to play the role, is caught by the detective on surveillance tapes, and they attend a cast party as their real selves.
Despite this multiplicity of views, there is no mistaking the clear lines of this narrative: the playwright searches for subject matter, the bomber seeks a target, and the detective stalks the filmmaker. Nor is there any difficulty locating Bouzaglo's ultimate targetenervated and impotent Israel, fully conscious of the threatening peril but incapable of meaningful action. Israel is Bouzaglo, the impotent fictional playwright cannibalizing his own life for his play. Israel is also the bankrupt soldier-entrepreneur who is the subject of the filmmaker's documentary, the cheating actors and actresses, and the cuckolded husband. They are all Israel because they are all helpless, caught in inaction or aimless action, as the bomber scans the landscape for his best target. All the characters can do as another bombing is reported is have sex and keep "score" of victims.
There is personal triumph, vindication, perhaps revenge at the end of this play within a story within a film, but viewers will be left aching for the state of Israel even as they are filled with admiration for Bouzaglo's memorable rendition of a nation's plight within the telling of an individual's story. | 9 | Flan2021 | imdb_reviews/plain_text:1.0.0 | zs_opt |
Sentence 1: A woman is slicing an onion.
Sentence 2: A woman is cutting an onion.
From 0 to 5 (0="no meaning overlap" and 5="means the same thing"), how similar are the two sentences?
+ 0.
+ 1.
+ 2.
+ 3.
+ 4.
+ 5. | 4 | 2 | Flan2021 | glue/stsb:2.0.0 | zs_opt |
Emma did not pass the ball to Janie although *she* saw that she was open.
Multi-choice question: Do "Emma" and "she" have the same meaning?
Select from:
[I] no.
[II] yes. | [II] | 1 | Flan2021 | super_glue/wsc.fixed:1.0.2 | zs_opt |
Versailles'sta on muodostunut ensisijainen paikka Ranskan itsenäisyydestä luopumiselle, kun pidetään mielessä, että Saksan valtakunta julistettiin siellä.
Could you please translate this to English? | Versailles has become the prime location for abdicating French sovereignty, bearing in mind that the German Empire was proclaimed there. | 2 | Flan2021 | wmt16_translate/fi-en:1.0.0 | zs_opt |
Sky of Avalon – Prologue to the Symphonic Legends is a studio album by German guitarist Uli Jon Roth marking a debut for his symphonic music project Sky of Avalon. It was produced at Sky Studios, Earl's Farm in Autumn 1995, except for "Starlight" and "Winds of War" produced in 1992 at Sky Studios, Seaford. It was released in 1996 in Japan and Europe, finally reaching the U.S. in 1998.
Does this next sentence follow, given the preceding text?
the "Winds of War" album was released in a country that has a five letter name.
Available choices:
[A]. Yes.
[B]. It's impossible to say.
[C]. No. | [C]. | 3 | Flan2021 | anli/r1:0.1.0 | zs_opt |
To protect its seagoing interests and trade routes, Portugal established strategic garrisons in Goa (India), Malacca (East Indies), and Hormuz in the Persian Gulf. Portuguese explorers then embarked upon Macau (now Macao), the Congo, and various other parts of Africa, including the Sudan. The Portuguese policy was to avoid armed strife and to develop a trade empire, rather than to conquer nations. To this end it succeeded with relatively few blood-soaked episodes in its colonial history. Adventures abroad, however, proved disastrous during the second half of the 16th century. In 1557 the 14-year-old boy-king Sebastião ascended the throne, the beginning of a calamitous reign that was to end at the battle of Alcacer-Quiber (Morocco) in pursuit of a vain crusade. Sebastião's untimely demise, alongside some 18,000 ill-prepared, badly led followers, set the stage for a crisis of succession. For many years afterwards, legends and rumors bizarrely insisted that the king was still alive, and imposters turned up from time to time claiming the throne; those who were plausible enough to be deemed a threat were summarily executed. In fact, the only rightful claimant to the crown was the elderly Prince Henry. But after two years of alternating between the throne and his sickbed, he died, heirless. Surveying the situation and smelling an opportunity, Spain occupied the power vacuum, and Portugal's neighbor and long-time antagonist became its master. Spanish rule dictated Portugal's inadvertent involvement in Spain's ongoing wars. In 1587 a squadron of British ships commanded by Francis Drake attacked the Algarve (now a "legitimate target" as Spanish territory) and sacked Sagres, thus depriving the world of the relics of Henry the Navigator. Nine years later Faro was torched. The 1386 Treaty of Windsor, by which Britain and Portugal had pledged eternal friendship, seemed a distant memory. Portugal's empire was gradually eroded, and many of its trading posts (with the notable exception of Brazil) were picked off by the British and Dutch. Finally, after 60 years of Spanish rule, Portuguese noblemen (aided by the French, then at war with Spain) organized a palace coup and restored independence. The Great Disaster Portugal's greatest misfortune struck on All Saint's Day, 1 November 1755.
After reading the above, is "200" the correct answer to the question "The Great Disaster occurred how many years after the sacking of Sagres?"?
[I] no.
[II] yes. | [I] | 6 | Flan2021 | super_glue/multirc:1.0.2 | zs_opt |
Read the text and determine if the sentence is true (see options at the end):
"All for Love" is a song written by Bryan Adams, Robert John "Mutt" Lange and Michael Kamen for the soundtrack " The Three Musketeers: Original Motion Picture Soundtrack". It was performed by Bryan Adams, Rod Stewart and Sting. The song was released as a CD single in the United States on November 16, 1993. It was a worldwide hit, reaching number one across Europe and North America.
Sentence: All for Love was written by three people.
Select from the following.
A). Yes
B). It's impossible to say
C). No | A). | 6 | Flan2021 | anli/r1:0.1.0 | zs_opt |
Most of the bacteria in a forest ecosystem are best classified as which of the following types of organisms? Choices: --consumers --decomposers --predators --producers
Your answer: | decomposers | 2 | Flan2021 | unified_qa_science_inst | zs_opt |
Multi-select problem: How does the next paragraph end?
How to stay visible when you have an invisible disease
Educate yourself.
If you want to stay visible and bring awareness to invisible illnesses, educate yourself on your illness. Do some research online and talk to your physician about any questions you have.
Available choices:
(A). You can also gain more information by reading online books or writing pamphlets about invisible illnesses. Talk to your physician about visibility questions to make sure everyone knows who you are.
(B). That way, you can explain your condition to others clearly so that they understand and you can answer questions that they may have. You may wish to raise awareness of your own illness, or invisible illnesses in general.
(C). You may even research ways to reduce your visibility of the illness. Look for evidence which will show the severity of the illness.
(D). Talk to your doctor about treatment options, like holistic treatments and special treatment methods for tourette's disease. Educate yourself by reading articles written in accredited journals or blogs. | (B). | 5 | Flan2021 | hellaswag:1.1.0 | zs_opt |
Ale no tak, tak jsem to nemyslela.
Translate this to English? | Come on, I didn't mean it like that. | 3 | Flan2021 | wmt16_translate/cs-en:1.0.0 | zs_opt |
Can we draw the following hypothesis from the context (see options)?
Context:
The Drake Hotel is a hospitality venue on Queen Street West in Toronto, Ontario, Canada near Parkdale. In addition to a nineteen-room boutique hotel, there is a restaurant lounge, corner café with street-level patio, Sky Bar roof top patio, and the Drake Underground basement nightclub and live performance venue.
Hypothesis:
The Drake Hotel has a street level patio
Available options: a. Yes b. It's impossible to say c. No | a. | 7 | Flan2021 | anli/r2:0.1.0 | zs_opt |
Write a sentence in Spanish. | realizamos a través de 3-D-CAD (SolidWorks) con definidos datos de 3-D. Interfaces para STEP, IGES, STL y PRT (ProE) están estandarizados y para Catia V5 disponemos de una interfaz de traducción propia. | 9 | Flan2021 | para_crawl_enes | zs_opt |
Multi-choice problem: Is "People are gripped because Paul writes so well." true if "Many people start to read Paul's books and can't put them down. They are gripped because Paul writes so well."?
Choices: * no; * yes; | yes | 8 | Flan2021 | glue/wnli:2.0.0 | zs_opt |
Generate a context and a hypothesis. | Context: Ancaster is a village and civil parish in the South Kesteven district of Lincolnshire, England, on the site of a Roman town. The population of the civil parish was 1,317 at the 2001 census increasing to 1,647 at the 2011 census. The civil parish includes the settlements of Sudbrook and West Willoughby.
Hypothesis: Ancaster has more settlements that just Sudbrook and West Willoughby. | 9 | Flan2021 | anli/r1:0.1.0 | zs_opt |
Answer this question: One 7.0 kg bowling ball is lifted to a storage shelf 1.0 m above the floor. A second 7.0 kg ball is lifted to a storage shelf 2.0 m above the floor. Which of the following best explains why the measured force of gravity on each ball is nearly identical?
Select from:
(1). The final potential energy of each ball increased..
(2). The amount of work required to lift each ball is identical..
(3). The distance of each ball from Earth's center of mass is almost identical..
(4). The gravitational force of each ball on the other cancels out the force of Earth's gravity... Answer: | (3). | 9 | Flan2021 | unified_qa_science_inst | zs_opt |
Background: Blake Colin Lewis (born July 21, 1981) is an American singer, songwriter, and beatboxer who was the runner-up on the sixth season of American Idol. His major label debut album A.D.D. (Audio Day Dream) was released on December 4, 2007 through 19 Recordings and Arista Records. On October 30, 2007, his first single "Break Anotha" was released. The album landed on number ten on the U.S. Billboard 200 as its highest peak position with 97,500 copies sold in its debut, and has sold over 350,000 copies.
Context: Lewis was born in Redmond, Washington to Dallas and Dinah Lewis. Dinah is a former rocker who still sings and plays guitar. He is an only child and is of Welsh, Swiss, German and Irish descent. He attended Kenmore Junior High and later Inglemoor High School in Kenmore, Washington. In high school, Lewis participated in many high school state competitions . He also took part in numerous musicals, as well as comedy and rap videos with his friends. In many of these videos, he portrayed his alter ego, Jimmie Walker Blue, the character he introduced during the semi-final round of American Idol. Lewis started beatboxing at seventeen. He picked up this talent purely by ear, listening to CDs of beatboxing, after he was inspired by Matthew Selby, a former member of the Los Angeles-based a cappella group M-Pact, of which fellow American Idol semi-finalist Rudy Cardenas was a member. Aside from singing and beatboxing, Lewis plays the guitar, keyboard, drums and has written many songs such as "She Loves the Way", "Emotional Waterfalls", "Dumpty Humpty" and "Jealousy". He describes himself as an improv musician and often uses devices such as loop pedals and the Kaoss Pad to layer beatboxing, instruments, vocals and effects to create a song live on stage. Being a member of the a cappella group Kickshaw for four years after graduating from high school in 1999, Lewis worked with the group on a 10-track album titled Put It In the Microphone, but he quit the group in 2002 to become a solo musician going by the stage name Bshorty, which was basically inspired by the nicknames of the members of 311 and "aggressive inline-skate videos during the 1990s", "doing drum and bass shows, and conscious hip hop shows, singer-songwriter stuff, and electronica and hip hop". He made connections with various musicians by performing regularly in many venues in Seattle such as Nectar Lounge in Fremont, SeaMonster Lounge, Lo-Fi Performance Gallery, Jet Deck in Everett (now in Mill Creek) and hosted shows like The Digital Lounge shows at ToST. Before Idol, he was working on a solo album with a number of tracks finished.
Question: What did he do after he quit the group?. Whats the answer? | but he quit the group in 2002 to become a solo musician going by the stage name Bshorty, | 5 | Flan2021 | quac:1.0.0 | zs_opt |
News article:
If you’re here, you’ve probably just been diagnosed, or suspect you have Macular Degeneration, or someone you care about has just been diagnosed or suspects they have the disease.
