Cure for Artery Hardening Killed by the "Free Market"
Posted 6:38 AM

Just one more example of why the free market and patented medicines don't mix.
Alagebrium was a drug with dramatic success in Phase I and Phase II clinical trials. However, the company which produced it failed to raise cash for Phase III, eventually bankrupting the company.

Alagebrium is a small, easily produced molecule that, for technical reasons, may be difficult to defend as a patent. Without a patent - a drug has no future in the free market. As a result, one of the companies investors were advised to back out. Word spread, and the venture community backed away from Algaebrium.

Also, the effects of Algaebrium treatments are slow, cumulative and their significant apparently varies from patient to patient. They are not the kind of dramatic effects that investors look for in a drug.

There are no other known treatments for reducing glycosic cross-links, and it's unlikely a Phase III trial will ever begin on this drug.
[View/Post Comments] [Digg] [Del.icio.us] [Stumble]

Stroller Injuries Just as Bad as Sling
Posted 7:45 AM

For the 10 year time period between 1995-2005, there were 22 stroller-related deaths for children under the age of 5 reported to CPSC. ^ref

There were an estimated 64,373 stroller-related injuries to children 3 years old and younger treated in hospital emergency departments in the United States during a 5-year study from 1993-1998. Most injuries involved the head (44%) or face (43%). (^ref. I would assume that hundreds (out of 64K hospitalizations!) of those cases were severer and life altering incidents with permanent damage to the child.

But regardless of the system you use... just paying attention is the best recipe for safety. Of the several recent cases of children dying in slings and strollers that were investigated the majority were ruled to be child abuse and neglect. (Sorry, I can't find the reference for this, it was on Elsevier).

Perhaps CPSC has stepped way out of line with their recent "sling warning", ignored the evidence and sided with a powerful and profitable industry lobby? Some research into the people who made this decision is definitely warranted.
[View/Post Comments] [Digg] [Del.icio.us] [Stumble]

Speak Blast
Posted 4:35 PM

I've been working on a project called SpeakBlast.com. If anyone is interested in trying it out (it's still alpha), you can sign up, add a bunch of phone numbers to a "channel" or "calling group". Then, you can call a number any time, and record a message that gets sent to everyone in that group.

It's good for sports teams, playgroups, etc. It works fine, but we're still getting the kinks out of the code, redoing the user interface, etc.

There are a number of other "use cases" for the core technology, but that's the most basic one.

Please feel free to try it at let me know what you think, what features you want, etc.
[View/Post Comments] [Digg] [Del.icio.us] [Stumble]

The Ultimate Loan Scenario Comparison Tool
Posted 3:58 AM

Totally unrelated, but this is the first time I've seen a web page dedicated to loans, that's useful, smart and isn't smothered in spam:

The Ultimate Loan Scenario Comparison Tool

I like it.
[View/Post Comments] [Digg] [Del.icio.us] [Stumble]

Overexpression of "Klotho" Cures Age-Related Diseases and Extends Lifespan
Posted 11:42 PM

Overexpression of the Klotho gene has repeatedly been shown to prevent, delay and even cure (1) osteoporosis, atherosclerosis, Alzheimer's (4), muscle loss and heart dysfunction. This has been investigated repeatedly for over 20 years. What research is currently being done on viral/ZFN vector delivery to overexpress this gene in primate models, or in human safety trials? From what I can tell, very little, or none at all.

I noticed that nearly every research article, directly following pronouncement that klotho extends health and life, follows that statement with "but we don't know why" (1,2,3,4).

Researchers are obsessed with understanding why. Researcher want to know why this hormone apparently cures everything. But there are no studies into whether it can be used today... on people who are dying today. FAIL: intellectual curiosity is trumping the needs of the terminally ill.

(1) "In Vivo klotho Gene Delivery Protects against Endothelial Dysfunction in Multiple Risk Factor Syndrome" (2000) Yuichiro Saito, et al.
(2) "Suppression of Aging in Mice by the Hormone Klotho" (2005) Hiroshi Kurosu, et al. doi:10.1126/science.1112766
(3) "Klotho as a regulator of oxidative stress and senescence" (2008) Makoto Kuro-o doi: 10.1515/BC.2008.028
(4) P4-186: Modulating Klotho expression to protect against age-induced neurodegeneration" (2008) Gwendalyn D. King

[View/Post Comments] [Digg] [Del.icio.us] [Stumble]

Saccharin's Turbulent History
Posted 3:56 PM

Saccharin, first synthesized in 1879 by fellows at JHU, eventually became a popular sugar substitute.

