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Bucks. Moolah. Dough. Whatever you call it, money matters, and so do banking, lending and investing.
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MintLife Blog | Personal Finance News & Advice
Countless action and mystery movies depict Swiss bank accounts as places for villains to hide ill-gotten fortunes. But today, offshore banking is much more than a haven for underhanded financial shell games. Increasingly, legitimate businesses and in...
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Dear Cecil:
Capuano to CEOs: No One Trusts You Anymore
February 11, 2009
Watch The Full Program
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Americans who want to save for the future get dunked in a big bowl of alphabet soup: 401(k)s, IRAs, 529s, HSAs. If you want to save that dollar in a tax-advantaged way, where to put it?
Find Your Lost Money At Unclaimed.Org
Barbara's Blog: Could You Afford to be Poor?
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No SSN
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MintLife Blog | Personal Finance News & Advice
MintLife Blog | Personal Finance News & Advice
The United States got tarred with a negative outlook on its credit rating by Standard & Poor's last month, but there are plenty of other countries in the same boat. Here's a look at where they stand, the good, the bad and ugly.
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Our special coverage of the closest race for years
Explore the personal stories of Syrian refugees in Lebanon
27 Feb 2012 16:56 GMT | Human Rights, Arts & Culture, France, Israel, Pakistan
The Artist, a black-and-white romance set in 1920s-era Hollywood, has won five Academy Awards and become the first silent film to bag best picture, the awards' highest honour, since the original Oscar ceremony 83 years ago.
This year's awards, given out in a customary glittering ceremony on Sunday, also broke new ground, anointing winners from Iran and Pakistan for the first time.
A Separation, about an Iranian couple choosing between a better life outside the country and remaining to care for an ailing parent, won best foreign-language film, while Saving Face, centred on women victims of acid attacks in Pakistan, won best short documentary.
"At a time of talk of war, intimidation and aggression is exchanged between politicians, the name of their county, Iran, is spoken here through her glorious culture, a rich and ancient culture that has been hidden under the heavy dust of politics," Asghar Farhadi, the director of A Separation, said as he accepted the Oscar.
"I proudly offer this award to the people of my country, the people who respect all cultures and civilizations and despise hostility and resentment."
Two nights before the Oscar ceremony, Israeli and Iranian artists came together in a show of peace, said Lior Ashkenazi, a star of the Israeli foreign language Oscar entry, Footnote.
"At the Academy event in honour of the foreign films, we sat, spoke and all the veils came off," Ashkenazi told Israel's Army Radio. "They are warm hearted people. We invited them to Tel Aviv and they invited us to Tehran."
Among the other prizes that went to The Artist, a black-and-white comic melodrama, were best actor for Jean Dujardin and best director for Michel Hazanavicius, who had been known best for making spy comedies in his native France.
The other top Oscars went to Meryl Streep as best actress for The Iron Lady, a portrayal of the former British prime minister, Margaret Thatcher, struggling with dementia, as well as Octavia Spencer as supporting actress for The Help and Christopher Plummer as supporting actor for Beginners.
Streep is the fifth performer in history to receive three Oscars. Dujardin is the first Frenchman to win an acting Oscar. French actresses have won before, including Marion Cotillard and Juliette Binoche.
Source: Agencies
Investigation finds that secretive selection group is 77 per cent male and 94 per cent white.
Human Rights, Arts & Culture
Week-long campaign commences for parliamentary elections that will likely highlight rivalry within conservative camp.
Politics, Middle East
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Activists in the Czech Republic demand that a pig farm built over a former Nazi concentration camp be shut down.
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In religiously conservative Brazil, women risk jail time and their lives to undergo the procedure that is illegal but commonplace.
Health, Human Rights, Latin America
Trash is a fast-growing import in the Scandinavian country, which turns it into heat for people's homes.
Environment, Europe, Sweden
Critics say the UK's home secretary is using Muslims as a 'political punchbag' in a bid to shore up right-wing support.
Human Rights, Politics, Racism
Election commission declares victory for former military ruler, Muhammadu Buhari, over incumbent Goodluck Jonathan.
Politics, Africa, Nigeria, Nigeria Decides
Legally installed government in Tripoli removes Omar al-Hassi as the head of National Salvation Government.
War & Conflict, Middle East, Libya
It is a source of sustenance but also of tension and new political realities are now increasing uncertainty.
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A media post-mortem into the UK's surveillance report. Plus, why five years on in Argentina the media looks so familiar.
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The untold story of how the Lebanese community overcame the odds and found their place in multicultural Australia.
Asia Pacific, Australia, Lebanon
How to keep a telenovela profitable and demanding sponsors happy while inspiring the production team to stay passionate.
Arts & Culture, Mexico, Latin America

subset: commoncrawl


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Graphic Novels
Looking for the latest and upcoming graphic novels? Forbidden Planet International has the largest collection of books at the lowest prices. Browse for collected editions from Marvel, DC, Image and Dark Horse as well as outstanding original independent works by Fantagraphics, Drawn & Quarterly and many more.
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Guardians of the Galaxy & X-Men : the Black Vortex Hardcover
£18.99 £13.10
Thor Volume 2 : Who Holds The Hammer Premiere Hardcover


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News - Networks/clubs
Mortgage Solutions | 11 Feb 2013 | 13:07
A former Honister Partners adviser has pleaded guilty to evading tax in a case brought by Her Majesty's Revenue & Customs (HMRC).
David Douglass, 45, from Silver Birch Drive, Hollywood, had been charged with cheating the public revenue contrary to common law.
HMRC argued Douglass had evaded tax estimated at £730,000.
He entered a guilty plea on 11 February and sentencing is due to take place on 19 April.
Douglass worked for Honister Partners, formally Bates, between March 2006 and July last year. He previously worked for Berry Birch & Noble Financial Planning.
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Adjusting to the Mustang's size?
Hey guys, I'm buying a Mustang v6 in a few months. I went on a test drive at my dealer this weekend, and I have some questions.
I'm coming from a tiny hyundai 4-door compact car.. getting in the mustang, it felt like a huuuuge car on the road. The windows seemed small, and the frame supports on the right and left side of the windshield seemed to really block my view.
Is it easy to adjust to the size of the car?
I didn't even dare park it in a parking spot because I couldn't tell how far I was away from the car in front of me. Now, I do have an eye condition which makes it difficult to see depth but this thing seemed massive on the road.
Going from a 98HP hyundai to a 305HP mustang was nuts though... wow is all I have to say about that.:icon_musclecar:
And yes, it isnt hard to manage, i adjusted quickly and just got in and drove
Essentially, I mainly look out of one eye and focus with one eye at a time, and the other eye sometimes floats around, or I can use it peripherally. So, only get focus from one eye, the other eye doesn't communicate with the brain, and thus no depth information. It's easy to drive once I know the vehicle, like my current car, I can park it just fine, but since I was in a new car it was difficult at first.
You'll be fine, the visibility becomes of limited issue after you spend some time in the car. I drove a Camry prior to the current mustang, and visibility is hugely better in the Camry, but after the first drive or two, the mustang didn't seem out of the ordinary at all. The convex blind-spot mirrors on either side mirror help to eliminate blind spots on your sides, and the back windshield (I even have the pedestal spoiler from the factory) allows for plenty of sight to see what's coming up behind you.
In terms of the hood out front, it just takes some adjustment and trial (preferably no error) when parking, etc. but again something that should definitely be easy to get used to. When pulling into parking spots, just imagine having closer to 5 feet extending in front of your car as opposed to probably 2.5 or 3 before.
You will get used to it. On the road I don't notice a size difference between my Mustang and my Celica I have been driving that last 15 years. Granted, I drive my wife's Explorer often and I am a manager in the transportation industry. I spend a lot of time driving tractor trailers.
