Popcorn

Microwave some corn kernels and a bit of magic makes popcorns. When I was a kid, I thought that popcorns can only be made in popcorn bags and that they must have butter for it to work.

I had no idea why microwaving the bag made popcorns but I knew that the sound associated with the bag was indicative of the progression of the popcorn making process.

Now, I realize at the heart of popcorn making is not magic, but science. Actually, all you need is sufficient heat and some popcorn kernels.

Although popcorn kernels seem dry, they are not devoid of moisture. When you heat up the popcorn, the water inside expands significantly. So when the pressure due to water expansion builds up significantly, the kernel breaks. The volume increases and the internal pressure drops to atmospheric. The fluffiness is due to the low density which arises due to this volume expansion.

I think the popping sound is due to the expansion rate being faster than the speed of sound. I'm not sure. It might just be the shell breaking. I guess a high speed camera may be able to provide some answers.

scientific terms

Recently, I've been thinking about definition of various things. In science, many things are defined operationally. I've come across some questions about whether glass is liquid or solid. There has been some misconception suggesting that glass is liquid and Derek addresses this (https://www.youtube.com/watch?v=c6wuh0NRG1s&feature=youtu.be&a).

But more importantly, it brings to light some interesting general problem. We have definitions and boundaries. Solids are things where atoms do not flow... but on what time scale? If you wait for a long time, solids can also "flow" (such as the earth's mantle). Are solids and liquids a continuum in actuality?

Like Derek suggests, these definitions and classifications create misconceptions. More troublesome is the fact that it creates a mental block. Is the world really made up of solids and liquids? I think no. These are models introduced by humans. I think by giving them names and using these term routinely, we forget that they are models describing the physical world around us. It is well known that there is a close tie between culture and language. But it seems language really shapes the way we think even in science. There is no perfect observer without bias.

microwave heating problem

I’m heating up my food using a microwave. I’m heating some sweet potatoes and I figured since I mash it with milk later, I can immerse them in milk during the heating. But, unlike the sweet potato alone which heats up really fast, the milk + sweet potato doesn’t heat up that fast… That got me thinking… Why?

Here’s my hypothesis. The increase in temperature is associated with increase in the AVERAGE thermal energy. In thermodynamics, this is an intensive property (does not scale with size). As opposed to the average, think about heat which is a measure of thermal energy. As the total amount increases, assuming the same temperature, the total heat increases. This is an extensive propery.

Now, let’s think about how much heat we need to put in to change the temperature. For example, we know (from experience) that metal heats up really fast. Metal has low heat capacity compared to say water. (We shouldn’t confuse between heat capacity and thermal conductivity. Metals have high thermal conductivity which means the heat propagates faster. It doesn’t say how much energy is needed to raise its temperature.)

Now, I think the answer is somewhat simple… The sweet potato has lower heat capacity and thus needs less energy to heat it. Assuming that the heat input is constant, this means that the temperature (how I measure “hotness”) is higher faster. Adding milk is like adding more stuff but also stuff with high heat capacity… you need more energy to change its temperature by the same amount.

But then one question remains… is the heat input really constant? I know that the microwave is operating at the same power (energy per time), but it does not tell me that the energy is used up as heat… Microwave works by injecting microwave radiation into the system which should absorb this radiation. Molecularly, the species that absorbs the radiation enters a higher energy vibrational mode which is translated as heat. But if you have more radiation absorbing species, conversion to thermal energy might be greater. I don’t think this plays a big role in my milk + sweet potato case… but I do wonder for other food matter… I know that water tends to absorb this radiation or at least a lot of posts online talk about how water absorbs this energy… but I’ll need to think more about what happens to almost completely dry materials.

Institutional corruption and off-label drug use

Today, I attended a presentation by an invited professor on institutional corruption and off label drug use. He introduced the problem of misalignment of interest. Public wants prescriptions that will solve their health issues. The pharmaceutical industry wants to maximize profits.

In particular he discussed the problem of off-label drug use. The idea is that the drug that was approved for indication A (indication is kind of a fancy word for illness) is used for indication B. This is obviously good for the pharmaceutical industry, because they can sell more. More importantly, they do not need to conduct very expensive clinical trials. However, this may not always be in the interest of the patient. It may be in the interest of the patient. Just because there is no direct scientific evidence for it, it does not mean that it is not effective.

