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Is Alibaba Comparable To a US Company?

ponos Re:Not sure (111 comments)

This IPO is interesting because it's a test case for how well China can provide a code of laws assurance to the worldwide investor. So far, so good. But the Chineese system has a similar habit of disenfranchising shareholders, and in this case, it could happen in the blink of an eye.

It's too early to say how it would function in an hypothetical situation. Clearly, that question will have to be settled in the coming decade: what happens when a Chinese company does not behave well? For the moment, people are just hoping for a quick buck, just as with most IPOs.

2 days ago
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Is Alibaba Comparable To a US Company?

ponos Re:Comparable? Not really. (111 comments)

Until recently, multiple classes of stock were prohibited for NYSE-listed companies, which tended to discourage doing this. (The classic exception was Ford, which has two classes of stock, the voting shares controlled by the Ford family. This predates that NYSE rule.)

Thanks for sharing this information. This explains some things.

2 days ago
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Is Alibaba Comparable To a US Company?

ponos Re:Comparable? Not really. (111 comments)

The market is fully capable of pricing the fact that Alibaba stockholders don't actually own a direct claim on Alibaba's Chinese assets and can't elect its board. Truth be told, shareholders don't "own" any company; they own whatever rights are specified in the share agreement........

You are right of course. Personally, I'm a bit bothered by stocks that don't give dividends (as a rule!) or voting rights. I know it's common and Alibaba is not the only example. Investing without any kind of control and without expecting dividends (I don't know if it's the case for Alibaba) only seems to reinforce the perception that stocks are some sort of casino. I prefer the vision of stock ownership as holding a small piece of a real business: contributing to decision-making and getting a part of the profits just like you would if you owned a percentage of the restaurant next-door. I feel that this would reinforce much more responsible corporate behavior and saner investment strategies. It's a pity that many technology companies operate this way.

2 days ago
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If We Can't Kill Cancer, Can We Control It?

ponos Re:How about the linked article? (140 comments)

Your criticism of the study I mentioned is reasonable, but in the domain of cancer treatment, a hazard ratio for death (a hard endpoint) of 0.67 is good and, in that sense, if you require much stronger evidence and even better trials you may deprive patients of a useful drug in the meantime. The FDA wants to strike a balance between getting an effective drug to patients as soon as possible and not letting pass ineffective treatments. So, as with most things in life, the kind of evidence I cited is often considered "good enough" even though imperfect.

The evidence for the impact of point mutations can be found in several domains, but the simplest observations comes from hereditary syndromes like Li-Fraumeni. A single change in a nucleotide of the TP53 gene and cancer risk increases to almost 100% in affected individuals. This has been repeatedly observed in many different famliies and also in different syndromes (say, retinoblastoma and RB1 gene). Anyway, the evidence for what is called the "somatic mutation theory" is overwhelming and, despite thoughtful criticism, it is probably accepted as the most plausible theory of carcinogenesis (for the moment!). That's why projects like "Cancer Genome Atlas" get massive funding.

So, yes, point mutations are extremely important. Aneuploidy is also important, but in contrast with a well-described mutation, like the BRAF V600E in melanoma, it does not present an immediate, specific target. As I said, people are working on aneuploidy and maybe something new will come from that, but I don't think it's a "low-hanging fruit".

PS Note that somatic mutations do not exclude aneuploidy and vice versa...

about a week ago
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If We Can't Kill Cancer, Can We Control It?

ponos Re:How about the linked article? (140 comments)

"Nevertheless, having a targeted treatment is often better than no treatment at all."

Perhaps, but I doubt there is any good evidence for this. Weak effects and noisy data don't mix well, we are probably taught all sorts of incorrect things based on spurious results. I would suggest getting away from these targeted treatments of at most limited benefit and work on figuring out how to turn aneuploidy as a drug target.

