text:
Winter is anew
Sunshine blotted out
Ready for a cold nap
The New Horizon
Winter is anew
Sunshine blotted out
Ready for a cold nap
The New Horizon
What's one piece of great advice you've read recently? Or what's the best bit of wisdom you've ever received?
"Always follow your dreams" – a message I saw on a billboard the other day while going down the notorious 1-94 in Michigan. Dreams are there to act upon. If you don't wake up and start doing something about them, they will never come true. The dreamer is a hopeless soul; the doer is the one with most success in life. Dreamers believe but never achieve; Doers believe and go right ahead getting done what needs to be done. They don't worry about the results – they learn to look at the bigger picture and see what they can do better.
If you ask some of the greatest chefs in the world what they did to get to their level of mastery in the culinary world, they would say they had to start right at the bottom and work their way to the top. They would say they didn't have a shortage of days where they just failed miserable and were critiqued badly, and where they kept hearing about the famous chefs above them opening 5-star restaurants and wondering if they were silly for thinking they could possibly do the same thing. But they kept fighting and kept their head above water, continuing to learn and grow and eventually get to their current spot in life
I want to be a doer but the dreamer side of me is still quite fascinated by the mythical thing known as success. A couple of times I've tried to act out these dreams of mine only to realize the tough reality: achieving them takes so much effort and a lot of luck. Much of achieving your dreams requires actually having other people around you to help, to collaborate and pitch in their own creative ideas. But when your people skills are not very good, going it alone always feels like the best choice, even if it would be extremely hard to achieve what you want to do.
My piece of advice, based on my previous experiences, is to not let the negativity get to you. Shut out the voices that say you're not good enough or not talented enough for your dream profession, whatever it is. Most of all, block out the haters that try to destroy your confidence and keep you from continuing on your path. Or leverage all of the negative talk and use it to make yourself the best ever. The grass is always greener on the other side – look to the alternatives to see what could be better.
Aerosmith tells us to "Dream on…dream until your dreams come true" but the song should really be "Wake up…wake up and make your make your dreams come true". Your dreams are hopeless without a plan set in motion. Like building a skyscraper, it always starts with a solid foundation.
If you're like most of us, you need to earn money by working for a living. Describe your ultimate job. If you're in your dream job, tell us all about it — what is it that you love? What fulfills you? If you're not in your dream job, describe for us what your ultimate job would be.
My ultimate job would be making videos on YouTube and earning money off of them, enough to make a good living. I have been making videos for sometime now (since 2009 when I was in my senior year) but have never made any significant amount of cash, about a dollar most likely, and have never gotten into any sort of rhythm, It has always been a passion of mine but I never really harnessed it. The thrill of putting a video together in my editing software (currently Corel VideoStudio X8) is intoxicating. I get into a creative zone and end up blocking everything and everyone else out. There are always new ideas for me to explore, even if previous ones did nothing with my viewers. My skills keep on improving each time. Before I started this blog, I was really into making videos but now that this is a priority, I can't spend too much time on them.
YouTube just turned 11 years old yesterday and the site just keep on growing exponentially. There's no telling where it will be in the next four years, when the 15th anniversary is held, but I boldly predict that it will be on the level of television eventually. I don't always watch videos on YouTube but when I do…I end up spending an entire night going on an epic video journey (he is the Most Interesting Man In the World).
I'm not saying this will likely be all I do for a living because I'd definitely need another job to make enough money. I currently give plasma two times a week now, a tedious and annoying process, and being able to find something to replace it would be great.
Writing is definitely a passion of mine as well and I would love to get a full time job on some website writing articles, whatever topic they may be about. Writing (and reading) has a way of making me feel rather comfortable and content. It is a way to unwind from an eventful day or when I am stressed out. If I could somehow earn money from blogging (an even more difficult task than YouTube I suspect), I would really harness its full potential.
That quote I provided by Steve Jobs sums up my passion fairly well. I don't want to spend my whole life trying to figure out what I want to be doing, wasting my time on something that is full of fruitless efforts. If Option A doesn't pan out, then it be best to move to Option B, and perhaps C.
"Yes: I am a dreamer. For a dreamer is one who can only find his way by moonlight, and his punishment is that he sees the dawn before the rest of the world."
― Oscar Wilde, The Critic as Artist
Shucks, I can't remember what it was I thought about before waking up this on this plain Jane morning. I know I was dreaming about something, but I can't remember what exactly the dream was about; it was very vivid and deep, I must say, and I didn't want to wake up just yet because of the story getting really dark and gritty but it started to fade as my morning mind took over, along with my uncle reminding me it was a plasma day. I vaguely remember the dream having something to do with the Pokerap that has been stuck in my head all day, after I featured it in my Throwback Thursday post yesterday, or all the entertaining YouTube videos I ended up watching after the original video was over, all within my blog. It started with Vsauce, a really entertaining channel of science, facts, and humor, and then trailed off into "the guy of a kajillion voices" and some 107 random facts about popular cartoons.
Of course, I thought of my blog, like on most days, contemplating what the Daily Prompt assignment is going to be about, wondering if I'll finally publish a post around the same time that the "core" of super bloggers do (not today either). I'm talking about the bloggers I frequently see publishing posts in the morning to early afternoon; one of those I'm following is nearly always first because of his typical short witty responses. I'm always late to the party, choosing my own time. It's this resentment, as well as my tiredness, to following along with this daily "sheep fest" that has me riding off the rails and wanting to do my own thing, for better or worse.
Explaining the title, one of the more humorous and strange things to happen today was my dad wearing a black masquerade "Batman" mask while driving down the highway on the way to the second of our weekly plasma donations, to a couple of concerned stares. He wore the mask into the plasma center as well, trying to seek attention but which wasn't happening, to his disappointment and sulking later on. The screening booth attendant told him to take it off and he complained. Seriously, what were you thinking? He was the only one wearing a mask, looking rather silly. It's not even Halloween yet – don't embarrass yourself.
Speaking of Halloween and masks, my costume this year will be a hasty redo of a previous year's edition. I'll likely don my Darth Vader mask again along with a black t-shirt, pants, and shoes – minus the plastic lightsaber, that would be too much – and head off to the "haunted" Halloween party just around the corner in the community clubhouse. I'm hoping I'm not the only 20-something there amidst a bunch of children, which I very much doubt, but will still enjoy myself with donuts, cider, and the many cliches of Halloween strung and laid all around.
In response to The Daily Post's writing prompt: "Comedy of Errors (and bonus assignment!)."
Do you keep a notebook next to your bed? Good. Today, jot down the first thought you have upon waking, whether or not it's coherent.
I used to keep a notebook next to my bed, when I was jotting down my dreams, but I got tired of that and lost interest. So, sorry to disappoint you, WordPress monkeys. Maybe next time you'll have luck making a "good" assumption about me.
Recently, I've been thinking about writing a post about things I would like to accomplish in life before it expires someday. It has come to my attention that there is so much I have never done yet, so much of this world to explore for me. I have created a rough, pending bucket list of the different sights, sounds, and activities I wish to witness. Some are within my grasp, while some might require some blood, sweat, and tears (and money) to complete. Hopefully I'm not about to kick the actual bucket like Morgan Freeman and Jack Nicholson when these come into play.
My dream list, in no particular order:
Most of these were thought off the top of my head, while some were inspired by ones featured on bucketlist.org. I may be crazy to think all, if any, of these will be possible, but it's better to dream big than to not dream at all. I believe the thing to creating a bucket list is to fantasize enough but keep realism in check, going with ideas in your head that you know are the most sensible. Probably the most important one on here is winning the lottery, followed closely by Times Square, visiting all 50 states, and skydiving.
Feel free to comment if you have something worth discussing on your personal bucket list.
I don't have a lot of nightmares. Lots of unusual, incomprehensible dreams but not nightmares where I could actually feel a sense of dread. There's just not enough nightmare fuel for anything creepy to popup or it might be that I'm quite immune to these things. Not even Five Nights At Freddy's could turn my slumber hours into an REM horror.
I think the last real nightmare I had consisted of my dad lying on a raft sinking into a dark swamp and being quickly covered in a bunch of rats (weird, I know). The worst part is when I simply walked ahead onto solid land just before a spooky forest of trees, looked back at my dad being swallowed by the swamp, and muttered, "He wasn't worth it anyway." He was lying face up on the makeshift raft in a way akin to one lying in their deathbed. I could sense a sort of sadness and despair, could slightly hear an eerie orchestra playing as a deep regrettable sorrow washed over me. I would miss him, but at the same time was glad to see him go.
I think this nightmare may stem from the fact that I haven't always seen eye to eye with my father. He's always tried to control my life, program me into doing everything his way but I've always had a free-spirited, independent mind to not be swayed the way his father did to him. I guess because there was a long stretch in my life where I only saw him maybe two times a week that I sort of drifted apart, became my own person instead of a chip off the old block, like they always say. I see him a lot more today than the times just after the divorce and he tends to want to help me with life, but there's still this gap between us, this valley of differences; he's living as he did maybe twenty years ago with the same haircut, clothes, and dry sense of humor while I've been a little more varied in my looks and tastes in just about everything.
I remember a version of this prompt being used a few months ago, my response to it being an assortment of dreams I had in the past and blended into a twisting story of fear and the supernatural.
In response to The Daily Post's writing prompt: "Nightmares."
Describe the last nightmare you remember having. What do you think it meant?
I tend to dream
About many things in general,
From past schoolmates to teachers,
To the first time I played Nintendo
They are usually short lapses and happen in a flash,
Like the one time I dreamed of having Jimmy Kimmel teach class
Sometimes it's nightmares and other crazy stuff,
As when my father was on a raft and rats were eating him up
I've been sent to scary castles and tested the waters,
Even got a job at Tuxler's and saw my five future daughters
There was the gothic girl in the locker,
And a bloody sliced throat,
Me riding my bike,
And some reptile on a boat
I sat down with Kimye at a table one day,
And a guy was wearing a watch and someone said, "Are you gay?"
Ran through the store, hip-hopped through cement,
Had a gun pointed at me and used a toy to defend
I don't know why I dream
These deliriously daffy dreams,
But it seems as if they come about
In response to not just one thing
And as the TV went missing,
And creepy Karl Childers came abrupt (mmm…taters),
I realized dreams are
Quite messed up
Radek is solving programming issues which he encountered at work. Most of them will be in C#, C++, JavaScript and HTML.
Random musings on life, society, and politics.
"You never know what you're going to find in the dreamscape"
Mental wanderings amongst stardust
The World's leading success industry
All posts copyright 2013–2020 by Mark Aldrich.
By Tony Single
A woman redefining the undefinable
YouTube and more
the literary asylum
seeking for happiness in the psalms of life......
Everything you say, will come back as a revolution one day.
Poems, Poetry Plus Passion


