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Success is the sum of small efforts

You are the only light, that can take me from zero to infinity

My heart is perfect when you are inside

I smile like an idiot when i think about you

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Hai pretty... I wish yourself more grace,more prosperity,more happiness, and more years..

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The earth has music for those who listen

Love is like a butterfly. It can stay or it can die

The sunset is better with you by my side

Cutline means ........

Who are the subjects in the picture or photos and what activity they do

Only who are the subjects in the pictures or photo

All the information which can explain

"Proudly standing on the land our heroes once fought for" The caption above is suitable for picture number ........

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What is the page mainly about? (Answer: C — Homes meet a basic need) A) House colors B) Old buildings C) Homes meet a basic need ✓ D) Travel What basic need do homes give? (Answer: B — Shelter) A) Food B) Shelter ✓ C) Clothes D) Money What does “basic need” mean here? (Answer: C — Something people must have to live) A) Something nice to have B) A school rule C) Something people must have to live ✓ D) A weekend plan Homes keep people ______ and ______. What are the two words from the page? (Answer: B — dry / safe) A) rich / tall B) dry / safe ✓ C) loud / fast D) clean / funny What else are homes for, according to the text? (Answer: B — Eating, sleeping, and being with family and friends) A) Shopping B) Eating, sleeping, and being with family and friends ✓ C) Driving D) Fighting What does the heading “Meeting our needs” tell you? (Answer: B — explains how homes fit the local climate) A) A joke is coming B) This part explains how homes fit the local climate ✓ C) It is a story D) It lists prices What does “climate” mean on this page? (Answer: C — the usual weather of a place) A) Yesterday’s forecast B) A big storm C) The usual weather of a place ✓ D) Room temperature Which roof is best for cold, snowy places? (Answer: D — Slanted) A) Flat B) Dome C) Glass D) Slanted ✓ Why is a slanted roof helpful in snowy places? (Answer: B — snow slides off more easily) A) It is cheaper B) Snow slides off more easily ✓ C) Birds like it D) It is quieter Why do many houses in hot places have many windows? (Answer: B — to let air move through and keep people cool) A) To block all light B) To let air move through and keep people cool ✓ C) To make walls heavy D) To reduce street noise Which detail best supports “climate changes home design”? (Answer: C — Hot → many windows; Snowy → slanted roofs) A) People like blue walls B) Kitchens are big C) Hot → many windows; Snowy → slanted roofs ✓ D) Cities are crowded What does the caption about a traditional Japanese house show? (Answer: C — People sit on mats on the floor to eat) A) People eat outdoors B) Families don’t eat together C) People sit on mats on the floor to eat ✓ D) People stand to eat Which sentence is LEAST connected to the main idea of the page? (Answer: D — Blue walls are relaxing) A) Homes protect people from weather B) Roofs can change with climate C) Windows help rooms stay cool D) Blue walls are relaxing ✓ Which text structure organizes the right paragraph? (Answer: C — Cause–effect) A) Timeline B) Problem–solution C) Cause–effect ✓ D) Description only What is the author’s purpose? (Answer: B — to explain how homes meet a human need) A) To sell houses B) To explain how homes meet a human need ✓ C) To tell a funny story D) To give building laws What can you guess about a flat roof in a snowy place? (Answer: B — snow can pile up and be unsafe) A) Best choice B) Snow can pile up and be unsafe ✓ C) Always cheaper D) Warmer in summer Which page feature helps you find ideas quickly? (Answer: C — Headings and photo captions) A) Rhyme B) Dialogue C) Headings and photo captions ✓ D) Footnotes Which sentence is the best summary of the page? (Answer: C — Homes give shelter; designs change with climate) A) Houses are beautiful in winter B) People prefer bright colors C) Homes give shelter; designs change with climate (slanted roofs, many windows) ✓ D) Windows are the most important part True/False or Short Answer (5) True/False: All homes have the same purpose, even if they look different. (Answer: True) True/False: In hot places, houses usually have fewer windows to keep heat in. (Answer: False — hot places → many windows for airflow/cooling) Short Answer (1–3 words): Homes provide shelter to keep people _____ and _____. (Answer: dry; safe) Short Answer (one example): Write one climate → design pair from the page. (Answer: cold/snowy → slanted roof OR hot → many windows) True/False: The photo shows people in Japan eating on mats on the floor. (Answer: True)