This entire site is dedicated to information regarding Macular Degeneration, but this page will give you a quick general overview to get you oriented.
Macular Degeneration
Macular Degeneration is the leading cause of vision loss, affecting more than 10 million Americans – more than cataracts and glaucoma combined.
At present, Macular Degeneration is considered an incurable eye disease.
Macular Degeneration is caused by the deterioration of the central portion of the retina, the inside back layer of the eye that records the images we see and sends them via the optic nerve from the eye to the brain. The retina’s central portion, known as the macula, is responsible for focusing central vision in the eye, and it controls our ability to read, drive a car, recognize faces or colors, and see objects in fine detail.
Illustrations of the anatomy of a normal human eye and loss of central vision:
One can compare the human eye to a camera. The macula is the central and most sensitive area of the so-called film. When it is working properly, the macula collects highly detailed images at the center of the field of vision and sends them up the optic nerve to the brain, which interprets them as sight. When the cells of the macula deteriorate, images are not received correctly. In early stages, macular degeneration does not affect vision. Later, if the disease progresses, people experience wavy or blurred vision, and, if the condition continues to worsen, central vision may be completely lost. People with very advanced macular degeneration are considered legally blind. Even so, because the rest of the retina is still working, they retain their peripheral vision, which is not as clear as central vision.
Types of Macular Degeneration
There are two basic types of Macular Degeneration: “dry” and “wet.” Approximately 85% to 90% of the cases of Macular Degeneration are the “dry” (atrophic) type, while 10-15% are the “wet” (exudative) type.
Stargardt disease is a form of macular degeneration found in young people, caused by a recessive gene.
Stages of Macular Degeneration
There are three stages of Age-related Macular Degeneration (AMD).
Early AMD – Most people do not experience vision loss in the early stage of AMD, which is why regular eye exams are important, particularly if you have more than one risk factor (see below). Early AMD is diagnosed by the presence of medium-sized drusen (yellow deposits beneath the retina).
– Most people do not experience vision loss in the early stage of AMD, which is why regular eye exams are important, particularly if you have more than one risk factor (see below). Early AMD is diagnosed by the presence of medium-sized drusen (yellow deposits beneath the retina). Intermediate AMD – At this stage, there may be some vision loss, but there still may not be noticeable symptoms. A comprehensive eye exam with specific tests will look for larger drusen and/or pigment changes in the retina.
– At this stage, there may be some vision loss, but there still may not be noticeable symptoms. A comprehensive eye exam with specific tests will look for larger drusen and/or pigment changes in the retina. Late AMD – At this stage, vision loss has become noticeable.
If you have already been diagnosed with Macular Degeneration, here are Ten Questions to Ask Your Doctor.
Causes of AMD
The specific factors that cause macular degeneration are not conclusively known, and research into this little understood disease is limited by insufficient funding. At this point, what is known about age-related Macular Degeneration is that the causes are complex, but include both heredity and environment. Scientists are working to understand what causes the cells of the macula to deteriorate, seeking a macular degeneration treatment breakthrough. They know the causes are not the same for Age-related Macular Degeneration as they are for Stargardt disease. Stargardt disease has a specific genetic cause in most cases, whereas AMD involves both genetic and environmental factors.
Dr. Carl Kupfer, the former Director of the National Eye Institute, National Institutes of Health, has stated that Macular Degeneration will soon take on aspects of an epidemic as the Baby Boomers’ age: “As the “baby boom” generation ages, and in the absence of further prevention and treatment advances, the prevalence of AMD is estimated to reach epidemic proportions of 6.3 million Americans by the year 2030.”
AMDF supports research on age-related macular degeneration symptoms, causes, and treatment.
Risk Factors
The biggest risk factor for Macular Degeneration is age. Your risk increases as you age, and the disease is most likely to occur in those 55 and older.
Other risk factors include:
Genetics – People with a family history of AMD are at a higher risk.
Race – Caucasians are more likely to develop the disease than African-Americans or Hispanics/Latinos.
Smoking – Smoking doubles the risk of AMD.
Click for more explanation of risk factors.
Treatment
There is currently no known cure for Macular Degeneration, but there are things you can do to reduce your risk and possibly slow the progression once you’ve been diagnosed. For example, one can pursue lifestyle changes like dieting, exercise, avoiding smoking, and protecting your eyes from ultraviolet light.
Click for more information on treatments for advanced stage AMD and 10 Things You Can Do to Improve Your Vision
How Does AMDF Support Macular Degeneration Research?
The American Macular Degeneration Foundation supports important research on the treatment macular degeneration. Your donations are critical to support ongoing research into the causes and treatment of macular degeneration. Click to learn how your generosity can contribute to treatment breakthroughs in macular degeneration. ||||| New U.S. research has found that blue light from digital devices such as smartphones and tablets can trigger a process in the retina of the eye which kill cells, and might increase the risk of blindness.
Led by Dr. Ajith Karunarathne and a team of chemists at the University of Toledo, the new research investigated how blue light from digital devices affected sight.
They found that exposing the eye to blue light causes a reaction which leads an essential light-sensitive protein in the retina, known as retinal, to generate poisonous molecules in photoreceptor cells, resulting in their death.
"It's toxic. If you shine blue light on retinal, the retinal kills photoreceptor cells as the signaling molecule on the membrane dissolves," explained Kasun Ratnayake, a student researcher in Karunarathne's cellular photo chemistry group. "Photoreceptor cells do not regenerate in the eye. When they're dead, they're dead for good."
The process leads to age-related macular degeneration, or the death of photoreceptor cells in the retina. Macular degeneration is an incurable eye disease that results in significant vision loss. It's the leading cause of blindness in the United States and average onset is at 50 to 60 years.
Karunarathne also exposed other types of cells to retinal molecules, including cancer cells, heart cells and neurons.
When exposed to blue light, these cell types also died as a result of the combination with retinal.
However, blue light on its own or retinal without blue light had no effect on cells.
"The retinal-generated toxicity by blue light is universal. It can kill any cell type," said Karunarathne, "No activity is sparked with green, yellow or red light."
The team noted that a molecule called alpha tocoferol, a form of Vitamin E, a natural antioxidant found in the eye and body, can stop the cells from dying. But as we age, or if the immune system is suppressed, we lose the ability to fight against attacks by retinal and blue light.
"We are being exposed to blue light continuously, and the eye's cornea and lens cannot block or reflect it," Karunarathne commented. "It's no secret that blue light harms our vision by damaging the eye's retina. Our experiments explain how this happens, and we hope this leads to therapies that slow macular degeneration, such as a new kind of eye drop."
The researchers are also investigating the light emitted from televisions as well as smartphones and tablet screens, to better understand how cells in the eyes are affected by everyday blue light exposure.
To protect your eyes from blue light, Karunarathne advises wearing sunglasses that can filter both UV and blue light outside, and to avoid looking at your cellphone or tablet in the dark.
The findings were published in Scientific Reports. ||||| Retinal absorbs blue light and induces translocation of PIP2 sensor to the cytosol
The objective was to examine whether retinal or blue light excited retinal, independent of photoreceptors, elicits PIP2 hydrolysis and inositol (1,4,5) triphosphate (IP3) generation in cells, because calcium and its regulatory pathways are suggested as key players of cytotoxicity in the retina5,23. We employed HeLa cells as the major cell line here to eliminate potential response contamination due to retinal and blue light activating endogenous photoreceptors in cells derived from retina. Upon retinal addition to HeLa cells expressing PIP2 sensor (mCherry-PH), cells did not show any change in sensor distribution (Fig. 1A, left). These cells were exposed to blue light at every one-second interval for 10 minutes. Starting blue light intensity was set to 0.22 µW, since this power is sufficient to activate retinal bound to photoreceptors. Cells were imaged for mCherry while gradually increasing blue light intensity. Intensities at 1 μW and above, cells exhibited mCherry-PH translocation to cytosol (Fig. 1A,B, Movie-S1). However, at these intensities, photobleaching of fluorescence proteins was not observed. Interestingly, the translocated mCherry-PH did not recover, even after termination of blue light exposure, suggesting the likelihood of irreversible photochemical perturbation of PIP2 by blue light excited retinal.
Figure 1 Comparison of photoreceptor dependent PIP2 hydrolysis vs photoreceptor independent PIP2 sensor translocation by photoexcited retinal. (A) Images of HeLa cells incubated with 50 µM ATR (retinal) expressing PIP2 sensor (mCherry-PH). Both images and the plot of F cy vs time show that cells exposed to 0.22 µW 445 nm blue light did not respond, while cells exposed to 4.86 µW and 9.70 µW blue light exhibited mCherry-PH translocation to cytosol (mean ± S.E.M.). (B) The plot of initial PIP2 sensor dislodging rate vs laser power of 445 nm blue light. (mean ± S.E.M., n = 6 cells in each experiments). (C) Images of HeLa cells expressing Gq-coupled Melanopsin and mCherry-PH. Cells were incubated with ATR (50 µM) for 5 minutes. A significant PIP2 hydrolysis was observed upon optical activation (OA = blue box) of melanopsin using short pulses of blue light (0.22 µW of 445 nm). Recovery of PIP2 sensor to the PM was observed even the blue light exposure is continued. The plot shows the dynamics of PIP2 sensor translocation in cytosol. Mean and S.E.M. are from 3 < independent experiments. (blue light (BL) = blue box). Scale = 5 µm. Full size image
Response signatures of mCherry-PH translocation induced by blue light (4.86 μW) excited retinal (BLE-retinal) were compared with PIP2 hydrolysis elicited by melanopsin-Retinal Schiff Base (RSB), to examine if both processes trigger similar chemical changes to PIP2. HeLa cells expressing melanopsin and mCherry-PH were incubated with ATR (50 µM) for 5 minutes in dark to allow RSB formation. Cells exhibited PIP2 hydrolysis upon exposure to low intensity blue light (0.22 µW), as indicated by the translocation of mCherry-PH from PM to cytosol (Fig. 1C, Movie-S2). The observed PIP2 hydrolysis was transient and recovered within 2–3 minutes. Gq-coupled GPCR activation induced-PIP2 hydrolysis recovers over time due to signaling adaptation24,25. Similar to melanopsin activation, addition of carbachol to HeLa cells expressing M3R and PIP2 sensor exhibited PIP2 hydrolysis. A similar recovery of PIP2 was also observed (Fig. S1, Movie-S3).
During PIP2 hydrolysis, IP3 moiety of PIP2 dissociates from PM anchored diacylglycerol (DAG) domain. The PH domain of PLCδ1 in the PH sensor moves to cytosol with IP3 upon PIP2 hydrolysis26. The irreversible translocation of mCherry-PH by BLE-retinal was further characterized to determine if this is due to PIP2 hydrolysis or a photochemical perturbation to PIP2, either by breaking the molecule or preventing PIP2 sensor binding. To examine whether BLE-retinal induces mCherry-PH translocation due to PIP2 hydrolysis, leaving DAG on the PM, DAG generation was imaged using cytosolic DAG sensor, YFP-DBD, that translocates to PM. Cells incubated with ATR failed to exhibit a detectable mCherry-PH translocation (Fig. 2A). When a selected cell in the field of vision (Fig. 2C, yellow arrow) was exposed BLE-retinal for 400 seconds, a robust mCherry-PH translocation only in blue light exposed cell was observed (Fig. 2B). However, the DAG sensor did not translocate to PM (Fig. 2B), indicating that, exposure to BLE-retinal does not leave DAG at PM. We also comparatively examined Gq-coupled M3-muscarinic receptor (M3R) activation in the same HeLa cells transiently expressing M3R. When cells were exposed to 10 µM carbachol, both PIP2 hydrolysis and DAG formation were observed (Fig. 2A). When this cell was exposed to YM254890 (1 µM), which inhibits Gαq heterotrimer activation, both PIP2 and DAG sensors reversed to their basal pre-activation status, suggesting PIP2 recovery (Fig. 2A). Interestingly, the cell exposed to BLE-retinal did not show such a recovery upon addition of YM254890 (Fig. 2B). This further confirms that BLE-retinal induced PIP2 distortion in cells is irreversible.
