Given all the brouhaha happening around the March for Science yesterday, I was a bit hesitant to see what would unfold. There was a lot of talk on the social media to be present at the march to protest my presence and the group I represented, the Alliance for Science.
As people started to gather for the rally, I started to see the protesters' signs out in the crowd from anti-corporate accusations and about the Papahanaumokuakea Monument. There was 4 gathered right in the front of the media folks with their anti-alliance signs to make it clear that I was not welcomed at this march. Oddly, organizers were told that any hot topic signs or gear would not be allowed at the march, however, these people were allowed openly. I even saw multiple people wearing anti-TMT shirts also.
A fan club protesting the Alliance for Science.
As the rally opened, more and more people gathered around. I didn't see more anti folks though. I was expecting to be heckled and yelled at but surprisingly, none of that happened. It might be because my 2 year old wanted to be held and my 6 year old wanted to show off her "Science feeds the world" sign she had drawn. It was a relief after I spoke, my children did not have to face rude adults.
After speaking, I headed towards the table I had set up to spark conversations and talk about science. I brought my beautiful red Indian corn cob, cotton bolls, photos of GM papaya and virus infected ones, diseased plants, Norman Borlaug stickers, some Alliance pens and stickers. Our table was filled with things to look at and touch to help bring curious people in.
It was really funny when people would lean in close and whisper quietly if we were about GMOs. People were afraid to ask us what we stood for. Between several of us volunteers there, we worked on educating people about evidence based policies and access to technology on a global scale. When they realized what the Alliance stood for, there were so many sighs of relief and so many shared their thoughts about how cool genetic engineering was looking out to be. Many great conversations happened.
My other Alliance member, James Green, was quite clever in his approach to manning the table. He stood with a cardboard sign with a graph of the Dunning-Kruger effect on one side and the other side explaining what it meant. He started out by explaining to curious people why there was such strong opinions about the technology but in reality, the true knowledge and expertise was not there. I'd have to say that many people learned about why GMOs sounded bad but in reality wasn't when you delved further.
As the day went on, one of the protesters decided to stand in front of our table with his sign raised over his head to show his stance against us. He stood there for several minutes and I realized that he'd probably stay there for a long time. I thought to myself, "What a rude guy to do this kind of shenanigan?" I assessed the situation make sure that if it got ugly, my kids were not around. I decided to talk to this guy and see what his deal was. I figured that if he'd do something ugly, there were lots of witnesses around.
The protester who decided to stand at our table.
I came in front of him and read his sign and said, "Why are you standing in front of our table and not coming to talk story? That is so not local style." He proceed to tell me that he heard that the Alliance for Science was being funded by Monsanto. In my own head I was like, oh, geez, again. I might have a crazy one ranting about all the horrible accusations. What have I gotten myself into now?
I continued to talk to him and said, "You think that I'm working for Monsanto because I'm supporting GMO technology?" He said that only Monsanto would put on a booth like this with all the information and stuff. I said no way. I told him that I was up until 2:30 in the morning getting prepared for today. I had set up the photos, stickers, and stuff and even paid for it myself. He was in disbelief and said that it couldn't be true. I replied that if he wanted to see my receipts, I'd be happy to show him. I continued to tell him my story about my dad and brother's farm being saved by technology.
As that story came out, he started to realize that I wasn't Monsanto and that GMOs like that were good. He said that he was a marine biologist with some training in molecular biology so he understood that. Then he said that GMOs are bad because of pesticides. I wanted to bang my head but instead, smiled and took his hand and brought him to my table. "Come here and let me show you what I'm talking about," I told him.
I pulled out one of the lectures I had heard at Cornell on GMOs. I showed him photos of the Bt eggplant damage from the shoot borer and how small farmers had to spray many times to prevent damage. Then I showed him a photo of the Bt eggplant and how it had no damage and needed little spraying if anything. I also talked to him about witchweed and how it destroyed people's crops but if the seed was coated in herbicides, a crop could grow and yield something. He told me that he was a scientist and agreed that this applications were a good thing.
Despite this he kept going on about how the pesticides was the issue. I responded that if he wanted less pesticides, then how could it be done? I waited for his answer and he realized that GM technology could be utilized to change the plant to need less spraying. I could see a light go on in his head when he realized that.
I pushed back on him a bit and asked why was he hanging out with anti-GMO people who were sitting across the way, refusing to interact. I told him that if he was a scientist and knows the benefit of GMOs, why isn't he educating his friends on it? He said that he knew the benefits of biotech being from Costa Rica but that some people don't understand it. I reiterated to him that if he wants less pesticides and better farming, we need research and science leading the charge. He agreed but then went back to Monsanto. I was losing my patience and said, "Would you please think about what we just talked about that it's not about Monsanto." He laughed and our conversation didn't divert but luckily, my attention went to someone else who wanted to talk to me, a cousin who found me on 23andme.
My newly found cousin found through genetic testing, Jason Higa!
After I had a great talk with Jason, I went back to help at the table and my protester was still hanging out. We continued talking and eventually got on to the subject of vaccinations which he surprisingly supported. He was upset at babies dying around the world because of the anti-vaccination movement. I pointed out to him that supporting the anti-GMO stance he had contributes the anti-vax movement by promoting science denial. I asked him if he wanted more babies dying because of this rejection of the evidence, to which he stated no. He was appalled at the anti-vaccination movement and the spread of preventable diseases like measles, whooping cough, and mumps.
My protester friend was still standing in front of our table but he had dropped his sign. We continued talking about the amazing things happening in the world of science and agriculture and decided to take a photo together. He said that he would try to educate his fellow anti friends that not all GMOs mean pesticides or corporations. I hope he follows through with his word.
Javier and I became friends after talking story.
A day that started out with a bit of apprehension actually turned out to be terrific as another person came to talk to me too. I had first encountered this student in a group on Facebook when she had posted some buffer zone links to gather testimony for it. I countered her on it to get her to look at the facts. I also encouraged her to dig deeper and find the actual evidence to her claims. She decided to stop by our table and talk story with me wanting to learn why I held the stances I did against the buffer zone laws.
I pulled out a photo of the papaya tree kicked down by my dad's fearful neighbor. I explained to her that this issue about buffer zones isn't based in science if people are taking those kinds of actions. She was a bit surprised because she had believed that children had been sickened which necessitated it. I asked her if she had looked up the evidence for the claim to which she couldn't answer. I told her that I'd be happy to show her the evidence so that she doesn't contribute to the attacks against farmers. She seemed more than willing to learn and gave me her card, which I'll be contacting her in the future.
As I spoke with many children and parents, it was clear to me that few understood the story of agriculture when they picked up my stickers. I asked them if they knew who was pictured on it. Very few were able to identify Norman Borlaug. I explained to the children that he believed that all people should have food, which they agreed upon was a very good thing.
A lot of learning took place at this March for Science event despite me being censored from talking about GMOs, the Thirty Meter Telescope, and vaccines. The mood of the marchers was so different than the marches against the TMT and GMOs. Those marches were full of angry people whose only bond was being against something. Anger bonded these people together and it made for some ugly after effects. This same anger fueled more anger and hate that spewed out into the social media for years to come. This group of people armed with emotion is what led to the breakdown of communities across our state because logic and rational thinking was lost in the equation.
However, at the March for Science, the atmosphere was very friendly and people were curious and willing to talk story with each other. We were all for something, with the exception of those protesters. The censoring didn't stop the truth from being discussed or heard. In fact there were lots of signs about science saving lives and astronomy.
When the march was done, the lawn wasn't full of garbage or signs thrown the ground like so many other marches. I saw many people taking home their signs instead of dumping it in the trash cans. Everyone cooperated and helped to fold up tables and chairs and put it back in it's place. The march for science brought out a different crowd indeed and it was pretty amazing to see the civility and cooperation come out in people from all walks of life. My daughters made many friends from various marchers and even took some photos with their signs.
What I learned from participating in this march is that those who support science and the scientists themselves must be willing to take the brave step in leading our communities in the right direction. When we are focused on a common goal that helps the greater good, we can put our energies towards the pressing problems ahead of us. Standing aside and being unwilling to even acknowledge another person isn't going to create a movement for a better world.
I learned the name of my protester that day. His name was Javier and despite starting the day feeling apprehensive about him, he is just another person and by taking the first step to talk to him, he was able to have a civil, factual, and rational conversation about a "hot topic." The rest of his friends who protested didn't even come near the information that was available to see and learn from. Even the environmentalist guy who showed up to protest me refused to even show an interest in our table, despite me sharing his post encouraging him to learn. Javier thanked me for coming up to him and talking with him and I said thank you for talking with me!
We need learners in this world who are willing to be curious about what is happening. Those who are capable of talking story so that we all can work together to make it better. The more we focus on collaboration, the better we can sustain our communities for all of humanity.
The ahu is symbolic of building communities and working together.
Tomorrow is the Hawaii March for Science. I'm not marching for science. Instead I'll be walking along scientists and their supporters.
A march is supposed to have a clear leader to guide the group in the right direction. With a coordinated attack against me and the Alliance for Science planned, it only tells me that there is no leader to guide the public on science. Instead, this march is one that has turned political where opposition is allowed to co-opt the evidence and anyone who stands by it.
I'm walking with scientists tomorrow to learn their stories and the work that they do.
I will walk with scientists who are trying to make farming more efficient and environmentally friendly. One day, they will have crops that won't need fertilizer or other inputs. These crops may even grow on more land and have better nutrition for people.
I will walk with scientists who are studying the oceans and learning about how to balance our need for food and yet sustain a way of living for island people. They will know what these creatures eat and see what needs to be done to keep their populations healthy.
I will walk with scientists working on improving the quality of life of those with debilitating illnesses and disability. One day, someone with paraplegia may be able to walk again and lead a normal life or a person with ALS can no longer fear a slow decline in function. There may be a scientist who is working on keeping dementia from robbing memories of a grandparent so that their grandchildren will no longer see them lose their loved one.
I will walk with scientists who are creating new ways to harness energy from the sun, oceans, and winds. One day, we will no longer have to fill our tanks with gasoline and our homes can be powered with the elements around us.
I will walk with a scientist who studies our island's indigenous plants and wildlife to help preserve it for generations to come. Our great grandchildren will be able to see the ohia tree dotting the forests with its beautiful blossoms.
I will walk with scientists to learn about their work and passions. I hope to see that these scientists will be the leaders of the march the help teach the public about the value of their work and why it needs to be leading the conversations around policies and innovation for the future. I want to see these scientists inspiring others to join their fields to help make this world a better place and improve the lives of people globally.
Science is universal and the best thing we've got at understanding our world and knowing what is happening. The scientists and their work must lead policymaking which is why this march was organized to begin with. Until scientists become the lead and speak up for their work and the evidence, I will walk with them. The day they lead us, I'll march with them.
It was announced a few weeks ago that Kamehameha Schools is looking to put in more affordable homes in Haleiwa. Despite the fact that this had been planned for nearly 10 years now, the community became very aware of the loss of ag lands. We all know what happens when farm land disappears. Homes come up and farms are gone forever and communities are changed.
As I watched the North Shore Community Hub group fill with these posts and complaints, I couldn't help but shake my head. Just a few years ago, the North Shore Chamber of Commerce had asked farmers to speak up at neighborhood board meetings to educate about agriculture. My dad and brother drove out there to speak up and was faced with a hostile crowd who thought conventional farms were poisoning them. At yet another meeting, long time farmer Dean Okimoto tried to speak to this same crowd and didn't face friendly people.
The imported disinformation campaign of the Center for Food Safety had dug deep into people's deepest emotions that there was a need to be afraid of the farmers out there. The well established farmers with proven track records were made to be thought of as horrible people.
Even in the community where my dad farmed in remains distrusting of our farm. It's evident when they call the ER afraid for their own health assuming my brother was poisoned but actually had a medication reaction. A neighbor there even posted this ill informed comment to the GMO Free Hawaii group the other week.
My brother and his coworker know firsthand the effects of misinformation on pesticides. Every time they go to the field to spray for pests, wary neighbors look out their car windows and wind them up as if they are being poisoned. My brother has a sense that he's the most hated person out there in Punaluu but he knows that he isn't doing anything wrong. It's the contaminated minds that are filled with fear that remains to be the problem.
What's wrong with fear mongering on pesticides? Well, eventually, the unintended consequences will be seen and right on cue, a Civil Beat article told the story of a Maui woman who is suffering from rat lungworm disease after consuming food from the Big Island. This has remained a problem on the Big Island and it's being studied there to figure out the best practices for dealing with this.
It's ironic that there's so much attention to pesticides on farms here in Hawaii but not much being said by the supposedly food safety group about this issue. One would think that given the increasing numbers of people being affected by this, the Hawaii Center for Food Safety would be right there working on an awareness campaign. Instead, in their last email newsletter, they are bragging about their new Pesticides in Paradise website. There's something wrong when people are getting sick and this group isn't doing a thing to protect them from a very preventable illness.
I asked why CFS and other groups like Shaka aren't informing followers of rat lungworm disease and a friend give the painful truth.
Misinformation has consequences and that is what we are seeing right now with this brain infecting parasite that's made a comeback partly due to the fear mongering of pesticides. The poison of fear has contaminated minds who can no longer think and question what they are being told and people start to suffer as a result. Facts can save one from a life of misery and pain if we use it.