So I might not be the best to answer the size thing.
The A pillars though, yeah, I have caught myself a time or three having a to stop because a car hid perfectly in them. That is exactly why you look left, right, left, right before you move.
I actually went in the opposite direction; from an SUV to the Stang. The SUV remains my DD but getting into the Stang is always a pleasure. The adjustment occurs quickly.
OP, ask your salesperson to take you to a lot with painted parking. Practice parking the car. If you really can't park it, consider hard if the mustang is the right car for you. Good luck with your purchase.
Adjustment is easy and will happen. The new mustangs are big and heavy even compared to earlier gens. Getting seat time is the only way to master your new car. When parking, take your time and learn to use the mirrors. Don't just go by feel. Have fun and good luck!
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The size and visibility of the new mustangs is on par with my 72 Mach1. Takes some getting use too. Another note sound like you have the same eye condition I do. I get bad headaches since my right eye does most of the work.
Just teasing you, bud. :icon_stooge:
For what it's worth, I drive a semi and my Mustang seemed tiny when I bought it. Now it seems just about perfect in size. It's not a boat and it's not some cheesy little Smart car... :)
Go test drive the camaro! LOl!
hey OP, if it helps you might back into parking spots, unbuckle, open the door a bit and lean out some looking back, and you can get a far better view of where you are in a spot. I do this alot at work where the curb is low enough to scrape my chin spoiler so I back in.
And for the rear pillar, adjust your mirrors out away from the car a bit. I got rear window covers which makes a HUUUGE blind spot and this helps as there is no reason to look at the side of the car in the mirrors and it covers my blind spot this way.
you'll get used to the car quickly, GOOD LUCK!
I had to adjust to the size and visibility of the mustang too. Coming from a 1980's hatchback, it was night and day. The size you get used to pretty quick. Just gotta remember the nose is long and the rear is short :D
To help with visibility I installed a license plate camera (was gonna do it anyways) and have small convex mirrors in the corners of my side mirrors like the 2011+s have. (let the judging begin). These things aren't NEEDED and i did fine without them but they definitely help and make daily driving easier.
edit: oh yea, in terms of the quarter windows...those dont' even get used...it's a pointless. I just use my mirrors(that's where the convex mirror come into play). I've almost run over padestrians cause those bastards hide in my A-pillar all the time. I've learned check the A pillar area by looking through the windshield and then moving my head to the side and looking out the side window just to make sure.
The hood is massive, but you will get use to it. If it is really a big problem for you, you can get front and rear parking assist installed for a fairly cheap price. Good luck and welcome to the forum.
Pretty much echo all the sentiments here but I'll add that my younger sister has and had a couple of Hyundai's. Something I'd personally never have. They certainly feel like a totally different class of vehicle and I understand what you are saying. As with any vehicle you will get accustomed to the size. I'd recommend picking up some traffic cones, going with a friend of family member you trust to an empty parking lot and practicing the parking thing with the cones. Churches are great during the week and schools during the weekend. The cones can simulate cars. Also, make sure that your side mirrors are properly adjusted. I used to adjust mine wrong like every other person I know until I took a class for a speeding ticket. One thing I gleaned was proper mirror adjustment to avoid blind spots and now there's no such thing as a blind spot! From a driving position, each mirror should be adjusted out until they are just past the point where you cannot see any of the side of your car without leaning slightly in the direction of said mirror.
If it makes you feel any better, my transition was from a Mazda Miata to a Mustang lol
Bottom line, just as most folks here have already said, you'll get used to it. It's certainly much (MUCH) bigger than my previous car, I've lost a little visibility due to the larger/higher engine compartment and hood scoop, and I can't easily see the ground all around me anymore, but by taking my time and quadruple checking mirrors for the first few days whenever maneuvering, I settled in in just a few days. Gauging the size of the vehicle in relation to where you are and your position in the car will come with time.
I test drove a Challenger and loved the car but it felt more challenging (no pun intended...really!) than the mustang. The Mustang felt like "my car" the first time I drove it. I did have to get out of it to see how close I was to things to learn how to park it.
I drove a Taurus before the Mustang and an Explorer before that and learned to drive all of them, and never hit anything because of depth perception. I just stress out about tight spaces more than I need to. I underestimate distances, which has got to be better than overestimating.
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Anyone interested in a plant swap in Concord NC area
gr82bgrammyApril 3, 2010
Hi, Last year there was a plant swap in the Concord area and I was wondering if any of you are interested in doing one this spring? With the warm weather, everything is beginning to bloom, so it would be a great time to meet and share our plants! Let me know.


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How Can Hepatitis A Be Avoided
Here's a taste of what TheBody.com has to offer on this topic:
Ask the Experts
how to avoid HEPATITISI have been tested for all forms of Hepatitis but I am very concerned about the possibility of catch it. How or where can I do to find out what the different kinds are and what I can do to avoid them.
Response from Barbara McGovern, M.D.
Tufts University School of Medicine...The risk factor for hepatitis A is ingestion of contaminated food and water. In US, hepatitis A outbreaks can occur sometimes related to a food-related outbreak, Read more »
hepatitis cif turmeric can help or harm pacient with hepatitis c and if no how to use it to help? tnx. Read more »
hep c transmission (Guide to Hepatitis C for People Living With HIV)Dear Dr. Bob:How exactly is Hep C transmitted?Best regards,Just Wondering Read more »
Update on Management of the HIV/Hepatitis B- or HIV/Hepatitis C-Coinfected Patient... Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) constitutes two of the leading causes of chronic hepatitis and cirrhosis worldwide. 1-3 Because HIV, HBV and HCV share common transmission routes involving blood -- for... Read more »
Hepatitis: Overview...healthy. Hepatitis can lead to serious scarring (cirrhosis) of the liver and liver failure, which can be fatal. Many cases of hepatitis aren't treated because people either don't feel sick at all, or think they have the flu. The most common... Read more »
Hepatitis B FAQs for the Public...cause hepatitis. Hepatitis is also the name of a family of viral infections that affect the liver>; the most common types are Hepatitis A, Hepatitis B, and Hepatitis C. What is the difference between Hepatitis A, Hepatitis B, and Hepatitis C?... Read more »
Hepatitis A FAQs for the Public...Hepatitis C People who are treated with clotting-factor concentrates People who work with Hepatitis A infected animals or in a Hepatitis A research laboratory How is the Hepatitis A vaccine given? The Hepatitis A vaccine is... Read more »
Connect With Others
insertive oral sex and vih and hepatitis b
Posted by nightsunami...can i infectet by hepatitis B for insertive oral sex?? i have a negative VIH test from 1 year... Read more »
hepatitis b and insertive oral sex
Posted by nightsunami...can i infected by hepatitis B from insertive oral sex??im negative test 5 monts and 2 weeks of HIV after my last encountrer- thanks Read more »
hepatitis B (duda solo por si hay algun medico)
Posted by Mairannnn, 2 Replies...cual es el periodo de ventana de la hepatitis b? y ya que estamos de la c? en que lapso de tiempo es aconsejable hacer una serologia? saludos Read more »
Any other guys out there had Hepatitis-B??
Posted by MarkyMark, 9 Replies...I have been goin through an acute episode of Hepatitis-B for 3 months now and cant seem to find anyone out there who has also gone through this and i have no one to talk to, I feel Read more »
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You are a fan of powers euro ? Come to discover the best forums powers euro on the internet and share your experience with a community fan of powers euro . You can also build a forum powers euro and create your online discussion.
Locksmith forum
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Free forum : A Roleplay center for all of you Hetalia fans!Come in, pick a country, and enjoy Rping to your heart's content.