Figure 2 Comparison of M3-muscarnic receptor mediated PIP2 hydrolysis vs blue light excited retinal (BLE-retinal) induced PIP2 sensor translocation. Images of HeLa cells expressing M3-muscarinic receptor, mCherry-PH (PIP2 sensor), DBD-YFP (DAG sensor). (A) Without blue light exposure, retinal addition does not change PIP2 or DAG sensor distribution (left), while the addition of carbachol resulted in PIP2 hydrolysis and DAG formation (middle). The addition of Gq inhibitor, YM254890 (1 µM) to cells resulted in reverse translocation of PIP2 and DAG sensors. (mean ± S.E.M., n = 6 cells) (B) When cells were exposed to blue light (4.86 µW of 445 nm) in the presence of retinal, they only showed PIP2 sensor translocation while no change in DAG sensor was observed (left). The addition of carbachol to these cells exhibited an additional PIP2 sensor translocation to the cytosol with a mild DAG sensor translocation to the PM (left) (mean ± S.E.M., n = 4 cells). Interestingly, addition of YM254890 only reversed both PIP2 and DBD responses elicited by carbachol. (C) The field of vision of cells shown in A and B. Mean and S.E.M. are from 3 < independent experiments. (blue light (BL) = blue box). Scale = 5 µm. Full size image
Characteristics of retinal photoexcitation in cellular environment
Compared to the light power required for opsin activation (~0.2 μW), a higher power of blue light (>1 μW) was required for free retinal to induce PIP2 distortion. This can be partly due to the bathochromic shift in the absorption spectrum of melanopsin-retinal Schiff base (m-RSB) with a λ max = 478 nm, compared to the λ max = 383 nm of free retinal (Fig. 3A,B). This allows m-RSB to have a greater spectral overlap with blue light (445 nm) that drives a larger population of molecules to the excited S 1 (π* ← π) state, compared to free retinal (Fig. 3C). Since quantum yield of m-RSB isomerization is estimated to be at near unity27,28,29, all absorbed photons result in GPCR activation. Additionally, the lower power requirement for melanopsin activation induced PIP2 hydrolysis is due to the enhanced photosensitivity of m-RSB and PIP2 hydrolysis being an enzymatic process while BLE-excited retinal induced PIP2 distortion is likely to be a non-enzymatic and stoichiometric reaction.
Figure 3 Energy and wavelength requirement for PIP2 solubilization by photoexcited retinal. (A) UV-VIS absorption spectra for both 11-cis retinal (11CR) and all trans retinal (ATR). Note that 445 nm blue light spectrally overlaps with both absorption spectra. (B) The absorption spectra of melanopsin and retinal (left), (ε ATR = 44180.0 M−1cm−1). (C) The energy level diagram and the population (pop.) of energy levels of free retinal (blue) and melanopsin (red) according to their respective absorption maxima (right). Note that blue light (445 nm) can highly populate melanopsin compared to that of free retinal. (D–F) Images of HeLa cells expressing PIP2 sensor (mCherry-PH). (D) Cells were incubated with ATR (50 µM) for 5 minutes. A substantial PIP2 sensor translocation was observed upon exposing cells to short pulses of blue light (4.86 µW of 445 nm). The plot shows the dynamics of PIP2 sensor translocation to cytosol. (E) In the absence of retinal, cells did not show a detectable PIP2 sensor translocation when exposed to blue light or other wavelengths. (F) Both blue light excited ATR (50 µM) and 11CR (50 µM) exhibited a permanent accumulation of PIP2 sensor cytosol. Compared to exposed cell (yellow arrow), control cell without blue light (BL) exposure (white arrow) did not show any detectable PIP2 response. The plots show the dynamics of PIP2 sensor translocation in cells shown in F (mean ± S.E.M., n = 6 cells). (G) All trans retinal and blue light induce PIP2 sensor translocation in cells with distinct origins. Images of RAW264.7, NIH3t3, ARPE-19, MDA-MB-468, BT-20, HCT116 and HEK293 cells expressing mCherry-PH (PIP2 sensor). ATR (50 µM) was incubated in cells for 5 minutes followed by continuous exposure of blue light for 5 minutes. Blue light exposure induced PIP2 sensor translocation from PM in all the cell types tested while cells that were not exposed to blue light did not respond. Mean and S.E.M. are from 3 < independent experiments. (blue light (BL) = blue box). Scale = 5 µm. Full size image
To examine the wavelength dependency of BLE-retinal induced PIP2 distortion, HeLa cells expressing mCherry-PH were exposed to 445 nm, 488 nm, 515 nm and 594 nm wavelengths of light at 4.86 µW respectively, in the presence or absence of retinal. Cells exposed to 488, 515 and 594 nm light, in the presence of retinal did not show a detectable signal (Fig. 3D). Control cells also did not exhibit PIP2 distortion with blue light in the absence of retinal (Figs 3E and S3). Retinal addition alone (without blue light) also showed no PIP2 distortion (Fig. 3F). Only the selected cell in the field of vision exposed to blue light exhibited PIP2 distortion (Fig. 3F, yellow arrow, Movie-S4). Similar to ATR, 11CR also induces PIP2 distortion when exposed to blue light (Fig. 3F). Unless specified, all the experiments henceforward employed blue light with the power of 4.86 µW to excite retinal. At this light power, photobleaching of fluorescent biosensors was not observed. All the cell types examined including RAW264.7 (mouse macrophage), ARPE-19, MDA-MB-468 (triple negative breast cancer), BT20 (triple negative breast cancer), HCT116 (colon cancer), NIH3t3 (mouse embryonic fibroblast), and HEK293 (human embryonic kidney) exhibited mCherry-PH translocation upon exposure to BLE-Retinal (Fig. 3G) which indicates a universal mechanism operated by BLE-retinal.
To decipher molecular features of retinal for its blue light-induced cellular effects, compounds with analogous functional groups such as retinol, retinoic acid, β-ionone (β-ionone ring of retinal) and conjugated linoleic acid (CLA- mimicking the extended π conjugated system) were examined as follows. HeLa cells expressing mCherry-PH were incubated for 10 minutes with the retinal-like molecules at 50 μM concentrations (Fig. 4). Interestingly, none of these compounds were able to induce PIP2 distortion upon exposure to blue light (Fig. 4A–D). Examination of absorption spectra of these screened molecules show that they do not have sufficient spectral overlaps with the blue light (Fig. S3). However, both retinol and retinoic acid exhibited mCherry-PH translocation when exposed to 365 nm ultra violet light (Fig. S4).
Figure 4 Retinal-like molecules exhibited no effect on PIP2 upon blue light exposure. Images of HeLa cells expressing PIP2 sensor (mCherry-PH) on PM. In all of the experiments conducted, cells were exposed to blue light (4.86 µW of 445 nm) which is indicated by the white box. Cells were incubated with (A) β-ionone (50 µM), (B) 10E, 12Z linoleic acid (50 µM), (C) Retinol (50 µM) and (D) Retinoic acid (50 µM), for 10 minutes followed by continuous exposure of short pulses of blue light for 200 s. In all experiments, cells did not show a detectable PIP2 sensor translocation. Plots show the dynamics of PIP2 sensor translocation in cells shown in A–E. (mean ± S.E.M., n = 5–10 cells). Mean and S.E.M. are from 3 < independent experiments. (blue light (BL) = blue box). Scale = 5 µm. Full size image
BLE-retinal induced PIP2 distortion is independent of GPCR-G protein activation
Retinal and blue light mediated activation of Gq-coupled GPCRs are suggested to trigger signaling and cytotoxicity in ARPE-19 photoreceptor cells5. This study measured degeneration of cells in the mouse retina, however the underlying mechanism was unclear. Upon GPCR activation, both Gαq-GTP and Gβγ can induce PIP2 hydrolysis since they activate PLCβ30. To examine whether BLE-retinal activates GPCR-G proteins pathways, PIP2 distribution was studied in the presence of Gαq inhibitor-YM254890 (1 µM) and Gi-pathway inhibitor-pertussis toxin (PTX) (50 ng/mL) respectively (Fig. 5A–D). Previously, we showed that pertussis toxin inhibits Gβγ mediated PIP2 hydrolysis since inhibition of Gi-pathway activation prevents generation of free Gβγ31. After inhibitor treatment, cells incubated with retinal were exposed to blue light for 2–3 minutes while imaging the PIP2 sensor response. Both inhibitors failed to inhibit BLE-retinal induced PIP2 distortion (Fig. 5B,D). Additionally, HeLa cells were treated with both Gαq and Gβγ inhibitors simultaneously to rule out the possibility of activation of PLCβ by BLE-retinal. Regardless of the collective inhibition of Gβγ and Gαq, BLE-retinal induced PIP2 disruption in cells (Fig. S5). This indicates that BLE-retinal induced responses are not due to the GPCR-G protein pathway activation. Control experiments show YM254890 and PTX inhibit Gq-pathway induced PIP2 hydrolysis and Gi-pathway induced Gγ9 translocation, respectively (Fig. 5A,C)32. In addition, retina-derived ARPE-19 cells exhibited PIP2 disruption upon BLE-retinal in the presence of Gαq, Gβγ and Gi pathway inhibitors (Fig. S6). Contrary to the previous reports7, these experiments and data confirm that free retinal with or without light does not activate GPCR pathways.
Figure 5 Photoexcited retinal induced PIP2 translocation is not due to GPCR pathway activation. (A) HeLa cells expressing M3 receptor and mCherry-PH, carbachol (10 µM) was added to activate M3R in the presence (left) and absence (middle) of Gq inhibitor (YM254890, 1 µM, 5 min). Only control cells (no YM254890), showed PIP2 hydrolysis (left). (B) Even in the presence of Gq inhibitor, blue light excited retinal induced PIP2 sensor translocation (middle). The plots show the dynamics of PIP2 sensor translocation in the cells shown in A and B. (C) To HeLa cells expressing CXCR4-GFP, mCh-γ9, SDF1α (100 ng/mL) was added to activate CXCR4 in the presence (left) and absence (middle) of Gαi inhibitor (pertussis toxin = Ptx, 50 ng/mL, overnight incubation). Only control cells with no added Ptx exhibited mCh-γ9 translocation from PM to IMs (left). (D) Exposure to photoexcited retinal induced PIP2 sensor translocation in cells treated with Ptx. The plots show the dynamics of mCh-γ9 and PIP2 sensor translocation. In all the experiments conducted, cells were exposed to 4.86 µW of 445 nm blue light. (mean ± S.E.M., n = 5–10 cells). Mean and S.E.M. are from 3 < independent experiments. (blue light (BL) = blue box). Scale = 5 µm. Full size image
PIP2 distortion by BLE-retinal is associated with an increase in intracellular calcium, [Ca2+] i
According to the crystal structure of IP3 receptor33, IP3 molecule forms H-bonds with the putative interacting domain (Fig. 6A, PDB code:1N4K). To examine whether distorted PIP2, that may be entering cytosol could also increase cytosolic calcium, HeLa cells expressing mCherry-PH were incubated with cell permeable calcium sensor fluo4-AM and exposed to BLE-retinal. Cells exhibited a robust upsurge of calcium and a synchronized mCherry-PH translocation response was observed (Fig. 6B,C, Movie-S5). Unlike Gq-coupled GPCR induced calcium response, which recovers over time (Fig. S7A), BLE-retinal induced response did not exhibit signaling adaptation (Fig. 6C). To examine the source of calcium mobilized by BLE-retinal, cellular calcium modulators were deployed as follows and percent change in fluo-4 fluorescence in the cell upon exposure to BLE-retinal was calculated with respect to fluo-4 fluorescence observed prior to blue light exposure. Upon BLE-retinal exposure, cells without a calcium modulator was considered as the control and exhibited a 55 ± 8% increase in fluo4 fluorescence compared to basal fluorescence. Cells incubated in extracellular calcium free medium (using BAPTA) and with intracellular calcium chelator, BAPTA-AM, induced only 25 ± 5% and ~16 ± 1% increases respectively, (Fig. 6D). Treating cells with IP3 receptor inhibitor, 2-aminoethoxydiphenyl borate (2-APB) resulted in ~21 ± 4% increase (Fig. 6D). These data indicate possible interactions of the IP3 domain of distorted PIP2 with IP3 receptors33. Calcium modulators above were validated as follows (Fig. S7). Cells incubated with BAPTA-AM showed only PIP2 hydrolysis but no calcium response upon M3-muscarinic receptor activation (Fig. S7B), while 2-APB treated cells showed a transient PIP2 hydrolysis with no calcium response (Fig. S7C). Compared to BLE-retinal induced calcium responses, M3R activation induced responses were rapid and transient. These results also show the ability of BLE-retinal to induce downstream signaling, independent of GPCR activation. Collectively, these data suggest that BLE-retinal induced distortion of PIP2 not only induces mobilization of stored calcium, but also stimulate influx of extracellular calcium.