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subset: commoncrawl


text:
Iran's goalball team defeated Egypt's team 12-2 in a match played in the southern Swedish city of Malmö on Sunday.
The Iranian men's national goalball team is slated to take on Brazil in its next match on Monday.
The 2018 IBSA Goalball World Championships started on June 3, and will finish on June 9, 2018.
The Iranian team is pitted against , Brazil, Canada, the Czech Republic, Egypt, Germany, Japan and the United States in Pool B of the tournament.
Algeria, Argentina, Australia, Belgium, China, Lithuania, Sweden and Turkey are drawn in Pool A.
Goalball is a team sport designed specifically for male and female athletes with visual impairment. Participants compete in teams of three, and try to throw a ball that has bells embedded in it into the opponents' goal.
Teams alternate throwing or rolling the ball from one end of the playing area to the other, and players remain in the area of their own goal in both defense and attack. Players must use the sound of the bell to judge the position and movement of the ball. Games consist of two 12-minute halves.


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An internet report suggested that if you want happiness, buy a scarf and gloves, and head to Norway—to experience real happiness.
An internet report suggested that if you want happiness, buy a scarf and gloves, and head to Norway—to experience real happiness. Norway is well-known for its good public services and political stability. Denmark is another country that is famous for happiness nurtured in its culture. Danes have a stable government, little public corruption, and access to high-quality education and healthcare. The country does have the highest taxes in the world, but the citizens happily pay the taxes because they believe higher taxes can create a better society.
What makes the people of a country happy? Is it economy? Is it environment? Is it education? Is it government policies? Well, all of these do contribute to people's happiness. But it is not necessary to have a higher economic pace and growth always. People are happier when they don't experience inequality in distribution of wealth; people don't mind paying taxes when there is fairness in tax structure. People are happy when government practises transparency in the implementing policies. People want safety, people want welfare, people want good infrastructure, hygiene, and people want good-quality education.
Corruption undermines government revenue and, therefore, limits the capacity of the government to invest in productive areas. Corruption distorts the decision-making in public investment projects. It's been observed that the higher the level of corruption in a country, the larger the share of its economic activity that will go subversive, beyond the reach of the tax authorities. Corruption discourages entrepreneurship and innovation; it only encourages inefficiency. It dislocates the human resources. It creates uncertainty among the citizens. And it diminishes legitimacy in all walks of life and increases crimes.
In all countries there are rich and poor, but when the levels of inequality are low, and the welfare systems are strong, the citizens are happy. People don't mind paying higher taxes. Look at Denmark, it ranks 158th in the world, and Switzerland is even worse, at 174th in the world and economic ranking standards.
The World Happiness Index Report is an annual publication of the United Nations Sustainable Development Solutions Network, which contains rankings of national happiness and analysis of the data from various perspectives. The first World Happiness Report was released in April 2012. In a high-level meeting of the UN, well-being and happiness were defined as new economic paradigms that drew international attention.
The report primarily uses data from the Gallup World Poll. Gallup is a credible polling organisation. It is respected highly in the media. Nevertheless, all researches including polling have some weaknesses that depend on the various methodologies and details of the poll and its questionnaires. Each research has few statistical limitations. Gallup ensures that each annual report is available to the public to download on the World Happiness Report website.
Happiness index is measured using parameters like housing, income, work, community, civic engagement, education, environment, health, life satisfaction, safety and life-work balance etc. Each report is organised by chapters that delve deeper into issues relating to happiness. The chapters also include mental illness, the objective benefits of happiness, the importance of ethics, policy implications that lead to subjective well-being. The report is based on how strong a country's social foundation and social trust is.
Bhutan is one of the Buddhist kingdoms in the world and, so far, has preserved much of its culture since the 17th century. Even with globalisation, Bhutan follows its Buddhist culture. It allows a certain number of foreigners into the country each year, and the $200 per a day that must be paid by every traveller is a deterrent for many. Internet, television and western dresses were banned from the country up until 10 years ago. But over the past 10 years, globalisation has proved to be a challenge to this tiny nation. Things have begun to change, but they are trying to balance things in their own way.
Bhutan is the only country in the world that has measures GNH, or Gross National Happiness. The process of measuring GNH began when Bhutan opened up to globalisation. It measures people's quality of life, and makes sure that both material and spiritual development happen together in its citizens' lives. Bhutan has balanced it rightly, so far.
Happiness is very important to both individuals and as a country. A happy individual is productive and creative. As human beings, although we possess cognitive abilities and are highly "thought-oriented," the quality of our lives is determined by our emotions. A happy human is emotionally strong because happiness protects heart, it strengthens immune system, it helps in combating stress, it has been found that happy people have fewer aches and pains.
All Nordic countries are among the happiest countries on the planet, as are Switzerland, the Netherlands, Canada, Australia and New Zealand. Finland is the winner in the 2018 report. Its 5.5 million residents enjoy more forest per square mile than any European country. They have maintained extremely high environmental standards. It's a peaceful place. Its immigrants are also happy. The World Happiness Report made a particular mention of the consistency in happiness between them and local born residents.
In the 2018 World Happiness Index Report, India ranks at 133rd place, with a drop of 11 places since the previous report. Pakistan is ranked 75th, while Nepal is ranked at 101st, Sri Lanka at 116th position and Bangladesh at 115th; Bhutan is at the 97th place. If you are wondering which is the world's least happy country? It is Burundi, followed by Central African Republic, South Sudan and Tanzania, due to condemnation of life in Africa.
By- Vidya Hattangadi, Management thinker and blogger
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Last week we covered the ten wedding dresses that never go out of style, so it's only fair we pay some much-needed attention to your big day accessories. Namely, the shoes! Though they tend to get far less attention, your wedding day shoes carry an equally important role. After all, what's the point of carefully choosing a timeless dress if your shoes are going to instantly date your look, anyway?
Your wedding shoes are guaranteed to be in at least a few wedding photos, so the pressure is on (sorry!). Even if you're rocking a big 'ol ballgown, you'll still kick up your heels for the garter toss. So, unless you want look back and cringe in a few years, don't choose an overly trendy style that's bound to be out after a season or two. Instead, click through the slideshow to check out ten shoes that will never go out of style, and shop accordingly.
For more wedding planning, don't miss how to throw the best bachelorette party ever, 10 photos to ask your wedding photographer to take and how to be the happiest bride ever.
[Photo: Nordstrom]