Kind of interesting in this problem is the role and interactions of say four independent bodies. First, there is the patient of course that supposedly knows nothing. Second, there is the doctor prescribing the medicine. Third, there is the manufacturer/distributor of the medicine (pharmaceutical companies). Fourth, there is the medicine regulator – the government agency/law (say FDA).

Suppose the patient was being prescribed something off-label. This is the doctor’s judgement (and taking these meds are patient’s judgement, but I assume here that they do as doctors say). The doctors are the final decision makers in this model. Pharmaceutical companies can influence their decision by advertisement and I guess some sort of more direct financial way. By law, they are not able to directly promote their medication for off-label use. However, they can indirectly promote their medication by providing evidence from other bodies suggesting efficacy for off-label use. They may for example fund independent parties to conduct such research.

The FDA has practically no role other than regulating the initial approval and subsequent off-label advertisements. However, even after paying these fines, it seems off-label advertisements can pay off. Once off-label use becomes the norm, marketing is not needed.

Dr Rodwin proposed three things to address this problem:

First, that off-label use should be tracked. Currently, it is difficult to manage or even understand the true implications of off-label use (although he did cite some statistics). This can be done by restricting reimbursements unless the purpose of the drug is provided.

Second, using this data, that if off-label use becomes a problem, the pharmaceutical industry (by law) conducts clinical trials.

Third, to remove the incentive for promoting off-label use. Only the on-label use should be earning them that patent premium. Using the off-label use data, only the manufacturing cost is paid to the pharmaceutical company and the remaining is taken back.

Overall, the proposal is very interesting. Obviously the caveat is that it may find a lot of resistance from the pharmaceutical companies. However, he believes that it is the same as with the implementation of previous regulations such as full disclosure of ingredients. Apparently in the 1900s, some new laws that potentially increased cost for the pharmaceutical companies have been passed. He believes that this seem to be at first difficult, but eventually become the norm.

Even aside from this caveat, some other profs in the room seemed to disagree slightly. They argued that the phara industry faces larger problems. For example, on-label use drugs may not be as safe as expected and the fact that it is on-label provides false sense of security. Making small adjustments makes new loop holes and fixes nothing. This was a very interesting idea, but for now I will hold back on this and talk about my opinion of the original claim.

I find that the proposal focuses too much on what the pharma industry should do. He believes that they will do things as long as they can make money. I like his general approach. He objectifies every entity and simplifies the system into a game almost. Each has their own roles. In this game, his role is to propose rules and regulations that will force the other entities (pharmaceutical industries and others) to act in a way that would benefit the patients. Although he has not formalized the system into a game theory setup, I can easily see this happening.

Following this scheme, he seems to think that the pharma companies have an upper hand over the doctors. His resolution involves only the pharma companies and not much of the doctors (the first is about the doctors reporting but he aims to incentivize this behaviour by blocking reimbursements unless the information is present). I particularly disagree with the second proposal. I do not understand why the pharmaceutical companies should pay to conduct such research just because they are making money from it. What if they believe that the research would result in a negative outcome? The clinical trial would seem like a complete waste of money (and of course they would also be blocking subsequent sales from this off-label use but let’s suppose they would rather NOT do research but stop the doctors from prescribing –which they don’t even have the ability to do!)

Ethically speaking, I think the doctors should be taking more precaution. We just need better doctors… not ones that induce babies just because they want to go home at 5pm -_- (not sure if this is true since I just read it on reddit). But I think as a policy maker, it is more reasonable to track the larger small numbered entities (ie. The pharma companies).

Back to the proposal, I think the off-label use incentive idea is quite good. Companies should be paid premium (patent associated price) for their on-label drug use only. That will motivate companies to acquire on-label drug use status for more stuff. It’s not the drug that needs approval. It’s the drug use. It’s like getting a patent for IDEA. It’s not the substance but the substance that materializes the idea that matters. The patent should not be for the drug but for the IDEA that the drug solves some problem.

There are just so many things I would like to change and I find this interesting. What is theoretically reasonable and good? What can actually be done about it?

At the end, who holds that power?