Hi, I'm John Green, this is Crash Course U.S. History, and today, we're going to talk about slavery, which is not funny. 0:06 Yeah, so we put a lei on the eagle to try and cheer you up, but let's face it, this is going to be depressing. 0:10 With slavery, every time you think, like, "Aw, it couldn't have been that bad," it turns out to have been much worse. 0:14 Mr. Green, Mr. Green! But what about – 0:15 Yeah, Me from the Past, I'm going to stop you right there, because you're going to embarrass yourself. Slavery was hugely important to America. 0:20 I mean, it led to a civil war and it also lasted what, at least in U.S. history, counts as a long-ass time, from 1619 to 1865. 0:29 And yes, I know there's a 1200-year-old church in your neighborhood in Denmark, but we're not talking about Denmark! 0:35 But slavery is most important because we still struggle with its legacy. 0:38 So, yes, today's episode will probably not be funny, but it will be important. 0:42 [Theme Music] North & South economic ties 0:51 So the slave-based economy in the South is sometimes characterized as having been separate from the Market Revolution, but that's not really the case. 0:57 Without southern cotton, the North wouldn't have been able to industrialize, at least not as quickly, because cotton textiles were one of the first industrially products. 1:04 And the most important commodity in world trade by the nineteenth century, and 3/4 of the world's cotton came from the American South. 1:11 And speaking of cotton, why has no one mentioned to me that my collar has been half popped this entire episode, like I'm trying to recreate the Flying Nun's hat. 1:18 And although there were increasingly fewer slaves in the North as northern states outlawed slavery, cotton shipments overseas made northern merchants rich. 1:26 Northern bankers financed the purchase of land for plantations. 1:29 Northern insurance companies insured slaves who were, after all, considered property, and very valuable property. 1:35 And in addition to turning cotton into cloth for sale overseas, northern manufacturers sold cloth back to the South, where it was used to clothe the very slaves who had cultivated it. 1:45 But certainly the most prominent effects of the slave-based economy were seen in the South. Slave-based agriculture in the South 1:49 The profitability of slaved-based agriculture, especially King Cotton, meant that the South would remain largely agricultural and rural. 1:56 Slave states were home to a few cities, like St. Louis and Baltimore, but with the exception of New Orleans, 2:00 almost all southern urbanization took place in the upper South, further away from the large cotton plantations. 2:06 And slave-based agriculture was so profitable that it siphoned money away from other economic endeavors. 2:11 Like, there was very little industry in the South. 2:13 It produced only 10% of the nation's manufactured goods. 2:16 And, as most of the capital was being plowed into the purchase of slaves, there was very little room for technological innovation, like, for instance, railroads. 2:23 This lack of industry and railroads would eventually make the South suck at the Civil War, thankfully. 2:27 In short, slavery dominated the South, shaping it both economically and culturally, and slavery wasn't a minor aspect of American society. Popular attitudes concerning slavery 2:35 By 1860, there were four million slaves in the U.S., and in the South, they made up one third of the total population. 2:42 Although in the popular imagination, most plantations were these sprawling affairs with hundreds of slaves, 2:47 in reality, the majority of slaveholders owned five or fewer slaves. 2:51 And, of course, most white people in the South owned no slaves at all, though, if they could afford to, they would sometimes rent slaves to help with their work. 2:57 These were the so-called yeoman farmers who lived self-sufficiently, raised their own food, and purchased very little in the Market Economy. 3:04 They worked the poorest land and, as a result, were mostly pretty poor themselves. 3:08 But even they largely supported slavery, partly, perhaps, for aspirational reasons, and partly because the racism inherent to the system gave even the poorest whites legal and social status. 3:18 And southern intellectuals worked hard to encourage these ideas of white solidarity and to make the case for slavery. 3:23 Many of the founders, a bunch of whom you'll remember, held slaves, saw slavery as a necessary evil. 3:29 Jefferson once wrote, quote, "As it is, we have the wolf by the ear, and we can neither hold him, nor safely let him go. 3:37 Justice is on one scale, and self-preservation in the other." 3:41 The belief that justice and self-preservation couldn't sit on the same side of the scale was really opposed to the American idea, 3:47 and, in the end, it would make the Civil War inevitable. 3:50 But as slavery became more entrenched in these ideas of liberty and political equality were embraced by more people, 3:55 some southerners began to make the case that slavery wasn't just a necessary evil. 3:59 They argued, for instance, that slaves benefited from slavery. 4:03 Because, you know, because their masters fed them and clothed them and took care of them in their old age. 4:07 You still hear this argument today, astonishingly. 4:09 In fact, you'll probably see asshats in the comments saying that in the comments. 4:12 I will remind you, it's not cursing if you are referring to an actual ass. 4:15 This paternalism allowed masters to see themselves as benevolent and to contrast their family-oriented slavery with the cold, mercenary Capitalism of the free-labor North. 4:26 So yeah, in the face of rising criticism of slavery, some southerners began to argue that the institution was actually good for the social order. 4:33 One of the best-known proponents of this view was John C. Calhoun, who, in 1837, said this in a speech on the Senate floor: 4:40 "I hold that, in the present state of civilization, 4:43 where two races of different origin and distinguished by color and other physical differences as well as intellectual, are brought together, 4:51 the relation now existing in the slave-holding states between the two is, instead of an evil, a good. A positive good." 4:59 Now, of course, John C. Calhoun was a fringe politician, and nobody took his views particularly seriously. 5:04 Stan: Well, he was Secretary of State from 1844 to 1845. 5:07 John: Well, I mean, who really cares about the Secretary of State, Stan? 5:10 Danica: Eh, he was also Secretary of War from 1817 to 1825. 5:13 John: All right, but we don't even have a Secretary of War anymore, so... 5:16 Meredith: And he was Vice President from 1825 to 1832. 5:19 John: Oh my god, were we insane?! 5:21 We were, of course, but we justified the insanity with Biblical passages and with the examples of the Greeks and Romans, 5:28 and with outright racism, arguing that black people were inherently inferior to whites. 5:33 And that not to keep them in slavery would upset the natural order of things. 5:37 A worldview popularized millennia ago by my nemesis, Aristotle. God, I hate Aristotle. 5:42 You know what defenders of Aristotle always say? 5:44 "He was the first person to identify dolphins." 5:47 Well, ok, dolphin identifier. 5:50 Yes, that is what he should be remembered for, but he's a terrible philosopher! Lives & experiences of enslaved people 5:53 Here's the truth about slavery: 5:55 It was coerced labor that relied upon intimidation and brutality and dehumanization. 6:00 And this wasn't just a cultural system, it was a legal one. 6:03 I mean, Louisiana law proclaimed that a slave "owes his master... a respect without bounds, and an absolute obedience." 6:09 The signal feature of slaves' lives was work. 6:12 I mean, conditions and tasks varied, but all slaves labored, usually from sunup to sundown, and almost always without any pay. 6:20 Most slaves worked in agriculture on plantations, and conditions were different, depending on which crops are grown. 6:25 Like, slaves on the rice plantations of South Carolina had terrible working conditions, 6:29 but they labored under the task system, which meant that once they had completed their allotted daily work, they would have time to do other things. 6:36 But lest you imagine this is like how we have work and leisure time, bear in mind that they were owned and treated as property. 6:42 On cotton plantations, most slaves worked in gangs, usually under the control of an overseer, or another slave who was called a "driver." 6:49 This was back-breaking work done in the southern sun and humidity, and so it's not surprising that whippings – or the threat of them – were often necessary to get slaves to work. 6:58 It's easy enough to talk about the brutality of slave discipline, but it can be difficult to internalize it. 7:03 Like, you look at these pictures, but because you've seen them over and over again, they don't have the power they once might have. 7:09 The pictures can tell a story about cruelty, but they don't necessarily communicate how arbitrary it all was. 7:14 As, for example, in this story, told by a woman who was a slave as a young girl: 7:18 "[The] overseer... went to my father one morning and said, "Bob, I'm gonna whip you this morning." 