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Corey Is Bothered... In stores now is the
soundtrack to the motion picture Spider-Man. In case you don't already know,
there is a song on the soundtrack titled "Bother".
"Bother", as written and performed by Slipknot's Corey Taylor. How did this come to be? What is the song all about? What does the song sound like?
Interview with Corey Taylor: "Bother", Spider-Man, and more (May 9th, 2002):
Roadrunner: Have you seen the movie Spider-Man yet?
Corey : I haven't had a chance to yet, man. I'm freakin' out, I've been waiting for this movie to come out since '93 when James Cameron was going to direct it. The movie I've been waiting for most of my life hits, and I'm in the studio working…but I'm probably going to see it tonight.
Roadrunner: Very cool, what are you in the
studio working on right now? Corey: Well, I'm working on my side project that
was entitled Superego, but now I think we're gonna call it Closure.
Roadrunner : I was going to ask you a bit about your side project. How many people are involved in it? You and…
Corey : Jim from Slipknot is in it. Two of the guys from Stone Sour, the band I was in before Slipknot. Actually, Jim was in Stone Sour as well. And a friend of mine who I've been working with for like 13 years plays guitar.
Roadrunner: How many songs do you guys have down?
Corey: We have 16 songs, including "Bother".
Roadrunner: So, "Bother", the recording and writing, that was purely you, right?
Corey: Yeah.
Roadrunner: "Biggest Spider-Man freak of all time", you have been quoted as saying. When did this all start? What is the attraction?
Corey : It started when I was a kid - my
mom actually kept a lot of comic books around. She just kind of had them stacked
all over the place. As a kid, we were really poor so I didn't have a
lot to read, but I was an avid reader. So I'd start picking up these comic books and reading them. I discovered Spider-Man and just fell in love with the character. Everybody likes to talk about his
sense of responsibility, and that he's cursed with these powers…what I liked was that he would just talk shit the whole time he was fighting the enemies. He didn't take any of it seriously - he's staring into
the face of danger and he's just like 'Guess what? If it's gonna happen it's gonna happen, I'm gonna win, and that's just the way it goes.' I really looked up to that, ya know?
Roadrunner: "Bother", this was written what, seven years ago you've said?
Corey: Yeah, about seven years ago. I
wrote it on the dashboard of my friend's car as I was moving back from Denver,
back to Des Moines. I wrote the lyrics in about six minutes.
When I finally got home I grabbed the guitar because I didn't want to lose it, and I worked the music out. It was basically just something that I would play once in a while just for myself.
And then when I was doing the demos for this side project, I went in and recorded it - just on a whim, real quick, real barebones, me and a guitar. It fell into the hands of Denise Louiso at Sony.
She heard it, she flipped out…it just kind of went from there.
Roadrunner: What's the song about?
Corey: The song is just about the time I
was moving back from Denver - I just felt really broken down because I moved to
Denver to try to move forward with my music. I just got to the
point where it was like 'nothing is going to happen for me in Des Moines.' Ya know, how ironic is that? I moved out to Denver and found out it was the same way all over the place.
It was actually worse in Denver because at the time nobody gave a shit about original music, it was all cover bands out there. I was so used to being able to do what I wanted in Des Moines.
I actually fractured my arm at a party and I lost my job out there so I was literally living off bottles and cans. It got to the point where I had to move back, just no way it was working for me
out there. So I move back to Des Moines and that song, I had been toying with the idea of that song for a while. And I just hit the dash lights and wrote it down in like 5-6 minutes, and I just kept
humming it the whole way home.
Roadrunner: Obviously, you had no end use in mind for this song at the time, correct?
Corey: No, no, not at all, man. Ya know, I
have forty or fifty songs just like that, all acoustic. I write that stuff for
me. It was just one of those songs where if I never get to do anything with it,
at least I have a recording of it.
So it just turned into that, and through the grace of God it ended up in somebody's hands. It's funny how fate works.
Roadrunner: The whole Spider-Man soundtrack, did you actually pursue that or did it just happen?
Corey: You know what, I'd been telling my
ex-manager to get me on the soundtrack for a year. As soon as I found out it was
happening, I was like 'look, I don't care what you do, I don't care
what you say, you need to get me on that soundtrack…'
Roadrunner: You wanted that song on it in particular.
Corey: Oh, absolutely. If there was any song that was going to be on there, it was going to be that one.
Roadrunner: And why was it "Bother" over any of the other 40 songs you have written acoustically?
Corey: Just for the fact that if you read
the lyrics, it's all about following your path in life even though you know it's
not the path that you want, and it's not the path you really have in mind.
And it kind of fits along with the whole Spider-Man theme, ya know? If you look at his powers, it's a blessing and a curse - he's cursed to fulfill his own destiny because of this, and yes
he gets to help people and what not, but at the same time he has to live with all this stuff going on in his life and really deal with the downside of everything. So the lyrics, the
feel of it really fit in with what is going on in the movie, I believe.
Roadrunner: Very well put, very well put. Couple more questions. The side project, how often you guys playing right now?
Corey: Actually, we just got done recording the album. We're just trying to get it mixed and mastered and all that stuff.
Roadrunner: You recorded all sixteen songs?
Corey: Yeah.
Roadrunner: What do people have to look forward to hearing, sound wise?
Corey: It's really good - It's real
melodic, it's more hard rock, but it's still heavy, by all means….it's really
heavy. But at the same time it's nowhere near as heavy as Slipknot is. This is
of like Metallica meets Alice In Chains. It's really good stuff and I hope people dig it.
Roadrunner: As for Slipknot, dvd is in the works right now, and you'll be playing some upcoming shows in Europe, so festivals…
Corey: Yeah, some festivals in August…
Roadrunner: Other future Slipknot plans in the works right now?
Corey: We (Slipknot) are gonna get together next year and start working on a new album. For right now, this side project is pretty much my only priority.
Roadrunner: You see this project touring this year.
Corey: Yeah, absolutely. Should be doing
America this year


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Cape Coral officials say a threatened lawsuit designed to replace a barrier removed from a city waterway is without merit and the issue is closed.
Officials with the state agency also named declined comment on the suit. They said, however, reinstallation would cause more harm than environmental good - the reason an environmental coalition filed a 60-day notice of a lawsuit Saturday against both the Florida Department of Environmental Protection and the city.
John Englehardt, local director of the Florida DEP, said he hasn't seen the notice letter and had no comment, but he said the city and the state did all they could to follow an agreement concerning the barrier.
"The city was required to file a permit to replace the barrier and we denied it," Englehardt said. "We found most of the water is tidal and just putting a barrier there would not have the impact we thought it would. Where the water comes in, it goes out."
Englehardt also said the barrier would have a negative impact on the smalltooth sawfish, a protected species.
Englehardt added the city developed the net ecosystem benefits package in lieu of the barrier, which satisfied the consent order and closed the case.
The coalition, though, says it will go to court to enforce a settlement agreement and that DEP consent order the group maintains requires the replacement of the Ceitus Barrier in the North Cape Coral Spreader Canal.
The replacement barrier must include either a boat lift or boat lock and must be located about 1,000 feet north of the previous barrier.
Phil Buchanan, one of the plaintiffs, said the coalition is taking over where the county left off, since Lee County was the original plaintiff.
"They voted 5-0 to bring the suit, but the election (that defeated Ray Judah) scared the rest of them into doing anything environmental anymore," Buchanan said. "When they didn't do it, I had to step in."
Other plaintiffs include Riverwatch, Responsible Growth Management Coalition, Greater Pine Island Civic Association, Calusa Land Trust, Watershed Council, and Sanibel-Captiva Conservation Foundation.
The lawsuit would ask the Circuit Court to enforce a 2008 settlement in which Cape Coral agreed to restore the Ceitus Barrier with a boat lift or boat lock, and to require the DEP to enforce its own consent orders, which the groups maintain also require restoration of the Ceitus Barrier.
"We all signed an agreement saying they would put the barrier back and they've welched on the agreement," Buchanan said. "They were supposed to get permits for a boat lift or lock, but did not in good faith get them. They applied for a denial of a permit."
Buchanan claims the city didn't supply the data needed to grant a permit.
Buchanan said the barrier serves a purpose to block off the water and require it to rise by 16 inches to allow it to flow through the wetlands to the west.
If this doesn't happen, the wetlands don't get the fresh water it needs for the fish nursery, the excess fresh water gets dumped in North Matlacha, and the salt water marine life cannot survive there, Buchanan said.
"The oysters and sea grass require salt water and if they don't get enough they die," Buchanan said. "The adult fish can swim in the fresh water, but the nurseries are a different story."
Rae Ann Wessel, natural resource policy director of the Sanibel-Captiva Conservation Foundation, said when no compromise could be found in lieu of a barrier, the order required the barrier to be put back in.
"In exchange for dropping our challenge back when it allowed the city to remove the barrier. We would enter into an ecosystem management approach designed to find an alternative to the barrier," Wessel said. "We did not come to a consensus."
Englehardt said alternatives to another barrier continue to be looked at.
"We're working at revisiting all those old flow ways that went from the spreader waterway into Matlacha Pass," Englehardt said. Bringing more flow in is a good thing. So, we're progressing on this."
Cape Coral Councilmember Kevin McGrail said, in his mind, the case is closed and doesn't believe it will be an issue at the next city council meeting.
"The issue has been resolved. This was vetted through the North Spreader Eco-Mangement Agreement process, was looked at by the FDEP and was considered when they made their ruling on the boatlift," McGrail said. "We lived up to our end of the bargain. We expected what would happen according to the science."
McGrail added the runoff released from Lake Okeechobee has done more damage than five years of removal of the boatlift, and that the city will live up to its agreement regarding the Utility Expansion Project in North 2, part of the agreement.
Most important, McGrail said, the Lee County Board of County Commissioners, which first brought forth the threat of a suit last year, isn't taking part.
"That should tell you that the environmental groups, who were never going to be happy with whatever we came forth with, are still not happy, yet the BOCC has decided the issue is put to rest," McGrail said, who believes this is a suit against the state (since they do the permitting) and that the city will be "in the second chair" should the case reach a courtroom.

subset: commoncrawl


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Supported access points
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Supported PMS systems
A full list of GuestTrack-compatible property management (PMS) systems can be found here.