Thermal oscillation cooking

So today I'm having guests over. I'll be serving pork rib rack. I love to read, so while I was reading about the best way to cook this, I found many differing opinions. To make this discussion more "scientific", I will qualify the best meat and limiting the goodness of meat to the tenderness and the moistness of meat as well as the flavor absorption.
So let's think about the meat cooking process more rigorously. First and most obvious I think is the the act of "cooking" and the associated denaturation of proteins. In more general terms, the proteins that make up the meat is deformed and often this leads to a shrinking of meat. Also obvious is the rendering of fat. The fat dissolves and somehow is expelled. There are many other levels to cooking, including the breakdown of collagen.
In our case, we are using heat to cook, so heat is the central driving force. Suppose we place the meat in the oven. What happens? Well, the meat heats up and the meat is cooked. Easy? Not so fast. The heat doesn't heat up the meat instantaneously. The heat must propagate to the center to cook everything. That's why the size of the meat is important. larger meat -> longer cooking time.
Similarly, the flavor absorption doesn't happen all at once. The flavor must diffuse into the meat. Thicker meat -> more time needed for similar flavor absorption. The absorption is faster for more porous material right? Poke holes. That works, but one possible problem is that the juices can also escape through these holes faster.
So let's talk about moistness. Moist meat is so because it has high water content. To make this possible, two things must happen. First, there should be sufficient moisture around. Second, the meat stuff must be able to hold on to moisture. The second part is often emphasized in cooking forums. Over-cooked meat cannot hold as must moisture (apparently). It makes some sense when we think about how moisture might be retained -between the flesh of the meat. If the meat contracts, this space is reduced.
Just a fun thought:
What if I oscillate the temperature so that I'm cooking at high temp and then low temp. If I choose some perfect frequency (or frequencies as a function of time), I think the cooking should be more even throughout since the diffusion would match the injection rate.
Or another possibility is to increase flavor absorption by expanding and then contracting. as the meat expands back, the flavors surrounding it will be sucked in.
Just a thought. I'm not really sure how reversible meat contraction is. I would guess that it is somewhat reversible since the purpose of meat resting is so that the juice will be retained when cutting. I venture to guess that the relaxation of the meat (reversible contraction) promotes moisture retention by increasing space between the flesh.

Mathematical models

I think I have emphasized the importance of models. In fact, I am currently trying to create a mathematical description of an observed physical phenomenon.

What is a model? In short, models are abstractions of the real world. Models provide a framework in which we can think about the problem. Using the framework, we can make predictions and explain more complex phenomena by combining different models. Every time a prediction is found correct, our models are confirmed.

Sometimes, models may lead to wrong predictions. But first, we should repeat the experiment to confirm that there were no errors. It happens... sometimes. I happen to be more of a theoretician, so I trust the model. However, as all scientists understand, the model is based on hypotheses and observations. Strictly speaking there is no reason why it should apply in an entirely new situation.

Anyhow, the incompatibility between the model and "reality" can be addressed in one of two ways. First, we can change the bounds where the model applies. For example, F=ma is a well known equation proposed by Newton. We now know however, that the Newton's second law (F=ma) does NOT apply when the speed of the moving object approaches the speed of light. To account for this, we can say that the F=ma provides sufficient match in "normal" regime. This means that it's NOT possible to describe movement of electrons using Newton's laws. As previously mentioned, the model is an abstraction. Consider some equation whose "true form" is G =  sin(x). You however have only encountered situations where x << 1. Through various measurements you conclude that G=x... this approximates sin(x) well. When you somehow become capable of measuring x > 1, you realize that the function G = x does not describe G well. However, it still holds that G = x describes the situation well x << 1.

The other way to fix the problem is somewhat obvious. We need a more "true" description that holds. This can be a modification of the previous model to cover new situations. In some cases, it might be a proposition of an entirely new model that can explain all the stories.

As a theoretician, I've always suffered from the possibility that models are wrong. At the end of the day, infinite number of models are capable of explaining a particular set of data. How do I know which one is correct?