Superficially, saccharin resembles sucrose in that it is composed of 2 organic rings.



Although the "sweetness triangle" theory is too simple to fully explain sweet-tasting molecules, it does provide a model that explains many, including saccharin - with its three hydrogen bonding oxygens and a hydrophobic base. (1)

In 1968 two studies linked cyclamate, a related sweetener, to bladder cancer. (2) Cyclamate was banned shortly afterward. (3) It remains banned in the United States, possibly because it has been found to have a broader range of toxic effects than saccharin (4, 5), but more probably, in my opinion, because there are enough acceptable alternatives.

Saccharin was, then, the only sweetener left on the market, and, in the wake of the ban, it was a highly suspicious substance - especially considering it's chemical and structural similarity. Implication in bladder cancer was repeatedly found, however, the dosage levels were so high that application to humans seemed unlikely (6, 7, 8). There was an attempt to ban saccharin in 1972 that failed. At that point there had been several studies that seemed to clear saccharin as a carcinogen, and that the mechanisms of it's action in mouse bladder cancer are not applicable to humans. (9, 10, 11).

Nevertheless, in 1977 the "Saccharin Study and Labeling Act" required a mandatory warning label. The response to this labelling was, paradoxically, highly increased usage. (3)

Saccharin has been found to inhibit digestive enzymes (12), cause ulcers (13), and cause some blood abnormalities (14). In at least two studies, saccharin use has been correlated with weight gain and, in 2008, a causative behavioral model was shown in rats. (15, 16)

Despite industry sponsorship of the molecule, it has never been shown that saccharin reduced mortality, obesity or weight gain among diabetics. One can only imagine, given the magnitude of the industry, how many unpublished studies there must be failing to conclude this relationship. The few published studies that there are seem to find the opposite.

Given that the benefits (unproven, possibly inverse) don't outweigh the risks (many), I would not recommend the use of saccharin to a diabetic. It is my opinion that, given the research, it is highly unlikely that saccharin is a carcinogen, however.


(1) "Computer Simulation of Chemical and Biological Properties of Saccharides" (1995) Dr. S. Immel
(2) "Production of Mouse Urinary Bladder Carcinomas by Sodium Cyclamate" (1970) George T. Bryan and Erdogan Ertürk
(3) "The Pursuit of Sweet: A History of Saccharin"
(4) Long-Term Toxicity and Carcinogenicity Study of Cyclamate in Nonhuman Primates (2000) S. Takayama, A. G. Renwick, S. L. Johansso
(5) "Effects of Sodium Cyclamate on the Rat Placenta: A Morphometric Study" (2006) Marcelo Alexandre de Matos; Alex Tadeu Martins & Reinaldo Azoubel, DOI: 10.4067/S0717-95022006000300001
(6) "Production of Urinary Bladder Carcinomas in Mice by Sodium Saccharin" (1970) George T. Bryan, Erdogbrevean Ertürk, and Osamu Yoshida
(7) "Evaluation of a new model to detect bladder carcinogens or co-carcinogens" (1975) Hicks RM, Wakefield J, Chowaniec J.
(8) "Response of the rat to saccharin with particular reference to the urinary bladder." J. Chowaniec and R. M. Hicks
(9) "Cancer Mortality and saccharin consumptionin diabetics" (1976) Bruce Armstrong
(10) "Feeding studies on sodium cyclamate, saccharin and sucrose for carcinogenic and tumour-promoting activity " (1970) F.J.C. Roe, L.S. Levy and R.L. Carter
(11) "A chronic study of artificial sweeteners in Syrian golden hamsters" (1975) J. Althoff, A. Cardesa, P. Pour and P. Shubik
(12) "The inhibition of urease and proteases by sodium saccharin." (1982) Lok E, Iverson F, Clayson DB.
(13) "Glandular stomach hemorrhage induced by high dose saccharin in young rodents" T. Okamura, E.M. Garlanda and S.M. Cohen
(14) "Haematological abnormalities induced by feeding a common artificial sweetener, saccharin, in ICR swiss mice" Om Prasada and Gulshan Raia
(15) "Artificial sweetener use and one-year weight change among women" (1986) Steven D. Stellman Ph.D. and Lawrence Garfinkel M.A.
(16) "A role for sweet taste: Calorie predictive relations in energy regulation by rats."(2008) Swithers, Davidson

[View/Post Comments] [Digg] [Del.icio.us] [Stumble]

Carbon Change and Ocean Acidification
Posted 7:20 AM

Man-made CO2 may not be warming the whole world, in fact there's even more evidence just in, that an anthropocene CO2 warmed arctic might induce an ice-age via a thermohaline slowdown.