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Orient Hostel
Orient Hostel is located between The Blue Mosque and The Haghia Sophiae while there are numerous museums are only a short walk away.
Enjoy a meals or quiet evening at the hostel's rooftop cafe. During the summer time you can enjoy BBQ also you can eat fresh and cheap traditional and very tasty Turkish foods at our famous open air terrace restaurant with great views of the Princes Islands and the Marmara sea. Meet travellers from around the world in the common room. Keep in touch with family and friends using the free internet and Wi-Fi.
FREE Breakfast (Omlette,Yoghurt Musli,Cornflakes, French Toast, Butter Bread Jam and Cheese) FREE Clean and fresh sheets, pillow, blanket. FREE City and Travel information FREE Book Exchange FREE Safe-box Deposit
FREE Backgammon,Chess, Scrabble, FREE Dictionary, Card Games FREE Luggage Room FREE Parking for Motorbike Travellers FREE Belly Dancing Show at Terrace Bar (Just High seasons)
Travel Library No curfew, No lockout
24 Hour Reception NO COMMISSION FOR CREDIT CARD PAYMENT !!!
CHECK IN TIME : 11:45 am CHECK OUT TIME : 10.00 am
AGE RESTRICTION: Older than 45 years old can not book Orient Youth hostel's dorm rooms (please respect this restriction)
Availability & RatesTo view availability and prices please select dates and click 'Update Dates'
Hostel Facilities & Policies
- 24 Hour Reception
- 24 Hour Security
- Airport Transfers
- Bar
- Bicycle parking
- Book Exchange
- Free Breakfast
- Café
- Credit Cards Accepted
- Currency Exchange
- Free City Maps
- Free Internet Access
- Free WiFi
- Hair Dryers For Hire
- Hot Showers
- Internet Access
- Late check-out
- Linen Included
- Security Lockers
- Luggage Storage
- No Curfew
- Outdoor Terrace
- Reception (limited hours)
- Restaurant
- Safe Deposit Box
- Tours/Travel Desk
- Towels For Hire
- Wi-Fi
Cancellation PolicyThis property has a 1 day cancellation policy. Failure to cancel within this time will result in a cancellation charge equal to the first night of your stay.
DirectionsShow MapHide Map
To get The Orient Hostel from ATATURK AIRPORT ( IST), you can take either a taxi (about 20) or take the METRO transfer to the tram in ZEYTINBURNU station ( direction to KABATAS or EMINONU) and get off at SULTANAHMET tram stop.
To reach Orient Hostel from SABIHA GOKCEN AIRPORT (SAW); you can take the HAVATAS bus to TAKSIM. From TAKSIM, the easiest way is to taking a taxi ( 8 EUR app.) or take the FUNIKULER ( subway) to KABATAS, change to TRAM and get off at SULTANAHMET tram stop. If you are 3 people, taking the taxi from TAKSIM costs the same amount by taking the public transportation.
To reach the Orient Hostel from the Bus Terminal (Otogar), you can take the METRO from the bus terminal to last stop AKSARAY, and transfer to the TRAM (direction KABATAS) and get off at SULTANAHMET tram stop.
From the SULTANAHMET tram station it is about 200 m walk. The tram service stops at midnight. Orient Hostel is open 24 hours a day. Please do not hesitate to contact us by phone.
If you need airport transfer our airport pick up service is 25 euros from Ataturk Airport and 60 euros from Sabiha Gokcen up to 3 people. Please feel free to contact if you need more information.
Located Near
Haghia Sophia, Blue Mosque, Topkapi Palace, Basilica Cistern, Cemberlitas and Beyazit Towers, Archeological, Islamic Arts and Carpet Museums , Grand Bazaar


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Metaphysics was a sub-field of philosophy that examined the nature of reality including relationships between the mind and matter. It can also deal with cosmology.
Kiri-kin-tha's first law of metaphysics states "Nothing unreal exists." (ENT: "The Forge"; Star Trek IV: The Voyage Home)
Emory Erickson, inventor of the transporter, denounced questioning if the person who arrived after a transport was the same person who left as "metaphysical chatter." (ENT: "Daedalus")
In 2266, Captain Kirk of the USS Enterprise engaged the supercomputer Landru in a metaphysical debate. Landru regarded itself as an exact copy of its maker, an ancient philosopher and engineer. Kirk exploited certain key differences between the creator and the created to set up a paradox that the machine could not resolve. These limitations, rooted in its understanding of the world and of itself, had prevented it from realizing the harm it was doing to the citizens of Beta III, in direct violation of its programming. They also prevented it from deducing a way to resolve that harm, and ultimately, it experienced catastrophic failure. (TOS: "The Return of the Archons")
In 2364, when the USS Enterprise-D crew were infected with polywater intoxication, the training division ordered officers to attend a lecture in metaphysics. (TNG: "The Naked Now")
Captain Phillipa Louvois felt that determining the nature of Data was a case of metaphysics. (TNG: "The Measure Of A Man")
In 2366, Data included information on metaphysics in the "education" of his offspring Lal. (TNG: "The Offspring"). Data also considered the interpretation of visions a metaphysical matter. (TNG: "Birthright, Part I")


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Until recently, public debate on co-existence hardly has existed in Slovenia. The topic was discussed primarily at conferences such as the co-existence workshop hosted in July 2005 by the Agricultural Institute of Slovenia in cooperation with EuropaBio. On 6 October 2005, the Agricultural Co-existence Conference was hosted by the embassy of the USA in Slovenia. In 2006, public debate intensified following the draft publication of the act on co-existence of genetically modified plants with other crops.
The Slovenian government has not stated its position on co-existence.
The political party Zares organised a conference on GMOs. Due to the expectation of a parliamentary hearing on the Act on the co-existence of genetically modified plants with other agricultural plants, co-existence also was one of the main topics of the conference. Many organic farmers who were present at the event expressed strong opposition to GMOs and to co-existence.
In 2004, organic farmers called for legislation on co-existence. In addition, they state a lack of belief in the actual possibility of co-existence and, consequently, propose the establishment of GMO-free regions. During public debate on the draft Act in 2006, the initiatives for GMO-free regions displayed an increase in strength.
Several initiatives are aimed against the planting of GMOs in Slovenia. Together with organic farmers from Austria and Italy, the association of Slovenian organic farmers has formed an group known as Bio Alpe Adria. The group intends to establish a GMO-free zone that consists of parts of Austria and of Italy as well as all of Slovenia.
The former Slovenian president, Dr. Janez Drnovšek, has established the association 'Gibanje za Pravičnost' in Razvoj. On the Internet pages of the association, some opinions are published against the use of GMOs and against co-existence.
On 22 April 2007, the Institute for Sustainable Development initiated a campaign for the establishment of GMO-free regions and communities. By the end of 2007, more than 70 communities had declared themselves as GMO-free. The main aims of the campaign are the stimulation of general debate on the use of GMOs in agriculture, the augmentation of public awareness of the issue, and the obligation of politicians and the government towards transparency with regard to the use and cultivation of GMOs.