My personal conclusion is that correctness is not important. It's the utility of these models. If a model is useful, it's correct at least partially. I can make predictions using this model with some specified confidence. This confidence comes from the experiments that confirm our model.

conservation of mass

When you lose weight, where does it go?
1. disappears
2. converted to energy
3. I poop and pee it out :)
4. I don't know
5. other: ________________
... the correct answer is 3 and 5. Surprisingly, you remove a LOT of waste through the mouth and skin. Even now, you are probably removing a lot of waste.
This waste is carbon dioxide. During respiration, carbon dioxide and water is produced as a byproduct. It's also obvious where the byproduct ends up. These are well established and known... I thought at least at first. If you didn't know this, you are not alone. Derek has asked many "normal people" and has found that some people think it's converted to energy (https://www.youtube.com/watch?v=lL2e0rWvjKI). But as a chemist, I know that conservation of mass must hold and thus that mass cannot be converted to energy (unless nuclear events take place in my body... which probably doesn't). More surprisingly, even doctors couldn't say where the lost weight ends up (http://www.bmj.com/content/349/bmj.g7257). The paper talks more indepth about the calculations. Honestly, though, I'm not sure if the "novel calculation" is new since assuming CO2 and H2O are the only byproducts, it's textbook material... Nonetheless, it is an interesting read. My only (tiny) objection would be that the fat may be transformed into other substances also. The fat burning that results in weightloss is definitely excreted as CO2 and H2O, but my guess is that some of the fat can end up as other storage form... maybe glycogen?

Why is Foaming Difficult?

When you mix water, you don't get foam. This is easy to understand. The difficult part is WHY?
There are many levels to explaining this commonly seen phenomenon.

First is the interfacial energy approach. It is well known that generating an interface costs energy. Thus, liquids for example try to minimize water-air interface by clumping together. When you foam liquids, you are increasing the total contact surface. If this isn't obvious to you, think about it like this: suppose you had 1ml of water as a sphere. What is the surface area here 4/3(pi)(r^2) = 4.835? What if you had lots of "1ml" sized spheres but only 0.02cm thick? the radius of the 1ml bubble is 0.62035 cm. Each of the 0.02cm thick bubbles would have a volume of 1 ml - 0.906363 ml = 0.093637 ml and the surface area would be 4.836 cm2 (outside) + 4.529 cm2 (inside) = 9.365 cm2. There are around 10 of these to make 1ml so the total interface is 93.65 cm2. That's around 20x more. So that's 20x more interfacial energy required. I believe I explained in a previous post how at equilibrium, things tend towards minimum energy state.

But water isn't perfectly circular on the floor. Right. But there's other energy things like gravity and the interfacial tension between the floor and water is not the same as water and air. By adopting a more flat shape, it can be in contact with more floor with possibly smaller interfacial energy per unit area. At the end, everything must be considered.

This brings me to the next point which is about how soap works. So soap works by decreasing interfacial energy per unit area. Soap molecules such as sodium dodecyl sulfate (part of dishsoap for example) have a hydrophilic (the water loving) part and a hydrophobic (the water hating) part as mentioned in the soap post. These two partition to the interface. Ultimately, the interface doesn't cost as much so it's easier to make it.

To me, the interface costing energy is very observational and doesn't provide much insight into WHY. Another way to rationalize this is by thinking about entropic energy costs. When there is a separation between things, you are organizing things into parts. This costs energy. When surfactant is added, it can lower the overall interfacial energy since there are huge enthalpic gains from the interaction of the two ends of the surfactant molecule. This also doesn't provide a lot of insight into why, but for now, I'm happy with this. A better understanding perhaps can come from statistical mechanics type approaches 

Chocolate

I love chocolate. I don't mean Hersheys and such but the "real" chocolate. Most chocolates are full of additives; things I would call bulking agents. Suppose you are buying gold. You get 10 g of gold and pay the "gold price". What if the merchant can exchange 50% of the gold mass with some cheap magical ingredient? The seller could be making twice as much money. That's the general idea behind a bulking agent in food industry. Undoubtably, the chocolate industry does this too. Apparently, Hershey's milk chocolate is around 11% cocoa[1]. Then what are we getting? What makes up that 89%? I found what's in Hershey's Canada: sugar, milk ingredients, cocoa butter, unsweetended chocolate, soy lecithin and natural flavor [2]. According to the nationalpost [2], Canadians are label readers and that's why they removed polyglycerol polyricinoleate... which is a fatty acid-like molecule. Cocoa butter and unsweetened chocolate and chocolate liquor are expensive things. To bulk the overall product, other fats are added and chocolate flavor is diluted with other flavors. Chocolate should have at most four ingredients: chocolate liquor, cocoa butter, sugar, and maybe soy lecithin or other emulsifying agent. Technically, the emulsifying agent is not necessary, but a very small amount (< 1%) can typically stabilize the overall product to increase shelf life, sheen, and the snap.