Figure 6 All trans retinal and blue light induced signaling in cells. (A) Crystal structure of the IP3 receptor bound with IP3 with H-bonding interactions (PDB code:1N4K), suggesting the PIP2 can have the majority of interactions exhibited by IP3. (B) HeLa cells expressing PIP2 sensor (mCherry-PH) and incubated with calcium sensor Fluo4. Fluo4 stained cells were incubated with ATR (50 µM) for 5 minutes, followed by exposure of blue light (4.86 µW of 445 nm) for 3 minutes. Here the whole cell was exposed to blue light. A substantial increase in cytosolic calcium is observed. (C) Dynamics of calcium responses and PIP2 translocation in the cells shown in B (mean ± S.E.M., n = 5 cells). (D) Calcium responses in control and calcium modulator-incubated (using BAPTA-AM and 2-APB) HeLa cells in regular and extracellular calcium free (using BAPTA) buffers. Here, cells were pre-incubated Fluo4 were incubated with 2-APB (5 µM for 15 min), BAPTA-AM (10 µM for 30 min), or BAPTA (5 µM for 5 min) in calcium free HBSS buffer. The cells were then incubated with ATR (50 µM) for 5 minutes, followed by continuous exposure of blue light for 5 minutes. The bar chart shows the changes in calcium sensor fluorescence in the cytosol before and after blue light exposure on cells for all the above mentioned experiments (mean ± S.E.M., n = 5–15 cells). Mean and S.E.M. are from 3 < independent experiments. (blue light (BL) = blue box). Scale = 5 µm. Full size image
Blue light-excited retinal induces cytotoxicity
The possibility of PIP2 distortion and calcium mobilization elicited by BLE-retinal to induce cytotoxicity was examined. Morphology of HeLa cells incubated in retinal containing medium was observed using time-lapse microscopy while only selected cells were exposed to blue light. PIP2 distortion and substantial morphological changes, including extensive bleb formation, were observed only in blue light exposed cells (Fig. 7A, Movie-S6). Unexposed control cells in the same field remained morphologically intact. To identify whether exposure of BLE-retinal induces cell death, HeLa cells were incubated with cell-death marker, propidium iodide (PI) and examined its inclusion, since apoptotic cells fail to exclude PI34,35. Cells were supplemented with 100 µL of PI (50 µg/mL) and 50 µM ATR, while selected cells were exposed to blue light. Control cells were either exposed to blue light without retinal or incubated with retinal without blue light exposure. Cells exposed to blue light in the presence of retinal showed gradual incorporation of PI, indicated by the increase in red fluorescence (Fig. 7B). Observed time curves of PI incorporation into cells were heterogenous (Fig. 7B, plot). Cells in both the control experiments did not incorporate PI (Fig. 7B). These results indicate that prolonged exposure of cells to BLE-retinal leads to cell death.
Figure 7 Photoexcited retinal induced cytotoxicity. (A) Fluorescence and DIC images of HeLa cells treated with ATR (50 µM) followed by blue light exposure (4.86 µW of 445 nm). Only the middle cell (yellow arrow) expresses PIP2 sensor. Blue light exposed (blue box) cell showed substantial change in cell shape and morphology. The PIP2 sensor also accumulates in cytosol upon blue light exposure. (B) HeLa cells were incubated with propidium iodide (PI) with ATR (50 µM) and exposed to blue light (4.86 µW) for 45 minutes. Incorporation of PI in to cells were observed upon light exposure. The control experiments performed with cells exposed to only to blue light or only to ATR, did not show PI incorporation into cells over time. Plot shows the different rates of PI incorporation into cells compared to control experiments. (C,D) Solvent dependent degradation and isomerization of ATR. (C) ATR (20 µL of 50 mM in ethanol) was exposed to blue LED light for 30 minutes. The blue light exposed ATR (injection sample: 1 µL of exposed ATR was diluted in 1 mL of ethanol) was analyzed by HPLC where degradation of ATR is observed by reduction of corresponding ATR peak in chromatogram. right: The degraded ATR (dATR) (1 µL) was added to HeLa cells (final volume of imaging buffer = 1 mL) expressing PIP2 sensor and continuously exposed to 445 nm light (4.86 µW). Cells did not show detectable PIP2 translocation upon blue light. Exposure of cells to fresh ATR (50 µM) and blue light (BL) induced PIP2 distortion (mean ± S.E.M., n = 12). (D) HPLC analysis of retinal in different solvents after exposing to white light for varying durations. Note that retinal in water degrades in seconds while in ethanol and hexane show over 100 times enhanced stability. Improved isomerizations were seen as well. Mean and S.E.M. are from 3 < independent experiments. (blue light (BL) = blue box). Scale = 5 µm. Full size image
mCherry-PH sensor translocation by BLE-retinal indicates distortion of the PIP2 molecule
To determine whether translocation of mCherry-PH is a common response exhibited by fluorescence proteins on exposure to BLE-retinal, a membrane anchor with a transmembrane domain (from mouse ICAM5) and a C-terminal mCherry, DenMark-mCherry was used36. In addition to DenMark-mCherry, HeLa cells were also expressed with YFP-PH. Upon exposure to BLE-retinal, PM localization of DenMark did not change, while YFP-PH translocated to cytosol (Fig. S8A,C). A saturated lipid anchor bearing glycoprotein, glycosylphosphatidylinositol (GPI) which anchors extracellularly to cells also did not respond to BLE-retinal (Fig. S8B,C). HeLa cells expressing GPI-GFP and NIH3t3 cells expressing GPI-mCherry were used for the experiment. BLE-retinal did not remove GPI anchored proteins from PM. This suggests that specifically PIP2, that contains an unsaturated arachidonoyl chain is susceptible to photochemical reactions elicited by BLE-retinal. Since PIP2 also contains one stearyl anchor, a saturated lipid, it is not clear how oxidation of only arachidonoyl anchor induces PIP2 solubilization. One possibility is that only a small fraction of distorted PIP2 undergoes additional cleavage from the stearyl anchor. This could result in a fraction of PIP2 molecules solubilizing to cytosol and induce calcium mobilization.
Cell membranes are likely to facilitate retinal photoexcitation and cellular damage
As the location of retinal in the cellular environment could be crucial, the next objective was to examine the subcellular environment that can support the photochemical reactions of retinal. When a 20 µL solution of ATR in ethanol (50 mM) was exposed to blue LED light (5 W, 460–470 nm) for 30 minutes, a significant retinal degradation was observed (Fig. 7C). The retinal content in the solution was analyzed using high performance liquid chromatography (HPLC), before and after blue light exposure. HeLa cells expressing mCherry-PH sensor were incubated with 1 µL of this pre-blue light exposed retinal for 10 minutes. However, the addition of pre-blue light exposed retinal did not exhibit PIP2 distortion in cells. Exposure of these cells to blue light at 4.86 μW intensity also failed to exhibit a detectable mCherry-PH translocation, suggesting that (i) the mixture does not have sufficient retinal left and (ii) extracellularly generated retinal photoproducts are not able to disrupt cellular PIP2. Nevertheless, addition of fresh retinal (50 µM) followed by blue light exposure resulted in mCherry-PH translocation (Fig. 7C). Next, we examined if household white fluorescent light also induces retinal degradation, since both fluorescent and LED light contain a peak ~450 nm. Retinal degradation observed under white light was lower in ethanol (Fig. 7D). When retinal in hexane was exposed to white light, it showed even lower degradation. Interestingly, retinal in water exhibited over a 100 times faster degradation (within seconds) than in ethanol or hexane (within minutes) (Fig. 7D). These experiments collectively suggest that in cellular context, retinal must retain in a relatively non-aqueous and hydrophobic environment, not in the cytosol. These data also show that retinal undergoes efficient isomerization, in non-aqueous media upon photon absorption. PM lipid bilayer of cells is likely to provide an ideal environment for retinal to undergo continuous photoisomerization over degradation.
Ability of retinal to harvest light and induce PIP2 distortion was examined to understand whether this process is governed by photosensitization of retinal. A known photosensitizer rose bengal (RB) absorbs green light (Fig. S9) and exhibits singlet oxygen generation37 and cell death38. HeLa cells expressing PIP2 sensor were incubated with RB (50 µM) and exposed to blue and green light respectively. Cells were imaged to observe whether RB too induces a similar PIP2 distortion. Both blue and green light exposure induced a significant PIP2 sensor translocation (Fig. 8A). To assess whether observed PIP2 distortion requires dissolved oxygen in cell culture media to produce singlet oxygen, HeLa cells were treated with CoCl 2 for 12 hours to expose cells to hypoxia39. Upon exposure to BLE-retinal, compared to control normoxic cells, hypoxic cells exhibited an attenuated PIP2 sensor translocation (Fig. 8B). To validate that BLE-retinal induced PIP2 distortion was governed through free radical/ROS mechanisms, prior to blue light exposure, cells were incubated with antioxidants, glutathione ethyl ester and alpha-tocopherol respectively (Fig. 8C,D). Alpha-tocopherol is lipid soluble while glutathione is water soluble and cytosolic. Only cells incubated with alpha-tocopherol exhibited an attenuated PIP2 sensor translocation (Fig. 8C,D). This indicates that reactions of oxidative damage induced by BLE-retinal are likely taking place in lipid membranes (Fig. 8E).