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Salty Kisses and Mermaid Wishes Wine Tumbler
Let's Be Witty wine tumblers accommodate 12 ounces of your favorite beverage, whether that's coffee or something a little stronger 😉 Extensive day drinking--ahem, testing--by the Witty team confirms these tumblers hold ice just as long as the major brands… and they're a whole lot cuter!
· Tumbler is made from stainless steel with a powder coated finish
· Double walled insulation keeps hot drinks hot and cold drinks cold with no sweating
· Twice the heat and cold retention of a plastic tumbler
· Measures 5" tall and 3.7" wide at its widest point
· Hand wash for best results. Washing in the dishwasher is NOT recommended


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You can renew and revitalize the DNA embedded in your cells to make improvements in your own health and live a longer and healthier life.
Drs. Oz and Roizen: Do-it-yourself gene therapy
At last, we've got solid proof: You can renew and revitalize the DNA embedded in your cells to make improvements in your own health and live a longer and healthier life. And you don't have to take questionable supplements (some good ones are mentioned later) or make a late-night agreement with someone who smells like sulfur to get it done. By adopting a handful of beneficial lifestyle habits, you'll actually be practising cutting-edge gene therapy!
So let us introduce you to the amazing — sound the trumpets — telomeres. They're the caps on the ends of your genetic material (like the plastic tips on shoelaces) that are designed to keep each cell's strings of DNA from fraying. Telomeres start out fresh and long, shrinking a bit every time one of the cells they're attached to divides. That's normal.
But health missteps also shrink your telomeres. They shrivel further and faster when your system is assaulted by inflammation, toxins and negative stress. For example, obesity seems to accelerate telomere shortening (or aging) by 30 per cent or more. Smoking speeds it up by a whopping 18 per cent!
When telomeres are super-short, cells die prematurely or become what one telomere researcher calls "zombie cells" — weak, ineffective, but still living. And bringing short, skimpy telomeres to the party is associated with an ever-growing list of health problems: heart disease, high blood pressure and clogged arteries, diabetes, breathing problems like emphysema, arthritis, brittle bones and dementia.
But the big news, according to our friends at the University of California San Francisco and California's Preventive Medicine Research Institute, is that you can do more than just protect these essential tips on your genetic material; you can reverse telomere shrinkage and make them longer! Longer telomeres can help you avoid those health hazards by helping cells duplicate and repair previous damage.
How do we know you have that much control? In a new case study of 35 guys with early-stage prostate cancer, 10 upgraded their diet, got regular physical activity, practised stress management every day and spent more time with friends and loved ones. Twenty-five other men stuck with their usual habits.
After five years, the first group's telomeres were 10 per cent longer on average; that's the equivalent of a 20-year-younger RealAge for a 55-year-old! And the guys' telomeres were even longer if they were super-conscientious about making healthy lifestyle changes.
The men who didn't make any lifestyle changes saw their telomeres shrink three per cent.
Ready to do a little at-home gene therapy? Start here:
No. 1:Remove the Five Food Felons from your diet: added sugars and sugar syrups, saturated fat, trans fats and any grains that aren't 100 per cent whole. Replace with plant-based edibles such as vegetables, fruit and plant-based proteins like walnuts, beans and tofu. And we do believe that supplements like DHA, lutein, zeaxanthin, vitamin D-3, calcium and half a multivitamin twice a day are a good insurance policy against an imperfect diet.
No. 2:Move for at least 30 minutes daily, heading for a goal of 10,000 steps or more! If it's too hot, too cold or too dark outside, whether you're at the gym, home or office, take a spin on a stationary bike, march in place or stride on a treadmill. To cement this habit, make it an everyday activity, maybe while you watch your favourite (recorded?) TV show. And we know what that is.
No. 3:Take time to relax daily. Guys in this study devoted an hour a day to managing stress. Don't have 60 minutes to spare? There's good evidence that even five minutes of tension-melting meditation can make a big difference. Find a quiet spot, sit comfortably, shut your eyes and pay attention to your breathing. Add progressive muscle relaxation, tensing and releasing muscle groups from your toes up to your head.
No. 4:Minimize exposure to harmful toxins such as first- and second-hand smoke and BPA-laced receipts. You can learn more about telomere-saving techniques at
Mehmet Oz, MD is host of The Dr. Oz Show, and Mike Roizen, MD is chief wellness officer and chair of Wellness Institute at Cleveland Clinic. To live your healthiest, tune into The Dr. Oz Show or visit


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I did notice screen-wrapping as well when adding it to a static object and moving it to the edge of the screen - but only on the "Y axis" (?), so 0 0 0 in worldspace. Horizontal seems okay for some reason ...
Not sure what to do about that though - though thankfully it's not going to affect what I want it for too much as it might help the player see invisible enemies when they approach.
One more thing I'd like to do, is to add a colour shade/tint/darken to it but don't know. I noticed you commented about modifying colour_exit:
//here you can modify colourexit if needed return colour_exit;I tried adding an rgba to colour_exit before the return and got the colouring - but lost all the transparency and wobble
Any hints for how I should be doing this?


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This is a top play for me too.
Huge situational angle. NYG +6
But you only need Hou to cover 2 (basically get the W) to cash $5K. I understand the eliminating the risk of loss of anything more than juice part with a shot at doublin up, but that's a narrow 5pt window. Unless you now feel there's a better chance of Hou basically losing the gm as winning by 9. With different #'s & a bigger window, I'd like it better but only needin to cover 2 think you could easily be walkin away from a relatively stress-free 5K. Good luck tho & hope we're both celebratin in about 8hrs
Dallas. On the road. Against a Baltimore team at home.
I don't see that one working out for you. But, I'm always wrong, so who knows haha
I hear you, but you'd be happy to just walk away from $5K if Hou wins by only 3 or more? For the chance to double up if they win by 3-7? Sorry, just doesn't make sense to me unless you think there's a really good chance the Jets cover 2 - in other words, basically get the W. GL anyhow - hope it works out for you.


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Snookz678 wrote:umm Hello I just wanted to say i'm really fascinated with lucid dreaming ever since one day i randomly woke up in a dream and was overwhelmed by my surroundings and i read most of your articles, but here is what i really wanted to say i'm only 15 and i read on how much you were dedicated to L.D. and how you started very young and i really want fast track but my parents don't believe L.D. is real, and since they have money and i cant get a job yet i was wondering if there are any more secrets,techniques,things to help me become a better L.D. such as you. If you would, anything would help. Thank You.
Carlos C.
Wow that's a very open question... I'm not sure I can give you the answer you want. I've shared pretty much everything I know on the website and in the course, and the bits I haven't shared I'm still exploring myself! (I don't want to misguide anyone.)
I recommend you work through the website and see how you get on. I promise I'm not withholding any "magic bullet" for lucid dreaming. The only missing ingredient from my tutorials is your personal commitment, so really you have to absorb each lesson - then go practice like you really want it. Good luck.


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Every person deserves the freedom to prosper. As you explore in our reporting what Utah will look like in the next quarter century, carefully consider the legacy you are creating for a rising generation that yearns for little more than the pursuit of genuine happiness. It is through a culture of responsibility, established by our collective choices, that Utah will meet the challenges of its changing demographics.
Today the Deseret News, in partnership with KSL, launches a series called "Coming to our Census." This series of reports takes a careful look at the issues posed by the changing demographics of Utah and the nation. In today's introductory article, Marjorie Cortez succinctly lays out the aim of the series by asking "By 2040, will Utah have met the challenges of its changing demographics?"
Demographic trends suggest that current ethnic and racial minorities will soon find themselves in the majority. The challenges posed by those trends stem from the poor assimilation of many ethnic and racial minorities into our social, political and educational institutions. So, for example, although most of the growth in primary and secondary education over the next several decades will come from our growing Hispanic population, Utah will fall far short of its full potential if the current disappointing pattern for Hispanic high school graduation, college enrollment and college completion continues as it is.
That pattern is best described by Octavio Villalpando at the University of Utah, who has shown that out of every 100 white children who enroll in Utah's elementary schools, 84 will graduate from high school and 26 will graduate from college. Out of every 100 Hispanic children who enroll in Utah's elementary schools, however, only 40 will graduate from high school and only four will graduate from college. Given the educational demands of the global economy, this pattern of failure is alarming.
The eminent 18th-century statesman Edmund Burke described society as a sacred partnership "not only between those who are living, but between those who are living, those who are dead, and those who are to be born. Each contract of each particular state is but a clause in the great primeval contract of eternal society."
This "Coming to our Census" series effectively adopts the spirit of Burke's intergenerational compact by challenging the Utahns of today to consider how to fulfill their responsibility to the Utahns of tomorrow. That responsibility, however, requires unusual insight and imagination because the next generation will look quite different from the current generation.
Of course, current policy choices regarding public spending have already shown callus disregard for the next generation of Americans, regardless of their race or background. By borrowing at unprecedented rates, governments are saddling the next generation with an unconscionable burden of debt that will stifle growth and opportunity. So although many of the issues discussed in our series might intuitively suggest increased public expenditure as a solution, it is very hard to imagine that significant public funds will be available, let alone help.
It is our opinion that although the next generation might appear different, they will, in fact, be very much like each successive wave of new Americans — eager to succeed through hard work, anxious to find a nurturing environment for their families and happy to contribute back to the institutions that support their quest for betterment.
Consequently, the challenge of meeting the deepest needs of successive generations is not so much a material challenge as it is a cultural one. Do our policies and culture place sufficient value on long-term sustainability? Are the institutions that contemporary society is bequeathing to the rising generation protecting the dignity and worth of all persons? Do they treat individuals as ends in themselves? Are they transmitting a shared and productive moral vision?
Some have suggested that cultural dimensions of the coming demographic shift may be particularly challenging because, unlike the last great wave of immigration at the turn of the 20th century, the latest wave comes from Latin America and Asia rather than Europe. But it is our opinion that it is the authority and resilience of the host culture that is most likely to determine the outcome of any cultural struggle.
If what we bequeath socially and culturally to the next generation were to come from a materialist popular culture that glorifies individualism, instant gratification and debt, then regardless of ethnicity or race, the next generation would face severe challenges. But if instead we were to bequeath vibrant families, congregations, schools and civic institutions — institutions that value community, responsibility and thrift — then we would help to re-establish the foundations for lasting prosperity.
Every person deserves the freedom to prosper. As you explore in our reporting what Utah will look like in the next quarter century, carefully consider the legacy you are creating for a rising generation that yearns for little more than the pursuit of genuine happiness. It is through a culture of responsibility, established by our collective choices, that Utah will meet the challenges of its changing demographics.