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It's twenty years in the future. A school has been established for those with supernatural powers. Strange people in black have been showing up lately, though. There's something wrong here.
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This is where duelist unlock their galactic powers!
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Free forum : Create your own character from the popular video game series, inFamous. Wether it be a conduit with amazing powers, a powerful gang member, or an ordinary civilian.
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Two rival schools for those Gifted with the power, which side will you choose ?
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Online community for people who are interested in trucks or simulator games, such as Euro Truck Simulator 2, Scania Truck Driving Simulator, German Truck Simulator, 18 wos Extreme trucker and others.
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Toyota Becomes New IOC TOP Sponsor Toyota, IOC Reportedly Strike TOP Deal IOC Could Alter Controversial Rule 40 Olympic Channel Aimed At Young People In The Works IOC Focusing On Virtual Reality, But Not 4K USOC Ready To Name '24 Bid City USOC Denies Boston Has Weakest '24 Bid IOC Passes Sweeping Reform IOC Releases Reform Agenda Could Oslo's Move Be Impetus For IOC Change?
Upcoming Conferences and Events
SBD/24/Front Page
Published January 24, 1995
"We'll take a breather. We'll let someone else carry the baton." -- Salt Lake Bid President Tom Welch, telling the IOC that Salt Lake would not bid for 2006 Games (ATLANTA CONSTITUTION, 1/24).


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A method to inhibit the growth of tumors in human patients, comprising treating the human patients with an effective amount of a combination of radiation and a non-radiolabeled protein receptor tyrosine kinase inhibitor, the overexpression of which can lead to tumorigenesis.
1. A method to inhibit the growth of tumors in human patients, comprising treating the human patients with an effective amount of a combination of radiation and a non-radiolabeled protein receptor tyrosine kinase inhibitor, the overexpression of which can lead to tumorigenesis.
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[0001] This application claims priority from U.S. Provisional Application No. 60/085,613 filed May 15, 1998.
[0002] Normal cells proliferate by the highly controlled activation of growth factor receptors by their respective ligands. An example of such receptors are the growth factor receptor tyrosine kinases.
[0003] Cancer cells also proliferate by the activation of growth factor receptors, but lose the careful control of normal proliferation. The loss of control may be caused by numerous factors, such as the autocrine secretion of growth factors, increased expression of receptors, and autonomous activation of biochemical pathways regulated by growth factors.
[0004] Some examples of receptors involved in tumorigenesis are the receptors for epidermal growth factor (EGFR), platelet-derived growth factor (PDGFR), insulin-like growth factor (IGFR), nerve growth factor (NGFR), and fibroblast growth factor (FGF).
[0005] Members of the epidermal growth factor (EGF) receptor family are particularly important growth factor receptor tyrosine kinases associated with tumorigenesis of epidermal cells. The first member of the EGF receptor family to be discovered was the glycoprotein having an apparent molecular weight of approximately 165 kD. This glycoprotein, which was described by Mendelsohn et al. in U.S. Pat. No. 4,943,533, is known as the EGF receptor (EGFR) and also as human EGF receptor-1 (HER1).
[0006] The EGFR is overexpressed on many types of epidermoid tumor cells. EGF and transforming growth factor alpha (TGF-alpha) are two known ligands of EGFR. Examples of tumors that express EGF receptors include glioblastomas, as well as cancers of the lung, breast, head and neck, and bladder. The amplification and/or overexpression of the EGF receptors on the membranes of tumor cells is associated with a poor prognosis.
[0007] Some progress has been made in treating cancer. Useful treatments include those that rely on the programmed death of cells that have suffered DNA damage. The programmed death of cells is known as apoptosis.
[0008] Treatments of cancer traditionally include chemotherapy or radiation therapy. Some examples of chemotherapeutic agents include doxorubicin, cis-platin, and taxol. The radiation can be either from an external beam or from a source placed inside a patient, i.e., brachytherapy.
[0009] Another type of treatment includes inhibitors of growth factors or growth factor receptors involved in the proliferation of cells. Such inhibitors neutralize the activity of the growth factor or receptor, and inhibit the growth of tumors that express the receptor.
[0010] For example, U.S. Pat. No. 4,943,533 describes a murine monoclonal antibody called 225 that binds to the EGF receptor. The patent is assigned to the University of California and licensed exclusively to ImClone Systems Incorporated. The 225 antibody is able to inhibit the growth of cultured EGFR-expressing tumor lines as well as the growth of these tumors in vivo when grown as xenografts in nude mice. See Masui et al., Cancer Res. 44, 5592-5598(1986).
[0011] Similarly, Prewett et al. reported the inhibition of tumor progression of well-established prostate tumor xenografts in mice with a chimeric form of the anti-EGFR 225 monoclonal antibody discussed above. The chimeric form is called c225. Journal of Immunotherapy 19, 419-427 (1997).
[0012] A disadvantage of using murine monoclonal antibodies in human therapy is the possibility of a human anti-mouse antibody (HAMA) response due to the presence of mouse Ig sequences. This disadvantage can be minimized by replacing the entire constant region of a murine (or other non-human mammalian) antibody with that of a human constant region. Replacement of the constant regions of a murine antibody with human sequences is usually referred to as chimerization.
[0013] The chimerization process can be made even more effective by also replacing the framework variable regions of a murine antibody with the corresponding human sequences. The framework variable regions are the variable regions of an antibody other than the hypervariable regions. The hypervariable regions are also known as the complementarity-determining regions (CDRs).
[0014] The replacement of the constant regions and framework variable regions with human sequences is usually referred to as humanization. The humanized antibody is less immunogenic (i.e. elicits less of a HAMA response) as more murine sequences are replaced by human sequences. Unfortunately, both the cost and effort increase as more regions of a murine antibodies are replaced by human sequences.
[0015] Another approach to reducing the immunogenicity of antibodies is the use of antibody fragments. For example, an article by Aboud-Pirak et al., Journal of the National Cancer Institute 80, 1605-1611 (1988), compares the anti-tumor effect of an anti-EGF receptor antibody called 108.4 with fragments of the antibody. The tumor model was based on KB cells as xenografts in nude mice. KB cells are derived from human oral epidermoid carcinomas, and express elevated levels of EGF receptors.
[0016] Aboud-Pirak et al. found that both the antibody and the bivalent F(ab′)2 fragment retarded tumor growth in vivo, although the F(ab′)2 fragment was less efficient. The monovalent Fab fragment of the antibody, whose ability to bind the cell-associated receptor was conserved, did not, however, retard tumor growth.
[0017] Attempts have also been made to improve cancer treatments by combining some of the techniques mentioned above. For example, Baselga et al. reported anti-tumor effects of the chemotherapeutic agent doxorubicin with anti-EGFR monoclonal antibodies in the Journal of the National Cancer Institute 85, 1327-1333 (1993).
[0018] Others have attempted to enhance the sensitivity of cancer cells to radiation by combining the radiation with adjuvants. For example, Bonnen, U.S. Pat. No. 4,846,782, reported increased sensitivity of human cancers to radiation when the radiation was combined with interferon. Snelling et al. reported a minor improvement in the radiation treatment of patients with astrocytomas with anaplastic foci when the radiation was combined with an anti-EGFR monoclonal antibody radiolabeled with iodine-125 in a phase II clinical trial. See Hybridoma 14, 111-114 (1995).
[0019] Similarly, Balaban et al. reported the ability of anti-EGFR monoclonal antibodies to sensitize human squamous carcinoma xenografts in mice to radiation when the radiation treatment was preceded by administration of an anti-EGFR antibody called LA22. See Biochimica et Biophysica Acta 1314, 147-156 (1996). Saleh et al. also reported better tumor control in vitro and in mice when radiation therapy was augmented with anti-EGFR monoclonal antibodies. Saleh et al. concluded that: �Further studies . . . may lead to a novel combined modality RT/Mab therapy.� See abstract 4197 in the proceedings of the American Association for Cancer Research 37, 612 (1996).