The science of chocolate tempering is also really interesting. Polymorphism is important in chocolates. In short, when crystals form, the molecules making it up are arranging themselves in a very specific way. Recently, there was an AMA by some professor studying this - link.

ref:

[1] http://www.washingtonpost.com/wp-dyn/articles/A24276-2004Jun8.html
[2] http://news.nationalpost.com/life/canadas-new-hersheys-chocolate-bar-recipe-is-less-cheesy-gritty-than-americas-thank-you-very-much

protein

Today, I want to talk about protein in many different angles. First, most people know protein as food type along with carbohydrates and fats. This is definitely true, but protein is more than just food. Just as other animals have fats and protein (and maybe some carbs), we are made of these things. We know perhaps from the media that muscle meat is rich in protein and low in fat. However, even in the most unexcercized parts, proteins definitely exist. In almost every cell, there are proteins, fats, and sugar... and lots of water.
Proteins are very interesting things. Essentially, they are many amino acids linked together in a linear manner by covalent bonds. However, they tend not to stay linear. Think about putting a string in your pocket. It doesn't stay stretched (there's an entropic cost to it). It folds. Amazingly, proteins typically fold in very specific ways and this special 3D conformation gives them biological function. For example, some proteins can link many different sugars together to make glycogen (our form of temporary sugar storage... before converting excess to fat). In fact, if we didn't have protein, all such cellular processes would shut down.
That made me ask why is protein emphasized when building muscle? Is it because muscle contains a lot of protein? Is this related? So... I did a quick search on the makeup of muscle cells and realized that yes the contracting mechanism requires protein. Actin and myosin are two important proteins that allow the muscle cell to function (I should have known this already...).
I'm sure there are more elaborate explanations, since just supplying the ingredients for making muscle doesn't mean more muscle (as I'm sure most sitters are aware :)).

... Time to stop living on a chair and get moving.

hair dryer

Normally, I don't use the hair dryer since I find it to be a waste of time to do stand around blowing hot air on my hair when it can be done naturally as I am typing this post for example. Obviously, I sometimes need to dry my hair more quickly and it comes to my rescue. But have you ever wondered why blowing hot air makes your hair dry faster?
I'm no expert, but here's my idea. So process of drying is synonymous to evaporating the moisture - basically the water on the hair. So the question can be reformulated as why does blowing hot air make water evaporate more quickly? Still there are two parts to this question - one is blowing HOT air and the other is just the act of blowing something. We may know from experience that just the act of blowing air accelerates the evaporation process. The other part of the question then is what does heat do?
So let's think about the process. When the water evaporates, water molecules first convert from the liquid state to the gas state and move from the "hair environment" to the near by air. Now, the near by air has more water molecules than before and it's "not as easy" for other water molecules move to the air state. Conceptually, this is very similar to getting salt out of the cucumber for pickling. Higher the outer salt content (ie. lower water content), the faster the rate of cucumber  dehydration. As time passes, the difference in water content is reduced. Blowing air is like changing the salt water the cucumber is in contact with. The humid air is replaced with dry air.
So let's tackle the second problem - what does heat do? I think there are two way to think about the effect that heat can have. Perhaps most obviously, heat supplies the energy required for the transition from liquid to gas. When you heat water sufficiently, water boils. This is because the liquid --> gas transition is happening very rapidly.  The other way to think about it is to consider the moisture holding capacity of hot vs cold air. Hot air can retain more water and so it's "easier for water to go into air". These are two sides of the same coin... for reasons I don't want to elaborate here (but to give you a hint, think about why hot air can retain more water)
It's important to re-evaluate the effect of the blowing air now. The air flow "refreshes" both moisture level and the heat level.
This is my theory as to how it works - I'm personally convinced this is the case... but I'm no authority... I guess this is a disclaimer.
refs:
Me?...

new model for cancer

Undoubtedly, one of the leading causes of death in North America is cancer [1]. However cancer is a very poorly understood disease [2]. One of the main reasons is that cancer has very heterogeneous origins. In the molecular level, cancer takes many different forms - the problem can be in wnt, Ras, p53, etc. They do have something in common - the normal balance of proliferation, differentiation, and apoptosis is gone. The cancer cell is programmed to grow. Cancer is a communication problem.