FDA approval typically requires randomized controlled trials, so when a treatment is available it has been tested at least against placebo (if that was the best available treatment at the moment of approval). That's why I say "better than no treatment". A drug that is not better than placebo usually does not make it past the approval stage (and if it does, approval can be quickly revoked, for example bevacizumab in breast cancer: http://www.nytimes.com/2011/11...)

What sort of evidence would you expect? For example, the study which established the targeted agent trastuzumab is available online: http://www.nejm.org/doi/full/1.... Bias and noise are unavoidable, but with my knowledge of statistics the result seems reasonably clear.

Anyway, with respect to your other comment, aneuploidy is not an obvious target but people are working on it and on drugs that interact with the mitotic machinery. Let's hope they will be successful.

about a week ago
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If We Can't Kill Cancer, Can We Control It?

ponos Re:How about the linked article? (140 comments)

Well, if the cancer cells are aneuploid (like the vast majority apparently are) and thus genetically unstable we shouldn't expect a targeted treatment like this to be effective for long.

Many targeted treatments have been disappointing in actual practice and very few are effective in the long term (imatinib is a good example). Nevertheless, having a targeted treatment is often better than no treatment at all. Furthermore, due to different, non-overlapping toxicites, these treatments are often feasible in patients who have received chemotherapy in the past or together with chemotherapy (trastuzumab, for example).

In the end, cancer is entropy. That's why it's hard.

about a week ago
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If We Can't Kill Cancer, Can We Control It?

ponos Re:Baking Soda May Help! (140 comments)

2) Consider the annual sales and profits of Big Pharma. Then the same for Big Food. IF there's a simple cure using natural food and basic ingredients that big pharma cannot patent, what's Coca Cola, Pepsico and other similarly large companies waiting for to steal big pharma's lunch?

Actually, if a cure was "known" Big Pharma "A" would want to produce it first and charge $$$$$, before Big Pharma "B" does it. It's not like Big Pharma works as a single organism. Multiple companies, competition and all that. Furthermore, don't forget "little pharma". The drug mentioned in the article comes from a little drug company, Agios, not some multi-billion behemoth.Several new drugs have been created by start-ups and were later sold. In fact, Big Pharma mostly does the last part of the pipeline (human trials, FDA accreditations and marketing) but the first part of the drug-discovery process often comes from little inventors who are not afraid to take risks.

I happen to know two people who are in the drug "startup" business and would be quite happy to make $$$$$ selling a cure for cancer to Big Pharma. These are the people that actually do in vitro/in vivo experiments and, trust me, if compound ZZZ were very effective they would be very happy to test it immediately, even if it meant loss of billions for other companies.

about a week ago
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If We Can't Kill Cancer, Can We Control It?

ponos How about the linked article? (140 comments)

Let me give you a brief summary of TFA:
- Some cancers have IDH1, IDH2 mutations that change cellular metabolism
- This drug is the first targeting the IDH2 enzyme that has been tested in humans
- 6 out of 7 patients whose disease (leucemia) had the specific IDH2 mutations had "objective response" to the drug, ie the disease burden was reduced. Note, this does not mean cure.

Now, this is obviously good news, in the same spirit as previous targeted agents like vemurafenib, erlotinib, trastuzumab, crizotinib, especially since it concerns a new aspect of cellular functioning (metabolism). It's too early to say whether the drug will have long lasting impact, but we'll know more after phase II/III trials. It does seem promising.

For patients with AML or MDS and documented IDH2 mutation, the study (NCT01915498) is still recruiting in several centers around the US and in Paris/France (Institut Gustave-Russy). More information can be found in clinicaltrials.gov (http://www.clinicaltrials.gov/ct2/results?term=NCT01915498&Search=Search).

about a week ago
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The MOOC Revolution That Wasn't

ponos Learning is hard (182 comments)

In other news, learning is hard. What did you expect, that people would magically learn the hardest of subjects simply because it is on t3h internetz? I have done MOOCs and I think it's great. I got the chance to hear some famous professors, read some good textbooks. I never expected it to be simple and I had to abandon some courses, but the final result is a net positive: I finished 2-3 courses I would never have had otherwise. So what if I didn't do the other 3 or 4?