7:22 Daddy said, "I ain't done nothing," and he said, "I know it, I'm going to whip you to keep you from doing nothing," 7:28 and he hit him with that cowhide – you know it would cut the blood out of you with every lick if they hit you hard." 7:33 That brutality – the whippings, the brandings, the rape – was real, and it was intentional, because, in order for slavery to function, slaves had to be dehumanized. 7:43 This enabled slaveholders to rationalize what they were doing, and it was hoped to reduce slaves to the animal property that is implied by the term "chattel slavery." 7:51 So the idea was that slaveholders wouldn't think of their slaves as human, and slaves wouldn't think of themselves as human. 7:57 But it didn't work. Let's go to the Thought Bubble. 7:59 Slaves' resistance to their dehumanization took many forms, but the primary way was by forming families. Family, love, & religion of enslaved people 8:05 Family was a refuge for slaves and a source of dignity that masters recognized and sought to stifle. 8:10 A paternalistic slave owner named Bennet H. Barrow wrote in his rules for the Highland Plantation: 8:15 "No rule that I have stated is of more importance than that relating to Negroes marrying outside of the plantation... It creates a feeling of independence." 8:23 Most slaves did marry, usually for life, and, when possible, slaves grew up in two-parent households. 8:28 Single-parent households were common, though, as a result of one parent being sold. 8:32 In the upper South, where the economy was shifting from tobacco to different, less labor-intensive cash crops, the sale of slaves was common. 8:40 Perhaps one-third of slave marriages in states like Virginia were broken up by sale. 8:45 Religion was also an important part of life in slavery. 8:47 While masters wanted their slaves to learn the parts of the Bible that talked about being happy in bondage, 8:52 slave worship tended to focus on the stories of Exodus, where Moses brought the slaves out of bondage, 8:57 or Biblical heroes, who overcame great odds, like Daniel and David. 9:01 And, although most slaves were forbidden to learn to read and write, many did anyway. And some became preachers. 9:07 Slave preachers were often very charismatic leaders, and they roused the suspicion of slave owners, and not without reason. 9:13 Two of the most important slave uprisings in the South were led by preachers. 9:16 Thanks, Thought Bubble. 9:17 Oh, it's time for the Mystery Document? Mystery Document 9:19 We're doing two set pieces in a row? All right. [buzzing noise] [music] 9:24 The rules here are simple. 9:26 I wanted to re-shoot that, but Stan said no. 9:29 I guess the author of the Mystery Document. 9:30 If I am wrong, I get shocked with the shock pen. 9:33 "Since I have been in the Queen's dominions I have been well contented, yes well contented for sure, man is as God intended he should be. 9:40 That is, all are born free and equal. 9:43 This is a wholesome law, not like the southern laws which puts man made in the image of God on level with brutes. 9:49 O, what will become of the people, and where will they stand in the day of judgment. 9:53 Would that the 5th verse of the 3rd chapter of Malachi were written as with a bar of iron, 9:59 and the point of a diamond upon every oppressor's heart that they might repent of this evil, and let the oppressed go free..." 10:06 All right, it's definitely a preacher, because only preachers have read Malachi. 10:10 Probably African American, probably not someone from the South. 10:13 I'm going to guess that it is Richard Allen, the founder of the African Methodist Episcopal Church? 10:18 [buzzing noise] DAAAH, DANG IT! 10:19 It's Joseph Taper, and Stan just pointed out to me that I should have known it was Joseph Taper because it starts out, 10:24 "Since I have been in the Queen's dominions..." 10:27 He was in Canada. He escaped slavery to Canada. The Queen's dominions! 10:31 All right, Canadians, I blame you for this, although, thank you for abolishing slavery decades before we did. 10:36 [electric sounds] AHHH! How people resisted & escaped slavery 10:37 So, the Mystery Document shows one of the primary ways that slaves resisted their oppression: by running away. 10:42 Although some slaves like Joseph Taper escaped for good by running away to northern free states, 10:47 or even to Canada, where they wouldn't have to worry about fugitive slave laws, even more slaves ran away temporarily, hiding out in the woods or the swamps, and eventually returning. 10:55 No one knows exactly how many slaves escaped to freedom, but the best estimate is that a thousand or so a year made the journey northward. 11:01 Most fugitive slaves were young men, but the most famous runaway has been hanging out behind me all day long: Harriet Tubman. 11:07 Harriet Tubman escaped to Philadelphia at the age of 29, and over the course of her life, she made about 20 trips back to Maryland to help friends and relatives make the journey north on the Underground Railroad. 11:17 But a more dramatic form of resistance to slavery was actual, armed rebellion, which was attempted. 11:22 Now, individuals sometimes took matters into their own hands and beat or even killed their white overseers or masters. 11:27 Like Bob, the guy who received the arbitrary beating, responded to it by killing his overseer with a hoe. 11:33 But that said, large-scale slave uprisings were relatively rare. 11:36 The four most famous ones all took place in a 35-year period at the beginning of the 19th century. Slave rebellions 11:41 Gabriel's Rebellion in 1800 – which we've talked about before – was discovered before he was able to carry out his plot. 11:45 Then, in 1811, a group of slaves upriver from New Orleans seized cane, knives, and guns, and marched on the city before militia stopped them. 11:52 And in 1822, Denmark Vesey, a former slave who had purchased his freedom, may have organized a plot to destroy Charleston, South Carolina. 11:59 I say "may have" because the evidence against him is disputed and comes from a trial that was not fair. 12:05 But regardless, the end result of that trial was that he was executed, as were 34 slaves. Nat Turner's Rebellion 12:09 But the most successful slave rebellion, at least in the sense that they actually killed some people, was Nat Turner's in August 1831. 12:15 Turner was a preacher, and with a group of about 80 slaves, he marched from farm to farm in South Hampton County, Virginia, 12:21 killing the inhabitants, most of whom were women and children, because the men were attending a religious revival meeting in North Carolina. 12:27 Turner and 17 other rebels were captured and executed, but not before they struck terror into the hearts of whites all across the American South. 12:34 Virginia's response was to make slavery worse, passing even harsher laws that forbade slaves from preaching, and prohibited teaching them to read. 12:42 Other slave states followed Virginia's lead and, by the 1830s, slavery had grown, if anything, more harsh. 12:47 So, this shows that large-scaled armed resistance was – Django Unchained aside – not just suicidal, but also a threat to loved ones and, really, to all slaves. How enslaved people resisted their oppression & why it matters 12:55 But, it is hugely important to emphasize that slaves did resist their oppression. 12:59 Sometimes this meant taking up arms, but usually it meant more subtle forms of resistance, 13:03 like intentional work slowdowns or sabotaging equipment, or pretending not to understand instructions. 13:08 And, most importantly, in the face of systematic legal and cultural degradation, they re-affirmed their humanity through family and through faith. 13:16 Why is this so important? 13:17 Because too often in America, we still talk about slaves as if they failed to rise up, 13:21 when, in fact, rising up would not have made life better for them or for their families. 13:26 The truth is, sometimes carving out an identity as a human being in a social order that is constantly seeking to dehumanize you, is the most powerful form of resistance. 13:34 Refusing to become the chattel that their masters believed them to be is what made slavery untenable and the Civil War inevitable, so make no mistake, slaves fought back. 13:45 And in the end, they won. I'll see you next week. Credits 13:48 Crash Course is produced and directed by Stan Muller. 13:50 The script supervisor is Meredith Danko. 13:52 Our associate producer is Danica Johnson. 13:54 The show is written by my high school history teacher Raoul Meyer and myself. 13:57 And our graphics team is Thought Cafe. 13:58 Every week, there's a new caption to the Libertage, but today's episode was so sad that we couldn't fit a Libertage in... 14:04 UNTIL NOW! [Libertage Rock Music] 14:08 Suggest Libertage caption in comments, where you can also ask questions about today's video that will be answered by our team of historians. 14:13 Thanks for watching Crash Course, and as we say in my home town, don't forget to be abolitionist.