Facebook reversed its cryptocurrency ad ban as bitcoin's price continues to tank amid high-profile hacks and regulatory crackdowns.
In reversing its policy today, the social media juggernaut said advertisers will have to apply and be approved before their ads can run on its massive global platform.
Facebook believes its restrictions will weed out the many scam artists that have proliferated in the market during bitcoin's recent bull run.
It's unclear if fellow social-media giants Twitter and Google will also lift their bans.
As the Inquisitr has reported, Twitter blocked cryptocurrency ads in March 2018, two weeks after Google instituted its ban. At the time, a Twitter rep said it made the move to protect its users from scams and fraud.
Bitcoin prices have fluctuated dramatically since last year. After starting 2017 at about $1,000, BTC prices approached a record high of almost $20,000 in December 2017. They have since plunged to about $6,200.
Analysts say the slump has been exacerbated by several high-profile hacks of crypto exchanges. The most recent attack occurred on South Korean exchange Coinrail on June 10. The next day, the total market capitalization of the entire crypto market plunged $42 billion.
Adding to the industry's woes is the growing anti-bitcoin sentiment among billionaires like Bill Gates and Warren Buffett, who are convinced that crypto is a passing trend that will implode soon.
In May 2018, the Department of Justice launched a criminal investigation into bitcoin price manipulation, as the Inquisitr has reported.
The DOJ wants to know if traders are manipulating the price of bitcoin and other cryptocurrencies by flooding the market with fake orders to manipulate other traders into buying or selling.
Skeptics have blasted bitcoin as a speculative bubble akin to blind gambling due to its erratic price movements.
A recent study by University of Texas finance professor John Griffin concluded that bitcoin prices have indeed been artificially inflated through market manipulation.
In his 66-page research paper titled "Is Bitcoin Really Un-Tethered?" Griffin said at least 50 percent of the increase in bitcoin prices in 2017 was manipulated using tether, a cryptocurrency pegged to the U.S. dollar.
Professor Griffin, who specializes in spotting financial fraud, cited evidence suggesting there was coordinated manipulation designed to keep bitcoin prices artificially high.


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Resources/Collections of History Lesson Plans NEH Lesson Plans Web-based lesson plans for U.S. history and American government teachers from the National Endowment for the Humanities EDSITEment. See also History and Social Studies and Introduction to Advanced Placement U.S. History Lessons. HistorySimulation.comThe word history comes from the Greek word historía which means to learn or know by inquiry. In the pieces that follow, we encourage you to probe, dispute, dig deeper — inquire. History is not static. Its fluid. It changes and grows and becomes richer and more complex when any individual ...A Note and a disclaimer. The Note: This great book should really be read by everyone.It is difficult to describe why it so great because it both teaches and inspires. You really just have to read it.Admission Essay, Personal Statement & Letter of Recommendation Editing & Writing Services for College, Law School, MBA or Business School, Medical School, and Graduate School5 January 1919. Heeding cries for help, U.S. Navy Sailors beat police and firefighters to the scene after over two million gallons of molasses, traveling at 35 miles per hour, destroyed homes, swept up railroad cars and much more.Use an anecdote. Depending on how formal an essay you're writing, you might be able to open with an anecdote. This could be from your own life, or a brief story or parable that you're quoting.The Bureau of Labor Statistics is the principal fact-finding agency for the Federal Government in the broad field of labor economics and statistics.Different tribes of Native Americans lived in the area that is now California for an estimated 13,000 to 15,000 years. Over 100 tribes and bands inhabited the area. Various estimates of the Native American population in California during the pre-European period range from 100,000 to 300,000. Californias population held about one-third of all Native Americans in what is now the United States.Dont see what youre interested in? See information on hundreds of jobs at our full Occupational Outlook Handbook.u s history essay help $divdiv

redpajama_set_name: RedPajamaCommonCrawl


These are some real problems experienced by HTS541280H9SA00 and Hitachi hard drives in general that we see in our lab. We are not affiliated in any way with hard drive manufacturers. All the information below is based solely on our experience and we do not make any claims regarding reliability of the specific model. We see mostly failed drives in our lab and therefore we don't have complete statistics.
The drive won't start: "No operating system found" appears in the screen. I just want to get the data out of it, all of my projects are there. Just tried to start the drive in another computer and failed to show any answer. HTS541280H9SA00(by Hitachi).
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The Dr. Naomi Morris Alumni Award is given annually to two members of UIC SPH alumni body, one from the UIC CoE in MCH and one from the Community Health Sciences Division. The selection committee particularly looks for individuals who have achieved national, regional, or statewide prominence either in their professional fields or through their involvement in civic, cultural, or charitable activities as they relate to the field of maternal and child health. Please contact the Office of Advancement with questions at 312.996.0760 or SPHadvancement@uic.edu.