Too much hype leads to disillusionment, as usual, but MOOCs have their place.

about two weeks ago
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Early iPhone 6 Benchmark Results Show Only Modest Gains For A8

ponos Custom software (207 comments)

Apple has absolute control of the software ecosystem and can probably gain significant performance from appropriate optimizations. The android landscape is much more heterogeneous and probably less optimized for each individual device. Think consoles vs PC.

Raw benchmarks like this one may not properly reflect user's perception of performance when different ecosystems are compared. In the end, I expect the iPhone 6 to feel at least as fast as the fastest Android devices in real use cases.

about two weeks ago
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DNA sequencing of coffee's best use:

ponos Re:Not quite (228 comments)

Not really, mainly because the two things we are talking about are consumed for their effect. Maybe I am not understanding your question?

Some of the effects are undesirable. Muscle tremor, anxiety are usually not reasons to drink coffee. Similarly, nausea and disequilibrium are not reasons to drink alcohol. With almost any pharmacologically active substance a spectrum of undesirable effects can become apparent before significant risk of lethality.

So, with reference to my initial post, I still believe that 1000mg of caffeine can induce toxic (not necessarily lethal, of course) effects that are, I suppose, undesirable for most people. I guess I can't make it clearer than that.

about two weeks ago
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DNA sequencing of coffee's best use:

ponos Re:Not quite (228 comments)

This is the first hit I get on Google for "dsm iv caffeine intoxication". Immediately under the title text it says "These criteria are obsolete"

Indeed, you are right. The DSM-IV is still in use but, technically speaking, it has been replaced by the newer DSM V, which also includes a diagnosis of caffeine intoxication. I don't have a DSM V handbook within reach, but I'm sure you can find out the details.

Does the fact that people suffer from side effects before dying surprise you? Using the reference you provided above, people die (LD50) at about 490g of pure alcohol (ie >1lt of hard liquor), yet most would agree that toxicity is apparent way before that amount. Caffeine is similar.

about two weeks ago
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DNA sequencing of coffee's best use:

ponos Re:Not quite (228 comments)

[quote]
Toxic levels of caffeine: 12,000 mg (for an 176 pound person) [just-think-it.com].
[/quote]
You are right with respect to the LD50, obviously referring to lethality. However, 1000mg of caffeine is certainly sufficient for caffeine intoxication as per the DSM-IV disorder (code 305.90). It all depends on how you interpret "toxic" in this context.

about two weeks ago
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How Scientific Consensus Has Gotten a Bad Reputation

ponos Consensus is about the process (770 comments)

I think there is a subtle difference between being right (in the usual sense of providing a model that happens to accurately represent measurable stuff) and the process of scientific discussion. Consensus is just an outcome of a process, ie collaboration. That process is extremely important but does not guarantee being right.

In the end, without resorting to unnecessary complicated terms, if a bunch of people who are supposed to know what they are saying all agree on something that is not immediately testable (say, long-term human impact on the climate), odds are they are more likely to be right than some random wacko or idiot reporter because they spent some time discussing together and have highlighted potential errors.

In the absence of definitive hard data, which will only be available in retrospect, we have to pick sides. Consensus seems a safer bet than the probability that some random guy is the new Galileo or Einstein.

about two weeks ago
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DNA sequencing of coffee's best use:

ponos Decaf makes some sense (228 comments)

I imagine taste depends a lot on environmental factors, like soil nutrients, sun and stuff like that. Creating a genetically engineered plant is probably harder than simply improving culture conditions to get a good product. Although you could probably improve some aspects of the product by bio-engineering, in real life I don't think anyone will care to improve taste. Most probably they would sell you cheaper beans that resist infection or transportation or bad climate. I never heard Monsanto advertise their products as "great taste", but then again I wouldn't know.