“There’s No Such Thing as Sound Science” by By Christie Aschwanden was a lead science writer for FiveThirtyEight. FiveThirtyEight, Science, Dec. 6, 2017 Science is being turned against itself. For decades, its twin ideals of transparency and rigor have been weaponized by those who disagree with results produced by the scientific method. Under the Trump administration, that fight has ramped up again. In a move ostensibly meant to reduce conflicts of interest, Environmental Protection Agency Administrator Scott Pruitt has removed a number of scientists from advisory panels and replaced some of them with representatives from industries that the agency regulates. Like many in the Trump administration, Pruitt has also cast doubt on the reliability of climate science. For instance, in an interview with CNBC, Pruitt said that “measuring with precision human activity on the climate is something very challenging to do.” Similarly, Trump’s pick to head NASA, an agency that oversees a large portion the nation’s climate research, has insisted that research into human influence on climate lacks certainty, and he falsely claimed that “global temperatures stopped rising 10 years ago.” Kathleen Hartnett White, Trump’s nominee to head the White House Council on Environmental Quality, said in a Senate hearing last month that she thinks we “need to have more precise explanations of the human role and the natural role” in climate change. The same entreaties crop up again and again: We need to root out conflicts. We need more precise evidence. What makes these arguments so powerful is that they sound quite similar to the points raised by proponents of a very different call for change that’s coming from within science. This other movement strives to produce more robust, reproducible findings. Despite having dissimilar goals, the two forces espouse principles that look surprisingly alike: Science needs to be transparent. Results and methods should be openly shared so that outside researchers can independently reproduce and validate them. The methods used to collect and analyze data should be rigorous and clear, and conclusions must be supported by evidence. These are the arguments underlying an “open science” reform movement that was created, in part, as a response to a “reproducibility crisis” that has struck some fields of science.1 But they’re also used as talking points by politicians who are working to make it more difficult for the EPA and other federal agencies to use science in their regulatory decision-making, under the guise of basing policy on “sound science.” Science’s virtues are being wielded against it. What distinguishes the two calls for transparency is intent: Whereas the “open science” movement aims to make science more reliable, reproducible and robust, proponents of “sound science” have historically worked to amplify uncertainty, create doubt and undermine scientific discoveries that threaten their interests. “Our criticisms are founded in a confidence in science,” said Steven Goodman, co-director of the Meta-Research Innovation Center at Stanford and a proponent of open science. “That’s a fundamental difference — we’re critiquing science to make it better. Others are critiquing it to devalue the approach itself.” Calls to base public policy on “sound science” seem unassailable if you don’t know the term’s history. The phrase was adopted by the tobacco industry in the 1990s to counteract mounting evidence linking secondhand smoke to cancer. A 1992 Environmental Protection Agency report identified secondhand smoke as a human carcinogen, and Philip Morris responded by launching an initiative to promote what it called “sound science.” In an internal memo, Philip Morris vice president of corporate affairs Ellen Merlo wrote that the program was designed to “discredit the EPA report,” “prevent states and cities, as well as businesses from passing smoking bans” and “proactively” pass legislation to help their cause. The sound science tactic exploits a fundamental feature of the scientific process: Science does not produce absolute certainty. Contrary to how it’s sometimes represented to the public, science is not a magic wand that turns everything it touches to truth. Instead, it’s a process of uncertainty reduction, much like a game of 20 Questions. Any given study can rarely answer more than one question at a time, and each study usually raises a bunch of new questions in the process of answering old ones. “Science is a process rather than an answer,” said psychologist Alison Ledgerwood of the University of California, Davis. Every answer is provisional and subject to change in the face of new evidence. It’s not entirely correct to say that “this study proves this fact,” Ledgerwood said. “We should be talking instead about how science increases or decreases our confidence in something.” The tobacco industry’s brilliant tactic was to turn this baked-in uncertainty against the scientific enterprise itself. While insisting that they merely wanted to ensure that public policy was based on sound science, tobacco companies defined the term in a way that ensured that no science could ever be sound enough. The only sound science was certain science, which is an impossible standard to achieve. “Doubt is our product,” wrote one employee of the Brown & Williamson tobacco company in a 1969 internal memo. The note went on to say that doubt “is the best means of competing with the ‘body of fact’” and “establishing a controversy.” These strategies for undermining inconvenient science were so effective that they’ve served as a sort of playbook for industry interests ever since, said Stanford University science historian Robert Proctor. The sound science push is no longer just Philip Morris sowing doubt about the links between cigarettes and cancer. It’s also a 1998 action plan by the American Petroleum Institute, Chevron and Exxon Mobil to “install uncertainty” about the link between greenhouse gas emissions and climate change. It’s industry-funded groups’ late-1990s effort to question the science the EPA was using to set fine-particle-pollution air-quality standards that the industry didn’t want. And then there was the more recent effort by Dow Chemical to insist on more scientific certainty before banning a pesticide that the EPA’s scientists had deemed risky to children. Now comes a move by the Trump administration’s EPA to repeal a 2015 rule on wetlands protection by disregarding particular studies. (To name just a few examples.) Doubt merchants aren’t pushing for knowledge, they’re practicing what Proctor has dubbed “agnogenesis” — the intentional manufacture of ignorance. This ignorance isn’t simply the absence of knowing something; it’s a lack of comprehension deliberately created by agents who don’t want you to know, Proctor said.2 In the hands of doubt-makers, transparency becomes a rhetorical move. “It’s really difficult as a scientist or policy maker to make a stand against transparency and openness, because well, who would be against it?” said Karen Levy, researcher on information science at Cornell University. But at the same time, “you can couch everything in the language of transparency and it becomes a powerful weapon.” For instance, when the EPA was preparing to set