[0020] While some of the studies described above suggest further experiments in humans, the results reported are for models in mice. Such models do not necessarilly provide a reasonable expectation for success in humans. As was stated in the New York Times of May 3, 1998, in regard to the spectacular success reported by Judah Folkman in treating tumors in mice with angiostatin and endostatin: �Until patients take them, he said, it is dangerous to make predictions. All he knows, Dr. Folkman said, is that �if you have cancer and you are a mouse, we can take good care of you.�� See page 1 of the New York Times of May 3, 1998.
[0021] Cancer continues to be a major health problem. The objective of the present invention is to provide an improved method for treating certain cancers in humans.
[0022] This, and other objectives as will be apparent to those having ordinary skill in the art, have been achieved by providing a new method to inhibit the growth of tumors in human patients. The method comprises treating the human patients with an effective amount of a combination of radiation and a non-radiolabeled protein receptor tyrosine kinase inhibitor, the overexpression of which can lead to tumorigenesis.
[0023] The present invention provides an improved method for treating tumors, particularly malignant tumors, in human patients who have cancer, or are at risk of developing cancer. The types of tumors that can be treated in accordance with the invention are tumors that overexpress one or more growth factor receptor tyrosine kinases. Some examples of growth factor receptor tyrosine kinases that can lead to tumorigenesis if overexpressed include the EGFR family of receptors, PDGFR family of receptors, IGFR family of receptors, NGFR family of receptors, TGF family of receptors, and FGFR family of receptors.
[0024] The EGFR family of receptors includes EGFR, which is also referred to in the literature as HER1; HER2, which is also referred to in the literature as Neu, c-erbB-2, and p185erbB-2; erbB-3 and erbB-4. In this specification, EGFR refers to the EGFR family of receptors. The specific member of the EGFR family of receptors that is also called EGFR will be referred to as EGFR/HER1.
[0025] The PDGFR family of receptors includes PDGFRα and PDGFRβ. The IGF family of receptors includes IGFR-1. Members of the FGFR family include FGFR-1, FGFR-2, FGFR-3, and FGFR-4. The TGFR family of receptors includes TGFRα and TGFRβ.
[0026] Any type of tumor that overexpresses at least one growth factor receptor tyrosine kinase, the overexpression of which can lead to tumorigenesis, can be treated in accordance with the method of the invention. These types of tumor include carcinomas, gliomas, sarcomas, adenocarcinomas, adenosarcomas and adenomas.
[0027] Such tumors occur in virtually all parts of the human body, including every organ. The tumors may, for example, be present in the breast, lung, colon, kidney, bladder, head and neck, ovary, prostate, brain, pancreas, skin, bone, bone marrow, blood, thymus, uterus, testicles, cervix, and liver. For example, tumors that overexpress the EGF receptor include breast, lung, colon, kidney, bladder, head and neck, especially squamous cell carcinoma of the head and neck, ovary, prostate, and brain.
[0028] The tumors are treated with a combination of radiation therapy and a non-radiolabeled growth factor receptor tyrosine kinase inhibitor. For the purposes of this specification, the inhibition of a growth factor receptor tyrosine kinase means that the growth of cells overexpressing such receptors is inhibited.
[0029] No particular mechanism of inhibition is implied. Nevertheless, growth factor receptor tyrosine kinases are generally activated by means of phosphorylation events. Accordingly, phosphorylation assays are useful in predicting the inhibitors useful in the present invention. Some useful assays for tyrosine kinase activity are described in Panek et al., Journal of Pharmacology and Experimental Therapeutics 283, 1433-1444 (1997) and in Batley et al., Life Sciences 62, 143-150 (1998). The description of these assays is incorporated herein by reference.
[0030] In the preferred embodiment, there is synergy when tumors in human patients are treated with a combination of an inhibitor of a growth factor receptor tyrosine kinase and radiation, as described herein. In other words, the inhibition of tumor growth from the combined treatment with an inhibitor and radiation is better than would be expected from treatment with either the inhibitor or radiation alone. Synergy may be shown, for example, by greater inhibition of tumor growth with the combined treatment than would be expected from treatment with either inhibitor or radiation alone. Preferably, synergy is demonstrated by remission of the cancer with the combined treatment with inhibitor and radiation where remission is not expected from treatment with either inhibitor or radiation alone.
[0031] The source of radiation can be either external or internal to the patient being treated. When the source is external to the patient, the therapy is known as external beam radiation therapy (EBRT). When the source of radiation is internal to the patient, the treatment is called brachytherapy (BT).
[0032] The radiation is administered in accordance with well known standard techniques with standard equipment manufactured for this purpose, such as AECL Theratron and Varian Clinac. The dose of radiation depends on numerous factors as is well known in the art. Such factors include the organ being treated, the healthy organs in the path of the radiation that might inadvertently be adversely affected, the tolerance of the patient for radiation therapy, and the area of the body in need of treatment. The dose will typically be between 1 and 100 Gy, and more particularly between 2 and 80 Gy. Some doses that have been reported include 35 Gy to the spinal cord, 15 Gy to the kidneys, 20 Gy to the liver, and 65-80 Gy to the prostate. It should be emphasized, however, that the invention is not limited to any particular dose. The dose will be determined by the treating physician in accordance with the particular factors in a given situation, including the factors mentioned above.
[0033] The distance between the source of the external radiation and the point of entry into the patient may be any distance that represents an acceptable balance between killing target cells and minimizing side effects. Typically, the source of the external radiation is between 70 and 100 cm from the point of entry into the patient.
[0034] Brachytherapy is generally carried out by placing the source of radiation in the patient. Typically, the source of radiation is placed approximately 0-3 cm from the tissue being treated. Known techniques include interstitial, intercavitary, and surface brachytherapy. The radioactive seeds can be implanted permanently or temporarily. Some typical radioactive atoms that have been used in permanent implants include iodine-125 and radon. Some typical radioactive atoms that have been used in temporary implants include radium, cesium-137, and iridium-192. Some additional radioactive atoms that have been used in brachytherapy include americium-241 and gold-198.
[0035] The dose of radiation for brachytherapy can be the same as that mentioned above for external beam radiation therapy. In addition to the factors mentioned above for determining the dose of external beam radiation therapy, the nature of the radioactive atom used is also taken into account in determining the dose of brachytherapy.
[0036] The growth factor receptor tyrosine kinase inhibitor is administered before, during, or after commencing the radiation therapy, as well as any combination thereof, i.e. before and during, before and after, during and after, or before, during, and after commencing the radiation therapy. The antibody is typically administered between 1 and 30 days, preferably between 3 and 20 days, more preferably between 5 and 12 days before commencing radiation therapy and/or termination of external beam radiation therapy.
[0037] Any non-radiolabeled inhibitor of a growth factor receptor tyrosine kinase, the overexpression of which can be tumorigenic, is useful in the method of the invention. The types of tumors that overexpress such receptors have been discussed above. The inhibitors may be biological molecules or small molecules.
[0038] Biological inhibitors include proteins or nucleic acid molecules that inhibit the growth of cells that overexpress a growth factor receptor tyrosine kinase. Most typically, biological molecules are antibodies, or functional equivalents of antibodies.
[0039] Functional equivalents of antibodies have binding characteristics comparable to those of antibodies, and inhibit the growth of cells that overexpress growth factor receptor tyrosine kinase receptors. Such functional equivalents include, for example, chimerized, humanized and single chain antibodies as well as fragments thereof.