Figure 8 Comparison of PIP2 sensor dissociation from PM by retinal vs a known photosensitizer, rose bengal. (A) Images of HeLa cells expressing PIP2 sensor (mCherry-PH). (A) PIP2 sensor translocation was induced by rose bengal (50 µM), incubated with cells for 5 minutes, in the presence of blue (4.86 µW of 445 nm) and green (light (0.22 µW of 515 nm) respectively. Plot shows the cytosolic fluorescence of PIP2 sensor in HeLa cells upon exposing to light. (mean ± S.E.M., n = 6). (B) HeLa cells were incubated with CoCl 2 (100 µM) for 24 h to expose cells to hypoxia. The control cells were kept in same conditions without CoCl 2 treatment. Cells were incubated with ATR (50 µM) and 445 nm imaging for 10 minutes was performed. Cell in hypoxic condition did not exhibit detectable PIP2 sensor accumulation in cytosol while control cells showed a gradual PIP2 sensor accumulation from PM to cytosol. (C,D) Antioxidants were tested to examine if they prevent PIP2 sensor translocation induced by retinal and blue light. HeLa cells expressing PIP2 sensor were incubated with antioxidants, alpha-tocopherol (1 mM) and reduced-glutathione ethyl ester (500 µM) overnight. Prior to imaging experiments ATR (50 µM) was added and incubated for 5 minutes followed by exposure of blue light (4.86 µW of 445 nm) for 5 minutes. (C) Cells treated with reduced-glutathione ethyl ester exhibited PIP2 sensor translocation from PM to cytosol upon blue light exposure. Plot shows the dynamics of PIP2 sensor (mean ± S.E.M., n = 14 cells). Overview of the antioxidant mechanism exert by reduced glutathione in vivo (right). (D) Cells treated with alpha-tocopherol showed a reduced rate and extent of PIP2 sensor translocation from PM to cytosol upon blue light exposure. Plot shows the dynamics of PIP2 sensor translocation (mean ± S.E.M., n = 6 cells). Note the reduction of PIP2 sensor accumulation in IMs of cells. Right: Overview of the antioxidant mechanism exert by alpha-tocopherol in vivo. (E) Proposed mechanism for blue light excited retinal induced PIP2 distortion process. (F) TD-DFT calculations (CAM-B3LYP/6–31++G**) of retinal’s energy states and the Jablonsky diagram shows strong absorption band due to the π → π* transition where triplet excited states are energetically and symmetrically matched to allow for efficient intersystem crossing and energy transfer to O 2 which allows for singlet oxygen and ROS generation. Mean and S.E.M. are from 3 < independent experiments. (blue light (BL) = blue box and green light (GL) = green box). Scale = 5 µm. Full size image |||||
What is a shorter version of the above article? | – Staring at your smartphone, tablet, or computer screen for hours on end may not only be fueling your online addiction—it could be wreaking havoc on your eyesight. So says a new study out of the University of Toledo, published in the Scientific Reports journal, and it's all because of the symbiotic relationship between a light-sensitive protein in our retinas and the blue light emitted from our digital devices. What happens when that blue light hits our eyes, per the chemists involved in the research: It triggers the protein, called retinal, to produce toxic molecules that kill off the eye's non-regenerative photoreceptor cells. And once those cells are dead, "they're dead for good," study co-author Kasun Ratnayake says, per CTV News. The retinal and blue light definitely need each other to cause their damage, too: Either one on its own wasn't found to kill cells. Over time, this process leads to age-related macular degeneration, which is the top cause of vision loss and can eventually lead to blindness. There is a Vitaman E molecule called alpha tocopherol that exists in our eyes and is able to fend off such cell deaths, but it apparently doesn't wield the same fighting powers as we age or if our immune systems are compromised. As researchers explore how to combat the problem—eyedrops that slow down macular degeneration is one such therapy on the table—study co-author Ajith Karunarathne suggests that people not check their devices when they're in the dark and to wear special glasses that can keep blue light from slamming into the retina. (Thinking about Lasik to help your own vision? There have been some concerns.) | 5 | Flan2021 | multi_news:1.0.0 | zs_opt |
Texas Monthly v. Bullock 489 U.S. 1 (1989) was a case brought before the US Supreme Court in November 1988. The case (initiated by the publishers of "Texas Monthly", a well-known general-interest magazine in Texas) was to test the legality of a Texas statute that exempted religious publications from paying state sales tax.
Can we infer the following?
Texas Monthly is the most popular magazine in Texas.
a). Yes; b). It's impossible to say; c). No;
The answer is: | b). | 4 | Flan2021 | anli/r2:0.1.0 | zs_opt |
Multi-choice question: Same meaning?
In an interview for the book , Avedon interpreted this phenomenon for Rowlands : `` It 's because Vreeland lasted .
Vreeland interpreted this phenomenon for Rowlands in an interview with the book : `` It 's because Avedon lasted '' .
Choose from: (I) no (II) yes | (I) | 6 | Flan2021 | paws_wiki:1.1.0 | zs_opt |
The Kissing Booth
During the next few weeks, Elle and Noah spend every day together before he has to leave for college. When it is time to go Elle goes with him to the airport and he leaves. After watching him leave, she drives off on Noah's motorcycle saying that she does not know if they will be together forever but she knows that a part of her heart will always belong to Noah Flynn. The story ends with Elle stating that everything happened just because of the Kissing Booth.
OPT: (I) no (II) yes
Is this statement correct "does elle end up with noah in the kissing booth"? | (II) | 8 | Flan2021 | bool_q:1.0.0 | zs_opt |
Sentence: 3Arena at North Wall Quay is owned by Live Nation Entertainment.
What data can be extracted from this sentence? | 3Arena, owner, Live Nation Entertainment; 3Arena, location, "North Wall Quay" | 8 | Flan2021 | gem/web_nlg_en:1.1.0 | zs_opt |
Add punctuation: Cut the bananas into slices if they werent already sliced when frozen and remove the stones from the avocado and the dates
| Cut the bananas into slices (if they weren’t already sliced when frozen) and remove the stones from the avocado and the dates. | 6 | Flan2021 | fix_punct | zs_opt |
Generate a sentence about this data: Ajoblanco COUNTRY Spain; Ajoblanco REGION Andalusia; Ajoblanco INGREDIENT Garlic
Sentence: | Ajoblanco is a dish from the Andalusian region of Spain and includes the ingredient garlic. | 5 | Flan2021 | gem/dart:1.1.0 | zs_opt |
Write the following list of characters into a correctly formed sentence: Shingles-isapainfulblisteringrash(swelling)causedbythereactivationofvaricellavirus.
| Shingles - is a painful blistering rash (swelling) caused by the reactivation of varicella virus. | 7 | Flan2021 | word_segment | zs_opt |
Answer by taking a quote from the following article:
Tammy Wynette (; born Virginia Wynette Pugh; May 5, 1942 - April 6, 1998) was an American country music singer-songwriter and one of country music's best-known artists and biggest-selling female singers. Wynette was called the "First Lady of Country Music", and her best-known song, "Stand by Your Man", is one of the best-selling hit singles by a woman in the history of country music. Many of her hits dealt with classic themes of loneliness, divorce, and the difficulties of life and relationships. During the late 1960s and early 1970s, Wynette charted 20 number-one songs.
In 1981, a TV movie about Wynette's life was aired called Stand by Your Man, which was based on her memoir of the same title. Actress Annette O'Toole portrayed Wynette in the film. Beginning in the early 1980s, however, her chart success began to wane, though, she did continue to have top-20 hits during this period, including "Starting Over" and "He Was There (When I Needed You)" (both 1980), a cover of the Everly Brothers' hit "Crying in the Rain" (1981), "Another Chance", "You Still Get to Me in My Dreams" (both 1982) and "A Good Night's Love" (1983). A 1985 cover of the '70s Dan Hill hit "Sometimes When We Touch", performed with Mark Grey, reached No. 6 in 1985. In 1982 she recorded a track with The Ray Conniff Singers, a rendition of "Delta Dawn", in order to be included in the Conniff's duets album "The Nashville Connection", but ultimately the track didn't enter. Meanwhile, her medical problems continued, including inflammations of her bile duct. In 1986, she acted on the CBS TV soap opera Capitol, playing beautician/singer Darlene Stankowski. In 1988, she filed for bankruptcy as a result of a bad investment in two Florida shopping centers. Wynette's 1987 album Higher Ground featured a neotraditional country sound and was both a critical and relative commercial success. The album featured contributions from Larry Gatlin, Vince Gill, Ricky Van Shelton, Rodney Crowell, Ricky Skaggs, Emmylou Harris and The O'Kanes. Two of the singles released from the album, "Your Love" and "Talkin' to Myself Again", reached the top 20 on the U.S. country singles charts; a third single, "Beneath a Painted Sky" (featuring duet vocals from Emmylou Harris) reached No. 25 in early 1988 (it would ultimately be Tammy Wynette's final top-40 country single).
Did she have other hits in the 80s? | You Still Get to Me in My Dreams" (both 1982) and "A Good Night's Love" (1983 | 2 | Flan2021 | quac:1.0.0 | zs_opt |
Answer the following question about this sentence:
The boy's hands were shaking.
What is the cause?
Select from: 1. He planned to ask the girl out. 2. His palms were cold and sweaty. | 1. | 7 | Flan2021 | super_glue/copa:1.0.2 | zs_opt |
Complete: i 'll spare you the details of what i had to do while you were in my shower in order to calm myself down after seeing you up close for the first time . my physical reaction to you did n't worry me . physical reactions are normal , and at that point , my heart still belonged to maggie . my heartbeats were all for maggie . they always had been , but the more time i spent with you , the more you started to unintentionally infiltrate and steal some of those | heartbeats | 6 | Flan2021 | lambada:1.0.0 | zs_opt |
Text: A prequel to Speaker for the Dead named Ender in Exile was released in November 2008. It involves Ender's journey to the first colony (and thus serves as a replacement for the last chapter of Ender's Game and as a sequel to the remainder of the novel), as well as his meeting a character from the parallel Shadow saga (effectively wrapping up a remaining plotline in the parallel series).
Question: is there a sequel to the enders game?
Available choices:
(a). no
(b). yes | (b). | 3 | Flan2021 | bool_q:1.0.0 | zs_opt |
Write down the solution for this math problem: Solve -u = -4*u - 6 for u. | -2 | 4 | Flan2021 | math_dataset/algebra__linear_1d:1.0.0 | zs_opt |
Solve 12 = -13*q + 10*q for q.. What is the answer?? | -4 | 9 | Flan2021 | math_dataset/algebra__linear_1d:1.0.0 | zs_opt |
This question has options. How would someone go about accomplishing this goal?
How to store pearl necklaces?
OPT:
(1). Wipe them with a soft dry cloth then wrap them in linen and place in the jewelry box.
(2). Wipe them with a soft damp cloth then wrap them in linen with the other jewelry and in the box. | (1). | 7 | Flan2021 | piqa:1.0.0 | zs_opt |
Friday: The Animated Series was a short-lived animated television series based on the "Friday" film series. The show is directed by Kevin Lofton and is co-produced and co-distributed by New Line Television, a subsidiary of New Line Cinema (the distributors of the "Friday" movies), MTV2, and Ice Cube's Cubevision. The series only lasted for 8 episodes.
Choose your answer: based on the paragraph above can we conclude that "Friday: The Animated Series was watched by lot of kids"?
OPTIONS:
[A]. Yes;
[B]. It's impossible to say;
[C]. No;
I think the answer is | [B]. | 0 | Flan2021 | anli/r2:0.1.0 | zs_opt |
In remarks during a ribbon-cutting ceremony here on Wednesday, Gov. George E. Pataki said he expected the facility to generate thousands more jobs in the Hudson Valley area for contractors and suppliers catering to the factory. He praised IBM for being "a critical partner in our economic development efforts" in New York state. In a brief speech, Samuel J. Palmisano, IBM's chief executive, emphasized that it was important to make long-term investments despite the current slump in the technology business. "To play to win in technology, you innovate and you lead," he said. But manufacturing technology products is a costly and cyclical business. In June, IBM announced that it was taking a charge of more than $2 billion against earnings. The largest single reasons for the charge were the cost of getting out of the business of manufacturing hard disks for storage, which it sold to Hitachi, and closing down some of its older semiconductor operations. But Kelly said the demand for advanced chips, like those produced at IBM's facility in Burlington, Vt., is strong. "I need more capacity in that end of the market," he said, "and this is factory is critical to meeting that growing demand." If IBM has miscalculated the demand, it will suffer badly as both the high operating costs and depreciation on the huge capital investment for the East Fishkill factory drag down earnings. But industry analysts said the plant should be insulated from a falloff in one or a few segments of the semiconductor market.
What question would one ask from this paragraph? | What Factory was just opened in Hudson Valley with a ribbon cutting ceremony? | 9 | Flan2021 | super_glue/multirc:1.0.2 | zs_opt |
What happens next in this paragraph?
How to clean grout with toilet cleaner
Look for a toilet cleaner that contains sodium hydroxide.