text:
Q: Linq wherein extension methods variable p errors I write this extensions method for wherein;
public static IQueryable<T> WhereIn<T, TValue>(this IQueryable<T> query,
                        IEnumerable<TValue> values, params Expression<Func<T, TValue>>[] valueSelectors)
        {
            return query.Where(BuildContainsExpression(values, valueSelectors));

        }
        private static Expression<Func<TElement, bool>> BuildContainsExpression<TElement, TValue>(
                        IEnumerable<TValue> values, params Expression<Func<TElement, TValue>>[] valueSelector)
        {
            if (null == valueSelector)
            {
                throw new ArgumentNullException("valueSelector");
            }
            if (null == values)
            {
                throw new ArgumentNullException("values");
            }

            Expression<Func<TElement, bool>> predicate = null;

            for (int i = 0; i < valueSelector.Count(); i++)
            {
                var param = valueSelector[i];
                ParameterExpression genericParameter = param.Parameters[0];

                TValue[] enumerable = values as TValue[] ?? values.ToArray();
                if (!enumerable.Any())
                {
                    return e => false;
                }

                if (!enumerable.Any())
                {
                    return e => false;
                }
                IEnumerable<Expression> equals = enumerable.Select(value => (Expression)Expression.Equal(param.Body, Expression.Constant(value, typeof(TValue))));
                Expression body = equals.Aggregate(Expression.Or);
                Expression<Func<TElement, bool>> partialPredicate = Expression.Lambda<Func<TElement, bool>>(body, genericParameter);

                if (predicate == null)
                    predicate = partialPredicate;
                else
                {
                    var orElse = Expression.OrElse(predicate.Body, partialPredicate.Body);
                    predicate = Expression.Lambda<Func<TElement, bool>>(orElse, genericParameter);
                }

            }

            if (predicate != null)
                return predicate;
            return null;
        }

predicate result is = {p => ((((Convert(p.Id) == 1) Or (Convert(p.Id) == 3)) Or (Convert(p.Id) == 5)) OrElse (((p.MemberId == 1) Or (p.MemberId == 3)) Or (p.MemberId == 5)))}

public class OrderDto { public string Id {get;set;} }

my input is:
var list = new List<int?> {1, 3, 5};
var orderList = Entity.Order.AsQueryable().WhereIn(list, p => p.Id, p => p.MemberId).Select(t => new OrderDto {Id =t.Id}); –

But I get this error;

variable 'p' of type 'OrderDto' referenced from scope '', but it is not defined

How can I fix it?

A: You are re-using the parameters from the given expressions.
ParameterExpression genericParameter = param.Parameters[0];

When you create new expressions, you also have to create new parameters.
ParameterExpression genericParameter = new ParameterExpression(...);

See here for more information from the master.

redpajama_set_name: RedPajamaStackExchange


UC Davis is defending its decision to pay consultants at least $175,000 to clean up its online image after students and alumni were pepper sprayed by police in 2011.
Assemblyman Mike Gatto (D-Glendale) called on UC Davis' chancellor to resign, citing the payment and other issues that have roiled the campus.
UC Davis officials released a statement late Thursday saying, "Increased investment in social media and communications strategy has heightened the profile of the university to good effect."
The statement said the effort was designed not to have the pepper spray incident overshadow the good work being done on campus.
"It is important that the excellent work underway at UC Davis with respect to educating the next generation of students, pursuing groundbreaking research, and providing important services to the state is not lost during a campus crisis, including the crisis that ensued following the extremely regrettable incident when police pepper-sprayed student protesters in 2011," the statement said.
Newly released documents obtained by the Sacramento Bee show the university worked to clean up both its own image and that of Chancellor Linda Katehi.
In one case, UC Davis worked with Maryland company Nevins & Associates on a six-month contract that paid $15,000 a month, according to a copy of the contract. That contract was signed in January 2013, just a few months after the UC regents agreed to pay a settlement to 21 UC Davis students and alumni who sued the university.
The widely criticized November 2011 incident, captured in videos that quickly went viral on the Internet, triggered nationwide controversy about the forceful response by university police to student protesters.
The videos showed an officer spraying seated students directly in their faces at close range during an Occupy rally. At the time, the Occupy Wall Street movement had spilled onto college campuses, combining with student anger over rising tuition and cuts to higher education to spur protests and sit-ins.
In addition to public outrage, the episode also spawned a raft of Internet memes that featured the "casually pepper spray everything cop."
As part of its contract, Nevins & Associates said it would work to remedy the "venomous rhetoric about UC Davis and the chancellor" through "strategic placement of online content."
The company agreed to launch an aggressive and comprehensive online campaign to eliminate negative search results through modifications to "existing and future content" and by creating more original content as needed.
One means of doing this, the company said, is by diluting negative viral content with a surge of positive stories on different topics. Nevins & Associates also suggested UC Davis adopt Google platforms to "expedite the eradication of references to the pepper spray incident in search results."
In June 2014, the university awarded the PR firm IDMLOCO a contract for $82,500 to design a "comprehensive search engine results management strategy." The documents outlining the contracts were released to the Sacramento Bee in response to requests filed under the California Public Records Act.
IDMLOCO said it would be able to achieve a "reasonable balance of positive natural search results" and identify "key messages and themes" the company could use to counter negative results.
The company was awarded two more contracts last year — one for $8,000 a month, up to a limit of $96,000, and another for $22,500 a month, for a maximum of $67,500.
Under those contracts, IDMLOCO said it would create an "integrated social media program for executive communications" and provide "an assessment of the University's Strategic Communications redesign."
Police at first contended that the spray was the most appropriate tool on hand to deal with what they described as an unruly mob encircling the officers.
However, a UC report in April 2012 declared that the pepper spraying violated policy and that school leaders badly bungled the handling of that campus protest. The investigating task force strongly rebutted campus police claims that the Occupy demonstrators, who had pitched tents on a UC Davis quad, posed a violent threat.
In 2013, the former UC Davis police officer who pepper sprayed the campus protesters received $38,055 in workers' compensation after claiming he suffered depression and anxiety as a result of the public outcry.
John Pike, who had filed for the compensation from the University of California system, also cited the stress he endured from death threats he received after the incident. Pike was fired in July 2012, after being on paid administrative leave for eight months.
Online reputations in particular are important to manage because of the sheer volume of people who surf the Web, said Ira Kalb, an expert in branding, image creation and marketing at USC. Managing these reputations and protecting them from being "hijacked" is a growing field, he said.
"Online is really an interesting thing because there are people who say all sorts of things," he said.