text: Having worked with large global IT organizations in the US, UK, Europe and India for almost two decades, I was keen to create, build and nurture something from scratch. Spraoi provided a perfect "startup" opportunity for me to apply all that I had learned.Together, we at Spraoi are building a global team of passionate engineers, innovators and insurance experts. We are delivering next generation, customer-centric insurance solutions. I take great pride in fostering a culture that is open-minded, collaborative and innovative. Spraoi is an awesome environment in which to learn and grow along with our young, energetic team.


text:
Planning for our next tour is always fun and between family time and living, this is what has been filling my thoughts of late and its led me to reflect on travel and family. After a number of years there still is simply so much of our beautiful country to see. Even revisiting places we love is a joy, as we get to see what time has made of them and then there is Family… yours.
Category Archives: Family
Around the Campfire
E-books in the Around the Campfire Series are available in ebook and print
A travel series
Around the Campfire.
The Sundowner's of Today's World
In years gone past the Australian Sundowner was a wanderer who arrived at dusk seeking work, usually the promise of work and in turn was given a meal. However when the sun rose the next day the promise of work never eventuated as the bloke had usually moved on during the early dawn. Or… another meaning was for the 5pm happy hour drinks.
Grey Nomads and The Digital Divide
When we set out on The Lap eighteen months ago we thought we were doing very well. I had actually convinced The Man that a smart phone was the way to go… so now we're duly armed with one each. This is progress. The Man hates mobile phones and while they are invaluable when trying to find him in a shopping centre, this was the only use he could think of for those pesky mobile phones.
Stepping Off the Edge – Aus' Has Changed
As we take a moment to plan, reflect and enjoy being on the Homesite before we are off on our next travel adventure there are things that I have now noticed about how the world, my world, has moved on without me.
Australia Day – A Peoples Celebration!
Free E-book, available for download from Amazon.com for a short time to celebrate Australia Day and its true meaning.
"Out on the Never Never" is a true Australian adventure in traveling our land. One celebrating the love of our Land as two Grannies, two pups in a 'Bitch Box' set out to cross the continent in their little caravan… join them on their journey to discover modern-day Australia.
Celebrating our love of the Land and our Freedom. This is the original meaning of the peoples celebration known as Australia Day, the 26th January.
Down through the history of Australia many groups, factions and Governors have tried to hijack what is and always was the "peoples" celebration, this to their own cause but it is truly time we reclaimed what rightfully belongs to the people.
The Season's Celebration … What is this Really?
Christmas is fast approaching on the horizon, we have skipped through Thanksgiving… irrelevant in Aus and the New Year is on the fast track including the Islamic New Year of Hijri (celebrated only since 622 AD or 615 depending on how you view it) and the Chinese New year or Spring Festival (celebrated since forever) as well as many others drawn from different cultures. So what is this all about and just what is it we all celebrate at this time of year?
In todays global society you are left wondering just what it is we all celebrate at different times but all in the same season and spirit. We should recognize our commonality and respect our differences but first we should also understand these things.


text:
Starbase Leonov was a Federation Starfleet facility in the 24th century.
Starbase Leonov was destroyed by the Borg during their 2381 invasion of the Federation. Following its destruction, a young Ferengi DaiMon attempted to salvage the wreckage to sell back to the Federation. He was stopped, and the material recovered by the USS Enterprise. (TNG novel: Losing the Peace)


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Individuals can also take advantage of the wealth of knowledge that VFX has to offer when exchanging foreign currency. Therefore, Customers assisted by VFX's dedicated team members to ensure they are getting the best deal possible in relation to their foreign exchange.
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Local Counsel with Kimberly A. (Sugawa-Fujinaga) Stuart
The Portland attorney tells us what's good in the neighborhood
Published in 2016 Oregon Super Lawyers Magazine — August 2016 on July 20, 2016
Updated on October 3, 2019
Best place to take a client - Higgins on SW Broadway. Win or lose, you'll leave satisfied.
Favorite watering hole - Laurelwood Brew Pub in Sellwood. Fantastic world-renowned craft beers. They also have draft root beer and a play area for kids.
Best restaurant - Nel Centro. In the summertime, they have outdoor seating with fire pits, and a great happy hour menu.
Weekend getaway - The Ocean Lodge at Cannon Beach. A pet-friendly beachfront hotel where the sand literally is at your doorstep.
Favorite historical resident - Judge Mercedes Deiz. In 1960, she became the first black woman to be admitted to the Oregon Bar. Nine years later, she was appointed a state district court judge, and in 1972 she was elected to the Multnomah County Circuit Court. An annual award in her honor is given by the Oregon Women Lawyers.
Favorite historical fact about Portland - Portland Shanghai Tunnels. Like many other coastal cities, we had a thriving illegal maritime practice of kidnapping able-bodied folks and shipping them off as indentured servants to other countries. Not exactly what folks think of when you mention Portland.
Favorite quote about Portland - "Where young people go to retire" – Portlandia.
Favorite city event - Naked Bike Ride. Portland's weird and we keep it that way.
Where to go after a win? - Dinner at Fogo de Chão.
Where to go after a loss? - Multnomah Whiskey Library.
Favorite courthouse perk - City Coffee is located between the Multnomah County Courthouse and the federal courthouse. In a city heavily influenced by Starbucks, it is one of the last local places to grab good joe and park a witness for trial.
Favorite thing about your office - The Standard Plaza building was one of the first high-rises in Portland. I also have a great view of the Portlandia statue, which is the second-largest copper repoussé sculpture in the United States—after the Statue of Liberty.
Best place to reflect - Lan Su Chinese Garden.
Favorite park - The Portland Rose Garden.
Most beautiful spot - The outside deck at Three Degrees in the RiverPlace Hotel. In the spring, there is nothing more beautiful than the cherry blossoms and watching the ships passing under Portland's bridges.
Best place for people-watching - South Park Blocks.
Favorite local shop - As a new mom, I love The Bull and The Bee. Major cuteness.
Favorite city law - It's not a city law, but under ORS 165.825 don't even think about selling your drugged horse in Oregon. Just don't do it.