new limits on particulate pollution in the 1990s, industry groups pushed back against the research and demanded access to primary data (including records that researchers had promised participants would remain confidential) and a reanalysis of the evidence. Their calls succeeded and a new analysis was performed. The reanalysis essentially confirmed the original conclusions, but the process of conducting it delayed the implementation of regulations and cost researchers time and money. Delay is a time-tested strategy. “Gridlock is the greatest friend a global warming skeptic has,” said Marc Morano, a prominent critic of global warming research and the executive director of ClimateDepot.com, in the documentary “Merchants of Doubt” (based on the book by the same name). Morano’s site is a project of the Committee for a Constructive Tomorrow, which has received funding from the oil and gas industry. “We’re the negative force. We’re just trying to stop stuff.” Some of these ploys are getting a fresh boost from Congress. The Data Quality Act (also known as the Information Quality Act) was reportedly written by an industry lobbyist and quietly passed as part of an appropriations bill in 2000. The rule mandates that federal agencies ensure the “quality, objectivity, utility, and integrity of information” that they disseminate, though it does little to define what these terms mean. The law also provides a mechanism for citizens and groups to challenge information that they deem inaccurate, including science that they disagree with. “It was passed in this very quiet way with no explicit debate about it — that should tell you a lot about the real goals,” Levy said. But what’s most telling about the Data Quality Act is how it’s been used, Levy said. A 2004 Washington Post analysis found that in the 20 months following its implementation, the act was repeatedly used by industry groups to push back against proposed regulations and bog down the decision-making process. Instead of deploying transparency as a fundamental principle that applies to all science, these interests have used transparency as a weapon to attack very particular findings that they would like to eradicate. Now Congress is considering another way to legislate how science is used. The Honest Act, a bill sponsored by Rep. Lamar Smith of Texas,3 is another example of what Levy calls a “Trojan horse” law that uses the language of transparency as a cover to achieve other political goals. Smith’s legislation would severely limit the kind of evidence the EPA could use for decision-making. Only studies whose raw data and computer codes were publicly available would be allowed for consideration. That might sound perfectly reasonable, and in many cases it is, Goodman said. But sometimes there are good reasons why researchers can’t conform to these rules, like when the data contains confidential or sensitive medical information.4 Critics, which include more than a dozen scientific organizations, argue that, in practice, the rules would prevent many studies from being considered in EPA reviews.5 It might seem like an easy task to sort good science from bad, but in reality it’s not so simple. “There’s a misplaced idea that we can definitively distinguish the good from the not-good science, but it’s all a matter of degree,” said Brian Nosek, executive director of the Center for Open Science. “There is no perfect study.” Requiring regulators to wait until they have (nonexistent) perfect evidence is essentially “a way of saying, ‘We don’t want to use evidence for our decision-making,’” Nosek said. Most scientific controversies aren’t about science at all, and once the sides are drawn, more data is unlikely to bring opponents into agreement. Michael Carolan, who researches the sociology of technology and scientific knowledge at Colorado State University, wrote in a 2008 paper about why objective knowledge is not enough to resolve environmental controversies. “While these controversies may appear on the surface to rest on disputed questions of fact, beneath often reside differing positions of value; values that can give shape to differing understandings of what ‘the facts’ are.” What’s needed in these cases isn’t more or better science, but mechanisms to bring those hidden values to the forefront of the discussion so that they can be debated transparently. “As long as we continue down this unabashedly naive road about what science is, and what it is capable of doing, we will continue to fail to reach any sort of meaningful consensus on these matters,” Carolan writes. The dispute over tobacco was never about the science of cigarettes’ link to cancer. It was about whether companies have the right to sell dangerous products and, if so, what obligations they have to the consumers who purchased them. Similarly, the debate over climate change isn’t about whether our planet is heating, but about how much responsibility each country and person bears for stopping it. While researching her book “Merchants of Doubt,” science historian Naomi Oreskes found that some of the same people who were defending the tobacco industry as scientific experts were also receiving industry money to deny the role of human activity in global warming. What these issues had in common, she realized, was that they all involved the need for government action. “None of this is about the science. All of this is a political debate about the role of government,” she said in the documentary. These controversies are really about values, not scientific facts, and acknowledging that would allow us to have more truthful and productive debates. What would that look like in practice? Instead of cherry-picking evidence to support a particular view (and insisting that the science points to a desired action), the various sides could lay out the values they are using to assess the evidence. For instance, in Europe, many decisions are guided by the precautionary principle — a system that values caution in the face of uncertainty and says that when the risks are unclear, it should be up to industries to show that their products and processes are not harmful, rather than requiring the government to prove that they are harmful before they can be regulated. By contrast, U.S. agencies tend to wait for strong evidence of harm before issuing regulations. Both approaches have critics, but the difference between them comes down to priorities: Is it better to exercise caution at the risk of burdening companies and perhaps the economy, or is it more important to avoid potential economic downsides even if it means that sometimes a harmful product or industrial process goes unregulated? In other words, under what circumstances do we agree to act on a risk? How certain do we need to be that the risk is real, and how many people would need to be at risk, and how costly is it to reduce that risk? Those are moral questions, not scientific ones, and openly discussing and identifying these kinds of judgment calls would lead to a more honest debate. Science matters, and we need to do it as rigorously as possible. But science can’t tell us how risky is too risky to allow products like cigarettes or potentially harmful pesticides to be sold — those are value judgements that only humans can make.