text:
Rapid CommunicationAccelerated Communication
Human UGT2B7 Catalyzes Morphine Glucuronidation
Birgit L. Coffman, Gladys R. Rios, Christopher D. King and Thomas R. Tephly
Drug Metabolism and Disposition January 1997, 25 (1) 1-4;
Birgit L. Coffman
Gladys R. Rios
Christopher D. King
Thomas R. Tephly
A human UDP-glucuronosyltransferase (UGT) catalyzing the glucuronidation of morphine has been identified. A full length cDNA was isolated from a human liver cDNA library and found to be identical to the UGT2B7 form having a tyrosine at position 268. This cDNA was transfected into HK 293 cells, and stable expression was achieved. Cell homogenates and membrane preparations from HK 293 cells expressing UGT2B7 catalyzed the glucuronidation of morphine and other clinically significant opioid agonists, antagonists, and partial agonists. UGT2B7 catalyzed morphine glucuronidation at the 3- and 6-hydroxy positions and also mediated the formation of codeine-6-glucuronide from codeine. This represents the first demonstration of a UGT capable of catalyzing the glucuronidation of both the 3- and 6-positions of opioids. Since humans excrete morphine-3-glucuronide and morphine-6-glucuronide after morphine administration, it is likely that UGT2B7 is a major isoform in humans responsible for the metabolism of this important drug and its surrogates.
Glucuronide conjugation is an important metabolic process in which xenobiotics and endobiotics are converted to hydrophilic metabolites through the mediation of UGTs1 (E.C. 2.4.1.17). UGTs are intrinsic membrane proteins of the endoplasmic reticulum and nuclear envelope of cells of liver and other organs, and are encoded by multiple genes of at least two families (1). After glucuronidation, conjugates are readily excreted by renal and hepatic mechanisms leading to rapid elimination of the aglycone from the body. At this time, >30 individual UGT isoforms have been identified either by cloning and expression or by purification procedures from hepatic microsomes. UGTs that are members of the UGT1 gene complex share common second through fifth exons, with at least seven separate exons encoding for specific proteins with unique N-terminal domains (2). In contrast, gene products of the UGT2 family are transcribed from unique genes. At least eight isozymes of the human UGT2 family have been identified (3), and the genes UGT2B4, UGT2B9, andUGT2B15 have been mapped to human chromosome 4 (4, 5).
Xenobiotics such as those of the opioid drug class are, in general, metabolized and excreted largely as glucuronides by the liver and kidney. Morphine is the best example of an opioid drug that is extensively glucuronidated. Morphine possesses hydroxy groups on the 3- and 6- positions of the molecule and both morphine-3-glucuronide and morphine-6-glucuronide are found in the urine of humans (6, 7), whereas codeine with a methoxy group on the 3-position is converted only to the 6-glucuronide.
A principal interest in this laboratory for many years has been the isolation and identification of the UGTs that catalyze the glucuronidation of opioids in rats and humans (8-10). We have recently shown that stably expressed human UGT1.1, often termed the major "bilirubin" UGT (11), reacts with high affinity and efficiency with the opioid partial agonist/antagonist, buprenorphine (12). Previous investigations by Miners et al.(13) and Wahlström et al.(14) suggested, that several isozymes mediate hepatic opioid glucuronidation in humans; however, no expressed human UGTs (other than UGT1.1) have been reported to participate in opioid glucuronidation.
This communication describes the cloning and expression of a cDNA encoding for a human liver microsomal UGT that catalyzes the glucuronidation of morphine and other opioids. Sequence analysis showed that the cDNA was identical to a human UGT, termed UGT2B7 variant (15), which had been shown previously to code for a UGT mediating glucuronidation of NSAIDs and certain forms of carboxylic acid-containing drugs. This UGT, UGT2B7, is likely to be the major isoform responsible for morphine glucuronidation in humans.
Chemicals.
UDP-GlcUA (319 mCi/mmol) was purchased from ICN Pharmaceuticals (Irvine, CA). Morphine sulfate was acquired from Merck (Rahway, NJ). Morphine-3-glucuronide, morphine-6-glucuronide, and codeine-6-glucuronide were acquired from Research Biochemicals (Natick, MA). All aglycones and l-α-phosphatidylcholine (type XVI-E from egg yolk), dithiothreitol, and UDP-GlcUA were purchased from Sigma Chemical Co. (St. Louis, MO). Protein assay reagents were from Bio-Rad (Richmond, CA).
Screening of the cDNA Library.
A human liver cDNA library in Bluescript SK (Stratagene, La Jolla, CA) was plated in XL1-Blue MRF′ cells. The library was screened by plaque hybridization with a full length rat liver cDNA, UGT2B1 (kindly supplied by Dr. Peter Mackenzie, Flinders Medical Centre, Bedford Park, South Australia, Australia). The probe was labeled with32P-dCTP by the nick-translation method following the protocol of the supplier (Boehringer Mannheim Biochemica, Indianapolis, IN), and hybridization was performed at 42°C in 50% formamide, 4.8 × standard saline citrate, 1 × Denhardt's solution, 10% dextran, and 0.1% SDS containing salmon testes DNA at 0.1 mg/ml. Bacteriophages that hybridized to the probe were isolated and purified.
Restriction enzyme analysis showed that one clone (HM1) contained a 2.2 kb pair insert. This clone was further characterized.
DNA Sequence Analysis.
Analysis was performed by the DNA Facility, University of Iowa, using an Applied Biosystems 373 A Automatic DNA Sequencer. The HM1 insert was initially sequenced in the Bluescript plasmid using primers to the T3 and T7 promoters. Subsequently, oligonucleotides were synthesized (Genosys Biotechnologies, The Woodlands, TX) and used as primers to generate additional and overlapping DNA sequences until both strands were sequenced.
Expression of HM1 in Human Embryonic Kidney (HK 293) Cells.
The HM1 insert was removed from Bluescript SK and was ligated into theBamH1/Xho1 site of the mammalian expression vector pcDNA3.1 (Invitrogen, San Diego, CA). This expression vector construct is referred to as pcDNA3-2B. The HK 293 cells were transfected using the calcium phosphate transfection method (16) and were grown in media containing geneticin (G418) (17). Cells were harvested after 1–4 passages of stable transfection for analysis of glucuronidation activity.
Glucuronidation Assays.
Cells expressing pcDNA3-2B protein were resuspended in TBS containing 0.5 mM dithiothreitol and disrupted by freeze-thawing 3 times in liquid nitrogen before homogenization. Glucuronidation activity toward opioids [5 mM morphine (pH 8.4), 5 mM codeine (pH 7.7), 2 mM nalorphine (pH 8.4), 2 mM naloxone (pH 7.7), 2 mM naltrexone (pH 7.0), and 0.5 mM buprenorphine (pH 7.0)] was assayed using the method described by Puig and Tephly (9). Determination of the kinetic parameters for glucuronidation of opioids was performed on membrane preparations from cells expressing pcDNA3-2B protein, prepared as described by Battagliaet al. (18). Membrane preparations were frozen in aliquots. Membranes were resuspended in TBS containing 0.5 mM dithiothreitol and homogenized by hand in a Potter-Elvehjem homogenizer. The glucuronides of morphine-3, morphine-6, and codeine-6 were identified and quantified using a modified HPLC method as described by Yue et al. (19). For HPLC analysis of morphine-3-glucuronide, morphine-6-glucuronide, and codeine-6-glucuronide conjugates, the samples were eluted from the Sep-Pak C18 cartridges with 2 ml of 15% acetonitrile in phosphate buffer at pH 2.1. Morphine-3-glucuronide and morphine-6-glucuronide or codeine-6-glucuronide standards were added to 400 μl of the eluent that was injected into the HPLC system and eluted with 25% acetonitrile in phosphate buffer (pH 2.1) and 1 mM SDS. The radioactivity eluted with the glucuronide standards was measured. Analysis of glucuronidation of nonopioids was conducted and analyzed as described by Green et al. (17).
Screening and Nucleotide Sequence of HM1.
Pritchard et al. (20) has previous reported that rat liver UGT2B1 exhibited glucuronidation activity toward morphine. Therefore, a human liver cDNA library was screened with the full-length cDNA, UGT2B1. Of 27 cDNA clones identified, two were full-length clones. One of these clones (HM1) was characterized and found to be identical to the human UGT2B7 variant as reported by Jin et al. (15). The deduced amino acid sequence has a tyrosine in position 268 instead of a histidine, as reported by Ritter et al. (21). Because there is no knowledge of the relative abundance of the two forms, there seems to be no reason to term either form as a variant at this time. Thus, we have designated HM1 as UGT2B7(Y) and the histidine form as UGT2B7(H).
Expression of UGT2B7(Y) in HK293 Cells.
Stably expressed UGT2B7(Y) catalyzes the glucuronidation of opioids (table 1), whereas opioid glucuronidation by vector-transfected and nontransfected HK293 cells was not detected. Of the opioids tested with stably expressed UGY2B7(Y), the glucuronidation rates for morphine, naloxone, and nalorphine were similar, whereas the rates for naltrexone and buprenorphine were <10% of that determined for morphine. The rates of codeine-6-glucuronidation were only ∼ 1% of the rate of morphine glucuronidation.
Glucuronidation of opioids by human UGT2B7(Y) expressed in HK 293 cells
Expressed UGT2B7(Y) had been shown previously to glucuronidate 4-hydroxyestrone and 4-hydroxyestradiol, and carboxylic acid-containing NSAIDs, such as ibuprofen and naproxen (15). Glucuronidation activities toward the four mentioned substrates were observed when the UGT2B7(Y) expressed in HK293 cells was studied using homogenate preparation (data not shown).
The HPLC chromatogram of the products from the glucuronidation of morphine by the stably expressed UGT2B7(Y) using [14C]UDP-GlcUA is shown in fig. 1. Carrier morphine-3-glucuronide and morphine-6-glucuronide were added to the incubation samples before HPLC analysis, and radioactivity coeluting with standards was measured. Both morphine-3-glucuronide and morphine-6-glucuronide were formed in reactions catalyzed by UGT2B7(Y). Preliminary results have also shown that expressed UGT2B7(H) also catalyzes morphine-3-glucuronide and morphine-6-glucuronidation (data not shown).2 Likewise, the HPLC analysis of the glucuronidation of codeine showed that radioactivity eluted along with the codeine-6-glucuronide standard (data not shown). This is the first demonstration of a UGT catalyzing the formation of an opioid-6-glucuronide.
HPLC chromatogram of a preparation from an incubation of morphine with a homogenate of HK 293 cells stably expressing UGT2B7(Y).
Experimental procedures are given in Materials and Methods.□, Absorbance at 210 nm; ◊, radioactivity dpm/1000.
Kinetic parameters were determined for the glucuronidation of morphine, codeine, nalorphine, and buprenorphine using membrane preparations from the HK293 cells expressing UGT2B7(Y) (table 2). Nalorphine and buprenorphine were found to produce substrate inhibition above 1.2 mM and 0.3 mM substrate, respectively. Buprenorphine and nalorphine are glucuronidated with higher efficiency than morphine, which is probably due to the increased length of the N-alkyl side chain of these opioids. The efficiency of codeine glucuronidation was 8 times less than that of morphine-6-glucuronidation.
Kinetic parameters of glucuronide formation in a membrane preparation from HK 293 cells stably expressing UGT2B7(Y)
Morphine is metabolized in humans to morphine-3-glucuronide and morphine-6-glucuronide; but, until now, no human UGT has been identified to catalyze the formation of morphine-3-glucuronide and morphine-6-glucuronide with significant efficiency. UGT1.1, which also catalyzes opioid glucuronidation (12), does not catalyze the formation of morphine-6-glucuronide (unpublished data). The ratio ofVmax for the formation of morphine-3-glucuronidevs. morphine-6-glucuronide by the expressed UGT2B7(Y) was found to be similar to ratios reported for human liver microsomes (∼ 7:1) (19, 22). These data suggest that the UGT2B7(Y) represents the major human morphine UGT catalyzing the glucuronidation of the 3-OH and the 6-OH positions in opioids. Morphine-6-glucuronide has been shown to be a potent analgesic in clinical studies in human subjects, and the analgesic properties of morphine in humans are enhanced by the action of morphine-6-glucuronide (23). Morphine-3-glucuronide, in contrast, has no analgesic effect but shows enhanced excitatory activity by a nonopioid mechanism (24). It has been suggested that certain adverse effects of morphine in humans is due to the morphine-3-glucuronide formed. Thus, glucuronidation processes in the case of opioid pharmacology (e.g. morphine) may lead to potentially enhanced drug action or adverse effects not usually considered in the process of glucuronidation of most drugs.
1,4-Benzodiazepine derivatives, such as diazepam and halazepam, are converted in vivo to oxazepam, an active metabolite that is subsequently excreted as the pharmacologically inactive diasterometric oxazepam glucuronide. Based on inhibition studies, Patel et al. (25) have suggested that the S and Rforms of oxazepam are glucuronidated by different UGT isozymes, and that UGT2B7 is the enzyme catalyzing the formation ofS-oxazepam glucuronide. Patel et al. (26) also have found that 10% of a population had a significantly lower ratio ofS- to R-glucuronide metabolites. This result correlated with the results of an in vitro study using microsomes from human livers, where 10% of the livers displayed an abnormal high KM for the formation of theS-glucuronide, but no differences were found forKM for the R-glucuronide formation. These investigators speculated that the differences could be caused by a polymorphism in the UGT2B7 gene, yet the only difference in the proteins of UGT2B7(H) and UGT2B7(Y) is a histidine instead of a tyrosine at the 268 position. This amino acid difference does not seem to alter the glucuronidation ratio of morphine-3-glucuronide to morphine-6-glucuronide.2 Whether the difference in one amino acid affects the glucuronidation of substrates other than morphine is unknown at the present time. In addition, the question remains as to which UGT2B7 form is predominant in the human population.
Buprenorphine and naltrexone are antagonists that are under investigation as potential drugs for the treatment of opioid (27) and alcohol (28) abuse, respectively. Stably expressed human UGT1.1 also catalyzes the glucuronidation of opioids, in addition to bilirubin. This isoform reacts with high affinity toward buprenorphine, but exhibits a low efficiency of glucuronidation toward naltrexone and nalorphine (12), which may explain why liver microsomes from Crigler-Najjar type I patients, who do not express an active UGT1.1 due to a defect in the first exon of the UGT1 gene, glucuronidate buprenorphine at low rates (12). Naltrexone is glucuronidated at normal rates in Crigler-Najjar patients (12) most likely because UGT2B7 is the major isoform involved in its glucuronidation. However, the use of naltrexone or buprenorphine in patients with perturbation of liver function, as in alcohol addiction, might pose some problems dependent on the adequacy of the UGT2B7, UGT1.1, and UDP-GlcUA levels in such patients. Moreover, possible drug–endobiotic interaction must be considered when morphine is administered with such substrates that also interact with UGT2B7 (e.g. catechol estrogens). Drug–drug interactions should likewise be considered, because UGT2B7 is a major isoform catalyzing NSAID and benzodiazepine glucuronidation. Further studies on the substrate specificity and kinetic analysis for UGT2B7(Y) and UGT2B7(H) need to be investigated to identify possible drug–endobiotic and/or drug–drug interactions.
Send reprint requests to: Dr. Thomas R. Tephly, 2-459 Bowen Science Building, Department of Pharmacology, University of Iowa, Iowa City, IA 52242.
This research was supported by the National Institutes of Health Grant GM26221.
↵2 T. R. Tephly et al., unpublished data.
Abbreviations used are::
UDP-glucuronosyltransferase
nonsteroidal anti-inflammatory drug
UDP-GlcUA
UDP-glucuronic acid
sodium dodecyl sulfate
10mM Tris, 0.9% NaCl, pH 7.4
hydroxy
Received September 19, 1996.
Accepted October 28, 1996.
The American Society for Pharmacology and Experimental Therapeutics
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The hardest part of selling a home, whether you do it yourself (FSBO) or use a Real Estate Agent, is putting a price on your property. Pricing a property too low or too high might keep you from getting all you can for your home or lead potential buyers to not consider your listing.
Valueing one's things more highly than other people do is called the endowment effect and it's a natural inclination. However, if you keep a few things in mind it's entirely possible to arrive at a price that works for both the seller and the buyer.
Counteracting the endowment effect is a key benefit of working with a Real Estate Agent. However, their objectivity comes from knowledge you can obtain for yourself. It starts with looking at what homes are selling for in your area. Also, attend open houses for properties currently on the market to see how yours stacks up. Then, to help you get into a buyer's frame of mind, ask yourself what you would pay for your house today if you did not already own it.
You may also want to consider paying for an appraisal. The buyer's bank will eventually insist they obtain one during the closing process. However, having your own done helps you value your property and lets you know what the bank's mortgage limit on your home would likely be.
Once you receive an offer, what you do next will ultimately determine your selling price. Here are some best practices to keep in mind when negotiating with potential buyers.
The first offer could be the best. Typically, the first offer is a good assessment of your market value. Though, there are some buyers who will start very low hoping you are in a hurry to sell. When an offer is too low, you have the option of not countering, but instead asking them to resubmit.
Consider conceding before countering. Often, offers come with concessions, like a request for a delayed closing, for instance. When an offering price is close to your listing price, you may want to accept a concession instead of immediately lowering your price.
Be a listener, not a talker. The less buyers know about your circumstances and reasons for selling, the better. Additionally, the more you know about the buyer's circumstances, the more leverage you have in a negotiation.
Know your limits. Before you list, determine your minimum sales price. Then, ask yourself how long you are willing and can afford to have your home on the market. You may come out money ahead by selling at a lower price due to your carrying costs, especially if you have already moved.
Know your facts. Create a history of upgrades you've made since you bought the home, the age of appliances, and how much it would cost to replace them. You may want to consider offering a home warranty to counteract any reluctance on a buyer's part. This relatively inexpensive insurance covers repair costs should something break down within the first year of you selling the home.
Follow the money. Understand the lending conditions your buyer is working with. That can help you determine whether you want to agree to a lower price to help them qualify for their mortgage in exchange for a larger participation from them in the closing costs, for example.
Successfully selling your home on your own may require a little more upfront research, but when you know what to negotiate, it should lead you to the results you originally sought from choosing an FSBO solution, a larger check at closing.