text:
What are the foundations of libertarianism? We explore that topic this week. Join us!
We start off with a discussion about what happened in Charlottesville, Virginia. Scott's baseline position is, "Let's talk thing out and not resort to violence."
Is it appropriate to punch a Nazi in the face for spouting bad ideas?
Christopher Cantwell, the racist from the Vice documentary, is a class A piece of shit nationalist.
Is there a peaceful way to deal with racists? Yep, and folks in Germany have proven it.
We also talk about the situation with national Libertarian Party chairman, Nick Sarwark, attacking Tom Woods out of the blue in a bout of virtue signaling. We think this was a bad move by Sarwark and he should not be alienating libertarian minded individuals.
We now get into the foundations of libertarianism.
What is the non-aggression principle?
Libertarians are not pacifists, but we do not believe in initation of agression. We will defend ourselves.
Libertarianism put simply is "don't hurt people and don't take their stuff."
We talk about moral foundations and useful diversions with Alan Barksdale.
We start off talking about Coinbase reversing their first memo about not supporting Bitcoin Cash at first. Now, they will be supporting Bitcoin Cash by the end of the year. They likely did this due to all of their pissed off customers and the big hit they would have taken for their initial stance on this issue.
Alan Barksdale is the secretary of the Masidon County Libertarian Party.
Moral foundations theory is a social psychological theory intended to explain the origins of and variation in human moral reasoning on the basis of innate, modular foundations. The original theory proposed five such foundations: Care/Harm, Fairness/Cheating, Loyalty/Betrayal, Authority/Subversion, and Sanctity/Degradation; however, its authors envisioned the possibility of including additional foundations.
How to do drugs with Scott and Adam on heroin.
Follow us on Facebook and Twitter, and make sure to check out our webpage for advertising options and swag.
Scott interviews medicinal cannabis advocate Seth Green of Greener Pastures Tennessee in this bonus episode.
Seth was born with Cerebral Palsy and started having seizures at age 13. He now has multiple illnesses because of this condition. He wants to give people information on alternative medicine that is out there for people like him.
Cannabis has helped him to get off of over 20 types of medications that were giving him even more seizures and mood swings.
Did John the Baptist use cannabis in the Bible?
Without cannabis, Seth suffers terribly and will have seizures. He typically uses cannabis by ingesting edibles and oil because it works better for his body. He generally stucks to indica strains after a lot of trial and error.
Seth is hoping that the Libertarian Party and new politicians can help Tennessee become a medical cannabis state soon. His goal is to create a grow site or to own a medical cannabis facility.
Find Seth Green on YouTube, Facebook, and Twitter for more information. Or, you can go to his website.


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Welcome to the Rim Station
The Rim Station is located on the Hoback Rim in Wyoming; a little over 30 minutes from the Jackson Hole area and less than 30 minutes from the Pinedale area.
Our RV Park borders the Bridger-Teton National Forest giving you unlimited opportunities to see the different wildlife that is in abundance here in Wyoming. Deer, moose, and antelope are seen daily in the spring and summer with elk spotted in the fall and winter months. Coyotes can be seen and heard throughout the year with an occasional spotting of wolves loping through the area.
Copyright 2010 Rim Station. All rights reserved.
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One of London's lesser-known emergency services has launched a campaign to raise awareness about its life-saving help.
London Air Ambulance, which "brings the hospital directly to the patients", can reach those who need assistance in just a matter of minutes.
Did you know that the service can perform open chest surgery for patients in cardiac arrest at the roadside, such as after a stab wound? The service has an 18% survival rate for this, which is the highest in the world.
You can find out more about the service here: https://londonsairambulance.co.uk/our-service


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Top Ten Tuesday is a weekly meme hosted by The Broke and the Bookish. This week's theme is a Valentines' Day freebie. So, I'm going with my favorite couples from novels.
Howl and Sophie from Howl's Moving Castle
Sophie has the great misfortune of being the eldest of three daughters, destined to fail miserably should she ever leave home to seek her fate. But when she unwittingly attracts the ire of the Witch of the Waste, Sophie finds herself under a horrid spell that transforms her into an old lady. Her only chance at breaking it lies in the ever-moving castle in the hills: the Wizard Howl's castle. To untangle the enchantment, Sophie must handle the heartless Howl, strike a bargain with a fire demon, and meet the Witch of the Waste head-on. Along the way, she discovers that there's far more to Howl—and herself—than first meets the eye.
Yelena and Valek from Poison Study
About to be executed for murder, Yelena is offered an extraordinary reprieve. She'll eat the best meals, have rooms in the palace—and risk assassination by anyone trying to kill the Commander of Ixia.
And so Yelena chooses to become a food taster. But the chief of security, leaving nothing to chance, deliberately feeds her Butterfly's Dust—and only by appearing for her daily antidote will she delay an agonizing death from the poison.
Colin Ames-Beaumont and Savitri Murray from Demon Moon
No one would call vampire Colin Ames-Beaumont kind, but one would call him unnaturally beautiful. For two centuries his tainted blood has kept him isolated from other vampires, sustained only by his beauty and vanity — bitter comforts. since a curse erased his mirror reflection, replacing it with a terrifying glimpse of Chaos.
Savitri Murray's insatiable curiosity has gotten her into trouble before but she's always escaped unscathed. Then Colin comes along. In the midst of Heaven, he gives her a taste of ecstasy — and of Chaos, Deadly creatures from that realm herald the return of an imprisoned Nosferatu horde, and Colin and Savi's bond is their only protection — and their only passion.
Jeremy and Jamie from No Humans Involved
Jaime, who knows a thing or two about showbiz, is on a television shoot in Los Angeles when weird things start to happen. As a woman whose special talent is raising the dead, her threshold for weirdness is pretty high: she's used to not only seeing dead people but hearing them speak to her in very emphatic terms. But for the first time in her life – as invisible hands brush her skin, unintelligible fragments of words are whispered into her ears, and beings move just at the corner of her eye–she knows what humans mean when they talk about being haunted.
Jim and Dali from Magic Dreams
Alpha Pack leader Jim Shrapshire has always been the strong, silent type. But something has come over him–a magic force currently residing in one of the Pack's headquarters. Were-tigress Dali Harimau has always wished she could get Jim's attention–but now he needs her help.
Stricken with a magic-sickness, Jim needs Dali's flair for magic. And to save him, she must challenge a powerful, dark being to a battle of wits.
Mary Russell and Sherlock Holmes from Laurie R. King's Mary Russell Series
A Monstrous Regiment of Women continues Mary Russell's adventures as a worthy student of the famous detective Sherlock Holmes and as an ever more skilled sleuth in her own right. Looking for respite in London after a stupefying visit from relatives, Mary encounters a friend from Oxford. The young woman introduces Mary to her current enthusiasm, a strange and enigmatic woman named Margery Childe, who leads something called "The New Temple of God." It seems to be a charismatic sect involved in the post-World War I suffrage movement, with a feminist slant on Christianity. Mary is curious about the woman, and intrigued. Is the New Temple a front for something more sinister? When a series of murders claims members of the movement's wealthy young female volunteers and principal contributors, Mary, with Holmes in the background, begins to investigate. Things become more desperate than either of them expected as Mary's search plunges her into the worst danger she has yet faced.
Doctor Rikki Kinn and Amiri from The Last Twilight
Doctor Rikki Kinn is one of the world's best virus hunters. It's for that reason she's in the Congo, working for the CDC. But when mercenaries attempt to take her life to prevent her from investigating a new and deadly plague, her boss calls in a favor from an old friend- the only one who can help.
Africa- a land of lush veldts and roaring falls, untamed splendor and primal fury: Amiri's home, where he was raised to race as a cheetah, to wake with the sun. It is also a land of lingering nightmare, where he was kidnapped and experimented upon by the evil group named the Consortium. Now, against his better judgement, Amiri has been asked to return to his homeland by his colleagues in Dirk & Steele- men who are friends and brothers, who like himself are more than human. He must protect a woman who is the target of murderers, who has unwittingly involved herself in a conflict that threatens not only the lives of millions, but Amiri's own soul… and his heart.
Daisy and Ian from Moonglow
Finally free of her suffocating marriage, widow Daisy Ellis Craigmore is ready to embrace the pleasures of life that have long been denied her. Yet her new-found freedom is short lived. A string of unexplained murders has brought danger to Daisy's door, forcing her to turn to the most unlikely of saviors . . .
Ian Ranulf, the Marquis of Northrup, has spent lifetimes hiding his primal nature from London society. But now a vicious killer threatens to expose his secrets. Ian must step out of the shadows and protect the beautiful, fearless Daisy, who awakens in him desires he thought long dead. As their quest to unmask the villain draws them closer together, Daisy has no choice but to reveal her own startling secret, and Ian must face the undeniable truth: Losing his heart to Daisy may be the only way to save his soul.
Taylor and Jason from Just the Sexiest Man Alive
Nothing fazes Taylor Donovan. In the courtroom she never lets the opposition see her sweat. In her personal life, she never lets any man rattle her—not even her cheating ex-fiancé. So when she's assigned to coach People's "Sexiest Man Alive" for his role in his next big legal thriller, she refuses to fall for the Hollywood heartthrob's charms. Even if he is the Jason Andrews.
Jason Andrews is used to having women fall at his feet. When Taylor Donovan gives him the cold shoulder, he's thrown for a loop. She's unlike any other woman he's ever met: uninterested in the limelight, seemingly immune to his advances, and shockingly capable of saying no to him. She's the perfect challenge. And the more she rejects him, the more he begins to realize she may just be his perfect match.
Brishen and Ildiko from Radiance
Brishen Khaskem, prince of the Kai, has lived content as the nonessential spare heir to a throne secured many times over. A trade and political alliance between the human kingdom of Gaur and the Kai kingdom of Bast-Haradis requires that he marry a Gauri woman to seal the treaty. Always a dutiful son, Brishen agrees to the marriage and discovers his bride is as ugly as he expected and more beautiful than he could have imagined.
Ildiko, niece of the Gauri king, has always known her only worth to the royal family lay in a strategic marriage. Resigned to her fate, she is horrified to learn that her intended groom isn't just a foreign aristocrat but the younger prince of a people neither familiar nor human. Bound to her new husband, Ildiko will leave behind all she's known to embrace a man shrouded in darkness but with a soul forged by light. Two people brought together by the trappings of duty and politics will discover they are destined for each other, even as the powers of a hostile kingdom scheme to tear them apart.