Many toilet cleaners contain sodium hydroxide and sodium hypochlorite. These two ingredients help to remove stains and grime on porcelain or tile surfaces as well as grout.
a). Though they can be toxic in large amounts, they do work to effectively clean grout. You may look for common brands of toilet cleaner at your local hardware store or in the cleaning aisle at your grocery store..
b). Check for the following : The brand of toilet cleaner that comes with the product. If you use more than one brand, choose the brand that has an easier time removing stains, off the label..
c). Some good brands of toilet cleaners include : Pine ash ash barbecue ash teething powder suet pine tar very sooty-smelling toilet cleaner Wear gloves or goggles when cleaning toilets. Since toilet cleaners can come in many different shades, look for a cleaning solution made specifically for toilets that contains mercury..
d). Check the label on the cleaner to find out if sodium hydroxide is safe. See if the cleaner has aluminum powder in it.. | a). | 0 | Flan2021 | hellaswag:1.1.0 | zs_opt |
Q: What incident caused the canning of a summit conference between Eisenhower and Khrushchev ?
Which one of the following options would the answer to this be?
OPT:
[i] description
[ii] entity
[iii] abbreviation
[iv] human
[v] numeric
[vi] location
A: | [i] | 8 | Flan2021 | trec:1.0.0 | zs_opt |
Add punctuation to the following sentence: Updated online 04052009 Printed catalogues do not include these corrections
| Updated online: 04.05.2009 (Printed catalogues do not include these corrections) | 7 | Flan2021 | fix_punct | zs_opt |
Write a short summary for this text: kyrgyzstan called on uzbekistan tuesday to return a journalism student arrested by uzbek border guards as he tried to cross into uzbekistan to investigate a crackdown there in may .
Summary: | kyrgyzstan demands return of journalist jailed in uzbekistan | 0 | Flan2021 | gigaword:1.2.0 | zs_opt |
Add spaces: Features:StainlessSteelCaseBrownLeatherStrapQuartzMovementCaliberG10.211SapphireCrystalIvoryDialDateDisplayChronographFunctionStainlessSteelBezelTachymeterLuminousHands100MWaterResistanceApproximateCaseDiameter:42.5mmApproximateCaseThickness:10.57mm
| Features: Stainless Steel Case Brown Leather Strap Quartz Movement Caliber G10.211 Sapphire Crystal Ivory Dial Date Display Chronograph Function Stainless Steel Bezel Tachymeter Luminous Hands 100M Water Resistance Approximate Case Diameter: 42.5mm Approximate Case Thickness: 10.57mm | 3 | Flan2021 | word_segment | zs_opt |
Use evidence from the fact that a desert environment contains very little food to answer the following question. Choose from options. "In an arid location, any various lifeforms will have to"
Pick from:
(a). work harder for nutriment;
(b). find food quite easily;
(c). find fast, easy nutriment;
(d). always eat their fill; | (a). | 4 | Flan2021 | openbookqa:0.1.0 | zs_opt |
Generate an approximately fifteen-word sentence that describes all this data: The Eagle eatType coffee shop; The Eagle food Italian; The Eagle priceRange high; The Eagle customer rating average; The Eagle area city centre; The Eagle familyFriendly no; The Eagle near Burger King
| Near the Burger King in the city centre is an Italian coffee shop called The Eagle. It is not child friendly, has an average customer rating and is in the high price range. | 2 | Flan2021 | gem/dart:1.1.0 | zs_opt |
Please answer this question: Which seeds are used to make tahini paste? | sesame | 0 | Flan2021 | trivia_qa/rc:1.1.0 | zs_opt |
Write a sentence not in English. | Trebuie, de asemenea, să folosim măsuri active pentru a promova mobilitatea şi încă odată, în acest context, flexibilitatea crescută a pieţelor muncii deţine un rol cheie. | 8 | Flan2021 | wmt16_translate/ro-en:1.0.0 | zs_opt |
Vonnegut's words are best experienced on paper. The tales he weaves are gossemar, silken strands of words and expressions that are not easily translated into a world of Marilyn Manson or Jerry Bruckheimer explosions. His words have been treated well once before, in the remarkable Slaughterhouse-5.
Mother night is probably one of the three novels Vonnegut has written I could take to a desert island, along with Slaughterhouse-5 and Bluebeard.
The film version deserves a 10, but the books are so permanently part of my interior landscape that I just can't do it...some of the scenes left out of the film are part of my memory...
Is the sentiment of this review positive or negative?
Choices:
(a). negative;
(b). positive; | (b). | 3 | Flan2021 | imdb_reviews/plain_text:1.0.0 | zs_opt |
Can we conclude that "The heavy book broke." if the statement "I put the heavy book on the table and it broke." is true?
Possible answers: A). no B). yes | A). | 6 | Flan2021 | glue/wnli:2.0.0 | zs_opt |
The Blitz:
Hitler's interest in this strategy forced Göring and Jeschonnek to review the air war against Britain in January 1941. This led to Göring and Jeschonnek agreeing to Hitler's Directive 23, Directions for operations against the British War Economy, which was published on 6 February 1941 and gave aerial interdiction of British imports by sea top priority. This strategy had been recognised before the war, but Operation Eagle Attack and the following Battle of Britain had got in the way of striking at Britain's sea communications and diverted German air strength to the campaign against the RAF and its supporting structures. The OKL had always regarded the interdiction of sea communications of less importance than bombing land-based aircraft industries.
Please answer a question about this article. If the question is unanswerable, say "unanswerable". What prevented the targeting of sea communications before? | Operation Eagle Attack and the following Battle of Britain | 0 | Flan2021 | squad/v2.0:3.0.0 | zs_opt |
Add punctuation: Stenbutikkendk has rare and very beautiful minerals with fantastic fluorine
| Stenbutikken.dk has rare and very beautiful minerals with fantastic fluorine | 6 | Flan2021 | fix_punct | zs_opt |
Cheetahs breed throughout the year; they are induced ovulators. Females become sexually mature at 21 to 22 months of age. Females are polyoestrus -- they have an oestrus (``heat'') cycle every 12 days (this can vary from 10 to 20 days), each oestrus lasting one to three days. A female can give birth again after 17 to 20 months; however, on the loss of a whole litter mothers can mate again. Urine-marking in males becomes more pronounced when a female in their vicinity comes into oestrus. Males fight among one another to secure access to the female; even males in a coalition may show some aggression toward one another on approaching a female. One male eventually wins dominance over the others. Mating, observed mainly at night, begins with the male approaching the female, who lies down on the ground. No courtship behaviour is observed; the male immediately secures hold of the female's nape and copulation takes place. The pair then ignore each other and part ways. However, they meet and copulate a few more times within the next few days. Polyandrous, females can mate with several males. The mean number of motile sperm in a single ejaculation is nearly 25.3 million.
Multi-choice problem: Is it true that does a cheetah keep its mate for life?
Options:
(i). no
(ii). yes
The answer is: | (i). | 1 | Flan2021 | bool_q:1.0.0 | zs_opt |
Answer this question: Denise was driving east over a hill in the afternoon, shortly after a rain shower. Suddenly the sun broke through the clouds, and she saw a rainbow ahead of her. Which of the following made the rainbow possible?
OPT: +Sunlight can be separated into all the colors of the rainbow. +Water reflects sunlight like a mirror to make it look colored. +Overhead black clouds reflect in puddles to cause a mirage. +Air pollution causes the sky to look colored under these conditions.. Answer: | Sunlight can be separated into all the colors of the rainbow. | 9 | Flan2021 | unified_qa_science_inst | zs_opt |
What is the debate topic for the following sentences?
1. U.S. Energy Information Administration , U.S. Imports by Country of Origin ,
2. Even if hypothetically Canadian relations were to turn frosty , the existence of the pipeline would nevertheless ensure that the US would remain the only viable market .
3. Due to political instability and the difficult US relations with these nations , US supplies can not be considered secure , and with the results of research into alternative sources of energy being decades away from fruition the United States needs alternative sources of oil today .
4. Currently , the United States imports nearly two-thirds of its Petroleum , with the leading suppliers including nations such as Nigeria , Venezuela and Saudi Arabia .
5. Canadas known reserves total 179 billion barrels , placing it third behind Saudi Arabia , but some estimates have put its total at as high as 2 trillion barrels .
6. One option is Canada , which is individually already the United States single largest energy supplier .
7. On the Canadian end , the increased market access would lead to rapid development , which in turn would increase Canadian capacity to the level to which it could reach a much greater portion of US demand .
8. The XL Pipeline project would help bring this oil overland into the United States .
9. In the case of the latter the Pipeline would allow the US to disengage from the region to a degree .
10. Furthermore , the United States enjoys close relations and an open border with Canada , meaning that this oil will likely arrive without the strings attached that come from buying from Venezuela or the Middle East . | This House would build the Keystone XL pipeline | 7 | Flan2021 | opinion_abstracts_idebate | zs_opt |
How is "Breakfast not best,hard bed and not given complimentary champagne as per booking." said in German? | Man sollte nicht das günstigste Zimmer wählen, denn das ist sehr klein und möglicherweise für deutschen Standard zu eng. | 6 | Flan2021 | wmt16_translate/de-en:1.0.0 | zs_opt |
Generate an approximately fifteen-word sentence that describes all this data: United States, language, English language; Angola, Indiana, isPartOf, Pleasant Township, Steuben County, Indiana; United States, ethnicGroup, Native Americans in the United States; Angola, Indiana, country, United States.
Sentence: | Angola, Pleasant Township, Steuben County, Indiana is part of The United States, home to Native Americans and includes the English language. | 7 | Flan2021 | gem/web_nlg_en:1.1.0 | zs_opt |
Produce a brief English sentence that would be considered grammatically as category: 1).
All categories: Available choices:
1). unacceptable;
2). acceptable; | How do you wonder whether John said that Mary solved the problem? | 9 | Flan2021 | glue/cola:2.0.0 | zs_opt |
Write a text based on this summary: israel arrests three press people in hebron unrest
Text: | israeli police on sunday arrested two palestinian cameramen and a woman journalist as they were filming a rally organised by the left - wing peace now group in hebron . | 8 | Flan2021 | gigaword:1.2.0 | zs_opt |
Lethal Weapon 4 is a 1998 American buddy cop action comedy film directed and produced by Richard Donner, and starring Mel Gibson, Danny Glover, Joe Pesci, Rene Russo, Chris Rock, and Jet Li (in his American film debut). It is the fourth and final installment in the "Lethal Weapon" series.
Does this next sentence follow, given the preceding text?
Lethal Weapon 4 is a 20th century movie which some people like and some people do not. It starred Mel Gibson and Danny Glover. The film is a realistic portrayal of cop life.
Possible answers:
(a). Yes;
(b). It's impossible to say;
(c). No; | (b). | 3 | Flan2021 | anli/r1:0.1.0 | zs_opt |
Last night , I visited the wake of a friend 's father somewhere in Cogeo . His father died of cardiac arrest . He was just diagnosed of having cancer of the tongue and was operated . During the wake , me and my friends were talking about death .
Select from: a. Sad. b. None of the above choices .. c. Tired. d. Happy.
Answer the following question: How may I feeling during this post ?
| a. | 2 | Flan2021 | cosmos_qa:1.0.0 | zs_opt |
Sentence 1: uh all of Mae West's movies and just kind of kind of go out and uh rent all the movies and uh uh you know just kind of go i guess you could do that you know get all of David Carradine's movies or uh um Segal to what's his first name
Sentence 2: We never rented movies.
OPTIONS:
(i) yes.
(ii) it is not possible to tell.
(iii) no.
Is this second sentence entailed by the first sentence?
| (iii) | 3 | Flan2021 | glue/mnli:2.0.0 | zs_opt |
Read this and answer the question
Foreign direct investment (FDI) in Egypt increased considerably before the removal of Hosni Mubarak, exceeding $6 billion in 2006, due to economic liberalisation and privatisation measures taken by minister of investment Mahmoud Mohieddin.[citation needed] Since the fall of Hosni Mubarak in 2011, Egypt has experienced a drastic fall in both foreign investment and tourism revenues, followed by a 60% drop in foreign exchange reserves, a 3% drop in growth, and a rapid devaluation of the Egyptian pound.
What has been the overall growth of economy since 2011? | 3% drop | 1 | Flan2021 | squad/v1.1:3.0.0 | zs_opt |
Answer the questions at the end based on the text.