text:
SLCC, Sixth-Graders Reveal 'Beloved Community' Photo Exhibit
SLCC's School of Arts, Communication and Media sponsored the photography project that taught students about Martin Luther King Jr.'s idea of "beloved community."
Sixth-grade students at Whittier Elementary School take part in the "Beloved Community" photography project, sponsored by Salt Lake Community College's School of Arts, Communication and Media.
The participating students' photography truly celebrates their cherished connections to the people and places in their own neighborhoods.
Salt Lake City, Utah (PRWEB) February 19, 2016
Salt Lake Community College instructors recently collaborated with sixth-grade students from Whittier Elementary to create an exhibit of photos that reflect Martin Luther King Jr.'s vision of a "beloved community." Sponsored by the SLCC School of Arts, Communication and Media, the exhibit will open to the public for the first time Feb. 24, 6-8 p.m. with a reception at SLCC's South City Campus, 1575 S. State Street, Salt Lake City, in the George S. & Delores Doré Eccles Art Gallery.
"The Beloved Community project provided a great opportunity to bring SLCC faculty together with local students to celebrate art, vision and community," said Josh Elstein, coordinator for SLCC's Center for Arts and Media. "The participating students' photography truly celebrates their cherished connections to the people and places in their own neighborhoods."
The exhibit will remain open to the public Feb. 24 to March 2 during normal business hours, featuring more than 50 original prints by the students. King popularized the phrase "beloved community" to represent his vision for societies to embrace notions of cooperation, unity and connection. A grant from SLCC's Office of Government and Community Relations funded the purchase of digital cameras used by the students. SLCC faculty members Whitney Hyans and Elisa Stone provided students with lessons about King's vision and the photography techniques they would need before searching for inspiration on what to document in their own communities.
SLCC's Center for Arts and Media is a state-of-the-industry facility with 130,000 square feet of additional space at its South City Campus, 1575 South State Street, Salt Lake City. World-class features include a 2,000 square-foot television studio and control room, a 3,000 square-foot film stage, a 36-seat screening room, three MIDI (Musical Instrument Digital Interface) classrooms, 22 editing bays, an animation lab, radio station and a recording studio with 64 channels for collaboration in as many locations throughout the building. The new center, which is physically connected to Innovations High School, serves an estimated 9,000 students and brings together 17 programs under one roof for SLCC's School of Arts, Communication and Media.
Stephen Speckman
@SaltLakeCC