[0040] Functional equivalents of antibodies include polypeptides with amino acid sequences substantially the same as the amino acid sequence of the variable or hypervariable regions of the antibodies of the invention. �Substantially the same� amino acid sequence is defined herein as a sequence with at least 70%, preferably at least about 80%, and more preferably at least about 90% homology to another amino acid sequence, as determined by the FASTA search method in accordance with Pearson and Lipman, Proc. Natl. Acad. Sci. USA 85, 2444-2448 (1988). The DNA molecules that encode functional equivalents of antibodies typically bind under stringent conditions to the DNA of the antibodies.
[0041] The functional equivalent of an antibody is preferably a chimerized or humanized antibody. A chimerized antibody comprises the variable region of a non-human antibody and the constant region of a human antibody. A humanized antibody comprises the hypervariable region (CDRs) of a non-human antibody. The variable region other than the hypervariable region, e.g. the framework variable region, and the constant region of a humanized antibody are those of a human antibody.
[0042] For the purposes of this application, suitable variable and hypervariable regions of non-human antibodies may be derived from antibodies produced by any non-human mammal in which monoclonal antibodies are made. Suitable examples of mammals other than humans include, for example, rabbits, rats, mice, horses, goats, or primates. Mice are preferred.
[0043] Functional equivalents further include fragments of antibodies that have binding characteristics that are the same as, or are comparable to, those of the whole antibody. Suitable fragments of the antibody include any fragment that comprises a sufficient portion of the hypervariable (i.e. complementarity determining) region to bind specifically, and with sufficient affinity, to a growth factor receptor tyrosine kinase to inhibit growth of cells that overexpress such receptors.
[0044] Such fragments may, for example, contain one or both Fab fragments or the F(ab′)2 fragment. Preferably the antibody fragments contain all six complementarity determining regions of the whole antibody, although functional fragments containing fewer than all of such regions, such as three, four or five CDRs, are also included.
[0045] The preferred fragments are single chain antibodies, or Fv fragments. Single chain antibodies are polypeptides that comprise at least the variable region of the heavy chain of the antibody linked to the variable region of the light chain, with or without an interconnecting linker. Thus, Fv fragment comprises the entire antibody combining site. These chains may be produced in bacteria or in eucaryotic cells.
[0046] The antibodies and functional equivalents may be members of any class of immunoglobulins, such as: IgG, IgM, IgA, IgD, or IgE, and the subclasses thereof. The preferred antibodies are members of the IgG1 subclass. The functional equivalents may also be equivalents of combinations of any of the above classes and subclasses.
[0047] Antibodies may be made from the desired receptor by methods that are well known in the art. The receptors are either commercially available, or can be isolated by well known methods. For example, methods for isolating and purifying EGFR are found in Spada, U.S. Pat. No. 5,646,153 starting at column 41, line 55. Methods for isolating and purifying FGFR are found in Williams et al., U.S. Pat. No. 5,707,632 in examples 3 and 4. The methods for isolating and purifying EGFR and FGFR described in the Spada and Williams et al. patents are incorporated herein by reference.
[0048] Methods for making monoclonal antibodies include the immunological method described by Kohler and Milstein in Nature 256, 495-497 (1975) and by Campbell in �Monoclonal Antibody Technology, The Production and Characterization of Rodent and Human Hybridomas� in Burdon et al., Eds, Laboratoty Techniques in Biochemistry and Molecular Biology, Volume 13, Elsevier Science Publishers, Amsterdam (1985). The recombinant DNA method described by Huse et al. in Science 246, 1275-1281 (1989) is also suitable.
[0049] Briefly, in order to produce monoclonal antibodies, a host mammal is inoculated with a receptor or a fragment of a receptor, as described above, and then, optionally, boosted. In order to be useful, the receptor fragment must contain sufficient amino acid residues to define the epitope of the molecule being detected. If the fragment is too short to be immunogenic, it may be conjugated to a carrier molecule. Some suitable carrier molecules include keyhold limpet hemocyanin and bovine serum albumen. Conjugation may be carried out by methods known in the art. One such method is to combine a cysteine residue of the fragment with a cysteine residue on the carrier molecule.
[0050] Spleens are collected from the inoculated mammals a few days after the final boost. Cell suspensions from the spleens are fused with a tumor cell. The resulting hybridoma cells that express the antibodies are isolated, grown, and maintained in culture.
[0051] Suitable monoclonal antibodies as well as growth factor receptor tyrosine kinases for making them are also available from commercial sources, for example, from Upstate Biotechnology, Santa Cruz Biotechnology of Santa Cruz, Calif., Transduction Laboratories of Lexington, Ky., R&D Systems Inc of Minneapolis, Minn., and Dako Corporation of Carpinteria, Calif.
[0052] Methods for making chimeric and humanized antibodies are also known in the art. For example, methods for making chimeric antibodies include those described in U.S. patents by Boss (Celltech) and by Cabilly (Genentech). See U.S. Pat. Nos. 4,816,397 and 4,816,567, respectively. Methods for making humanized antibodies are described, for example, in Winter, U.S. Pat. No. 5,225,539.
[0053] The preferred method for the humanization of antibodies is called CDR-grafting. In CDR-grafting, the regions of the mouse antibody that are directly involved in binding to antigen, the complementarity determining region or CDRs, are grafted into human variable regions to create �reshaped human� variable regions. These fully humanized variable regions are then joined to human constant regions to create complete �fully humanized� antibodies.
[0054] In order to create fully humanized antibodies that bind well to antigen, it is advantageous to design the reshaped human variable regions carefully. The human variable regions into which the CDRs will be grafted should be carefully selected, and it is usually necessary to make a few amino acid changes at critical positions within the framework regions (FRs) of the human variable regions.
[0055] For example, the reshaped human variable regions may include up to ten amino acid changes in the FRs of the selected human light chain variable region, and as many as twelve amino acid changes in the FRs of the selected human heavy chain variable region. The DNA sequences coding for these reshaped human heavy and light chain variable region genes are joined to DNA sequences coding for the human heavy and light chain constant region genes, preferably γ1 and κ, respectively. The reshaped humanized antibody is then expressed in mammalian cells and its affinity for its target compared with that of the corresponding murine antibody and chimeric antibody.
[0056] Methods for selecting the residues of the humanized antibody to be substituted and for making the substitutions are well known in the art. See, for example, Co et al., Nature 351, 501-502 (1992); Queen et al., Proc. Natl. Acad. Sci. 86, 10029-1003 (1989) and Rodrigues et al., Int. J. Cancer, Supplement 7, 45-50 (1992). A method for humanizing and reshaping the 225 anti-EGFR monoclonal antibody described by Goldstein et al. in PCT application WO 96/40210. This method can be adapted to humanizing and reshaping antibodies against other growth factor receptor tyrosine kinases.
[0057] Methods for making single chain antibodies are also known in the art. Some suitable examples include those described by Wels et al. in European patent application 502 812 and Int. J. Cancer 60, 137-144 (1995).
[0058] Other methods for producing the functional equivalents described above are disclosed in PCT Application WO 93/21319, European Patent Application 239 400, PCT Application WO 89/09622, European Patent Application 338 745, U.S. Pat. No. 5,658,570, U.S. Pat. No. 5,693,780, and European Patent Application EP 332 424.
[0059] Preferred antibodies are those that inhibit the EGF receptor. Preferred EGFR antibodies are the chimerized, humanized, and single chain antibodies derived from a murine antibody called 225, which is described in U.S. Pat. No. 4,943,533. The patent is assigned to the University of California and licensed exclusively to ImClone Systems Incorporated.