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Furnish the home you never want to leave
Issue 18, Autumn 2017
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The beaker for when a cup of tea just isn't enough
Royal Crown Derby is one of the world's most respected ceramic brands, manufacturing the highest quality Fine English Bone China. The prestigious ceramic artisans present the Equus Collection, designed especially to celebrate the Year of the Horse. Beautifully illustrated, these pieces can be used in a practical capacity or as ornaments to decorate the home. The colour palette here is Black, White and 22 carot Gold
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These beautiful beakers are part of the Equus Charnwood collection. The beakers feature a spirited illustration of an ebony horse on a stark white background. Expertly crafted in England from fine English Bone China. Also available in Gold & Black, with a small or large horse design.
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London Craft Week 2019
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In Stargate: United Front you will be part of an elite SG team made up of international representatives of the major powers of the Earth. The United States of America, United Kingdom, France, Russia, China and Canada are all member countries which head up a new stargate command centre located off-world. As part of this team, you will be sent out on a variety of missions, including but not limited to, reconnaissance, assault, acquiring items and technology, aiding allies and protecting Earth against any and all threats. At this point, Stargate: United Front is a Co-op and Multiplayer Mod. The Co-op aspect of our mod will follow an episodic manner, meaning the story will go through a series of episodes, linked together and bringing exciting challenges at each part of the journey. The Multiplayer aspect will not follow any particular storyline but just be an arrangement of maps and game play.
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I got an email from Ms. Laurina Cashin the other day and it struck my fancy.
"I hope you already know about El día de los niños, el dia de los libros/Children's Day, Book Day, called Día, the family literacy initiative founded by Pat Mora and now housed at the Association of Library Service to Children, a division of ALA. I work with Pat and we're gearing up for our month-long, online celebration, Díapalooza. New this year is our project, Día Author and Illustrator Ambassadors, created to increase awareness and support for Día. We've put up a special page on Pat's Día site (http://www.patmora.com/dia/dia_ambassadors.htm ) to highlight the Ambassadors, all who've agreed to do two advocacy actions for Día this year, through social media, videos, and face-to-face presentations."
This is a celebration I'd vaguely heard of in the past but hadn't had a chance to examine more closely. Looking into it I found a lot of great information. It's all beautifully organized. There's Pat's letter to authors and illustrators about the day. There's the website dedicated to Dia with lots of background information. And sure as shooting ALSC does indeed have a Dia site where they encourage libraries to register their own Dia 2012 programs. There's another advantage to having a Dia program above and beyond that, though. Libraries that participate can apply for the 2012 Estela and Raul Mora Award which grants $1000 to a library that promotes the day in some way. Check it out, folks. Your library system might be eligible.
So gear up for April 30th! Even if your library has never celebrated it before, there's no time like the present. Thanks to Laurina for the info!


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A Summer "Must Read"
for Job Seekers
Me 2.0 shows job seekers and established professionals alike how to leverage the power of online media for personal empowerment and career success.
Some highlights from the
book include:
NEW in the Revised Edition (October
5th, 2010)
NEW case studies, from people of all generations, on how they've used social media to become well-known brands.
NEW chapter on how to use the top social networks, including Facebook, LinkedIn, and Twitter, for job searching, with real success stories.
NEW insight on how to turn your passion into a business through the personal branding process.
NEW tools you can use to network professionally and grow your presence, including Google Buzz, mobile branding, and location-based social networking.
NEW research, examples, and more resources that will support your online brand campaign.
Bottom line: This is the
handbook for surviving and thriving in the digital age
Free chapters, tips and much
- Daniel H. Pink, New York Times bestselling author of
A Whole New Mind


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Whether you are a parent or you are a preschool teacher you need to know the tricks to keep your kids engaged in activities which not help in building their creative abilities but also provide them the best opportunities of indulging in fun. Trying to find such activity becomes difficult when you are least aware of the coloring pages available for free (as most of them are available for free online). Internet is a hub of a variety of Disney and Christmas coloring pages which can be easily downloaded and printed for free. These coloring pages help in sustaining the interests of kids for a good length of duration. Moreover, it doesn't carry any kind of risk or potential harm to kids while coloring.
Children who lack intellectual maturity and emotional satisfaction can be appreciated through the assignment of task involving coloring their favorite characters. In the beginning they may start up with whacky coloring but eventually their skills tend to enhance. They gain emotional satisfaction and also build up essential motor skills like concentration of eyes and hand, hand dexterity etc. it is a kind of wholesome enjoyable task. Most kids love Disney characters very much and when they get their hands onto coloring they forget everything else. They become like angels and always try to express their best by coloring.
Similarly Christmas Eve coloring pages are very popular during this season. They involve a variety of brightful colors. Kids learn color coordination by eventually thinking about what color pairs best with the other. They learn about the natural colors. The funniest part to it is that not only kids enjoy coloring but adults also love coloring these pages. There are numerous websites over the internet which also offer online coloring to both kids and adults for free. There are articles too to read, tips on coloring and make effective patterns or designs.


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***Claim form required. Certain restrictions and limitations apply. Limit 1 reward per each set of 4 eligible tires purchased; limit 3 rewards per household, customer or address. For eligible tires and complete details, see your participating Firestone retailer or FirestoneTire.ca. Eligible tires must be purchased in-store from a participating Firestone retailer's inventory April 15–May 26, 2019. Offer excludes Costco purchases and General Motors Scotiabank Visa Promotion. Cannot be combined with any other offer.
**The Visa Prepaid Card is issued by Peoples Trust Company pursuant to a license by Visa Int. No cash access or recurring payments. Card valid for up to 6 months; unused funds will be forfeited at midnight EST the last day of the month of the valid thru date. Card terms and conditions apply; see MyPrepaidCenter.com/site/visa-univ-can.
*Trademark of Visa Int., used under license.
And many more!
<-------- This product is not currently licensed. Please license this product by clicking here. -------->


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Possible Duplicate:
"<handler> scriptProcessor could not be found in <fastCGI> application configuration" when accessing PHP script in subfolder
I have a configuration problem with php on IIS 7.5.
It is a practically fresh install made with the MS Web PI on Win7.
I created a simple php testpage. It works in the root level
http://localhost/test.php and in the first sub-level
http://localhost/site/test.php, but not in
http://localhost/site/subfolder/test.php, there I get HTTP 500 error:
<handler> scriptProcessor could not be found in <fastCGI> application configuration
Everything seems to be configured as specified in http://www.iis.net/ConfigReference/system.webServer/fastCgi/application
Could there be some kind of filter that disables processing at specific folder-level / or enable it just in the first 2 levels?
What should I check?


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Will Ferrell jumps way outside of his goofy screen persona to play an alcoholic at the end of his rope in "Everything Must Go."
The movie opens during a disastrous day that ends with the loss of his job, car, house and marriage in a matter of hours. With all his belongings on the front lawn of his former home, he is clearly in need of a life-changing garage sale.
But first, he spends days guzzling gallons of beer and annoying his neighbors.
Rebecca Hall plays a pregnant newcomer across the street who lends insight and a helping hand to his situation. His AA sponsor arranges a last chance for him to get straight without police intervention.
But it's a latch-key kid played by Christopher Jordan Wallace who helps turn his personal catastrophe into the possibility of redemption.
There's a nice touch of heart and humor to temper the adversity at hand. This is a quiet indie flick that shines a needed light on a common problem that profoundly affects many people.
Females carry funny wedding films
"Bridesmaids" is a real gut-buster in the raunchy tradition of "Wedding Crashers" and "The Hangover" on what can go wrong in the days leading up to a wedding.
It's loaded with sex, romance, and an ensemble with spot-on timing. Oh, yes, and most of the cast is female.
Kristen Wiig of "SNL" stars as Annie, maid of honor for lifelong friend and newly engaged Lillian (Maya Rudolph). Poor Annie, lately nothing goes as planned — not her business, love life or the bridal luncheon. It's both painful and hilarious.
Behind the laughter is a knowing commentary on the social and financial insecurities that plague us all. Writers Wiig and Annie Mumalo (who plays her seatmate on a doomed flight) sure know how to throw a party.
'Jumping the Broom'
Raucously funny "Jumping the Broom" is a less graphic take on wedding day blues.
The ladies again steal the show when two diverse families meet for the first time before some very lavish nuptials in Martha's Vineyard.
Uptight, wealthy Angela Bassett squares off against working-class, outspoken Loretta Devine as mothers of the bride and groom, respectively. Each carries a chip on her shoulder that has nothing to do with the wedding, and each has her own rigid code of values.
Paula Patton and Laz Alonso are the beautiful couple whose love and loyalties are tested by all this mama drama. Love, laughter, tears, and fabulous scenery — what more could a hopeful romantic ask for?
JOHN DEPKO is a retired senior investigator for the Orange County public defender's office. He lives in Costa Mesa and works as a licensed private investigator.
SUSANNE PEREZ lives in Costa Mesa.