Todd is a small boy in the town of Rocksville. Todd thinks his town is the best place in the world, and out of all the places in Rocksville, Todd loves to play in Lake Keet the most. Lake Keet is a small lake with fish, plants, and even little shells. Todd's favorite part was the big rock in the middle of the lake. Todd lives pretty close to the lake, so he gets to go there a lot, but could never to get to the rock in the middle. Todd's dad never lets him swim too far because Todd can't swim very well. During summer, Todd told his dad that he wanted to get to the rock before break ended. Todd's dad told him he had to try his hardest. If he did, then Todd's dad would watch him swim every day. If Todd wanted to try and get to the rock, his dad would follow him there to make sure he was safe. Todd's dad wrote this down in his notebook so he wouldn't forget. After a week, Todd made his first try to get to the rock, and his dad followed him like he said he would. Todd didn't make it to the rock before he got tired and had to turn around. He practiced even harder for the next two weeks and wanted to try again. So, a month after summer started, Todd tried to reach the rock again. This time, Todd gave it his all and got all the way to the rock. He was very happy, and his dad was very proud of his son's hard work. To celebrate, Todd's dad carved Todd's name and the date into a tree. This way, they would always remember Todd's hard work.
1. Where does Todd like to have fun?
2. Is he a good swimmer?
3. What did he like best at the lake?
4. When did he get there?
5. Did the boy carve his name in a tree?
6. Who did?
7. What happened on his first try?
8. Did he give up?
9. How long did he practice harder for?
10. What would his dad do as a reward?
Numbered answers: | 1. Lake Keet
2. no
3. the big rock
4. in a month
5. no
6. Todd's dad
7. he didn't make
8. no
9. two weeks
10. carved Todd's name | 2 | Flan2021 | coqa:1.0.0 | zs_opt |
Triple: The Eagle food Italian
What is a sentence that describes this triple? | Italian food is served at The Eagle and customers rate it highly. | 0 | Flan2021 | gem/dart:1.1.0 | zs_opt |
Sams Wedding<br>The big day had finally come, Sam was going to be married. After getting ready, her bridesmaids met her in the hotel lobby. Waiting, the limo was over an hour late. After a few calls, the limo had been parked just out of sight. After entering the limo, Sam screamed at the driver for being late.
Can we draw the following conclusion?
Sam hesitated from going to his wedding.
Available choices:
--Yes
--It's impossible to say
--No | No | 2 | Flan2021 | anli/r3:0.1.0 | zs_opt |
This question has options. Select from options: Read this fact: "wind causes erosion"
Now answer this question: "I left a statue outside away from water for 100 years, when I come back it is significantly smaller, why?"
Choices: i. The Wind; ii. Birds; iii. Tiny Trolls; iv. Ants; | i. | 1 | Flan2021 | openbookqa:0.1.0 | zs_opt |
Here are some keywords about a restaurant:
name = The Olive Grove, eatType = pub, priceRange = more than £30, familyFriendly = yes. Write a sentence that describes the following attributes of a restaurant. | The Olive Grove offer drinks at a high price. They are a family friendly pub. | 3 | Flan2021 | gem/e2e_nlg:1.1.0 | zs_opt |
Yonas: You like Scheck Wes?
Marie: You mean Sheck Wes?
Yonas: Yes haha
Marie: I adore him
Marie: His single Mo Bamba is like a
Marie: masterpiece!
Yonas: I know!
What was that dialogue about, in two sentences or less? | Yonas and Marie like Sheck Wes and his song Mo Bamba. | 3 | Flan2021 | samsum:1.0.0 | zs_opt |
The shepherd opened the gate of the pen. He sent his dog into the pasture to round up the sheep. The dog herded the sheep towards the gate. The sheep moved together into the pen.
Write the next sentence, by choosing from:
Pick from: - The shepherd then went back to his house. - The shepherd then released the sheep. | The shepherd then went back to his house. | 3 | Flan2021 | story_cloze/2016:1.0.0 | zs_opt |
Danny: Do I need to bring anything?
Frank: No, no, we’re sorted, just waiting for all of you to come :)
Leo: Grace and I are bringing some wine.
Frank: Cool! xxx
What was that dialogue about, in two sentences or less? | Danny and Leo are going to visit Frank. Leo's bringing some wine. | 3 | Flan2021 | samsum:1.0.0 | zs_opt |
A Pentagon committee and the congressionally chartered Iraq Study Group have been preparing reports for Bush, and Iran has asked the presidents of Iraq and Syria to meet in Tehran.
Question with options: Based on the paragraph above can we conclude that "Bush will meet the presidents of Iraq and Syria in Tehran."?
pick from the following. a). yes. b). no. | b). | 0 | Flan2021 | super_glue/rte:1.0.2 | zs_opt |
Produce a long descriptive sentence that uses all these words: Alfred Moore Scales, almaMater, University of North Carolina at Chapel Hill; Alfred Moore Scales, successor, James W. Reid (politician).
Sentence: | Alfred Moores Scales, whose alma mater was the University of North Carolina at Chapel Hill, was succeeded by the politician James W Reid. | 6 | Flan2021 | gem/web_nlg_en:1.1.0 | zs_opt |
Find the right ending to this passage.
(CNN) -- A senior manager at Morgan Stanley pleaded not guilty Friday to assault and hate-crime charges in connection with the stabbing of a New York City taxi driver over the cost of a fare. William Bryan Jennings, a bond-underwriting senior manager at Morgan Stanley, entered the plea in Connecticut Superior Court in Stamford, according to court documents. His next court date is set for April 12. Jennings is accused of attacking Mohamed Anmar with a 2.5-inch blade, using racial slurs against Anmar, who is of Middle Eastern descent, and failing to pay for services rendered. The racial slurs resulted in a charge of intimidation by bigotry or bias, which is classified as a hate crime, according to court documents.
After the disagreement,
OPTIONS:
- Anmar said he tried to call police from his cell phone, but he couldn't get mobile service and began driving to look for a patrol car, according to the affidavit.
- CNN said he tried to call police from his cell phone, but he couldn't get mobile service and began driving to look for a patrol car, according to the affidavit.
- Connecticut Superior Court said he tried to call police from his cell phone, but he couldn't get mobile service and began driving to look for a patrol car, according to the affidavit.
- Jennings said he tried to call police from his cell phone, but he couldn't get mobile service and began driving to look for a patrol car, according to the affidavit.
- Middle Eastern said he tried to call police from his cell phone, but he couldn't get mobile service and began driving to look for a patrol car, according to the affidavit.
- Mohamed Anmar said he tried to call police from his cell phone, but he couldn't get mobile service and began driving to look for a patrol car, according to the affidavit.
- Morgan Stanley said he tried to call police from his cell phone, but he couldn't get mobile service and began driving to look for a patrol car, according to the affidavit.
- NYC said he tried to call police from his cell phone, but he couldn't get mobile service and began driving to look for a patrol car, according to the affidavit.
- New York City said he tried to call police from his cell phone, but he couldn't get mobile service and began driving to look for a patrol car, according to the affidavit.
- Stamford said he tried to call police from his cell phone, but he couldn't get mobile service and began driving to look for a patrol car, according to the affidavit.
- William Bryan Jennings said he tried to call police from his cell phone, but he couldn't get mobile service and began driving to look for a patrol car, according to the affidavit.
- William Jennings said he tried to call police from his cell phone, but he couldn't get mobile service and began driving to look for a patrol car, according to the affidavit.
| Anmar said he tried to call police from his cell phone, but he couldn't get mobile service and began driving to look for a patrol car, according to the affidavit. | 2 | Flan2021 | super_glue/record:1.0.2 | zs_opt |
Birliğin sahip olduğu toplumsal model, pazarları daha esnek hale getirme ihtiyacı ile çatışıyor.
Translate to English
English: | Its social model appears to be in conflict with the need to make markets more flexible. | 1 | Flan2021 | wmt16_translate/tr-en:1.0.0 | zs_opt |
Multi-choice problem: Read the following paragraph and determine if the hypothesis is true:
So who knows? In a generation or two some of the New Crowd may attain true respectability, perhaps to be displaced in turn by a later flock of unscrupulous raptors. Or perhaps Wall Street, when it has suffered enough, will realize that finance is a service industry, and change its ethos.
Hypothesis: finance is a service industry
Pick from: A). Yes. B). No. C). It's impossible to say. | A). | 5 | Flan2021 | super_glue/cb:1.0.2 | zs_opt |
Write a sentence that about [Bacon sandwich INGREDIENT Ketchup; BLT DISH_VARIATION Club sandwich; Bacon sandwich DISH_VARIATION BLT]. | A BLT is a variation of both the bacon sandwich (which contains ketchup) and the club sandwich. | 6 | Flan2021 | gem/dart:1.1.0 | zs_opt |
Single/multi-select question: Is it possible to conclude that "A workman is drilling into a wooden pole." if "A construction worker drives a crane."?
Options:
(I) yes.
(II) it is not possible to tell.
(III) no....I think the answer is | (III) | 7 | Flan2021 | snli:1.1.0 | zs_opt |
Write a dialog with this premise "Lily had a husband, who died in Iraq in a horrible way.". | Tamara: I can't understand Lily sometimes, she can be so mean
Peter: I know, but she changed so much after her husband died
Meg: She had a husband?!
Meg: I didn't know!
Peter: yes, she had one.
Mel: He died in Iraq. Apparently in a very horrible way. She was devastated
Tamara: god, I had no idea
Tamara: I'm really sorry now | 9 | Flan2021 | samsum:1.0.0 | zs_opt |
By Michael Zennie A Blackwater security contractor threatened to kill a State Department investigator in Iraq who was looking into allegations of the company's cost over-runs, boozy parties, mistreatment of migrant workers and violence against civilians, according to a newly-released report. Daniel Carroll, Blackwater’s project manager in Iraq, allegedly told Jean C. Richter that 'he could kill me at that very moment and no one could or would do anything about it as we were in Iraq,' in August 31, 2007, Richter claimed in an official report he filed after the fact. But instead of Mr Carroll, a former member of the elite Navy SEAL Team Six, being disciplined, Mr Richter was the one sent home. U.S. Embassy officials in Baghdad told him he had to end his investigation and leave Iraq because he was disrupting the security options Blackwater was providing for diplomatic staff, the New York Times reports.
They also over-billed the State Department and falsified records,
OPTIONS:
- Baghdad alleges.
- Blackwater alleges.
- Carroll alleges.
- Daniel Carroll alleges.
- Embassy alleges.
- Iraq alleges.
- Iraqi alleges.
- Jean C. Richter alleges.
- Michael Zennie alleges.
- Navy SEAL alleges.
- Navy SEAL Team Six alleges.
- New York Times alleges.
- Nisour Square alleges.
- Richter alleges.
- State Department alleges.
- U.S. alleges.
- Washington alleges.
| Jean C. Richter alleges. | 1 | Flan2021 | super_glue/record:1.0.2 | zs_opt |
Witherspoon et al. (2007) have argued that even when individuals can be reliably assigned to specific population groups, it may still be possible for two randomly chosen individuals from different populations/clusters to be more similar to each other than to a randomly chosen member of their own cluster. They found that many thousands of genetic markers had to be used in order for the answer to the question "How often is a pair of individuals from one population genetically more dissimilar than two individuals chosen from two different populations?" to be "never". This assumed three population groups separated by large geographic ranges (European, African and East Asian). The entire world population is much more complex and studying an increasing number of groups would require an increasing number of markers for the same answer. The authors conclude that "caution should be used when using geographic or genetic ancestry to make inferences about individual phenotypes." Witherspoon, et al. concluded that, "The fact that, given enough genetic data, individuals can be correctly assigned to their populations of origin is compatible with the observation that most human genetic variation is found within populations, not between them. It is also compatible with our finding that, even when the most distinct populations are considered and hundreds of loci are used, individuals are frequently more similar to members of other populations than to members of their own population."