[0060] The 225 antibody is able to inhibit the growth of cultured EGFR/HER1-expressing tumor cells in vitro as well as in vivo when grown as xenografts in nude mice. See Masui et al., Cancer Res. 44, 5592-5598 (1986). More recently, a treatment regimen combining 225 plus doxorubicin or cis-platin exhibited therapeutic synergy against several well established human xenograft models in mice. Basalga et al., J. Natl. Cancer Inst. 85, 1327-1333 (1993).
[0061] The chimerized, humanized, and single chain antibodies derived from murine antibody 225 can be made from the 225 antibody, which is available from the ATCC. Alternatively, the various fragments needed to prepare the chimerized, humanized, and single chain 225 antibodies can be synthesized from the sequence provided in Wels et al. in Int. J. Cancer 60, 137-144 (1995). Chimerized 225 antibody (c225) can be made in accordance with the methods described above. Humanized 225 antibody can be prepared in accordance with the method described in example IV of PCT application WO 96/40210, which is incorporated herein by reference. Single chain 225 antibodies (Fv225) can be made in accordance with methods described by Wels et al. in Int. J. Cancer 60, 137-144 (1995) and in European patent application 502 812.
[0062] The sequences of the hypervariable (CDR) regions of the light and heavy chain are reproduced below. The amino acid sequence is indicated below the nucleotide sequence.
[0063] In addition to the biological molecules discussed above, the inhibitors useful in the present invention may also be small molecules. For the purposes of this specification, small molecules include any organic or inorganic molecule, other than a biological molecule, that inhibits the growth of cells that overexpress at least one growth factor receptor tyrosine kinase. The small molecules typically have molecular weights less than 500, more typically less than 450. Most of the small molecules are organic molecules that usually comprise carbon, hydrogen and, optionally, oxygen, nitrogen, and/or sulfur atoms.
[0064] Numerous small molecules have been described as being useful to inhibit EGFR. For example, Spada et al., U.S. Pat. No. 5,656,655, discloses styryl substituted heteroaryl compounds that inhibit EGFR. The heteroaryl group is a monocyclic ring with one or two heteroatoms, or a bicyclic ring with 1 to about 4 heteroatoms, the compound being optionally substituted or polysubstituted. The compounds disclosed in U.S. Pat. No. 5,656,655 are incorporated herein by reference.
[0065] Spada et al., U.S. Pat. No. 5,646,153 discloses bis mono and/or bicyclic aryl heteroaryl carbocyclic and heterocarbocyclic compounds that inhibit EGFR and/or PDGFR. The compounds disclosed in U.S. Pat. No. 5,646,153 are incorporated herein by reference.
[0066] Bridges et al., U.S. Pat. No. 5,679,683 discloses tricyclic pyrimidine compounds that inhibit the EGFR. The compounds are fused heterocyclic pyrimidine derivatives described at column 3, line 35 to column 5, line 6. The description of these compounds at column 3, line 35 to column 5, line 6 is incorporated herein by reference.
[0067] Barker, U.S. Pat. No. 5,616,582 discloses quinazoline derivatives that have receptor tyrosine kinase inhibitory activity. The compounds disclosed in U.S. Pat. No. 5,616,582 are incorporated herein by reference.
[0068] Fry et al., Science 265, 1093-1095 (1994) discloses a compound having a structure that inhibits EGFR. The structure is shown in FIG. 1. The compound shown in FIG. 1 of the Fry et al. article is incorporated herein by reference.
[0069] Osherov et al., disclose tyrphostins that inhibit EGFR/HER1 and HER2. The compounds disclosed in the Osherov et al. article, and, in particular, those in Tables I, II, III, and IV are incorporated herein by reference.
[0070] Levitzki et al., U.S. Pat. No. 5,196,446, discloses heteroarylethenediyl or heteroarylethenediylaryl compounds that inhibit EGFR. The compounds disclosed in U.S. Pat. No. 5,196,446 from column 2, line 42 to column 3, line 40 are incorporated herein by reference.
[0071] Batley et al., Life Sciences 62, 143-150 (1998), disclose a compound called PD161570 that inhibits members of the FGF are family of receptors. PD161570 is identified as t-butyl-3-(6-(2,6-dichlorophenyl)-2-(4-diethylamino-butylamino)-pyrido(2,3-d)pyrimidin-7-yl)urea having the structure shown in FIG. 1 on page 146. The compound described in FIG. 1 on page 146 of the Batley et al. article in Life Sciences 62, 143-150 (1998) is incorporated herein by reference.
[0072] Panek, et al., Journal of Pharmacology and Experimental Therapeutics 283 1433-1444 (1997) disclose a compound identified as PD166285 that inhibits the EGFR, PDGFR, and FGFR families of receptors. PD166285 is identified as 6-(2,6-dichlorophenyl)-2-(4-(2-diethylaminoethoxy)phenylamino)-8-methyl-8H-pyrido(2,3-d)pyrimidin-7-one having the structure shown in FIG. 1 on page 1436. The compound described in FIG. 1 on page 1436 of the Panek et al. article is incorporated herein by reference.
[0073] Parrizas, et al., Endocrinology 138, 1427-1433 disclose tyrphostins that inhibit the IGF-1 receptor. The compounds disclosed in the Parrizas et al. article, in particular those in Table 1 on page 1428, are incorporated herein by reference.
[0074] The administration of small molecule and biological drugs to human patients is accomplished by methods known in the art. For small molecules, such methods are described in Spada, U.S. Pat. No. 5,646,153 at column 57, line 47 to column 59, line 67. This description of administering small molecules is incorporated herein by reference.
[0075] The biological molecules, preferably antibodies and functional equivalents of antibodies, significantly inhibit the growth of tumor cells when administered to a human patient in an effective amount in combination with radiation, as described above. The optimal dose of the antibodies and functional equivalents of antibodies can be determined by physicians based on a number of parameters including, for example, age, sex, weight, severity of the condition being treated, the antibody being administered, and the route of administration. In general, a serum concentration of polypeptides and antibodies that permits saturation of the target receptor is desirable. For example, a concentration in excess of approximately 0.1 nM is normally sufficient. For example, a dose of 100 mg/m2 of C225 provides a serum concentration of approximately 20 nM for approximately eight days.
[0076] As a rough guideline, doses of antibodies may be given weekly in amounts of 10-300 mg/m2. Equivalent doses of antibody fragments should be used at more frequent intervals in order to maintain a serum level in excess of the concentration that permits saturation of the receptors.
[0077] Some suitable routes of administration include intravenous, subcutaneous, and intramuscle administration. Intravenous administration is preferred.
[0078] The peptides and antibodies of the invention may be administered along with additional pharmaceutically acceptable ingredients. Such ingredients include, for example, adjuvants, such as BCG, immune system stimulators and chemotherapeutic agents, such as those mentioned above.
[0079] In a clinical trial, human patients were treated with anti-EGFR chimeric monoclonal antibody c225 at the indicated doses along with 2 Gy (per fraction) of external beam radiation per day, five days a week, for seven weeks, a total of 70Gy. The results are shown in the table, wherein CR means complete response, PR means partial response, and TBD means to be determined.
[0080] The invention as claimed is enabled in accordance with the above specification and readily available references and starting materials. Nevertheless, Applicants have, on May 13, 1998, re-deposited with the American Type Culture Collection, 12301 Parklawn Drive, Rockville, Md., 20852 USA (ATCC) the hybridoma cell line that produces the murine monoclonal antibody called m225. This antibody was originally deposited in support of U.S. Pat. No. 4,943,533 of Mendelsohn et al. with accession number HB8508.
[0081] The re-deposit was made under the provisions of the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure and the regulations thereunder (Budapest Treaty). This assures maintenance of a viable culture for thirty (30) years from date of deposit. The organism will be made available by ATCC under the terms of the Budapest Treaty, and subject to an agreement between Applicants and ATCC which assures unrestricted availability upon issuance of the pertinent U.S. patent. Availability of the deposited strains is not to be construed as a license to practice the invention in contravention of the rights granted under the authority of any government in accordance with its patent laws.