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Pharmaceutical industry
Pharmaceutical industry, the discovery, development, and manufacture of drugs and medications (pharmaceuticals) by public and private organizations.
The modern era of the pharmaceutical industry—of isolation and purification of compounds, chemical synthesis, and computer-aided drug design—is considered to have begun in the 19th century, thousands of years after intuition and trial and error led humans to believe that plants, animals, and minerals contained medicinal properties. The unification of research in the 20th century in fields such as chemistry and physiology increased the understanding of basic drug-discovery processes. Identifying new drug targets, attaining regulatory approval from government agencies, and refining techniques in drug discovery and development are among the challenges that face the pharmaceutical industry today. The continual evolution and advancement of the pharmaceutical industry is fundamental in the control and elimination of disease around the world.
The following sections provide a detailed explanation of the progression of drug discovery and development throughout history, the process of drug development in the modern pharmaceutical industry, and the procedures that are followed to ensure the production of safe drugs. For further information about drugs, see drug. For a comprehensive description about the practice of medicine and the role of drug research in the health care industry, see medicine.
The origin of medicines
Medicines of ancient civilizations
The oldest records of medicinal preparations made from plants, animals, or minerals are those of the early Chinese, Hindu, and Mediterranean civilizations. An herbal compendium, said to have been written in the 28th century bc by the legendary emperor Shennong, described the antifever capabilities of a substance known as chang shan (from the plant species Dichroa febrifuga), which has since been shown to contain antimalarial alkaloids (alkaline organic chemicals containing nitrogen). Workers at the school of alchemy that flourished in Alexandria, Egypt, in the 2nd century bc prepared several relatively purified inorganic chemicals, including lead carbonate, arsenic, and mercury. According to De materia medica, written by the Greek physician Pedanius Dioscorides in the 1st century ad, verdigris (basic cupric acetate) and cupric sulfate were prescribed as medicinal agents. While attempts were made to use many of the mineral preparations as drugs, most proved to be too toxic to be used in this manner.
Many plant-derived medications employed by the ancients are still in use today. Egyptians treated constipation with senna pods and castor oil and indigestion with peppermint and caraway. Various plants containing digitalis-like compounds (cardiac stimulants) were employed to treat a number of ailments. Ancient Chinese physicians employed ma huang, a plant containing ephedrine, for a variety of purposes. Today ephedrine is used in many pharmaceutical preparations intended for the treatment of cold and allergy symptoms. The Greek physician Galen (c. 130–c. 200 ad) included opium and squill among the drugs in his apothecary shop (pharmacy). Today derivatives of opium alkaloids are widely employed for pain relief, and, while squill was used for a time as a cardiac stimulant, it is better known as a rat poison. Although many of the medicinal preparations used by Galen are obsolete, he made many important conceptual contributions to modern medicine. For example, he was among the first practitioners to insist on purity for drugs. He also recognized the importance of using the right variety and age of botanical specimens to be used in making drugs.
Pharmaceutical science in the 16th and 17th centuries
Pharmaceutical science improved markedly in the 16th and 17th centuries. In 1546 the first pharmacopoeia, or collected list of drugs and medicinal chemicals with directions for making pharmaceutical preparations, appeared in Nürnberg, Ger. Previous to this time, medical preparations had varied in concentration and even in constituents. Other pharmacopoeias followed in Basel (1561), Augsburg (1564), and London (1618). The London Pharmacopoeia became mandatory for the whole of England and thus became the first example of a national pharmacopoeia. Another important advance was initiated by Paracelsus, a 16th-century Swiss physician-chemist. He admonished his contemporaries not to use chemistry as it had widely been employed prior to his time in the speculative science of alchemy and the making of gold. Instead, Paracelsus advocated the use of chemistry to study the preparation of medicines.
In London the Society of Apothecaries (pharmacists) was founded in 1617. This marked the emergence of pharmacy as a distinct and separate entity. The separation of apothecaries from grocers was authorized by King James I, who also mandated that only a member of the society could keep an apothecary's shop and make or sell pharmaceutical preparations. In 1841 the Pharmaceutical Society of Great Britain was founded. This society oversaw the education and training of pharmacists to assure a scientific basis for the profession. Today professional societies around the world play a prominent role in supervising the education and practice of their members.
In 1783 the English physician and botanist William Withering published his famous monograph on the use of digitalis (an extract from the flowering purple foxglove, Digitalis purpurea). His book, An Account of the Foxglove and Some of Its Medicinal Uses: With Practical Remarks on Dropsy and Other Diseases, described in detail the use of digitalis preparations and included suggestions as to how their toxicity might be reduced. Plants containing digitalis-like compounds had been employed by ancient Egyptians thousands of years earlier, but their use had been erratic. Withering believed that the primary action of digitalis was on the kidney, thereby preventing dropsy (edema). Later, when it was discovered that water was transported in the circulation with blood, it was found that the primary action of digitalis was to improve cardiac performance, with the reduction in edema resulting from improved cardiovascular function. Nevertheless, the observations in Withering's monograph led to a more rational and scientifically based use of digitalis and eventually other drugs.
Isolation and synthesis of compounds
In the 1800s many important compounds were isolated from plants for the first time. About 1804 the active ingredient, morphine, was isolated from opium. In 1820 quinine (malaria treatment) was isolated from cinchona bark and colchicine (gout treatment) from autumn crocus. In 1833 atropine (variety of uses) was purified from Atropa belladonna, and in 1860 cocaine (local anesthetic) was isolated from coca leaves. Isolation and purification of these medicinal compounds was of tremendous importance for several reasons. First, accurate doses of the drugs could be administered, something that had not been possible previously because the plants contained unknown and variable amounts of the active drug. Second, toxic effects due to impurities in the plant products could be eliminated if only the pure active ingredients were used. Finally, knowledge of the chemical structure of pure drugs enabled laboratory synthesis of many structurally related compounds and the development of valuable drugs.
Pain relief has been an important goal of medicine development for millennia. Prior to the mid-19th century, surgeons took great pride in the speed with which they could complete a surgical procedure. Faster surgery meant that the patient would undergo the excruciating pain for shorter periods of time. In 1842 ether was first employed as an anesthetic during surgery, and chloroform followed soon after in 1847. These agents revolutionized the practice of surgery. After their introduction, careful attention could be paid to prevention of tissue damage, and longer and more-complex surgical procedures could be carried out more safely. Although both ether and chloroform were employed in anesthesia for more than a century, their current use is severely limited by their side effects; ether is very flammable and explosive and chloroform may cause severe liver toxicity in some patients. However, because pharmaceutical chemists knew the chemical structures of these two anesthetics, they were able to synthesize newer anesthetics, which have many chemical similarities with ether and chloroform but do not burn or cause liver toxicity.
The development of anti-infective agents
Discovery of antiseptics and vaccines
Prior to the development of anesthesia, many patients succumbed to the pain and stress of surgery. Many other patients had their wounds become infected and died as a result of their infection. In 1865 the British surgeon and medical scientist Joseph Lister initiated the era of antiseptic surgery in England. While many of the innovations of the antiseptic era are procedural (use of gloves and other sterile procedures), Lister also introduced the use of phenol as an anti-infective agent.
In the prevention of infectious diseases, an even more important innovation took place near the beginning of the 19th century with the introduction of smallpox vaccine. In the late 1790s the English surgeon Edward Jenner observed that milkmaids who had been infected with the relatively benign cowpox virus were protected against the much more deadly smallpox. After this observation he developed an immunization procedure based on the use of crude material from the cowpox lesions. This success was followed in 1885 by the development of rabies vaccine by the French chemist and microbiologist Louis Pasteur. Widespread vaccination programs have dramatically reduced the incidence of many infectious diseases that once were common. Indeed, vaccination programs have eliminated smallpox infections. The virus no longer exists in the wild, and, unless it is reintroduced from caches of smallpox virus held in laboratories in the United States and Russia, smallpox will no longer occur in humans. A similar effort is under way with widespread polio vaccinations; however, it remains unknown whether the vaccines will eliminate polio as a human disease.
Improvement in drug administration
While it may seem obvious today, it was not always clearly understood that medications must be delivered to the diseased tissue in order to be effective. Indeed, at times apothecaries made pills that were designed to be swallowed, pass through the gastrointestinal tract, be retrieved from the stool, and used again. While most drugs are effective and safe when taken orally, some are not reliably absorbed into the body from the gastrointestinal tract and must be delivered by other routes. In the middle of the 17th century, Richard Lower and Christopher Wren, working at the University of Oxford, demonstrated that drugs could be injected into the bloodstream of dogs using a hollow quill. In 1853 the French surgeon Charles Gabriel Pravaz invented the hollow hypodermic needle, which was first used in the treatment of disease in the same year by Scottish physician Alexander Wood. The hollow hypodermic needle had a tremendous influence on drug administration. Because drugs could be injected directly into the bloodstream, rapid and dependable drug action became more readily producible. Development of the hollow hypodermic needle also led to an understanding that drugs could be administered by multiple routes and was of great significance for the development of the modern science of pharmaceutics, or dosage form development.
Drug development in the 19th and 20th centuries
New classes of pharmaceuticals
In the latter part of the 19th century a number of important new classes of pharmaceuticals were developed. In 1869 chloral hydrate became the first synthetic sedative-hypnotic (sleep-producing) drug. In 1879 it was discovered that organic nitrates such as nitroglycerin could relax blood vessels, eventually leading to the use of these organic nitrates in the treatment of heart problems. In 1875 several salts of salicylic acid were developed for their antipyretic (fever-reducing) action. Salicylate-like preparations in the form of willow bark extracts (which contain salicin) had been in use for at least 100 years prior to the identification and synthesis of the purified compounds. In 1879 the artificial sweetener saccharin was introduced. In 1886 acetanilide, the first analgesic-antipyretic drug (relieving pain and fever), was introduced, but later, in 1887, it was replaced by the less toxic phenacetin. In 1899 aspirin (acetylsalicylic acid) became the most effective and popular anti-inflammatory, analgesic-antipyretic drug for at least the next 60 years. Cocaine, derived from the coca leaf, was the only known local anesthetic until about 1900, when the synthetic compound benzocaine was introduced. Benzocaine was the first of many local anesthetics with similar chemical structures and led to the synthesis and introduction of a variety of compounds with more efficacy and less toxicity.
Transitions in drug discovery
In the late 19th and early 20th centuries, a number of social, cultural, and technical changes of importance to pharmaceutical discovery, development, and manufacturing were taking place. One of the most important changes occurred when universities began to encourage their faculties to form a more coherent understanding of existing information. Some chemists developed new and improved ways to separate chemicals from minerals, plants, and animals, while others developed ways to synthesize novel compounds. Biologists did research to improve understanding of the processes fundamental to life in species of microbes, plants, and animals. Developments in science were happening at a greatly accelerated rate, and the way in which pharmacists and physicians were educated changed. Prior to this transformation the primary means of educating physicians and pharmacists had been through apprenticeships. While apprenticeship teaching remained important to the education process (in the form of clerkships, internships, and residencies), pharmacy and medical schools began to create science departments and hire faculty to teach students the new information in basic biology and chemistry. New faculty were expected to carry out research or scholarship of their own. With the rapid advances in chemical separations and synthesis, single pharmacists did not have the skills and resources to make the newer, chemically pure drugs. Instead, large chemical and pharmaceutical companies began to appear and employed university-trained scientists equipped with knowledge of the latest technologies and information in their fields.
As the 20th century progressed, the benefits of medical, chemical, and biological research began to be appreciated by the general public and by politicians, prompting governments to develop mechanisms to provide support for university research. In the United States, for instance, the National Institutes of Health, the National Science Foundation, the Department of Agriculture, and many other agencies undertook their own research or supported research and discovery at universities that could then be used for pharmaceutical development. Nonprofit organizations were also developed to support research, including the Australian Heart Foundation, the American Heart Association, the Heart and Stroke Foundation of Canada, and H.E.A.R.T UK. The symbiotic relationship between large public institutions carrying out fundamental research and private companies making use of the new knowledge to develop and produce new pharmaceutical products has contributed greatly to the advancement of medicine.
Establishing the fight against infectious disease
Early efforts in the development of anti-infective drugs
For much of history, infectious diseases were the leading cause of death in most of the world. The widespread use of vaccines and implementation of public health measures, such as building reliable sewer systems and chlorinating water to assure safe supplies for drinking, were of great benefit in decreasing the impact of infectious diseases in the industrialized world. However, even with these measures, pharmaceutical treatments for infectious diseases were needed. The first of these was arsphenamine, which was developed in 1910 by the German medical scientist Paul Ehrlich for the treatment of syphilis. Arsphenamine was the 606th chemical studied by Ehrlich in his quest for an antisyphilitic drug. Its efficacy was first demonstrated in mice with syphilis and then in humans. Arsphenamine was marketed with the trade name of Salvarsan and was used to treat syphilis until the 1940s, when it was replaced by penicillin. Ehrlich referred to his invention as chemotherapy, which is the use of a specific chemical to combat a specific infectious organism. Arsphenamine was important not only because it was the first synthetic compound to kill a specific invading microorganism but also because of the approach Ehrlich used to find it. In essence, he synthesized a large number of compounds and screened each one to find a chemical that would be effective. Screening for efficacy became one of the most important means used by the pharmaceutical industry to develop new drugs.
The next great advance in the development of drugs for treatment of infections came in the 1930s, when it was shown that certain azo dyes, which contained sulfonamide groups, were effective in treating streptococcal infections in mice. One of the dyes, known as Prontosil, was later found to be metabolized in the patient to sulfanilamide, which was the active antibacterial molecule. In 1933 Prontosil was given to the first patient, an infant with a systemic staphylococcal infection. The infant underwent a dramatic cure. In subsequent years many derivatives of sulfonamides, or sulfa drugs, were synthesized and tested for antibacterial and other activities.
Discovery of penicillin
The first description of penicillin was published in 1929 by the Scottish bacteriologist Alexander Fleming. Fleming had been studying staphylococcal bacteria in the laboratory at St. Mary's Hospital in London. He noticed that a mold had contaminated one of his cultures, causing the bacteria in its vicinity to undergo lysis (membrane rupture) and die. Since the mold was from the genus Penicillium, Fleming named the active antibacterial substance penicillin. At first the significance of Fleming's discovery was not widely recognized. It was more than 10 years later before British biochemist Ernst Boris Chain and Australian pathologist Howard Florey, working at the University of Oxford, showed that a crude penicillin preparation produced a dramatic curative effect when administered to mice with streptococcal infections.
The production of large quantities of penicillin was difficult with the facilities available to the investigators. However, by 1941 they had enough penicillin to carry out a clinical trial in several patients with severe staphylococcal and streptococcal infections. The effects of penicillin were remarkable, although there was not enough drug available to save the lives of all the patients in the trial.
In an effort to develop large quantities of penicillin, the collaboration of scientists at the United States Department of Agriculture's Northern Regional Research Laboratories in Peoria, Ill., was enlisted. The laboratories in Peoria had large fermentation vats that could be used in an attempt to grow an abundance of the mold. In England the first penicillin had been produced by growing the Penicillium notatum mold in small containers. However, P. notatum would not grow well in the large fermentation vats available in Peoria, so scientists from the laboratories searched for another strain of Penicillium. Eventually a strain of Penicillium chrysogenum that had been isolated from an overripe cantaloupe was found to grow very well in the deep culture vats. After the process of growing the penicillin-producing organisms was developed, pharmaceutical firms were recruited to further develop and market the drug for clinical use. The use of penicillin very quickly revolutionized the treatment of serious bacterial infections. The discovery, development, and marketing of penicillin provides an excellent example of the beneficial collaborative interaction of not-for-profit researchers and the pharmaceutical industry.
Discovery and development of hormones and vitamins
Isolation of insulin
The vast majority of hormones were identified, had their biological activity defined, and were synthesized in the first half of the 20th century. Illnesses relating to their excess or deficiency were also beginning to be understood at that time. Hormones, produced in specific organs, released into the circulation, and carried to other organs, significantly affect metabolism and homeostasis. Some examples of hormones are insulin (from the pancreas), epinephrine (or adrenaline; from the adrenal medulla), thyroxine (from the thyroid gland), cortisol (from the adrenal cortex), estrogen (from the ovaries), and testosterone (from the testes). As a result of discovering these hormones and their mechanisms of action in the body, it became possible to treat illnesses of deficiency or excess effectively. The discovery and use of insulin to treat diabetes is an example of these developments.
In 1869 Paul Langerhans, a medical student in Germany, was studying the histology of the pancreas. He noted that this organ has two distinct types of cells—acinar cells, now known to secrete digestive enzymes, and islet cells (now called islets of Langerhans). The function of islet cells was suggested in 1889 when German physiologist and pathologist Oskar Minkowski and German physician Joseph von Mering showed that removing the pancreas from a dog caused the animal to exhibit a disorder quite similar to human diabetes mellitus (elevated blood glucose and metabolic changes). After this discovery, a number of scientists in various parts of the world attempted to extract the active substance from the pancreas so that it could be used to treat diabetes. We now know that these attempts were largely unsuccessful because the digestive enzymes present in the acinar cells metabolized the insulin from the islet cells when the pancreas was disrupted.
One of the first successful attempts to isolate the active substance was reported in 1921 by Romanian physiologist Nicolas C. Paulescu, who discovered a substance called pancrein in pancreatic extracts from dogs. Paulescu found that diabetic dogs given an injection of pancrein experienced a temporary decrease in blood glucose levels. Although he did not purify pancrein, it is thought that the substance was insulin. That same year, working independently, Frederick Banting, a young Canadian surgeon in Toronto, persuaded a physiology professor to allow him use of a laboratory to search for the active substance from the pancreas. Banting guessed correctly that the islet cells secreted insulin, which was destroyed by enzymes from the acinar cells. By this time Banting had enlisted the support of Charles H. Best, a fourth-year medical student. Together they tied off the pancreatic ducts through which acinar cells release the digestive enzymes. This insult caused the acinar cells to die. Subsequently, the remainder of the pancreas was homogenized and extracted with ethyl alcohol and acid. The extract thus obtained decreased blood glucose levels in dogs with a form of diabetes. Banting and Best worked with Canadian chemist James B. Collip and Scottish physiologist J.J.R. Macleod to obtain purified insulin, and shortly thereafter, in 1922, a 14-year-old boy with severe diabetes was the first human to be treated successfully with the pancreatic extracts.
After this success other scientists became involved in the quest to develop large quantities of purified insulin extracts. Eventually, extracts from pig and cow pancreases created a sufficient and reliable supply of insulin. For the next 50 years most of the insulin used to treat diabetes was extracted from porcine and bovine sources. There are only slight differences in chemical structure between bovine, porcine, and human insulin, and their hormonal activities are essentially equivalent. Today, as a result of recombinant DNA technology, most of the insulin used in therapy is synthesized by pharmaceutical companies and is identical to human insulin (see below Synthetic human proteins).
Identification of vitamins
Vitamins are organic compounds that are necessary for body metabolism and, generally, must be provided from the diet. For centuries many diseases of dietary deficiency had been recognized, although not well defined. Most of the vitamin deficiency disorders were biochemically and physiologically defined in the late 19th and early 20th centuries. The discovery of thiamin (vitamin B1) exemplifies how vitamin deficiencies and their treatment were discovered.
Thiamin deficiency produces beriberi, a word from the Sinhalese meaning "extreme weakness." The symptoms include spasms and rigidity of the legs, possible paralysis of a limb, personality disturbances, and depression. This disease became widespread in Asia in the 19th century because steam-powered rice mills produced polished rice, which lacked the vitamin-rich husk. A dietary deficiency was first suggested as the cause of beriberi in 1880 when a new diet was instituted for the Japanese navy. When fish, meat, barley, and vegetables were added to the sailor's diet of polished rice, the incidence of beriberi in the navy was significantly reduced. In 1897 the Dutch physician Christiaan Eijkman was working in Java when he showed that fowl fed a diet of polished rice developed symptoms similar to beriberi. He was also able to demonstrate that unpolished rice in the diet prevented and cured the symptoms in fowl and humans. By 1912 a highly concentrated extract of the active ingredient was prepared by the Polish biochemist Casimir Funk, who recognized that it belonged to a new class of essential foods called vitamins. Thiamin was isolated in 1926 and its chemical structure determined in 1936. The chemical structures of the other vitamins were determined prior to 1940.
Emergence of modern diseases and treatment
The rapid decline in the number of deaths from infections due to the development of vaccines and antibiotics led to the unveiling of a new list of deadly diseases in the industrialized world during the second half of the 20th century. Included in this list are cardiovascular disease, cancer, and stroke. While these remain the three leading causes of death today, a great deal of progress in decreasing mortality and disability caused by these diseases has been made since the 1940s. As with treatment of any complex disease, there are many events of importance in the development of effective therapy. For decreasing death and disability from cardiovascular diseases and stroke, one of the most important developments was the discovery of effective treatments for hypertension (high blood pressure)—i.e., the discovery of thiazide diuretics. For decreasing death and disability from cancer, one very important step was the development of cancer chemotherapy.
Hypertension has been labeled the "silent killer." It usually has minimal or no symptoms and typically is not regarded as a primary cause of death. Untreated hypertension increases the incidence and severity of cardiovascular diseases and stroke. Before 1950 there were no effective treatments for hypertension. U.S. Pres. Franklin D. Roosevelt died after a stroke in 1945, despite a large effort by his physicians to control his very high blood pressure by prescribing sedatives and rest.
When sulfanilamide was introduced into therapy, one of the side effects it produced was metabolic acidosis (acid-base imbalance). After further study, it was learned that the acidosis was caused by inhibition of the enzyme carbonic anhydrase. Inhibition of carbonic anhydrase produces diuresis (urine formation). Subsequently, many sulfanilamide-like compounds were synthesized and screened for their ability to inhibit carbonic anhydrase. Acetazolamide, which was developed by scientists at Lederle Laboratories (now a part of Wyeth Pharmaceuticals, Inc.), became the first of a class of diuretics that serve as carbonic anhydrase inhibitors. In an attempt to produce a carbonic anhydrase inhibitor more effective than acetazolamide, chlorothiazide was synthesized by a team of scientists led by Dr. Karl Henry Beyer at Merck & Co., Inc., and became the first successful thiazide diuretic. While acetazolamide causes diuresis by increasing sodium bicarbonate excretion, chlorothiazide was found to increase sodium chloride excretion. More importantly, by the mid-1950s it had been shown that chlorothiazide lowers blood pressure in patients with hypertension. Over the next 50 years many other classes of drugs that lower blood pressure (antihypertensive drugs) were added to the physician's armamentarium for treatment of hypertension. Partially as a result of effective treatment of this disease, the death rate from cardiovascular diseases and stroke decreased dramatically during this period.
The discovery of chlorothiazide exemplifies two important pathways to effective drug development. The first is screening for a biological effect. Thousands of drugs have been developed through effective screening for a biological activity. The second pathway is serendipity—i.e., making fortunate discoveries by chance. While creating experiments that can lead to chance outcomes does not require particular scientific skill, recognizing the importance of accidental discoveries is one of the hallmarks of sound science. Many authorities doubt that Fleming was the first scientist to notice that when agar plates were contaminated with Penicillium mold, bacteria did not grow near the mold. However, what made Fleming great was that he was the first to recognize the importance of what he had seen. In the case of chlorothiazide, it was serendipitous that sulfanilamide was found to cause metabolic acidosis, and it was serendipitous that chlorothiazide was recognized to cause sodium chloride excretion and an antihypertensive effect.
Early progress in cancer drug development
Sulfur mustard was synthesized in 1854. By the late 1880s it was recognized that sulfur mustard could cause blistering of the skin, eye irritation possibly leading to blindness, and severe lung injury if inhaled. In 1917 during World War I, sulfur mustard was first used as a chemical weapon. By 1919 it was realized that exposure to sulfur mustard also produced very serious systemic toxicities. Among other effects, it caused leukopenia (decreased white blood cells) and damage to bone marrow and lymphoid tissue. During the interval between World War I and World War II there was extensive research into the biological and chemical effects of nitrogen mustards (chemical analogs of sulfur mustard) and similar chemical-warfare compounds. The toxicity of nitrogen mustard on lymphoid tissue caused researchers to study the effect of nitrogen mustard on lymphomas in mice. In the early 1940s nitrogen mustard (mechlorethamine) was discovered to be effective in the treatment of human lymphomas. The efficacy of this treatment led to the widespread realization that chemotherapy for cancer could be effective. In turn, this realization led to extensive research, discovery, and development of other cancer chemotherapeutic agents.
Pharmaceutical industry in the modern era
The pharmaceutical industry has become a large and very complex enterprise. At the end of the 20th century, most of the world's largest pharmaceutical companies were located in North America, Europe, and Japan; many of the largest were multinational, having research, manufacturing, and sales taking place in multiple countries. Since pharmaceuticals can be quite profitable, many countries are trying to develop the infrastructure necessary for drug companies in their countries to become larger and to compete on a worldwide scale. The industry has also come to be characterized by outsourcing. That is, many companies contract with specialty manufacturers or research firms to carry out parts of the drug development process for them. Others try to retain most of the processes within their own company. Since the pharmaceutical industry is driven largely by profits and competition—each company striving to be the first to find cures for specific diseases—it is anticipated that the industry will continue to change and evolve over time.