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Antibody vs. HIV in a clash of evolutionary titans
Edited by Peter K. Vogt, The Scripps Research Institute, La Jolla, CA, and approved August 15, 2005 (received for review June 17, 2005)
HIV has evolved many strategies to avoid neutralizing antibody responses, particularly to conserved regions on the external glycoprotein spikes of the virus. Nevertheless, a small number of antibodies have been evolved by the human immune system to recognize conserved parts of the glycoproteins, and therefore, have broadly neutralizing cross-strain activities. These antibodies constitute important tools in the quest to design immunogens that can elicit broadly neutralizing antibodies in humans and hence contribute to an effective HIV vaccine. Crystallographic analyses of the antibodies, in many cases in an antigen-complexed form, have revealed novel and, in some instances, remarkable structural adaptations to attain virus recognition. Antibodies, like HIV, can evolve relatively rapidly through mutation and selection. It seems that the structures of these broadly neutralizing antibodies bear witness to a heroic struggle between two titans of rapid evolution.
Despite emerging in the human population only relatively recently (1), HIV has unleashed a pandemic that has killed ≈20 million people. Currently, ≈40 million individuals are infected (2), most in resource-poor countries, and many or most of these are expected to die of AIDS. The virus has been so successful in part because it has evolved many mechanisms of immune evasion (3–8). The means by which HIV evades the antiviral effects of antibodies are mostly attributable to the characteristics of the envelope spike decorating the viral surface, which is the target for antiviral (neutralizing) antibodies.
The functional envelope spike of HIV is thought to consist of a trimer of heterodimers formed of two glycoproteins, gp120 and gp41. gp120 is a highly glycosylated protein, with approximately half of its mass being N-linked carbohydrates (9). Sequence analyses from different HIV isolates reveal that gp120 can be organized into variable (V1–V5) regions and conserved (C1–C5) regions. The glycoprotein has a receptor site for the CD4 molecule, which defines the tropism of HIV for CD4 T cells, and a second site for binding to chemokine receptors, usually CCR5 or CXCR4. The crystal structure of the conserved core of gp120, lacking most of the variable domains or loops and the C and N termini, and with trimmed carbohydrate chains, revealed that the protein has two domains linked by a bridging sheet (10, 11). This structure provided clues as to some mechanisms of viral evasion from neutralizing antibodies (3). Much of the surface of the core of gp120 is covered by carbohydrate, and most of the rest is expected to be involved in interaction with gp41 or other gp120 units in the trimeric envelope spike. The relatively conserved CD4 binding site is recessed and arguably difficult for antibody to access. The conserved coreceptor site is largely inaccessible on monomeric gp120 unless CD4 binds and triggers conformational changes to expose the site to antibody. Further, a recent structure of the core of simian immunodeficiency virus (SIV) gp120 suggests that the coreceptor site may not be formed in the absence of CD4 (12). The coreceptor site also appears to be hidden on trimeric gp120 in Env spikes. However, CD4 binding in the context of viral infection does not appear to expose the coreceptor site sufficiently for antibody binding. It appears that the binding of CD4 arrayed on a target cell membrane reveals the coreceptor site in a more sterically restricted environment than on monomeric gp120, and this environment is associated with limited antibody access (see below).
The role of gp120 is primarily to attach HIV to its target cells and to bring the virus close to the membrane of these target cells. Once that is achieved, the transmembrane protein gp41 occupies center stage because it now mediates the fusion of viral and target cell membranes to enable the genetic information of the virus to flow in to the target cell (13). gp41 is relatively well conserved, and most of its surface appears to be hidden from antibody recognition in Env spikes before attachment and fusion (14).
The enormous variability of HIV is an effective mechanism for evading neutralizing antibody. The sequence variation in one isolate from a single HIV-infected individual sampled a few years after infection is greater than the global variation of an influenza epidemic strain during a flu season (15). In HIV Env, sequence variability is concentrated in the variable loops (V1–V5), which appear to be a major target for neutralizing antibody responses. Escape from these responses is readily achieved by mutations in the loops that have only minor consequences for viral fitness. Longitudinal studies in humans show that a neutralizing antibody response to the dominant virus does develop but, once a threshold is reached, an escape variant is selected (16, 17). In turn, an antibody response to this variant develops over time that results in the selection of a new escape variant and further repetition of the process. Antibodies that can recognize many different variants of HIV, so-called broadly neutralizing antibodies, are thought to evolve slowly and only in some individuals. It is precisely these type of antibodies that one would like to elicit by vaccination, and so they have attracted special interest.
In fact, a small panel of broadly neutralizing mAbs has been identified (18). These mAbs are important in vaccine design but, unexpectedly, elucidation of their 3D structures has provided remarkable insight into the adaptability of antibodies when challenged by a virus that has developed an extensive armament of anti-antibody features. Here, we review the structures of these broadly neutralizing antibodies that are, importantly, most often in complex with an Env antigen. The approximate locations of the epitopes recognized by the mAbs are mapped onto a model of the Env spike in Fig. 1.
b12: An Antibody That Recognizes the CD4 Binding Site of gp120
The crystal structure of b12 was originally solved as an intact human IgG1 molecule (19). The most prominent feature of the antibody combining site is a heavy-chain complementarity-determining region 3 (CDRH3) that extends directly out from the surface of the antibody like a finger (Fig. 2). The finger structures are seen on two independent Fabs in the crystal asymmetric unit and in different crystal forms, suggesting that the extended finger is not an artifact of crystallization. Computerdocking and mutagenesis studies on gp120 and b12 have been used to argue that the finger probes the recessed CD4 binding site of gp120 (19–21). The CDRH3 is 18 aa long, which is exceptionally long, compared with those typically found in well studied mouse mAbs to protein antigens (average CDRH3 length of about 10 residues). It also is relatively long, compared with the average in anti-protein human antibody reported to be about 13 residues (22). However, human antibodies to viral pathogens seem to have longer-thanaverage CDRH3 regions (22). Indeed, it is an attractive notion that recessed receptor sites on pathogens could be recognized by extended CDR fingers on human antibodies. Clearly, more antibodies in other systems need to be studied before definitive conclusions can be made.
The CD4 binding site of gp120 is recognized by many other human mAbs that do not broadly neutralize HIV. Current evidence suggests that, although these mAbs are able to recognize monomeric g120, they cannot do so in the context of gp120 organized in Env spikes on the viral surface (23–25). It appears that only b12 of these antibodies described to date is able to gain access to the CD4 binding site on the Env spike, indicating a strong selection pressures on HIV to conceal this crucial and conserved site from antibody recognition. Interestingly, a number of the nonneutralizing mAbs also have long CDRH3 regions, but their structures have not yet been determined (26). Finally, it should be noted that b12 was originally derived from an immune phage library in which heavy and light chains are shuffled. However, the heavy chain, at the very least, is believed to be the one used in vivo according to well rehearsed arguments (26, 27).
Antibodies That Recognize the Coreceptor Binding Site on gp120 [CD4-Induced (CD4i) Antibodies]
During infection, the interaction of Env spikes on the virus with CD4 on target cells makes available the conserved coreceptor binding site on gp120 for interaction with the chemokine receptors CCR5 or CXCR4. Similarly, the coreceptor site on monomeric gp120 is revealed by CD4 ligation, when it is also then recognized by a set of CD4i antibodies. CCR5 is a seven transmembrane-domain protein that interacts with gp120 in part through its extracellular N-terminal peptide (28). This peptide is rich in tyrosines, many of which are sulfated, thereby providing negative charge for interaction with the largely basic coreceptor binding site (29). In a stunning demonstration of convergent evolution, a number of CD4i antibodies have acquired posttranslational modifications in the form of sulfated tyrosines on their CDRH3 regions; these tyrosines, in some cases, are important in gp120 binding (30). Thus, for the first time, a chemical modification of an antibody has been correlated with evolution of antibody specificity.
The crystal structures of five CD4i antibodies (31) have been determined, two of them, 17b (10, 11) and X5 (P. Kwong, personal communication), in complex with gp120. The CD4i antibodies fall into two classes, those with long CDRH3s and those with short CDRH3s. Only for a subgroup of the long CDRH3 antibodies does tyrosine sulfation contribute to antigen binding. Otherwise, these antibodies have a high frequency of acidic residues on the CDRH3 loops. Initially, some excitement arose from studies of the Fab fragment of X5 isolated from a phage library because it showed neutralizing activity against a range of HIV-1 primary isolates (32). However, the intact Ig, IgG1X5, lacked such activity (33). In fact, it seems that a number of CD4i antibodies have neutralizing activity as antibody fragments with an inverse relationship between molecular size and neutralization, i.e., single-chain Fv > Fab > IgG in neutralizing potency. Thus, it appears that during infection, the virus exposes the coreceptor site sufficiently to allow access by CCR5 and antibody fragments but not by the physiologically relevant IgG molecule. These observations are consistent with the expected close proximity of the coreceptor site to the target cell membrane and the orientation and mode of access from the target cell membrane side that would be required for antibody recognition of the coreceptor site (Fig. 3).
447–52D: An Antibody to the V3 Loop of gp120
The V3 loop of gp120, as its name implies, varies in sequence between different isolates of HIV. However, the crown of the loop has a relatively conserved sequence motif GPGR or GPGQ that may be important in binding to the coreceptor (34). The antibody 447–52D (hereafter shortened to 447) neutralizes a range of isolates bearing the GPGR motif (35–37). The crystal structure of 447 complexed with a V3-loop peptide reveals how an antibody can evolve to recognize a motif with a conserved core but with a good deal of flanking variation (38). The antibody interacts specifically with the GPGR crown of the V3 loop, but the flanking sequence is bound by interaction with main-chain atoms (Fig. 4). A parallel is with MHC recognition of peptides (39), where the MHC class I and class II interact with the main-chain atoms of a variable peptide sequence in combination with conserved anchor residues (40). Perhaps in response to selection pressure by antibodies akin to 447, many primary viruses appear to have reduced accessibility of the V3 loop to the point where they are no longer recognized by such antibodies (37, 41).