Try to answer this question if possible (otherwise reply "unanswerable"): People are more frequently similar to members of what populations? | other populations | 4 | Flan2021 | squad/v2.0:3.0.0 | zs_opt |
Write a question about the following article: Coming off their divisional road win over the Panthers, the Falcons went home a Week 11 divisional duel with the Tampa Bay Buccaneers. Despite QB Joey Harrington giving Atlanta two-straight wins, QB Byron Leftwich was given the start. In the first quarter, the Falcons trailed early as Buccaneers QB Jeff Garcia completed a 44-yard TD pass to WR Joey Galloway for the only score of the period. In the second quarter, Atlanta continued to trail as Tampa Bay CB Ronde Barber returned a fumble 41 yards for a touchdown. In the third quarter, the Buccaneers continued their beatdown with kicker Matt Bryant nailing a 23-yard field goal, while Garcia completed a 21-yard TD pass to TE Alex Smith. In the fourth quarter, Tampa Bay sealed the win with RB Earnest Graham getting a 26-yard TD run. The Falcons avoided the shutout as Harrington came onto the field and completed a 7-yard TD pass to WR Adam Jennings.
Question about the article: | How many yards was the third longest touchdown? | 8 | Flan2021 | drop:2.0.0 | zs_opt |
Write a sentence about a restaurant with all the following attributes: name = The Waterman, eatType = pub, food = Fast food, customer rating = average, area = riverside
Sentence: | There is a pub called The Waterman serving Fast food in the riverside area with an average customer rating. | 6 | Flan2021 | gem/e2e_nlg:1.1.0 | zs_opt |
How can I find out for sure my boyfriend is cheating and lying to me?
How can I find out if my boyfriend cheated on me with my mother?
Choose your answer. Are these two questions paraphrases of each other?
Pick from:
A). no;
B). yes; | A). | 4 | Flan2021 | glue/qqp:2.0.0 | zs_opt |
What's an example of a movie review? | I had the privilege of watching "Holly" at the Edinburgh Film Festival last week. What a powerful and moving story! Holly is a 12 yr old Vietnamese girl who is sold into prostitution by her own family and living in a brothel in Cambodia. Patrick (an American) comes into Holly's life and decides he wants to help her. When Holly is sold again, Patrick desperately searches for her. We follow they're difficult journey through Cambodia and hope for their reunion.
Holly is one of millions of children who are sold and trafficked every day. The movie portrays this difficult issue without crossing the line. I walked away wanting to know more about the issue of child trafficking and asking how can I help? This movie should be seen by everyone because it is a beautiful story and it exposes an issue that we should no longer ignore. | 9 | Flan2021 | imdb_reviews/plain_text:1.0.0 | zs_opt |
What is the cause of the following sentence?
The milk stayed cold.
Available choices: A). It was pasteurized.. B). I stored it in the refrigerator..
The answer is: | B). | 6 | Flan2021 | super_glue/copa:1.0.2 | zs_opt |
Question with options: can we draw the following hypothesis from the context?
Context:
Lawyer David Gibbs pleaded with the appeals court to order Schiavo's feeding tube reinserted to give her parents a chance to make a complete argument before a federal court that her rights are being violated.
Hypothesis: The appeals court was their last best chance to get that feeding tube reinserted into their daughter.
OPTIONS:
a). yes
b). no
A: | b). | 7 | Flan2021 | super_glue/rte:1.0.2 | zs_opt |
Q: Which characteristic is shared by all cells?
What is the correct answer to this question?
Choose from: a). They need energy.; b). They reproduce sexually.; c). They make their own food.; d). They move from place to place.;...A: | a). | 3 | Flan2021 | ai2_arc/ARC-Easy:1.0.0 | zs_opt |
In a large bowl, sift together the flours, spices, sugar, salt, and yeast. In a different small bowl, whisk together the butter and hot water to melt the butter. When the butter has melted, whisk in the milk. Crack the egg into a small bowl and whisk it briefly. Add the egg, oil, and butter and milk to the dry ingredients. Use a wooden spoon to mix all the ingredients together. Continue mixing until the ingredients come together to form a smooth dough. If mixing with the spoon becomes difficult, knead the dough with your hands instead. Cover the bowl with a damp cloth and place it somewhere warm to rise for one to two hours. It’s important to cover the dough so that it doesn’t dry out. A good warm place for the dough to rise is an oven that’s turned off, but with the oven light turned on. When the dough is ready, cover your hands with a layer of oil and turn the dough out onto a flat surface. Roll the dough out with your hands into a long cylinder that’s two inches (5 cm) thick. Cut the dough cylinder into smaller pieces that are one to two inches (2.5 to five cm) long. Arrange the dough pieces on two baking sheets and leave them to rise for another 30 to 40 minutes. While the dough is rising for the second time, prepare the syrup. The doughnuts will be fried and then dunked into the syrup right away, so it needs to be ready for when the doughnuts are fried. Combine the sugar, water, and spices in a medium saucepan. Bring it to a boil over medium heat, stirring frequently to prevent the sugar from burning. When it comes to a boil, lower the heat and continue simmering and stirring until the syrup becomes thick. Lower the heat again and keep the syrup warm over low heat until the doughnuts are ready. Fill a deep fryer or deep frying pan with oil and heat it over medium–high heat. Drop a pea-sized piece of dough into the oil. When it begins to cook and sizzle, you know the oil is ready. Take a piece of dough and stretch it out slightly to get an oval shape. Repeat with every dough piece before frying. Drop a couple oval dough pieces into the oil, but don’t crowd them. Fry the dough until the koeksisters become golden brown, about one to two minutes. Remove the doughnuts from the oil one at a time using a slotted spoon. Place them on a paper towel to remove some of the excess oil. Poke a few holes in each doughnut with a fork. Transfer the doughnuts to the warm syrup and roll them around to coat all sides. When the doughnuts are drenched in syrup, remove them one at a time with the slotted spoon. Allow the excess syrup to drain off over the saucepan. Roll each doughnut in the shredded coconut to coat them completely. Transfer them to a serving plate and enjoy!
Summary: | Mix the dry and wet ingredients separately. Combine all the wet and dry ingredients. Leave the mixture to rise. Roll out the dough. Make the syrup. Stretch and fry the dough. Dip the doughnuts in the syrup. Roll in coconut before serving. | 0 | Flan2021 | gem/wiki_lingua_english_en:1.1.0 | zs_opt |
Solve 2043*c + 233 = 2276*c for c.
Solve this problem. | 1 | 7 | Flan2021 | math_dataset/algebra__linear_1d:1.0.0 | zs_opt |
Translate the following.
English: The fact that the episode was focused mainly on the personal lives of Jackson has nonetheless made overshadow April. His role was crucial and decisive for the evolution of Jackson on his relationship with his father; It is thanks to her that Jackson decides what to do and what position taken with regard to Robert (that is, consider it a closed chapter, with the awareness of being a better father than he).
Spanish: | El hecho de que el episodio se centró principalmente en la vida personal de Jackson ha hecho sin embargo eclipsar Abril. Su papel fue crucial y decisiva para la evolución de Jackson sobre su relación con su padre; Es gracias a ella que Jackson decide qué hacer y qué posición tomada con respecto a Robert (es decir, parece un capítulo cerrado, con la conciencia de ser un mejor padre que él). | 7 | Flan2021 | para_crawl_enes | zs_opt |
Chapter XV.
Return to the Congo Mouth.
In the evening there was a palaver.
I need hardly say that my guide, after being paid to show me Nsundi, never had the slightest intention to go beyond the Yellala. Irritated by sleeping in the open air, and by the total want of hospitality amongst the bushmen, he and his moleques had sat apart all day, the picture of stubborn discontent, and
"Not a man in the place But had discontent written large in his face."
I proposed to send back a party for rum, powder, and cloth to the extent of £150, or half the demand, and my factotum, Selim, behaved like a trump. Gidi Mavunga, quite beyond self-control, sprang up, and declared that, if the Mundele would not follow him, that obstinate person might remain behind. The normal official deprecation, as usual, made him the more headstrong; he rushed off and disappeared in the bush, followed by a part of his slaves, the others crying aloud to him, "Wenda!"-- get out! Seeing that the three linguisters did not move, he presently returned, and after a furious address in Fiote began a Portuguese tirade for my benefit. This white man had come to their country, and, instead of buying captives, was bent upon enslaving their Mfumos; but that "Branco" should suffer for his attempt; no "Mukanda" or book (that is, letter) should go down stream; all his goods belonged of right to his guide, and thus he would learn to sit upon the heads of the noblesse, with much of the same kind.
1. What was proposed?
2. For what?
3. For how much?
4. Who behaved like a trump?
5. What chapter is this?
6. What is the title?
Provide a numbered list of answers. | 1. to send back a party
2. rum, powder, and cloth
3. £150
4. Selim
5. Chapter XV
6. Return to the Congo Mouth | 7 | Flan2021 | coqa:1.0.0 | zs_opt |
Select the correct sentiment of the following review: We really enjoyed Grey Owl: a simple tale well told in classic Attenborough fashion: a little over-romanticized, with archetypes, humor, and a stress of dignity and values.
Beautifully shot and told at a nice pace this is the true story of Archie, an Englishman who turned native Indian, and went to live and trap in Canada.
Solid performances from all makes this film with a message easy viewing.
Two of the stars of the film are without a doubt the cutest we have ever seen - and the message is a good one with its ecoleanings. It must have been great to meet or read Grey Owl in the 1930s, a unique character and this is a fitting film tribute.
OPT:
A). negative;
B). positive; | B). | 5 | Flan2021 | imdb_reviews/plain_text:1.0.0 | zs_opt |
Generate a short summary this sentence:
wall street blue-chip stocks rose today , pushing the dow industrials to new record high .
Summary: | wall street blue-chip stocks rise higher | 2 | Flan2021 | gigaword:1.2.0 | zs_opt |
From the following options, what is the question "Name Dondi 's adoptive grandfather ." asking about?
Available options: A. description B. entity C. abbreviation D. human E. numeric F. location | D. | 5 | Flan2021 | trec:1.0.0 | zs_opt |
Select the correct answer: Which is an appropriate title for this article?
Ask Jeeveswill launch a test version of its desktop search tool on Wednesday, following the launch of similar tools by rivals Microsofton Monday and Google in October, and ahead of expected entries from America Online(AOL) and Yahoo.
Choose from:
(A). World;
(B). Sports;
(C). Business;
(D). Science/Tech; | (D). | 6 | Flan2021 | ag_news_subset:1.0.0 | zs_opt |
if your chosen card is higher than the original face-up card, you double your winnings.
Capitalize this past sentence correctly. | If your chosen card is higher than the original face-up card, you double your winnings. | 3 | Flan2021 | true_case | zs_opt |
Write a sentence about the following things:
carrot, celery, cucumber, tray | Tray of vegetables with cucumber, carrots, broccoli and celery. | 4 | Flan2021 | gem/common_gen:1.1.0 | zs_opt |
Write the answer: Who was the last member of The Beatles to marry? | paul mccartney | 2 | Flan2021 | trivia_qa/rc:1.1.0 | zs_opt |
Great location and a friendly staff. There is not a lot of parking, but the facility is nice and welcoming. If there is an event here, you are in luck.
Choose: was this review given positively or negatively?
Options are: -- negative -- positive | positive | 2 | Flan2021 | yelp_polarity_reviews:0.2.0 | zs_opt |
What's an example of a grad-school level question? | Which graph is best to present data collected on yearly water usage in the United States? | 8 | Flan2021 | ai2_arc/ARC-Challenge:1.0.0 | zs_opt |
What is the version of the following sentence with correct punctuation?
The Jews therefore said to him Now we know that thou hast a demon Abraham has died and the prophets and thou sayest If any one keep my word he shall never taste death
| The Jews therefore said to him, Now we know that thou hast a demon. Abraham has died, and the prophets, and thou sayest, If any one keep my word, he shall never taste death. | 9 | Flan2021 | fix_punct | zs_opt |
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