Chapter 22 Antihypertensive Drugs Hypertension Defined (JNC-8) Pharmacology Overview 7 main categories of drugs to treat HTN Adrenergic drugs (old friend) Angiotensin-converting enzyme (ACE) inhibitors Angiotensin II receptor blockers (ARBs) Calcium channel blockers (CCBs) Diuretics Vasodilators Direct renin inhibitors A. Adrenergic Drugs: 5 Subcategories and where they act A1. Adrenergic neuron blockers (central and peripheral)- we won’t talk about this A2. Alpha1 receptor blockers (peripheral) A3. Alpha2 receptor agonists (central) A4. Beta receptor blockers (peripheral) A5. Combined α and β receptor blockers (peripheral) A2. Peripherally Acting Adrenergic DrugAlpha1 Blockers (we’ve met these) Doxazosin, prazosin, alfuzosin Block alpha1-receptors which causes BP to decrease Reduces peripheral vascular resistance and BP by dilating both arterial and venous blood vessels Main Use: benign prostatic hyperplasia (BPH) Alpha1 Blockers REMEMBER Tamsulosin (Flomax)* is an α1 blocker BUT *Tamsulosin is not used to control BP, just for BPH. A3. Centrally Acting Adrenergic DrugsAlpha 2 agonist Clonidine and methyldopa 1- Stimulate alpha2-adrenergic receptors. in the brain Decreases sympathetic outflow from the CNS which decreases NE production 2. Stimulate alpha2-adrenergic receptors in kidneys remember alpha 2 opposes alpha 1 Dilates peripheral blood vessels → lowers peripheral resistance → Results in decreased BP So ….Clonidine (Catapres) Used primarily for its ability to decrease blood pressure in an urgent setting Also use in opioid withdrawal as previously discussed Oral (multiple times a day), and topical patch formulations Do not stop abruptly as it may lead to rebound hypertension In reality, Clonidine and methyldopa Not prescribed as first-line home antiHTN drugs High incidence of unwanted adverse effects: orthostatic hypotension, fatigue, and dizziness MIGHT be uses as adjunct drugs after other drugs have failed, in conjunction with other antiHTN such as diuretics A4. Adrenergic Drugs Selective Beta 1 Blockers Metoprolol, Atenolol Reduction of HR through β1 receptor blockade (remember adrenergic blocking of this receptor???) HR results in BP Cause reduced secretion of renin = BP A4. Adrenergic Drugs Selective Beta1 Blockers Nebivolol (Bystolic) Uses: hypertension and HF Action: blocks β1 receptors and produces vasodilatation, which results in a decrease in SVR High doses loses selectivity and blocks both β1 and β2 Less sexual dysfunction All BB- Do not stop abruptly; must be tapered over 1 to 2 weeks A4. Adrenergic Drugs NONSelective Beta Blockers Propranolol Acts equally on β1 and β2 Other uses include situational anxiety associated with public speaking, test taking As mentioned on previous slide, nebivolol at high doses becomes beta nonselective A5. Dual-Action Adrenergic Drugs α1 and β Receptor Blockers Dual antihypertensive effects of reduction in heart rate (beta1 receptor blockade) and vasodilation (alpha1 receptor blockade) Examples are carvedilol (common) and labetalol (not as common) A5. Dual-Action Adrenergic Drugs α1 and β Receptor Blockers Carvedilol (Coreg) Widely used drug that is well tolerated Uses: HTN, mild to moderate HF in conjunction with digoxin, diuretics, and ACE inhibitors Contraindications: severe bradycardia or unstable HF, bronchospastic conditions such as asthma, and various cardiac conduction problems Adrenergic Drugs Indications - HTN But also for Glaucoma (topical) BPH: doxazosin, prazosin, and terazosin (2 for 1) Management of severe HF when used with cardiac glycosides and diuretics Contraindications Acute HF- have to stabilize first MOAIs- yeah doesn’t everything interact with MAOIs? Peptic ulcers Severe liver/kidney disease Asthma (with beta blockers) Adrenergic Drugs: Adverse Effects Orthostatic hypotension 1st-dose syncope Rebound hypertension with abrupt discontinuation Most common: Dry mouth, drowsiness, constipation, sedation Interactions- always check for specific drug interactions Can cause additive CNS depression with alcohol, benzodiazepines, opioids Question #1 When administering an alpha-adrenergic drug for hypertension, it is most important for the nurse to assess the patient for the development of what response? Hypotension Hyperkalemia Oliguria Respiratory distress Answer A Hypotension This is a key point in patient education These drugs have strong vasodilating properties and may cause severe hypotension, especially at the beginning of therapy. B. Angiotensin-Converting Enzyme Inhibitorsaka ACE Inhibitors or ACEi Large group of safe and effective drugs Currently are 10 ACEi Often used as first-line drugs for HF and hypertension May be combined with a thiazide diuretic, loop diuretic, or Calcium Channel Blocker (CCB) You need to understand the basics ACE Inhibitors: Review RAAS ACE converts angiotensin I, formed through the action of renin, to angiotensin II Angiotensin 2 is a potent vasoconstrictor and also induces aldosterone secretion by the adrenal glands Aldosterone stimulates sodium resorption (H20 follows Na Both act to raise BP which causes kidneys to reduce renin production ACEi= Great drug to treat HTN BUT contraindicated in pregnancy (2nd,3rd trimester due to fetal renal damage) and breastfeeding first few weeks after birth B. ACE Inhibitors - PRIL Lisinopril (Prinivil) super common, often the 1st drug Enalapril (Vasotec) also common Captopril (Capoten) great if liver disease present Benazepril (Lotensin) Fosinopril (Monopril) Perindopril (Aceon) Quinapril (Accupril) Ramipril (Altace) Trandolapril (Mavik) Primary Effects of the ACE Inhibitors Prevent Na (and H2O) resorption by inhibiting aldosterone secretion (volume reduction) (GO BACK TO RAAS DIAGRAM) blood volume decreases work of the heart preload, or the left ventricular end-diastolic volume which is important in HF ACE SUMMARY OF ACTIVITY 1) Prevent vasoconstriction caused by angiotensin 2 (2) Prevent aldosterone secretion  less sodium and water resorption Cardioprotective Effects of ACEi They slow progression of left ventricular hypertrophy (ventricular remodeling) after MI so considered cardioprotective