2G12: An Antibody That Recognizes Glycans on the Silent Face of gp120
gp120 is ≈50% carbohydrate by weight, with the majority of the glycosylation being N-linked glycans. The structure of the core of gp120 reveals that the N-glycans are arranged on one face of the protein (3, 42). This structural feature was termed the silent face, denoting immunosilence, because glycans are attached by the host glycosylation machinery and are, therefore, expected to be "self" and nonimmunogenic. In essence, the dense carbohydrate shield protects the protein from antibody recognition. Therefore, initial reports suggesting that the neutralizing mAb 2G12 recognized glycans were carefully qualified to include likely polypeptide involvement in binding (43). However, it was subsequently shown that 2G12 does indeed recognize glycans exclusively, and a number of oligomannose candidates were identified (44, 45). This discovery led to a number of key questions. How did 2G12 apparently break tolerance to recognize what is expected to be a self-antigen? How does 2G12 achieve nanomolar binding affinity when typical antibody affinities for glycans are in the micromolar range? How can the oligomannose chains predicted to be involved in 2G12 binding be accommodated within a typical antibody footprint when they are quite spatially separated on the gp120 surface?
These questions were resolved when the crystal structures of 2G12 free and complexed with the disaccharide Manα1–2Man and with the oligosaccharide Man9GlcNAc2 were determined (Fig. 5) (46). A previously uncharacterized structure in which the two Fabs of the IgG assemble into an interlocked VH domain-swapped dimer was revealed. Biochemical, biophysical, and mutagenesis data strongly supported an Fab-dimerized antibody as the predominant form that recognizes gp120. The extraordinary configuration of this antibody provides an extended surface consisting of two classical binding sites (VL–VH) and one previously uncharacterized dimer interface region (VH–VH) for multivalent interaction with a conserved cluster of oligomannoses on gp120. Similar clusters do not appear to be present on any other proteins, because 2G12 is uniquely reactive with high affinity for gp120. Therefore, although individual oligomannose chains are self, the cluster of oligomannoses can be regarded as nonself. The unusually high affinity of 2G12 can be understood in terms of the recognition of a multivalent array of oligomannose residues by an equivalent array of antibody combining sites that match the spacing of the individual sugars within the oligomannose cluster on gp120. Finally, the dimeric configuration of 2G12 is consistent with the relatively large footprint required to cover multiple oligomannose moieties on gp120 as described above.
The unusual architecture of 2G12 is achieved by a number of changes to the typical residues found in antibody V domains. These changes include the acquisition of a proline in the bridge between VH and CH1 domains, mutations that destabilize the usual VH–VL interface, and mutations that stabilize the new VH–VH interface and, hence, dimer formation. The changes are achieved by extensive somatic mutation from the closest germ-line antibody VH and VL genes and suggest that 2G12 is the product of many cycles of mutation and selection. At the present time, the frequency of occurrence of domainexchanged antibodies in human responses is unknown, although it is likely to be relatively low. Nevertheless, this experiment of nature provides a powerful insight into how antibodies could be engineered for high-affinity recognition of repeating epitopes, such as those that might be found on cell or microbial surfaces.
2F5 and 4E10: Antibodies That Recognize the Membrane-Proximal External Region (MPER) of gp41
Although most of the surface of gp41 appears to be occluded from antibody binding on Env spikes, a region close to the viral membrane, the MPER (47), has some accessibility to the neutralizing human mAbs 2F5 and 4E10 (47–53). The description of broadly neutralizing mAbs that recognize contiguous epitopes on HIV-1 suggests that the MPER could be a highly promising vaccine target (47). Some evidence has emerged that the epitopes of these two mAbs are accessible, and possibly more so, after CD4 binding to gp120 (54). Both mAbs appear to recognize linear gp41 epitopes in that they bind with relatively high affinity to short peptides corresponding to cognate gp41 sequences, and their neutralizing activity can be effectively inhibited by such peptides. However, all attempts to date to generate neutralizing activity by immunization with sequences from these epitopes, either as peptides or incorporated into proteins, have been unsuccessful. These results have suggested that the antibodies may have evolved to recognize the gp41 peptide sequences in a specialized context, such as their proximity to the viral membrane. The MPER is very rich in tryptophans, which may aid interaction of this region of gp41 with the viral membrane.
The structure of 2F5 was originally described in complex with its short core epitope (55). A recent structure in complex with a longer 17-mer peptide confirms that the core epitope adopts a β-turn and reveals the peptide otherwise to be in a relatively extended conformation (56). Notably, the peptide makes contact with the base of the 22-aa-long CDRH3 region but not with much else of this loop. However, mutagenesis studies have shown that changes in the apex of the loop can reduce antibody binding to peptide and have an even more pronounced adverse effect on neutralization by 2F5 (57). These results suggest not only that the long loop is required for the creation of the peptide binding site, but also that the tip of the loop may be involved in further interactions. A favored current hypothesis is that the loop may interact with the viral membrane, and some support for this view is provided by observations of enhanced 2F5 binding to MPER peptides when attached to a membrane (56, 58).
In contrast to 2F5, a 13-residue peptide containing the core epitope for 4E10 adopts a helical conformation in complex with antibody (59). The key contact residues map to one face of the helix and bind in a highly hydrophobic pocket in the 4E10 antibody combining site. As for 2F5, the CDRH3 is long and not apparently directly involved in peptide binding. The CDRH3 region contains a number of tryptophan residues. The epitope for 4E10 is even closer to the viral membrane than that for 2F5; a small number of residues separate the putative C terminus of the epitope and the transmembrane domain. Therefore, the possible interaction of the tryptophans on the CDRH3 with the viral membrane is an attractive hypothesis (Fig. 6). Again, this notion is supported by enhanced antibody binding to the MPER in the context of a membrane (56, 58). Very recent studies (60) have highlighted cross-reactivity of 2F5 and 4E10 with cardiolipin; this cross-reactivity may reflect the hydrophobic nature of the combining sites of these antibodies rather than any autoimmune origin. In any case, the two antibodies provide a very interesting paradigm for recognition of protein epitopes close to a membrane and should be further studied.
Concluding Remarks
The study of broadly neutralizing antibodies has revealed some remarkable adaptations by the antibody molecule to counter the molecular trickery of HIV. The virus can evolve very rapidly because of the combination of the relatively poor fidelity of transcription associated with reverse transcriptase and the high rate of virus production in vivo. Antibodies evolve more slowly, but long-term exposure to antigen during persistent HIV infection provides the opportunity for the selection, in some individuals, of antibody variants able to recognize many different viral isolates. Under these conditions, the titans are most evenly matched. In established infection, the very rapid evolution of the virus will ultimately triumph by the selection of variants that are resistant even to the most broadly neutralizing antibodies (61, 62). However, if the antibodies are present before infection (for example, by vaccination) and before virus diversification, then they are likely to be much more effective.
The adaptations of antibody under HIV challenge could be exploited directly in antibody engineering. For instance, the 2G12 framework may allow the development of antibodies with high affinity for other carbohydrates or even other repeating antigens, such as those found on natural pathogens. The 2F5 and 4E10 antibodies have provided clues as to how one should design antibodies that need to bind close to cell membranes. Our primary interest in these broadly neutralizing antibodies is driven by what they can teach us about HIV vaccine design. The novelty of the antibodies could then work against elicitation of similar antibodies by a putative vaccine. Certainly, some of the antibodies show a high degree of somatic mutation from germ-line genes. However, this observation is not, in itself, a barrier to success. Many of the antibody mutations that have accumulated during a natural response to the virus are probably not required for high-affinity antigen binding. An appropriately designed immunogen should then elicit the requisite antibodies without the need for so many mutations. Nevertheless, there is little doubt that the step from antibody–antigen structures to immunogen design is a huge one that will challenge our understanding of molecular structure and immunology to the limits.
This work was supported by funding from the National Institutes of Health, the International AIDS Vaccine Initiative, and the Pendleton Trust.
↵ ‡ To whom correspondence may be addressed. E-mail: burton{at}scripps.edu or wilson{at}scripps.edu.
Author contributions: D.R.B., R.L.S., and I.A.W. wrote the paper.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: CD4i, CD4-induced; MPER, membrane-proximal external region; SIV, simian immunodeficiency virus; CDRH3, heavy-chain complementarity-determining region 3.
- Copyright © 2005, The National Academy of Sciences
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- b12: An Antibody That Recognizes the CD4 Binding Site of gp120
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- 447–52D: An Antibody to the V3 Loop of gp120
- 2G12: An Antibody That Recognizes Glycans on the Silent Face of gp120
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Global LGBTQ Health
LGBTQ people around the world face significant challenges to health and wellbeing. Our lab works with international datasets to understand global variations in LGBTQ people's experiences and creates interventions to support LGBTQ individuals living in structurally challenging contexts.
- Leluţiu-Weinberger, C., Rendina, H. J., Mirandola, M., Gios, L., Folch, C., Rafila, A., & Pachankis, J. E. (2018). The role of gay-related stigma in HIV-risk behavior among sexual minority men in Europe. AIDS and Behavior, 1-11.
- Pachankis, J. E., & Bränström, R. (2018). Hidden from happiness: Structural stigma, sexual orientation concealment, and life satisfaction across 28 countries. Journal of Consulting and Clinical Psychology.
- Pachankis, J. E., Hatzenbuehler, M. L., Hickson, F., Weatherburn, P., Berg, R. C., Marcus, U., & Schmidt, A. J. (2015). Hidden from health: Structural stigma, sexual orientation concealment, and HIV across 38 countries in the European MSM Internet Survey. AIDS, 29(10), 1239-1246.
- Pachankis, J. E., Hatzenbuehler, M. L., Mirandola, M., Weatherburn, P., Berg, R. C., Marcus, U., & Schmidt, A. J. (2017). The geography of sexual orientation: Structural stigma and sexual attraction, behavior, and identity among men who have sex with men across 38 European countries. Archives of Sexual Behavior, 46(5), 1491-1502.