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By Eugenia Woo
As a project of "The Next Fifty" Docomomo US/WEWA and Historic Seattle presented a three-part lecture series at Seattle Center in June 2012 that focused on the architecture and design heritage of the Seattle World's Fair and its influence and impact beyond the Fair's original campus. As part of the larger six-month long (April – October 2012) 50th anniversary celebration organized by the Seattle Center Foundation ("The Next Fifty"), Docomomo US/WEWA was thrilled to present talks by locally and nationally prominent speakers including Docomomo US President Theodore Prudon. The lecture series and project, titled "Welcome to the Future: Century 21 and Living Modern," presented a great opportunity for Docomomo US/WEWA to develop partnerships and sponsorships with Historic Seattle, The Next Fifty and Pacific Science Center, with grant funding provided by 4Culture and the National Trust for Historic Preservation. We also produced a project website/blog at century21mod.com.
Docomomo US/WEWA hosted Theodore Prudon during his visit to the Pacific Northwest. As the third and final speaker of the lecture series, Theo's June 19 presentation on "Modern Building Technology" was well received by local modernist enthusiasts and people seeking to learn more about preserving the modern. The lecture series was a big success overall with the first two lectures focusing on the social and cultural context of the Seattle World's Fair—presented by Seattle writer and journalist Knute Berger, and northwest architects of the Century 21 Exposition—presented by Docomomo US/WEWA Board member, chapter co-founder and architect Susan Boyle.
We began the evening of the event in fine fashion with a reception in the sun-drenched (yes, it finally stopped raining!) courtyard of the Minoru Yamasaki-designed Pacific Science Center, originally built for the Fair in 1962 as the US Science Pavilion. Theo presented his lecture in the newly renovated PACCAR Theater, a historic space in which Charles and Ray Eames are credited with designing. With Theo's current research on the work of Seattle-born Yamasaki , the designated Seattle landmark Pacific Science Center was the ideal venue for his lecture.
Photo (right, l-r): Eugenia Woo, Theodore Prudon, Kathleen Brooker, Historic Seattle Executive Director
During his whirlwind trip, Docomomo US/WEWA Board members toured Theo around some modern sites in Seattle. In addition to a behind-the-scenes private tour of Pacific Science Center, we strolled through the former fairgrounds (now Seattle Center); the Eastlake neighborhood (contains several fine examples of regional modern commercial architecture); and the University of Washington campus. Although known for its Olmsted Bros-designed plan and Gothic Revival style architecture, the UW has an interesting collection of modern buildings on campus including the Nuclear Reactor Building, an ongoing preservation advocacy issue for Docomomo US/WEWA. We ended our day of touring with cocktails in the lounge of Canlis Restaurant, a Seattle institution and modernist gem built in 1950 prominently situated overlooking Lake Union.
Photo (left): Theodore Prudon with Docomomo WEWA Board members Alan Michelson (center) and Andy Phillips (right) at the Nuclear Reactor Building, University of Washington.
Docomomo US/WEWA Board members Susan Boyle, Kathleen McNeely, Alan Michelson, Andy Phillips, Kate Smith, Greg Walton and Eugenia Woo enjoyed the opportunity to spend time with Theo to discuss local issues and view regional modern architecture. We look forward to collaborating more in the future.