A must-have guide to customizing WordPress themes So if you are new to WordPress, you've probably come to the bewildering question: "How can I make my website look different? "Layer offers you a robust suite of entry-level layout, colour and font customisation utilities, but what if you want to do something more specialized, such as adding textures to interior pages or changing the colour of the hub in your navigation tool?
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I think you need a kid themes, though: Do you want to redesign a design without or beyond what the WordPress Customizing control elements or other plug-ins allow you to do when you need to find a plug-in or create an enhancement? Subordinate topics serve the purpose of presentations, while enhancements serve to enhance functions. Children's themes and styles kit contain some user-defined styles, but are not the same.
This is a set of preset files that have been created from the Layers Customizer. Is used when a stylesheet is not sufficient and typically contains more than one stylesheet, extra scripting, and a feature set that defines user-defined operations allow you to include a user-defined feature or piece of coding at a particular location. Use the WordPress action API to generate a customized Action to append or subtract arbitrary text to an already created kernel Action by specifying an already created hook.
Layer also provides an API to include in our own user-defined operations. Allows you to insert text to the bottom of a layer. You can do this by creating a new feature that contains your customized coding, and then connecting it to the main interaction OR connecting it to the Layer action API to take full benefit of better positioning.
For example, the operation prints a user-defined item directly above the copyrights pane. User-defined operations differ from user-defined filters because you can use user-defined operations to apply or delete arbitrary codes to your work. User-defined filters allow you to substitute certain information (e.g. a tag or a CSS class) within an active operation.
The WordPress Codex: WorldPress pages are unbelievably versatile things, so it's no wonder they run 25% of the web. In a little bit of timing and scheduling, you can turn your Layers page into virtually anything by using one or a combinations of these technologies. Stay tuned for this section as we take in custom-made CSS tips and take a close look at some of the fantastic free and premier enhancements and children's themes to help you reach your targets.
Which are some of your favourite WordPress customisation utilities?
Where do I start a blog?


Is the new enforcement of the Federal Zone on beachfront houses going to affect the condos built on the beach also?
The enforcement of keeping public lands on the beaches open in Mexico is not new. A 'Notario' (government authorized land attorney) may be your best bet for info on a specific area or property.
The developers of the condo's would/should have gotten a permit (concession) for building in the Federal Zone (if they built within it) from the government. By the time you buy a condo that permit stuff is 'usually' done long ago & paid for by the developer/owner of the project.
If your really concerned just ask your condo association or the management office if your condo project has one.
The Federal Zone at the beach is public property for access & enjoyment of all citizens. To bypass the law you just buy a permit from the government & pay a fee.