ACE inhibitors have been shown to decrease morbidity and mortality in patients with HF Renal Protective Effects of ACEi ACE inhibitors: reduce glomerular filtration pressure by volume reduction Cardiovascular drug of choice for patients with diabetes since it helps protect kidneys by reducing pressure. Sometimes used low dose for kidney protection with DM without HTN B. ACEi Enalapril (Vasotec) Only ACEi available in both oral and IV Enalapril IV does not require cardiac monitoring Oral enalapril: prodrug (metabolized in liver) Improves patient’s chances of survival after an MI Reduces the incidence of HF B. ACEi Captopril (Capoten) Uses: prevention of ventricular remodeling after MI; reduce the risk of HF after MI Shortest half-life Must be administered multiple times throughout the day so this limits its use Not a prodrug so good for patient with liver disease Question #2 A patient with diabetes has a new prescription for the ACE inhibitor lisinopril. She questions this order because her provider has never told her that she has hypertension. What is the best explanation for this order? The doctor knows best The patient is confused This medication has cardioprotective properties This medication has a protective effect on the kidneys for patients with diabetes Answer D ACE inhibitors have been shown to have a protective effect on the kidneys because they reduce glomerular filtration pressure. This property makes them the cardiovascular drug of choice for patients with diabetes. Question #3 A patient with a history of pancreatitis and cirrhosis is also being treated for hypertension. Which drug will most likely be ordered for this patient? Clonidine Prazosin Diltiazem Captopril Answer D Captopril Captopril is not a prodrug; therefore, it does not need to be metabolized by the liver to be effective. This is an advantage in patients with liver disease. ACE Inhibitors: Adverse Effects *Dry, nonproductive cough, which reverses when therapy is stopped. This is a class effect Dizziness- Note: First-dose hypotensive effect may occur Headache & Fatigue Possible hyperkalemia ** Angioedema: rare but potentially fatal Not safe in pregnancy-are contraindicated during the second and third trimesters of pregnancy because of increased risk of fetal renal damage C. Angiotensin II Receptor Blockers(ARB) Considered an alternative to ACEi Less likely to cause a dry cough and hyper K+ that is common with ACE inhibitors Angiotensin II Receptor Blockers: Mechanism of Action Go back to RAAS diagram! ARBs affect primarily 2 places 1. Vascular smooth muscle - blocks vasoconstriction 2. Adrenal gland -Selectively blocks the binding of Ang 2 to certain Ang 2 receptors inhibiting secretion of aldosterone Lowers volume retention and BP Angiotensin II Receptor Blockers -ARTAN Losartan (Cozaar)- very common Eprosartan (Teveten) Valsartan (Diovan) Irbesartan (Avapro) Candesartan (Atacand) Olmesartan (Benicar) Telmisartan (Micardis) Azilsartan (Edarbi) C. ARB Losartan (Cozaar) Beneficial in patients with HTN and HF Used with caution in patients with kidney or liver dysfunction and in patients with renal artery stenosis ***Not safe for breastfeeding women and should not be used in pregnancy (Cat C 1st trimester, Cat D 2nd-3rd trimester), potential fetal toxicity Appear to be equally effective for the treatment of hypertension and well tolerated ARBs less likely to cause cough and hyperK+ but can still happen Evidence that ARBs are associated with lower mortality after MI than ACE inhibitors Never take ACEi and ARBs at the same time* 5. Calcium Channel Blockers (CCB) Primary use: HTN, angina, some dysrhythmias Cause smooth muscle relaxation by blocking the binding of calcium to its receptors, preventing muscle contraction Results in: Relaxed blood vessels to the heart Decreased peripheral smooth muscle tone Decreased SVResistance Decreased BP E. Diuretics First-line antiHTN in JNC 8 guidelines Decreases fluid volume The results from diuresis: preload, Peripheral resistance Overall effect  Decreased workload of the heart and decreased BP Thiazide diuretics are the most commonly used diuretics for HTN Ie hydrochlorothiazide (HCTZ), chlorthalidone We will discuss diuretics further in the chapter on diuretics F. Vasodilators Directly relax arterial or venous smooth muscle (or both) Results in: Decreased SVR Decreased afterload Peripheral vasodilation Indicated for treatment of HTN May be used in combination with other drugs F. Vasodilators Hydralazine (Apresoline) Orally: routine cases of essential hypertension Injectable: hypertensive emergencies BiDil: specifically indicated as an adjunct for treatment of HF in African-American patients F. Vasodilators Sodium Nitroprusside (Nitropress) *Sodium nitroprusside and IV diazoxide are reserved for the management of hypertensive emergencies. Contraindications: severe HF, known inadequate cerebral perfusion (especially during neurosurgical procedures) F. Vasodilators Adverse Effects Hydralazine: dizziness, headache, tachycardia, edema, dyspnea, N/V/D, vitamin B6 deficiency, rash Sodium nitroprusside: hypotension, bradycardia, decreased platelet aggregation, rash G. Direct Renin Inhibitors Aliskirin (Tekturna) Blocks the RAS pathway at the point of activation. Inhibiting renin production prevents the downstream production of Ang II (potent vasoconstrictor) Adverse effects: N/V, severe hypotension, hyponatremia, hyperkalemia… Contraindicated in patients with DM taking ACEi or ARB Miscellaneous Antihypertensives Eplerenone (Inspra) Newer class of drugs called selective aldosterone blockers (remember RAAS?) Reduces BP by blocking the actions of aldosterone at its corresponding receptors in the kidney, heart, blood vessels, and brain Indications: routine treatment of hypertension and for post-MI HF Contraindicated if serum potassium levels are high (above 5.6 mEq/L) A Special Form of HTNTreatment of Pulmonary Hypertension Sildenafil and Tadalafil Commonly used for erectile dysfunction Used for pulmonary hypertension but with different trade names Sildenafil: Revatio* (Viagra for ED) Tadalafil: Adcirca* (Cialis for ED)