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scary! but very beautifulOct 13th, 2013 Reply
Wonderful work man!Aug 20th, 2013 Reply inspire & be inspired
A masterpiece , great interpretation of mental illness ♥Aug 16th, 2013 Reply
Mad crazy great--the skulls in the hair? Woah.Jul 27th, 2013 Reply
amazing work Paul! Respect!Jul 23rd, 2013 Reply
you`re welcome my friend!Jul 28th, 2013 Reply


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Probability Of Getting AIDS From Cut In Mouth
Here's a taste of what TheBody.com has to offer on this topic:
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What Is AIDS?...extremely low. There are no documented cases of HIV being transmitted by tears or saliva, but it is possible to be infected with HIV through oral sex or in rare cases through deep kissing, especially if you have open sores in your mouth or bleeding gums. For more information, see the following Fact Sheets: 150: Stopping the Spread of HIV 151: Safer Sex Guidelines 152: How Risky Is It? The Centers for Disease Control and Prevention...
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Can a pet licking sweat or a cut from a HIV positve persons skin cause them to get sick or even HIV but in animal form whatever that may be? (CATS AND DOGS AND HIV, 2009)Hello there. This may sound like a weird question but I have to ask because the only way to know is to ask, also someone else may be wondering the same thing. First of all I am currently on meds and undectable my question doesn't pertain to humans...
Response from Robert J. Frascino, M.D.
The Robert James Frascino AIDS Foundation...Oral sex with family dog Mar 8, 2007 I enjoy having oral sex with our family dog (sucking his penis) until he ejaculates in my mouth while my husband films it. Is there any physical danger to this type of oral sex? Response from Dr. Frascino... Read more »
Dr. BOB! Help a Bio Student! Lotion, HIV, OPEN CUT?Dr. Bob, So basically I'm trying to come to a rational decision so that I can get a whoo hoo from you for not freaking out and not thinking through whole situations. So, my roommate has just found out that he is HIV+. I didn't even know what to say...
Response from Robert J. Frascino, M.D.
The Robert James Frascino AIDS Foundation...Hey College Friend,Relax Max. You're fine. Your HIV risk is completely nonexistent. Tell your roommate about this site. There is information here that he may well find very helpful. Read more »
HIV Test and Index Value (SIGNAL-TO-CUT OFF RATIO) (INDEX VALUE)I am sending donation for your grate service. I would like to know about Index Value in HIV 1&2 Antibody Test. After six months from the possible exposure I have conducted a HIV 1&2 Antibody & p24 Antigen Compo Test. The Test Result is:-Index Value ...
Response from Robert J. Frascino, M.D.
The Robert James Frascino AIDS Foundation...about if I should worry or not could really make the difference in my life. I can't sleep and I started shaking of fear! My mouth is so dry that it hurts. I'm having even suicidal thoughts and that is just so not like myself!!. Its horrible. I... Read more »
Sweat and CutsI am a nursing student and recently came into contact with a patient that just found out that he was HIV positive. I was doing a general physical assessment and when I went to palpate his neck I didn't realize it was drenched in sweat- I was not...
Response from Robert J. Frascino, M.D.
The Robert James Frascino AIDS Foundation...active, and two-thirds of STIs affect people under age 25. Many young people also use drugs and alcohol, which can increase the likelihood that they will engage in high-risk sexual behavior. For many years, there were no effective treatments for... Read more »
Oral Sex: What's the Real Risk for HIV?...HIV.) Avoid vaginal oral sex during menstruation to prevent contact withblood. Take care of your mouth. The likelihood of oral HIV transmission increasesif you have bleeding gums, ulcers, cuts, sores, or infections in... Read more »
Systemic Candidiasis...can be frequent, can cause great discomfort and can add to the decline of health in HIV disease. Candidiasis can occur in the mouth, throat, windpipe, vagina or on the skin. It can also spread throughout the body. While this is rare, it is... Read more »
Stopping the Spread of HIV...HIV, but no documented cases of HIV have been caused by sweat, saliva or tears. However, even small amounts of blood in your mouth might transmit HIV during kissing or oral sex. Blood can come from flossing your teeth, or from sores caused by gum... Read more »
HIV and Safer Sex...condom that has been cut open. Then stretch the dam or condom over the vagina or anus with the lubed side facing away from your mouth. This gives you a thin barrier between your mouth and the vagina or anus. (NOTE: Some people use plastic food... Read more »
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Some Info on ARS, Seroconversion and the Rest
Posted by Anonymous, 6 Replies...that's joint pain Pharyngitis (40.0%) - sounds mysterious, means sore throat Oral ulcer (40.0%) - herpetic/aphthous lesion in the mouth Weight loss (34.3%) - over 10 pounds in 1 week Odynophagia (34.3%) - lack of saliva production, dry mouth,... Read more »
Can I catch HIV infection this way?
Posted by Anonymous, 4 Replies...the presence of mind to discard it? I can't understand. Now I have to live with the thought that I may have exposed myself to HIV infection. I mean, the toilet paper which came into contact with the seat actually also came into contact with my... Read more »
HIV risk from a handshake with a tiny cut
Posted by mountainman1970, 1 Reply...question would be..IF and that is IF there had been a cut place or any blood on the barber mans hands or fingers, how long does hiv stay active outside the body in blood? I am so terrified of having to test again. I tested a few years back over... Read more »
hiv transmits through kissing
Posted by maruti, 2 Replies...this is vipin my age is 26,last week i kissed one girl its a open mouth kiss for 20secs,there was no blood in my mouth,no cuts,there is any chance to get hiv infection for me,plz help me i was scared Read more »
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Blackhawks' streak strains the laws of probability
As good as the Blackhawks have been, it takes a bit of good fortune to play 24 games in the NHL, and accumulate a point in every single one. But how much good fortune?
Stephen Stigler, PhD, professor of statistics at the University of Chicago since 1979, says it's a matter of determining how good the Blackhawks really are, but their run is not as improbable as it sounds.
"They are not violating the laws of nature in the probability of what's been happening," said Dr. Stigler.
As Stigler explained, with all things being equal, the chance of an average team getting a point in a single game is .75 (or 75 percent). Under those circumstances, "the chance of getting a point in 24 straight games, well then it's one-in-1000."
Obviously, the Blackhawks are not an average team and Stigler acknowledged that this model was too simple for figuring out how unlikely their run has been.
To dig deeper, Stigler started by determining the probability of a team winning 18 out of 24 games in regulation. For an average team, Stigler calculated that the chances of winning 18 out of 24 to be one-in-100. Stigler then adjusted the formula to "correspond to data on top teams" and changed the probability in his formula that the Blackhawks would win any game to 60 percent. With that assumed, Stigler calculated the probability of the Blackhawks winning 18 out of 24 as one-in-10.
"Not that extraordinary," Stigler said. "What makes it a bit more extraordinary is if you factor in also the chance that of the non-wins, they were all ties."
Since the Blackhawks have gone 3-3 in shootouts, Stigler classified them ties for the sake of his calculation, and pitted the probability of the Blackhawks not having a single overtime loss at two-in-50. The odds of 18 regulation wins and no overtime losses happening at the same time?
"What we're observing has a chance of about one-in-50," Stigler said.
For the Blackhawks to repeat the feat in the second half of the season, there are more factors at work than simply nailing another one-in-50 shot. Stigler himself acknowledged "The Blackhawks have been incredibly healthy."