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The Sonic Exchange: An Argument for Crafting a More Just and Sustainable Market for Music
By Spencer King | November 30, 2016 | 9:20am
Photos: Hulton Archive, George Marks/Getty Politics Features Musical Economy
The American music industry does not frequently garner great recognition as a player in the overall economy, but it has firmly made its stake as a capitalist entity and exemplified its adaptability to the rapidly changing technology of recent decades. It seems as though the halcyon days of music exist in a haze of hardworking, self-sufficient artists, but the truth reveals that the recording industry at large has been one of exploitation and unfair treatment of musicians since its genesis. The nature of the music industry and its generation of popular music and artists parallels the trend of the "throwaway economy," marked by cheap goods that are not built to last. Suited for the current fashion, their obsolescence in the music scene is planned.
Major music labels such as Universal, Sony, and Warner dominate the industry, but as we progress further into the digital age, small, independent labels have gained traction—cornering a part of the market that caters towards musicians that have yet to be "discovered" on a larger scale. This notion presents an interesting aspect of the musical economy that corresponds to the overall economy: stagnation means failure, growth means success. From the smallest of independent artists, to the most well known, frequently touring acts, the song remains the same; the end-goal is large success and a multi-million dollar record deal. Perhaps this trend could be blamed on culture, pop-icon idolatry, or a deep-seated quest for personal fulfillment – perhaps the blame better falls on the teachings of capitalism and a growth based-economy. The commodification of music and artists' work is indicative of the exploitive practices of capitalist ventures, the current nature of the musical economy is simply not working for the majority of those who are operating within it. However, in many circles within the musical economy, artists are beginning to take back their space, their music, and their creative means.
In the past decade and a half, the popularity of digital music has skyrocketed. Since the introduction of the Apple iPod in 2001, the entire perception of music buying, selling, and sharing has experienced a great shift. With the introduction of the online music economy, singles released by artists and record labels could be sold individually on a large scale with no need for physical media. Spotify, Apple Music, and online radio such as Sirius and Pandora now dominate the non-physical music marketplace. While fans widely appreciate the free or low price streaming services, artists and labels both big and small are experiencing an economic slump. Many artists are beginning to rally against free music streaming, and some are going so far as to create their own, more ethical method of music streaming. Free online streaming is largely an answer to the growing problem of music piracy. Adapting to the changing culture of music consumption was a critical move for the music industry. Artists who feel cheated by online streaming services are still operating within capitalist values – perhaps if the musical economy were to shift into a more community oriented, sharing-style economy, there would be more contentedness among artists.
In the age of digital music, it would seem that physical media would no longer be a point of attention for record labels. However, Record Store Day (RSD) is a national biannual event that arose in response to failing record stores and decreasing physical media sales in the mid-2000s, when many record stores began to shut down. The event garnered huge success, grabbing nationwide attention and gathering larger numbers of RSD customers each year. In 2014, vinyl record sales reached an all time for the past two decades. However, the twice-yearly event began to receive more criticism as it gained success, its decriers are owners and patrons of small, independent record stores. The popularity of RSD has created a difficult situation for many independent record store owners who may not be able to afford the venture capital it takes to purchase special RSD releases, especially when they are not sure if they will sell out their stock or be fated to keep boxes of it in their storerooms, accumulating dust as they depreciate in value.
In 2008, seven independent Swedish music labels formed an alliance intended to transform the musical economy. The premise of their restructuring model was to encourage the sharing of free music, rather than fighting the losing battle against it. The valuation of musical creations as sellable units detracts from what many consider to be the purpose of the creation of art.. The intersection between art and money often results in frustration, disillusionment, and feelings of betrayal and exploitation. Artists become trapped in contractual obligations to record labels that capitalize on their creativity, selling their music for profit while the artists are left without a feeling of satisfaction.
The practice of selling creative "goods" intrinsically diminishes the meaning of the work – by putting a price on a song, album, or discography, the artists' work becomes subjectively capitalized and commoditized. The meaning behind the work becomes abstracted by the price that is placed upon it. By refraining from the pricing of musically creative goods, the focus is shifted away from the monetary success of the artist unto the creative and community impact of the artist. It focuses on the influence that they may have on the overall well-being of the community and its members. Within the Swedish Model, a key component is the ease of which fans can find and listen to bands, which generates positive feedback for the artists, labels, and producers. When the songs are given away for free – as gifts – their value becomes entirely determined by the listeners, how much that song gets shared thenceforth reflects the intrinsic value of the song.
The shift to a gift economy may be exactly what the music industry needs to create a more just and sustainable place for artists and producers – as well as listeners. Of course, for this style of economy to work in a practical manner, the overall economy would have to shift towards something more akin to a community-style economy – but perhaps within the artisanal sector a balance could be struck. Valuing artists based on their talent and ambition will make their work more rewarding to both them and their fans. The goal of gaining prestige and adoration and foregoing the quest for large monetary success is reflective of the romanticized struggle of the artist. The switch to a gift economy will certainly require a change in values of success and gratification.
The shift that is required on an overall industry level will have to begin at a grassroots level and take a bottom-up approach – many independent artists already partake in a musical gift economy, emphasizing the importance of community support and inter-band alliances. Independent artists have been crafting their own niche place within the music industry since the ability to record at home became a possibility. At this time, the production of music was almost entirely reliant upon the industry producers who were in control of the recording equipment and distribution of the physical goods of vinyl records.
However, advances in technology allowed for a new space in the musical economy to be opened. Further technological advances have made it increasingly easy for independent artists to record on their own and now easily distribute their music to anyone with an Internet connection. The MP3 allows for music to be shared and reproduced endlessly. The MP3 is allowing artists to take back production of their music (or rather, take control of it for the first time). Additionally, because the MP3 is a nonphysical good, it requires no capital investment to reproduce and therefore more easily contributes to a gift economy. The construction of this gift economy through digital music allows for widespread sharing of creative goods that inevitably undermine (if only slightly) the music industry at-large. Independent artists have been and will continue to be an integral part of the crafting of a more just and sustainable space for musicians.
The notion that the music industry is a corrupt, monolithic empire holds true in many circles of musical consumers. When independent artists sign on with a major record label and become part of the music industry, fans often label them as "sell-outs" and renounce their adoration for the band, reminiscing about the idyllic days prior to their participation in the big-label music scene. This anger that results from artists signing onto major labels exemplifies the devaluation of meaning when money is introduced to art. LCD Soundsystem, fronted by James Murphy, is often heralded as an example of how to reject the corruption of corporatized music. The group disbanded in 2011, citing that they could no longer ethically sustain playing such large shows with expensive tickets. (Though they have since reunited.)
The growth oriented goal of the capitalist music industry alienates fans and artists alike—the establishment of a gift economy would mitigate the issue of alienation by shifting the focus of music production to be more about the intrinsic value of art.
Perhaps the language in this argument thus far has been too generalizing – the "music industry" at large as I have referred to it is in reality a collection of articulated groups with a common interest. Additionally, the music industry and the recording industry have been discussed as one unit whereas they are actually separate entities operating in a similar space – this generalization is made by most on the large scale. The generalization of the music industry as a homogenized unit is arguably unfair. Recognizing the diversity within the music industry is an important step to realizing its potential in converting to a gift economy – when the veneer of the music industry as a monolith is stripped away, one can view the independent players that operate within its intricacies. The Swedish Model should be analyzed and critiqued, but also considered as a model for the American music industry. Viewing the actors within the industry as separate entities allows for dialogue about an economic shift to be opened more easily. Operating within the music industry is comparable to operating within the overall economy; there are independent persons, big and small, that culminate into something larger than themselves. The systems that are in place are both created and perpetuated by its participants.
Changing the overarching dialogue about how the music industry operates and interacts with the community and with itself will require a shift in the economic conventions used to trade music. Recognizing the music industry as a cultural institution, not simply as a monolithic empire, is an imperative acknowledgement required prior to shifting to a gift economy within the musical exchange. Articulating the music industry as a collection of individuals acting within a set of conventions reframes it in a way that gives musicians more agency to determine how they want their music shared and distributed.
The digital age has brought with it an ability to create a new space for musicians that is more just and sustainable than ever before – crafting this space will require deliberate effort on the part of both the creators and consumers of music. This new sustainable space for artists and consumers will reinforce community bonds and strengthen the interconnectivity potential for musicians. Building a new musical economy that focuses on the music and artistic potential of musicians' work, rather than the monetary prospects, will create a more genuine piece of work. When a song is valued for its individuality and artistic agency, it transcends conventional worth – there is no ceiling for how valuable it is to individuals or communities. This new method of valuation, along with the creation of a gift economy for musical exchange will create an intentional, deliberate community that appreciates music for its intrinsic, artistic value.
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You are able to do It! stocks the muse of Stanley A. Dashew--the guy who expected the bank card economic climate. after which invented the instruments that made it ensue! classes for all times and company jump from the tale of his personal demanding situations , beginning with discovering a task in the course of the good melancholy. His process continues to be as pertinent this present day as while he utilized it over the process 90 years.
Ultimately, Pieter-Dirk Uys, South Africa's most famed political satirist, entertainer and AIDS activist, has penned a memoir. he's taking us again to his upbringing in apartheid South Africa, his early days within the theatre, and the beginning of his adjust ego, Evita Bezuidenhout, the ambassador to the fictional fatherland of Bapetikosweti.
The concord of technology and Soul indicates that the twenty first century place of work is looking extra from staff than ever prior to. we're present process a revolution in how we glance at paintings and the way it will get performed. The sufferer is the human spirit. writer paintings Bobrowitz publicizes how religious writings and nice discoveries in technological know-how are relative to private management and office productiveness.
Lauchlin Currie's contribution to financial conception and rules through the New Deal and within the postwar interval while he grew to become the most very important monetary advisors to numerous presidents of Colombia is the topic of this biography. Currie used to be an immense financial consultant to president Franklin D. Roosevelt, and as his administrative assistant from 1939 till the president's loss of life in 1945 contributed to shaping Roosevelt's pondering on fiscal matters.


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Iwona Blicharz (ur. 25 kwietnia 1959 w Warszawie) – polska charakteryzatorka filmowa.

Życiorys
Nagrodzona w 2010 roku Złotymi Lwami na Festiwalu Polskich Filmów Fabularnych w Gdyni. Członkini Stowarzyszenia Filmowców Polskich oraz Polskiej Akademii Filmowej. Jest absolwentką Policealnego Studium Charakteryzacji w Warszawie. Praktycznie zawodu uczyła się na planie Odjazdu (1991) Magdaleny i Piotra Łazarkiewiczów, Końca gry (1991) Feliksa Falka. Jako samodzielna charakteryzatorka zadebiutowała na planie Samowolki (1993) Falka. Ma na swym koncie blisko czterdzieści filmów fabularnych.

Filmografia

Charakteryzacja

 1993: Samowolka
 1993: Dwa księżyce
 1994: Polska śmierć
 1995: Tato
 1995: Prowokator
 1995: Iwanow
 1996: Złote runo
 1996: Wirus
 1996: Panna Nikt
 1996: Na Warszawskiej Starówce
 1996: Kociokwik
 1997: Polowanie
 1997: Kiler
 1997: Historie miłosne
 1997: Złotopolscy
 1998: Razem
 1998: Matki, żony i kochanki
 1999: Tydzień z życia mężczyzny
 1999: Oczarowanie Fryderyka
 1999: Kiler-ów 2-óch
 2000: Zakochani
 2000: Święta polskie
 2000: Duże zwierzę
 2000–2001: Przeprowadzki
 2000-obecnie: M jak Miłość
 2002: Święta polskie
 2002: Libre Circulation
 2002–2010: Samo życie
 2003: Pogoda na jutro
 2004–2008: Kryminalni
 2007: Regina
 2007: Korowód
 2009: Prymas w Komańczy
 2010: Joanna
 2010: Duch w dom
 2012: Felix, Net i Nika oraz Teoretycznie Możliwa Katastrofa