A solution is composed of a solute dissolved in a solvent. In the sugar water described in Figure 5-1, the solute was sugar and the solvent was water, and the solute molecules diffused through the solvent. It is also possible for solvent molecules to diffuse. In the case of cells, the solutes are organic and inorganic compounds, and the solvent is water. The process by which water molecules diffuse across a cell membrane from an area of higher concentration to an area of lower concentration is called osmosis (ahs-MOH-sis). Because water is moving from a higher to lower concentration, osmosis does not require cells to expend energy. Therefore, osmosis is the passive transport of water. Direction of Osmosis The net direction of osmosis depends on the relative concentra- tion of solutes on the two sides of the membrane. Examine Table 5-1. When the concentration of solute molecules outside the cell is lower than the concentration in the cytosol, the solution outside is hypotonic to the cytosol. In this situation, water diffuses into the cell until equilibrium is established. When the concentration of solute molecules outside the cell is higher than the concentration in the cytosol, the solution outside is hypertonic to the cytosol. In this situation, water diffuses out of the cell until equilibrium is established. Observing Diffusion Materials 600 mL beaker, 25 cm dialysis tubing, funnel, 15 mL starch solution (10 percent), 20 drops Lugol’s solution, 300 mL water, 100 mL graduated cylinder, 20 cm piece of string (2) Procedure 1. Put on your disposable gloves, lab apron, and safety goggles. 2. Pour 300 mL of water in the 600 mL beaker. 3. Add 20 drops of Lugol’s solution to the water. CAUTION: Lugol’s solution is a poison and eye and skin irritant. 4. Open the dialysis tubing, and tie one end tightly with a piece of string. 5. Using the funnel, pour 15 mL of 10 percent starch solution into the dialysis tubing. 6. Tie the other end of the dialysis tubing tightly with the second piece of string, forming a sealed bag around the starch solution. 7. Place the bag into the solution in the beaker, and observe the setup for a color change. Analysis What happened to the color in the bag? What happened to the color of the water around the bag? Explain your observations. Quick Lab www.scilinks.org Topic: Osmosis Keyword: HM61090 mb06se_homs01.qxd 11/27/07 8:52 AM Page 98 HOMEOSTASIS AND CELL TRANSPORT 99 When the concentrations of solutes outside and inside the cell are equal, the outside solution is said to be isotonic to the cytosol. Under these conditions, water diffuses into and out of the cell at equal rates, so there is no net movement of water. Notice that the prefixes hypo-, hyper-, and iso- refer to the relative solute concentrations of two solutions. Thus, if the solution outside the cell is hypotonic to the cytosol, then the cytosol must be hyper- tonic to that solution. Conversely, if the solution outside is hypertonic to the cytosol, then the cytosol must be hypotonic to the solution. Water tends to diffuse from hypo- tonic solutions to hypertonic solutions. How Cells Deal with Osmosis Cells that are exposed to an isotonic external environment usually have no difficulty keeping the movement of water across the cell membrane in balance. This is the case with the cells of ver- tebrate animals on land and of most other organ- isms living in the sea. In contrast, many cells function in a hypotonic environment. Such is the case for unicellular freshwater organisms. Water constantly diffuses into these organisms. Because they require a relatively lower concentration of water in the cytosol to function normally, unicel- lular organisms must rid themselves of the excess water that enters by osmosis. Some of them, such as the paramecia shown in Figure 5-2, do this with contractile vacuoles (kon-TRAK-til VAK-y ̄ ̄o ̄ ̄o-OL), which are organelles that remove water. Contractile vacuoles collect the excess water and then contract, pumping the water out of the cell. Unlike diffusion and osmosis, this pumping action is not a form of passive trans- port because it requires the cell to expend energy. Copyright © by Holt, Rinehart and Winston. All rights reserved. (a) (b) Vacuole filling with water Vacuole contracting TABLE 5-1 Direction of Osmosis Condition External solution is hypotonic to cytosol External solution is hypertonic to cytosol External solution is isotonic to cytosol Net movement of water into the cell out of the cell none H2O H2O H2O H2O H2O H2O The paramecia shown below live in fresh water, which is hypotonic to their cytosol. (a) Contractile vacuoles collect excess water that moves by osmosis into the cytosol. (b) The vacuoles then contract, returning the water to the outside of the cell. (LM 315) FIGURE 5-2 100 CHAPTER 5 (a) HYPOTONIC Cell walls (b) HYPERTONIC (a) ISOTONIC (b) HYPOTONIC (c) HYPERTONIC Other cells, including many of those in multicellular organisms, respond to hypotonic environments by pumping solutes out of the cytosol. This lowers the solute concentration in the cytosol, bring- ing it closer to the solute concentration in the environment. As a result, water molecules are less likely to diffuse into the cell. Most plant cells, like animal cells, live in a hypotonic environ- ment. In fact, the cells that make up plant roots may be surrounded by water. This water moves into plant cells by osmosis. These cells swell as they fill with water until the cell membrane is pressed against the inside of the cell wall, as Figure 5-3a shows. The cell wall is strong enough to resist the pressure exerted by the water inside the expanding cell. The pressure that water molecules exert against the cell wall is called turgor pressure (TER-GOR PRESH-er). In a hypertonic environment, water leaves the cells through osmosis. As shown in Figure 5-3b, the cells shrink away from the cell walls, and turgor pressure is lost. This condition is called plasmolysis (plaz-MAHL-uh-sis), and is the reason that plants wilt if they don’t receive enough water. Some cells cannot compensate for changes in the solute con-

What is the main purpose of family traditions according to the text? A) To showcase wealth B) To connect generations and preserve cultural identity C) To compete with other families D) To change cultural practices How are traditions typically passed down in many cultures? A) By modernizing them B) By adding new practices C) By maintaining core elements while adding unique touches D) By discarding old customs

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What is the hebrew translation for the following words: accurate, agency, agent, ahead of, attend college, balance, bomb, description, mile, network, nuclear, once again, open, oppose, order, power, public, secretary, shadow, shock, spy, state, step, sunset, trarget, the West, turn down, victory, well known,

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