Ryan Wagman of Hockey Prospectus identified the Blackhawks' defense as a driving -- and possibly luck-related -- factor in the Blackhawks' success. He pointed out that the Blackhawks' team save percentage (.933 through Thursday) was well-above what the career averages of Corey Crawford and Ray Emery would suggest is sustainable.
However, Wagman also identified the Blackhawks' shooting percentage (the rate of shots on goal that resulted in scores) as being at a unexpectedly low 8.99 percent on Feb. 26th, and predicted that it would rise to a degree that would cancel out the harm done by a decline in goaltending performance.
"The pieces are in place for an historic regular season," Wagman said, "Outside of injuries (debatably) their current record is not the result of rampant good luck but of a well-built team."
No team goes 24 games without a regulation loss without beating the odds, but a well-built roster can go a long way toward making the game looked fixed. Even though the math says otherwise, Stigler understands if people start to think that chance is no longer part of the equation.
"The inference to be made is that the Blackhawks are playing at a level that they're almost certain to win every night," he said.


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Don Q + Diddy = Dance Party!
Don Q's latest web-promotion involves a round trip for two to Los Angeles, CA on May 24-26, 2010 for the premier of Diddy's new flick Get Him To The Greek. We're thinking a few Don Q cocktails and the dance floor's probably going to look like this. Click through for details.


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That's some lemonade
After hearing about the Fargo/Moorhead radio station that was raising money for Rainbow playground equipment for Wadena (Froggy 99.9 "Rainbow After the Storm"), Pam (Miller) Carlson's children decided to enlist the help of their friends in Two Harbors, Minn., and sell lemonade for a week.
Carlson is a 1984 graduate of Wadena High School.
About 15 families set up lemonade stands throughout Two Harbors last week and raised a grand total of $1,856.62.
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Staten Island, NY 10306
$1150 -
1-2 Beds
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Staten Island,
(Oakwood, Staten Island)
1005 units |
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(917) 746-6873
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You can find Oakwood apartments and rentals along winding lanes and forested trails. Then again, you might opt to live down by the Atlantic Ocean and the surf swept beach, all in Oakwood. This desirable neighborhood on Staten Island's east coast has a country feel to it, but developers are making inroads. For each weather-beaten bungalow that comes down, two or more town houses go up. Still, this area remains pleasant and peaceful.
Up until the middle of the 20th century, Oakwood was split between farmland up hill and resorts along the sea. After the Verrazano-Narrows Bridge opened, however, the area joined suburbia. These days, Oakwood is middle-class with a commercial strip along Hylan Boulevard. The neighborhood is enclosed by Ebbitts Street, the tracks of the Staten Island Railroad, Gateway National Recreation Area, and the Atlantic Ocean.
Like in many of the neighborhoods on this side of Staten Island, most of the businesses in Oakwood are located along Hylan Boulevard. You can find a pocket of shops and restaurants near the Oakwood Heights Staten Island Rail Road station as well.
Gateway National Recreation Area, colloquially called Great Kills Park, covers about 1,200 acres of beach, salt marsh, and woods. There's also a man-made harbor inside the park. Amundsen Trail offers joggers 4.5 miles of room to run. The beach is great for boating, swimming, and fishing.
If you're looking for a rental in Oakwood, you'll mostly find one- and two-bedroom family homes and garden apartments. Median rents in the area come in at around $1,320 a month. Your neighbors in Oakwood will likely be a bit wealthier than in towns farther north up the coast. Most people are married, but don't have kids.
For commuters, the Oakwood Heights railway station will put you on a train up to the Staten Island Ferry. There's also bus service along Amboy Road and Hylan Boulevard. In either case, you're looking at some significant time spent commuting.
From Oakwood, the closest public library and US Post Office are both in New Dorp. There's also a branch of the New York Public Library in Richmondtown. Staten Island Community Board No. 2 covers Oakwood.
The zip code for Oakwood is 10306.
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Canning Bananas?
Just ran across a blog post ( http://theprudenthomemaker.com/index.php/canned-bananas )about canning bananas to use for banana bread, etc. It's an interesting idea, but I've never seen an approved recipe for this. Thoughts?
She suggests "a small amount of lemon juice (a couple of teaspoons per 4 quarts or so), Fruit Fresh or citric acid to prevent browning" - at no point does she address bananas being low acid, or higher in ph than is in the range recommended as safe.
I wouldn't touch it. Bananas are available for approximately the same price year round here and we're hardly banana growing climate :), I can mash a few in about one minute.
Ripe bananas are 5.0-5.29 pH, which is well above the line for water bath canning. They are also dense, which presents additional problems. I suppose that's why no testing has been done to determine the appropriate amount of acid to add, but I'm guessing it would alter the flavor significantly.
Aside from that I can't imagine expending the jars and utilities when a few extra bananas can be tossed in the freezer. Given the usual low price of bananas, I can't see the advantage of stocking up in bulk, even if it were possible to do safely.
Agree with all of the above. Even some of the most adventuresome canners I know - those who make me cringe with some of the things they will can - don't recommend this one. Freeze or dehydrate bananas is the standard practice.
If safety in canning is at all of interest then stick with reputable sources rather then things like this.
You should seriously consider dehydrating them instead of canning -- definitely "shelf stable" for a couple of years IF dried and packed properly. And, very easily rehydrated for cooking IF they make it that far -- they make a wonderful snack food.
I am not at all trying to be argumentative. Just curious.
Here is a recipe I have used in the past from Sure-Jell. Is this recipe not safe?
Here is a link that might be useful: Sure Jell Banana Butter Recipe
It is safe because it has added acid, and it also has sugar to help preserve it. The high amount of sugar binds up the water, which allows bacteria to grow. It is called water activity. That is why dehydration works for most foods, it removes the water/moisture so the foods don't have a food source to grow.
Just canning bananas with some lemon juice will NOT be safe.
You will also notice that recipe contains a half-cup of lemon juice, which is quite a lot. That changes the equation considerably. It might be more accurate to say it's Banana-Lemon Butter.
Recipes like that are tested, which Sure-Jell, like other big companies, has the resources for.
Thank you Carol and Linda Lou. That's what I needed to know. I appreciate your expertise. I've been reading a lot of different references and I have been sticking with the Certo, Sure-Jell, Ball Blue Book and NCHFP and I like the book Small Batch Preserving (Ellie Topp?). Anyway, thanx for taking the time to provide the explanation! I sure do like making jams and jellies! But, safety is my priority. I figured Sure-Jell was ok, I just needed to know why. Thanx again!


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Identify China Cabinet Please
slocke94May 29, 2014
I am selling the china cabinet in an upcoming estate sale, and I'm not sure how to price this. It says made in Mexico on the back. If anyone can help please feel free to give me your input! Thank you!
Nice, probably Mexican pine, but nothing special and definitely not antique. I'd price it at about 30% of what a similar piece sells for new.
"Made in Mexico" means it was made for export. Made for use in Mexico says "Hecho en Mexico" or has no marks at all.


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Fired — and not liking it at all
Don Bauder 9:30 p.m., March 30
Posted August 9, 2011
Oh, man. That smell. That barbecue smell, reaching out and pulling you in by the nose. It's coming from Phil's BBQ, right past the sports arena. Even now — it's early evening — streams of ...


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Product Details
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Every Customer can leave a review about our service and the product that was purchased. In order to leave your review for your new product, please follow the link in the email you receive after completing your purchase. You can rate appearance, ease of installation, price/value and product quality.Coverking® - Spacer Mesh Custom Seat CoversAverage Rating: 4 of 5APPEARANCEEASE OF INSTALLATIONPRICE/VALUEQUALITYAll Coverking Reviews(4)APPEARANCEEASE OF INSTALLATIONPRICE/VALUEQUALITY2010 Kia Optima
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