Współpraca charakteryzatorska
 1991: L'Entorse
 1991: Le Septieme Enfer
 1991: Cheat
 1991–1993: Kuchnia polska
 1992: Wielka wsypa
 1992: Pierścionek z orłem w koronie
 1992: Le Violeur Impuni
 1992: Enak
 1999: Gorący oddech pustyni
 2010: Śluby panieńskie
 2011: Róża
 2013: Drogówka
 2014: Kamienie na szaniec
 2016: Wołyń

Asystent charakteryzatora
 1991: Odjazd
 1991: Koniec gry
 1993: Pora na czarownice
 1995: Odjazd

Przypisy

Polscy filmowcy
Polscy charakteryzatorzy
Urodzeni w 1959
Ludzie urodzeni w Warszawie

redpajama_set_name: RedPajamaWikipedia


We are pleased to announce the speakers we will be hosting at this year's Terroir Creative Writing Festival. You will find we've put together a stellar mix of poets, prose and fiction writers, bookbinders and makers to provide you with a full literary experience on April 18, 2015 at Chemeketa's Yamhill Campus.
Please follow us and check-back soon for registration information.
Barbara Drake lives with her husband on a small farm and vineyard in Yamhill County. Her most recent book of poems is Driving One Hundred from Windfall Press (2009), and her new collection of essays, Morning Light, is forthcoming from OSU Press in the fall of 2014.
Rene Denfield has written for many publications including The New York Times Magazine, The Oregonian, and the Philadelphia Inquirer. She has published three non-fiction books .In addition to her writing career, Rene Denfield is a death penalty investigator who works with men and women facing execution.
Adam Gallardo has lived in Oregon for more than 25 years, the last ten of those in Salem. He began writing professionally for comic books with Star Wars: Infinities – Return of the Jedi. He's also created a pair of creator-owned series, 100 Girls and Gear School. His first YA horror novel, Zomburbia, was published in 2014. The sequel, Zombified, was published earlier this year.
Emily Grosvenor is a magazine writer, columnist and essayist who writes for Sunset, Salon.com, The Atlantic and others. She is the books editor for Eugene Magazine. She lives in McMinnville, where she is writing a humorous memoir about connecting to place through scent.
Harold Johnson was born during the heart of The Great Depression into the small African-American community of Yakima, Washington. He came to Portland for college, and throughout a long career teaching English and art in Portland, he has been active in music, sports, visual arts, and writing. Citizenship, published by Many Voices Press, is his first full-length volume of poetry.
Sean Jones has over 25 years of experience in the book industry, reviewing books for publication, consulting with authors, and opening bookstores and training management teams all over the United States, Europe, and the Pacific Rim. Sean is an Oregon native and has a BS in both Sociology and History.
Stephanie Lenox is the author of Congress of Strange People (Airlie Press) and The Heart That Lies Outside the Body (Slapering Hol Press). Her poems and prose are forthcoming in Passages North, Crab Creek Review, and Juked. She teaches creative writing at Willamette University in Salem, Oregon.
Lisa Ohlen Harris is a writing coach and freelance editor living in Newberg. She is the author of the Middle East memoir, Through the Veil, and of The Fifth Season: A Daughter-in-Law's Memoir of Caregiving.
Paulann Petersen was Oregon's sixth Poet Laureate, and she has six full-length books of poetry, most recently Understory from Lost Horse Press. She was a Stegner Fellow at Stanford University, and received the 2006 Holbrook Award from Oregon Literary Arts. She serves on the board of Friends of William Stafford, organizing the January Stafford Birthday Events.
Peter Sears is a graduate of Yale and the Iowa Writers Workshop. He has taught at Reed College and Pacific University and has served as Dean of Students at Bard College, community services coordinator for the Oregon Arts Commission, and director of the Oregon Literary Coalition. He splits his time between Corvallis and Portland.
Stephanie Shaw completed her Bachelor of Science degree in Education at Oregon State University and her Master of Arts in Counseling Psychology at Lewis and Clark College. Her career has included school counseling, school administration, and teaching children with severe emotional disabilities.
Samuel Snoek-Brown lives in Portland, OR, where he teaches writing and serves as production editor for Jersey Devil Press. His short fiction has appeared in dozens of journals, and he is the author of the flash fiction chapbook Box Cutters and of the novel Hagridden, for which he received a 2013 Oregon Literary Fellowship.
Juniper White is a mom, writer, teaching artist, and letterpress printer who cultivates handwork throughout the Northwest, and grooves on making things. A graduate of The Evergreen State College and the Rainier Writing Workshop MFA Creative Writing at Pacific Lutheran University, she founded Dwell Press in 2010.
John Sibley Williams has an MFA in Creative Writing and MA in Book Publishing and works as Marketing Director of Inkwater Press and as a freelance literary agent. The author or editor of nine poetry collections, John enjoys navigating authors through the wealth of contemporary media to help them reach their audience.
Marilyn Worrix took a bookbinding class many years ago, which turned her general love of books into an obsession for making them. She finds that creating books is a continuing evolution of ideas, form, content, and materials. Marylin Worrix is the Founder and Director of the Book Arts Center of McMinnville.


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Dr. Kayode Fayemi - Insurgency has declined since PMB's administration
Chairman of the Nigeria Governors' Forum and Ekiti State Governor, Dr Kayode Fayemi, has said insurgency declined in the country since the advent of the administration of President Muhammad Buhari in 2015.
The Former Minister of Minerals and Steel noted that Nigerians are yet to applaud the All Progressives Congress (APC) efforts at achieving its promises made in 2015 because of the existence of incessant insecurity crisis in the country.
Fayemi stated this in Lagos on Saturday at the 2021 edition of the annual conference, The Platform, organised by the Senior Pastor of the Covenant Christian Centre, Lagos, Poju Oyemade.
"Many may disagree, but I will argue that at least on insurgency – it may be a distinction without a difference – we have witnessed a decline.
"In 2015, we promised many things but with the greatest respect, I think the most attractive promise that people bought into that we made was integrity.
"You could argue that we have put in a lot of efforts in those areas, but have they earned the kudos of the citizens as they should? No, they haven't because we still have insecurity in the land.
"In relation to the problem of insurgency, which was the most prominent in 2015 when we were coming in, remember UN House bombing, the churches that were burnt, Abuja was a no-go area and the North-East. But that problem witnessed a decline in the first four years of the Buhari administration."
Fayemi stated civil servants, not politicians, debar Nigeria's progress.
Also speaking at the event, an international legal scholar and consultant, Charles Omole, said the biggest challenge stalling the country's progress is not the politicians but the civil servants.
Omole, who spoke on the theme of the programme 'Is Devolution of Powers the Solution to Nigeria's Problem?', noted that civil servants play a huge role in bringing about change in the country and wield power even more than a federal minister.
"Many people in Nigeria feel the biggest problem we have is the politicians. What if I tell you that is not true? Do you know what the biggest problem we in Nigeria? The biggest challenge we have to change this country is in our civil service.
"Those who know how civil service works know that they can grind any system to a halt," Omole said.
He lamented that many civil servants are against innovation and modernisation.
"Many of them oppose modernisation. They oppose innovation. They like things being done manually. I wonder why. How many of you know that constitutionally, no federal minister in this country can sign a contract to give you a job? How many of you understand that? It is the Permanent Secretary that does that.
"So how can a minister steal without the civil service? In fact, many times, it is the civil servants that teach the novice minster how to do it," he said.
News Insurgency


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Q: Transformation of a random variable, example. This is an example from Wasserman's "All of Statistics" that I don't understand:
If we have $X \sim \operatorname{Uniform}(-1, 3)$ and we want to find the pdf of $Y = X^2$ if the density of $X$ is:
\begin{equation}
  f(x)=\begin{cases}
    1/4, & \text{if $-1<x<3$}.\\
    0, & \text{otherwise}.
  \end{cases}
\end{equation}
I would consider the set $A_y = \{ x: x \leq \sqrt{y}\}$ and perform the integral $\int_{A_y} f_X(x) \, dx$ that is equal to the cdf $F_Y(y)$ and then derivating we get $f_Y(y) = F'_Y(y)$. This is what the book teaches.
But he considers two separated cases; one with $0 < y < 1$ and the other with $1 < y < 9$. Why that separation for $y = 1$? I can't see any reason for that, any inflection point or similar.

A: It's necessary to consider the cases $0\leq y\leq 1$ and $1<y\leq 9$ separately because $X\geq -1$:
If $0\leq y\leq 1$ then $0\leq \sqrt{y}\leq 1$ as well, so $X^2\leq y$ implies that $-\sqrt{y}\leq X\leq y$.
On the other hand, if $1<y\leq 9$ then $\sqrt{y}>1$, so since $X\geq -1$, $X^2\leq y$ implies that $-1\leq X\leq \sqrt{y}$.