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Sept. 27, 2008
NEW HAVEN, Conn. - Saturday afternoon, the Yale men faced off against Harvard in the 95th annual Yale-Harvard dual meet, one of the oldest traditions in collegiate cross-country. The weather cleared enough that the race was able to be contested at the usual venue of the Yale Golf Course. The Bulldogs battled the Crimson over the soggy, 8,000-meter course, led by senior John Hinkle's third-place finish, but ultimately finished in second place with 36 points behind Harvard's score of 21.
Harvard sophomore Daniel Chenoweth won the individual honors this year, crossing the line in 25:43.
Hinkle was the first scorer for the Bulldogs, completing the course in a time of 26:20; this was Hinkle's first cross-country race leading the Yale pack. Fellow senior Murat Kayali was not far behind Hinkle, finishing fourth in 26:30. Rounding out the top five scorers were sophomore Max Walden (eighth, 26:42), junior Jeff Perrella (tenth, 26:46) and junior Max Brown (eleventh, 26:49).
This week, the Bulldogs ran without the contribution of captain Jake Gallagher-the individual champion in this meet against Harvard for the past two years.
Next up for the Bulldogs is the Murray Keatinge Invitational, which will be hosted by the University of Maine on Saturday, Oct. 4th.
Report by Bevin Peters '09, Yale Sports Publicity