Adding caffeine is also so simple that you shouldn't have to modify plants to get it. In fact, caffeine is dirt cheap (http://www.alibaba.com/showroom/caffeine.html). Even pharma-grade caffeine for the lab is like $0.50 for an almost toxic dose of 1000mg, if you want to "enrich" your coffee.

Decaf, if you enjoy it, would be an interesting bio-engineering project. I don't know if the plant really needs the caffeine for something else (it is somewhat related to DNA, being itself a purine), but simply deleting or attenuating the gene that catalyzes the conversion should be really simple. In fact, you don't need the whole genome sequence to do that, only the locus of the gene.

Anyway, bio-engineering something that tastes good and is healthy is probably at least as hard as all other aspects of the production, even if you have the DNA sequence. Being a fan of the KISS principle, I'd rather have my coffee prepared by people with some decent traditional know-how.

about two weeks ago
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RAYA: Real-time Audio Engine Simulation In Quake

ponos Re:It's a shame Creative will be suing this. (89 comments)

There was a company back in 1997 that had a fantastic (series of) cards that did all this 3d transformation, reflection, deflection and occlusion of audio in hardware.

AMD TrueAudio on Kaveri processors and newer GPUs supposedly does just that. I haven't seen any game supporting it, though. Would be a nice feature I think.

about three weeks ago
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Ask Slashdot: Life Beyond the WRT54G Series?

ponos Re:Enterprise grade AC (427 comments)

Thanks for the information!

I have tried some modest consumer-level equipment with disappointing results so I was thinking of either going high-end consumer or even pro. In the end, I'm probably going to take the plunge. As you say, I don't want to change equipment every year...

about a month and a half ago
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Ask Slashdot: Life Beyond the WRT54G Series?

ponos Re:Enterprise grade AC (427 comments)

This is an expensive solution, but I am tempted. Is it better than the equivalent top-end consumer grade products like the Netgear R7000 or the Asus RT68? Specifically, I was thinking of the combination Ubiquiti EdgeRouter PoE + Ubiquiti UniFi AP AC which is almost $700 of gear. Is it worth it for a gigabit home network with a 300MBps fiber connection?

about a month and a half ago
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Ask Slashdot: Life Beyond the WRT54G Series?

ponos Re:NETGEAR Nighthawk AC1900 (427 comments)

Any other experiences with the Nighthawk AC1900? The hardware seems quite good. I don't mind the price, up to about $250, but I plan on getting 300MBps fiber so I need a router that can reliably route that plus handle my gigabit home network.

about a month and a half ago
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The Doctor Will Skype You Now

ponos Value of physical examination (97 comments)

A classical article on the subject, quite old now, has concluded that approximately 80% of diagnoses can be made from the history (ie a structured interview) with a further maybe 10% from physical examination and maybe 5% from additional investigations (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1673456/). Obviously, the requirements for modern medicine and the available means are a bit different. Nevertheless, any serious doctor will tell you that the history taking and the physical examination are the most important parts of an encounter with a patient.

This is a direct result of Bayes theorem: the interview and physical define the "prior" probability for any diagnosis and any further investigations will only serve to modify it by a certain degree (confirm or exclude). With the exception of some quite aggressive diagnostic methods, like a biopsy or laparoscopy, which will never be recommended upfront, most investigations are generally not sufficiently sensitive or specific enough to give a conclusive diagnosis.

Finally, the physical (which cannot be done via Skype) is also a very important component of the physician and patient relationship. An encounter without physical examination seems, in my humble opinion, quite superficial. Patients are generally more satisfied if you take the time to carefully examine them.

That being said, Skype can be a decent solution for people living in remote areas where transportation can be a real problem. Skype for people living in major cities is a bit silly, I think.

PS. I am physician, but I am curious to hear what you think about the value of physical examination.

about a month and a half ago

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