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Deborah Pagani
Emerald Pill Link Necklace
The ultimate link necklace, with three different types of links. This chain can be worn six different ways and counting. Multiple links on the necklace open to adjust for different styles. The necklace includes an additional removable piece with nine links, including a large pill with emerald, diamond, and enamel detail, that is made to be attached to the necklace, as well as worn alone as a bracelet.
Our pieces are made to order. Please allow 6-8 weeks for delivery.
Please contact for customization: email@example.com
22", 18K Yellow Gold Interlocking Pill Link Necklace with emeralds, white diamonds, and emerald enamel


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London Home Page > Accommodation > Parking space to let > Ability Place Parking Space - Canary Wharf - Safe, Secure, 24 hour monitored!
An ideal secure, parking space available under Ability Place in Canary Wharf. The parking space is available right now for occupancy. Ideal location on Millharbour, this parking space is monitored 24-hour by security and a short 2 minute walk to South Quay DLR or 5 minute to Canary Wharf. Taking on the parking space provides convenient access to Millharbour / Marsh Wall and a Tesco Express for those last minute shopping needs! Available on a monthly basis or discounted for longer term arrangements.


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Antique sapphire and diamond ring. Set to centre with one oval old cut natural unenhanced Burmese sapphire in an open back claw setting with an approximate weight of 1.50 carats, decorated by sixty two round single cut diamonds in open back grain and rubover settings with a combined approximate weight of 0.75 carats, to an elegantly formed cluster with an open gallery featuring scrolling open work and shaped backholing, enhanced throughout with millegrain edging flanked by trumpeting diamond set shoulders with leaf motifs continuing down to a solid ridged shank. Tested yellow gold with platinum settings, circa 1905, accompanied by Gemmological Certification Services report #5776-6050.