But there's no contest that man-made CO2 is causing ocean acidification. And the creepy thing about acidification (as anyone who's done a titration experiment can tell you), it's loaded with "tipping points". These are points in which chemical reactions, which, at one pH, are favorable, suddenly stop or go in reverse.

Some recent articles in the CS Monitor and NY Times point to legal trends in this area.

I wondered how climate deniers would deal with this. In my email to the "Global Warming Hoax" website, he replied that he "didn't know anything about it", but that "it was probably another hoax", and that I should "check my sources". It seems they're gearing up already, a casual search for "acidification hoax" turns up lots of results from creepy sites with lots of pop-up ads.


[View/Post Comments] [Digg] [Del.icio.us] [Stumble]

How to Fix Blogger's FTP Bug
Posted 7:30 AM

Google is canceling support for FTP in blogger. Fortunately, there's an easy fix and you get to keep your domain, and keep everything working the way it was.

1. Switch to hosting your blog on blahblah.blogspot.com ... but don't finish the migration (read step 2).

2. DONT LET GOOGLE FILL YOUR OLD BLOG WITH REDIRECTS. This will ruin your site's ranking and be, in general, a bad user experience.

3. Use a script to synchronize the blogspot domain pages with your real custom domain blog. Here's the script I'm using, it works well and uses ETags so is remarkably efficient. I'm running 12 blogs from a cron job now, 5 of my own.

4. Turn OFF any indexing services for the new blogspot domain (Allow search engines to find this site? NO). You don't want two sets of content out there. Many search engines, not just Google, will punish your site's ranking for having multiple versions.

5. (Rant: I don't believe, for a minute, that the engineers at Google couldn't figure out how to run FTP affordably. I do over a terabyte of FTP crap every month for free at memebot.com ... and I never even look at it.... paid for twice over with cheap ads. They're either liars or they are incompetent.)

6. ADD this script to the HEAD section of your template... so people won't use your blogspot domain:

<SCRIPT language="JavaScript">
<!--
var str=location.href; 
if (str.indexOf('blogspot.com') > 0) {
  var newStr = str.replace('http://YOURBLOGSPOTNAME.blogspot.com','').replace('http://www.blogger.com/blog-preview.g','');
  window.location='http://www.YOURDOMAINHERE'+newStr;
}
//-->
</SCRIPT>

7. I made a form so people could sign up to have their blog sync'ed if they don't know what a cron job is. If you use rsync, I don't need your password. (Why didn't Google use rsync?). I have a bunch of dedicated servers for other reasons, so it's no problem for me for now (not too many people so far):

New Blogspot Site:
FTP Host (aka custom domain):
FTP Path (for example /blog/):
FTP Username:
FTP Pass (optional):
Use Rsync*:

* NOTE: To use rsync, you'll need click here and put this public key in your authority file (~/.ssh/authorized_keys). This way your password doesn't have to be entered anywhere.

Labels: google, programming

[View/Post Comments] [Digg] [Del.icio.us] [Stumble]

Catalytic Antibodies Simply Explained
Posted 1:17 AM

Catalysis is the process of speeding up a chemical reaction by lowering its activation energy - the energy hump a reaction has to go over before it can roll downhill. Efficient catalysts of chemical reactions are extremely commercially valuable and widely researched.

Enzyme Catalysis Basics: Biological enzymes are known to catalyze (speed up) chemical reactions, in part, by stabilizing the transition state (halfway point at the top of the hump) of an otherwise energetically-favorable (downhill) reaction. Some catalysts work by moving chemicals next to each other that would otherwise not randomly meet that often. (1) Some enzymes are known to change their shape (conformation) after binding and during the reaction - driving catalysis (2).