text: A butcher shop in Paris, which prominently advertises that it sells halal meat. Michel Euler/AP hide caption toggle caption Michel Euler/AP The Salt French Muslims Ease Cultural Tensions With French-Halal Food April 2, 2012 Halal meat butchers have a reputation for quality in France. And with an estimated 6 million Muslims now living there, halal products are becoming increasingly popular, and sometimes political. Now one French-Algerian restaurant is trying to make French-Halal fusion food official.


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Fox Broadcasting is overhauling much of its prime-time lineup after a disappointing season.
The network, which endured steep declines in overall viewers and in the coveted 18-to-49-year-old demographic, said it will premiere 12 new shows next season. Only two of the shows it launched this season -- the comedy "Brooklyn Nine-Nine" and the drama "Sleepy Hollow" -- made it to next fall.
Gone are freshman comedies "Dads," "Enlisted" and "Surviving Jack," and dramas "Almost Human" and "Rake."
Veteran comedy "Raising Hope" and the musical talent show "The X Factor" were also shown the door.
"This past one was a tough one for us," said Fox Entertainment Chairman Kevin Reilly. According to Nielsen, not including sports, Fox's prime-time lineup averaged about 5.9 million viewers. viewers. Last season Fox averaged 6.7 million viewers.
New shows weren't Fox's only problem this season. The juggernaut "American Idol" came crashing to Earth. Last week, one of the episodes of "American Idol" averaged just 7 million viewers. The median age for the show is now over 50. When it made its debut more than a decade ago, the typical "Idol" viewer was about 30.
The number of hours allotted for "American Idol" will be scaled back dramatically next season, to 37 from more than 50 this season. Reilly said he is optimistic that Jennifer Lopez, Harry Connick Jr. and Keith Urban will return as judges.
But the days of "American Idol" dominating the ratings are over, Reilly said.
"'Idol' is not going to come back as the ratings champion it once was," Reilly said. But the network isn't ready to throw in the towel. Reilly said it can be a "potent" show "for many years to come."
The network's new programs include "Gotham," a prequel of sorts to "Batman" starring Benjamin McKenzie ("Southland") as a young Commissioner Gordon rising up through the ranks by putting down the bad guys. The noirish "Gotham" also stars Donal Logue and Jada Pinkett Smith. It will air at 8 p.m. Mondays as a lead-in to "Sleepy Hollow."
"This is sure to be this season's biggest and noisiest hit," Reilly predicted.
Fox's other big fall drama bet is "Red Band Society," a quirky drama about high school kids living in a pediatric ward of a hospital. Oscar winner Octavia Spencer plays a nurse in charge of the ward and the executive producers include Steven Spielberg and Justin Falvey, whose credits include FX's critically acclaimed "The Americans." "Red Band Society" is scheduled for Wednesdays at 9 p.m., following the reality show "Hell's Kitchen.
Fox will also try its luck with "Gracepoint, a remake of the British hit "Broadchurch" about the murder of a child and the effect it has on a small California town. Called an event series by the network, "Gracepoint" will run for 10 weeks in the fall at 9 p.m. on Thursdays, following the veteran crime drama "Bones." It stars Anna Gunn of "Breaking Bad" fame and Nick Nolte.
The network's other big move is relocating "Brooklyn Nine-Nine," a low-rated critical darling, from Tuesday at 8:30 p.m. to Sunday at 8:30 p.m. where it will have a strong lead-in from "The Simpsons." Fox is also debuting the new comedy "Mulaney" at 9:30 p.m. Executive produced by "Saturday Night Live" creator Lorne Michaels, "Mulaney" stars John Mulaney as a comedian who ends up writing for an obnoxious game show host played by Martin Short.
For Fox, this marks the first time in several years it is attempting live-action comedies on Sunday night, which previously has been all animation.
On the reality front, Fox will try its own version of the long-running CBS hit "Survivor." Called "Utopia," it will strand 15 people in an undeveloped part of the world for a year and film them trying to create their own society. "Utopia" will air on Tuesdays at 8 p.m. and Fridays at 9 p.m.
Reilly said "Utopia" is a "very big bet" and the most compelling unscripted show in "quite some time."
Fox also announced several shows for the spring, including the drama "Empire" and the comedy "The Last Man on Earth."
"Empire" stars Terrence Howard as the head of a powerful music label whose biggest threat may be his own family. Lee Daniels, the director of "The Butler" and "Precious," created the series. "The Last Man on Earth" is a dark comedy starring Will Forte as literally the last man on the planet who roams the country in an RV looking for others.
Also returning next season are "Glee," "The Mindy Project" and "New Girl."