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High Performance Computing (HPC) is a key and enabling technology for advance scientific researches. HPC tools allow modeling and simulation for many complex systems. HPC has a wide range of applications such as: complex design and manufacturing for industrial engineering, data mining for big data in computer science, computational physics, computational biology, computational chemistry, and computational linguistic. Many institutions in South East Asia countries have invested HPC infrastructure for local scientists. In Indonesia, LIPI already maintains an HPC infrastructure in two campuses, Bandung and Cibinong. The facilities are open for public, in particular scientific communities. The school is intended to provide a training ground for the potential users from both Indonesia and neighboring countries.
In 2013, the HPC was conducted in Bandung focused on the HPC administration and maintenance, including building cluster from scratch, the introduction of some parallel programming concept and some representative parallel codes in computational science.
This year school is the continuation of the 2013 HPC school. It is focused on some technical skills for the HPC users, in particular the molecular dynamics simulation using Large-Scale Atomic/Molecular Massively Parallel Simulator (LAMMPS).
Venue and Date
Research Center for Informatics
Gd. 20 (3rd floor), LIPI Cisitu, Jl. Cisitu
Bandung – Indonesia
1-5 December 2015
For further information, please visit: http://www.lipi.go.id/www.cgi?pengumuman&1446813409&&2015&&ina


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Are you at a crossroads now, determining which type of hosting best fits your needs? This is certainly an essential determination as it will influence how your enterprise will run on the webspace in the potential. So, just before you begin submitting a ticket to the assistance department or calling the revenue department of any hosting provider to inquire with regards to your confusion, consider a seem at the tips and guidelines which I am about to introduce to you. First of all, inquire yourself, which type of net business are you planning to get concerned in? Next, I'll present you the benefits, down sides and characteristics supplied to you by the two shared hosting and dedicated server hosting. Ahead of I proceed more, let us refresh your mind with the definition of the two varieties of hosting. Shared hosting, as most of you ought to be nicely-versed, is hosting in which a great deal of web sites share the exact same assets in one particular server. Resources here basically suggest the total webspace, the memory, the processor speed, as nicely as the bandwidth. Dedicated server on the other hand, give you the freedom of currently being alone. Alone signifies you are the sole proprietor of the server. You can do whatever you want and no other websites share the assets with you. It positive comes with a value as dedicated server is way more high-priced than shared hosting. However, if you believe that the benefits which I shall be listing in a quick whilst are the benefits you long to have, then it's wise to conclude that these benefits can outweigh the high-priced value (but nevertheless inexpensive) of dedicated server.
Facing the issues in the world of sharing!
Here is a basic analogy renting a space on your very own or locating a roommate to share the space with you. Merely, that is the problem or dangers you might be dealing with when you opt for shared hosting. Shared hosting is just like you rent a space with a number of other roommates. Will not it be congested to share in a modest space? However, there is a cause why individuals select to uncover roommates. Cost is the major concern. Very same goes to hosting business. Shared hosting is more affordable and more inexpensive in contrast to dedicated hosting. Presently, you can uncover shared hosting with the value of USD4 to USD15 per month. Therefore, if you feel that value is an concern and you are nevertheless green in hosting world and your online enterprise has nevertheless to achieve heavy traffic, the best solution is to go for shared hosting first. Consequently, you have to bear the disadvantages of shared hosting but if you select a reliable and experienced hosting provider (probably in a hosting business for close to three-four years), the provider will make sure the most minimal disadvantages for its consumers. In shared hosting surroundings, you will experience particular down sides as follows: Sharing Very same IP Possessing the exact same IP address in shared hosting is the major concern when other websites in the server is really currently being blacklisted for unethical routines such as spamming or creating illegal script. Considering that, you share the exact same server, it's evident you will share the exact same IP address. So, when other websites are blacklisted, these sharing the exact same IP with them will also regrettably share the exact same fate – currently being banned altogether by search engine. You will be the victim of crime which you do not commit. However, there are instances in which you can acquire yourself a dedicated IP but this generally is not required except if you are receiving yourself an SSL certificate. In circumstances such as this one particular, it depends on your hosting provider on how they deal with consumers who do illegal and unapproved routines. Usually, a reliable and responsible host will suspend these websites which carry out spamming in purchase to rescue other websites who are innocent. In quick, to get yourself a shared hosting, get to know how your provider deal with these websites which are hosted in the exact same server as you. Slow Server Response Time Utilizing the exact same analogy as above, if you and your room-mates want to use the bathroom, you have to queue up, correct? Therefore, it will slow down your everyday operate. Very same goes to shared hosting. If one particular of your neighbours have heavy everyday traffic, it will consume most of the bandwidth and when issues get tighten up, you will come to feel the slow response time such as problems accessing your web site. This is since server will respond to the requested file in purchase of the queue. If one particular of the visitor occurs to request it later and is on a long queue, that visitor will knowledge slow response time and might ultimately finish up leaving your web site. Server Crashes Frequently The factor to server crashes more often than normal, is the truth that particular scripts are produced and it can overload a server's assets. If webhosting provider does not check the server's action, these poorly-written CGI script can give you more headache than relief. Therefore, it's important for host provider to check the server routinely to stop server from crashes and to defend your internet site from currently being impacted. You as a client, please do consider the initiative to query your companies on how they consider precautions for circumstances like this one particular. A nicely-knowledgable and reliable host provider will be capable to solution your query to your satisfaction. Regardless of aforementioned poor points, a great deal of web sites also use this shared hosting solution and if a suitable provider is picked, you can be assured that such incidents will barely occur.
Dedicated Hosting – A world of your very own
What tends to make individuals opt for dedicated hosting as an alternative of shared hosting? Once more, the most essential criterion is cash. If you can afford a pricey solution like this, go ahead. However, do not just basically go ahead without having weighing the pros and cons of dedicated hosting. Even if you have cash, and you are just a modest medium enterprise, feel twice for investing in dedicated hosting. Explanation is since dedicated hosting is primarily for big and active websites such as portal, search engine, online content provider, heavy traffic forums and and so forth. In addition, dedicated hosting generally calls for more technical-savvy expert to check it. Listed under are some of the benefits why dedicated hosting is a well-known selection: You are the boss! Here, it signifies you have more management of every little thing. You can set up whatever applications and scripts you want. You can do script testing and if anything at all were to occur, no one particular else to blame but yourself. You will have the potential to customise the hardware and softwares installed on your server, which you are not able to uncover this privilege if you are below shared hosting. No more limitation in bandwidth usage Assess to shared hosting, you might get yourself a "warning letter" from your hosting provider if you exceed the greatest bandwidth allotted to you. With dedicated hosting, you have the quantity of bandwidth of a server. Therefore, downloading and uploading any supplies from your internet site will not be a problem if you have a great deal of everyday guests carrying out such action. Much more Secured Possessing a dedicated server is in truth more secured in contrast to shared hosting. This is since dedicated server will be supplied its very own firewall. Therefore, the info stored in dedicated server is much less vulnerable to attacks by hackers or any malicious codes. In addition, hosting provider will generally give backup for you with extra fee, but, in terms of safety, it's really worth it. Much better Efficiency Considering that dedicated hosting signifies only you alone are hosted in that server, the response time of the server to requested files will be so considerably quicker in contrast to shared hosting. Visitors who browse your web site will come to feel pleased since your pages will appear on their browser quick enough to satisfy them. Quickly loading time will always brighten anyone's day! Usually, deciding on which type of hosting solely depends on your needs. So, to make a wise determination, do more researches and evaluations as nicely as check with these hugely technical savvy individuals. Don't forget that a great and wise determination will establish your web sites achievement.
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An Evening With A Perfect Circle
Oct 10 , 2018 Doors: 7 p.m. Show: 7:30PM
The GRAMMY Museum is pleased to welcome A Perfect Circle to the Clive Davis Theater for an intimate conversation on their career and a live performance of songs from their latest album, Eat The Elephant. The evening will be hosted by GRAMMY Museum Artistic Director, Scott Goldman. Eat The Elephant is one of rock music's success stories of 2018, debuting at #1 on the Billboard Rock and Independent Albums' charts, #2 on the Top Current Albums chart (for physical album sales) and at #3 album on the Top 200. The Atlantic said the 12-song release features a "well-honed sense of expansiveness, beauty and rage" while Mojo described the album as both "brooding and beautiful." The Dave Sardy, Billy Howerdel and Maynard James Keenan produced collection is also A Perfect Circle's fourth consecutive release to enjoy a top 5 debut on Billboard's Top 200 with the band's debut, Mer de Noms, claiming the title of the highest selling debut rock album of all time at the time of its release. As a nod to the band members' appreciation for the integration of visual artistry and music, BMG and Sundance award-winning filmmaker Steven Sebring worked closely with A Perfect Circle to craft the world's first hologram album viewable via a specially created prism.
Event Schedule
- Wednesday, October 10, 2018 at 7:30pm Add to Calendar