The immune system can be stimulated to respond to a incredibly diverse range of molecules by producing antibodies which bind (cling, stick) to these molecules. The theory of "catalytic antibodies" was that if an antibody was purified that bound to the transition state of a reaction, it would, in the same manner as an enzyme (above), stabilize that state (drag it up the hill) and accelerate the reaction. In order to generate such an antibody, a "transitions state analog" (TSA) - molecule that looks like the known transition state of a reaction - is used. Antibodies that are generated (usually by injection into a mouse) to bind to that TSA are then screened until one is found that catalyzes the reaction. Surprisingly, to me, this works very well. (3)

However, these "abzyme" catalysts are never as efficient as enzymes for many reasons. The abzyme may strongly bind to the product of the reaction (not letting go when it's done), greatly inhibiting its effectiveness. Also there is the difficulty of creating a TSA - they may differ in bond angles or polarity, etc. Many enzymes form strong (covalent) bonds during their catalysis mechanism, but this is not known to be possible with abzymes. Enzymes also employ conformational changes, metals and other cofactors to accelerate catalysis.

Abzymes are being aggressively researched, however. For example, it may be possible to engineer abzymes which bind to prosthetic groups to be used in metal-catalyzed reactions. Abzyme reactions which employ several cofactors have already been demonstrated. (4,5)

(1) "Chemical basis for enzyme catalysis", 2000, TC Bruice, SJ Benkovic
(2) "Catalysis by Enzyme Conformational Change", 2004 Jiali Gao1, Kyoungrim Lee Byun, and Ronald Kluger
(3) "Catalytic antibodies" (Biochem. J.), 1989, G. Michael BLACKBURN,t Angray S. KANG
(4) "Pyridoxal 5?-Phosphate-dependent Catalytic Antibody" (1996) Svetlana I. Gramatikova, Philipp Christen
(5) "A cofactor approach to copper-dependent catalytic antibodies" Kenneth M. Nicholas, Paul Wentworth, Jr

Labels: biotech

[View/Post Comments] [Digg] [Del.icio.us] [Stumble]

Nofollow, Viagra, Google & I told You So
Posted 8:05 AM

When someone links to a website, Google and other search engines have, in the past, considered that a "vote" of confidence for the site linked to. The higher reputation a site has, the more it's vote counts... (sort of, there's lots of other factors).

The idea behind "nofollow" is that you can link to a site, but also mark it as "I'm not voting for it". That way someone who has, for example, a list of comments on their blog, won't simply "vote" for everyone who posts a comment. Presumably that would prevent spammers from posting a million comments in the hopes of getting their discount Viagra ad's search ranking up.

It's a solid concept, but in practice it has backfired because it was coupled with a "punishment" system for linking to spam sites.

This punishment system has led sites like Wikipedia, which are, for the most part, extremely reputable, to put "nofollow" on every single link in an attempt to prevent spam. These links are, usually, extremely well-vetted votes of confidence for the site in question. Wikipedia, despite its problems, remains one of the foremost authorities on "link quality".

Other quality sites that have adopted "nofollow" on every link include Digg and Twitter.

You see where this is going. Rather than rely on top authorities with quality information, like Wikipedia, Digg, etc. Google now has to rely only on links originating from people who don't know or care about their link voting/ranking, etc. In other words, generally less knowledgeable or lower quality votes are the only votes used for ranking.

This ultimately harms Google's page ranking system. What Google needs to learn is that "open" is not the right way to go for search rankings. Heavy use of personalized and regional results is the only thing they've done to halt this trend. Here's the next step: allow someone to mark another Google user as "trusted" for search results. In other words, I should be able to mark friends of mine as "trusted" (on a scale of 1 to 5 maybe), for personalized search results.

That way personalization will dominate the results, be highly relevant, and impossible to game.

Google, the last time I emailed told you to track clicks you listened...and it helped. But you never thanked me! Get back to me when this multilevel personalized trust system is done.

Labels: google

[View/Post Comments] [Digg] [Del.icio.us] [Stumble]

Myoglobin Pov-Ray
Posted 9:34 AM

One of my assignments from biochem class was to play around with VMD and Pov-Ray. It was fun. The red sphere is supposed to be an oxygen.... (I know it's not that big, or shiny, or red and there's no heme prosthetic to bind it with.)

You can click on the image to zoom in.

Labels: biotech

[View/Post Comments] [Digg] [Del.icio.us] [Stumble]