Normal cells (of a multicellular organism) communicate with each other. Based on this signal, they make decisions - they might proliferate (divide to increase the number cells), differentiate (become a specialized cell that handles specific tasks), undergo apoptosis (programmed cell death), or "do nothing" (status quo). Cancer cells have mutations that somehow inhibit their communications in a way that promotes growth.

As they grow in an uncontrolled manner, they accumulate mutations. Eventually, there is some critical mutation which triggers metastasis - spreading to other regions. Cancer spreads to other parts of the patient. Eventually, the cancer takes over the vital organ (s) and the patient dies. Conventionally, this has been the view. However, a recent new hypothesis [3] suggest that the underlying cause of cancer is weakening of normal cells. It’s like how when your grass is strong, the weeds don’t grow well. When your healthy cells are strong, even when some cancer cells arise (ex. due to mutations), the cancer cells are outcompeted by the healthy cells and cannot grow. As interesting and plausible as this hypothesis sounds, I’m not sure if it’s the first time this has been suggested. When I was in university, the cancer researcher professor talked about cells as being in some competitive ecosystem and how it faces its own set of hardships. He didn’t think about healthy cells as direct competition, but in an abstract sense, the model was somewhat similar (in my opinion). What they [3] did do is build out a more elaborate and purposeful model. They also built a simple mathematical model that goes along with the model to show how some data can be explained using this model.

I value high level understanding, but I also value the mathematical models that can be built to more precisely pin down that high level understanding. It gives us a higher predictive capability. Mix 5g of citric acid to 100ml of pure water. The high level understanding would tell you that the pH will decrease and that the resulting solution be more acidic. The mathematical model will tell you that the final pH is 1.87.

refs:

[1] http://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm

[2] according to the professor that taught me about cancer in university

[3] Rozhok and DeGregori (2015). Toward an evolutionary model of cancer: Considering the mechanisms that govern the fate of somatic mutations. Proceedings of the National Academy of Sciences 112(29), 8914-8921.

efficiency

Today’s post will be a side post about efficiency. It won’t be about reaction efficiency and yield or some sort of scale up process efficiency. Rather, simple and general task efficiency. I love to be more efficient. How or what can I do to complete tasks more efficiency? I think this is something that everyone should be thinking about when at work especially (and of course when doing chores:))

I don’t think it’s necessary for me to elaborate on why it’s important to complete tasks efficiency, because it’s obvious.

The real question is what people can do to be more efficient. I think that the first step is to think about this question all the time. When performing tasks, simply ask yourself whether there is a better way to do this. A LOT of times, the answer is YES! If you answered YES, you probably have some new method in mind. Before running off to implement this new method, ask again… is this method really the best… Suppose you found the best method, now think about how best to implement this method. When considering the implementation – think about the costs – both monetary and time. For example, you can hire someone to implement something. That may cost a fortune, but it will take minimal time (hopefully -_-). More importantly, think about whether it will help you solve FUTURE problems more easily.

I want to emphasize the latter. A lot of people do things using method A because it’s how it’s always been done. There is an initial learning stage where you would be slower and this makes people move away from improvement. But this temporary backstep is sometimes necessary for the leap forward. People are so fixated on NOW that they lose sight of what lies on beyond that small hill or obstruction.

In my personal experience, I found programming to be one of the most amazing skills to have. I don’t have to be amazingly skilled. Just the basics are enough. Think about having to perform the same tasks over and over and over and … anyhow you get the point. You can write a program to complete the task. When evaluating automation I think there are three important questions to ask:

1.    How quickly can I make it happen?

2.    How much time will I save (total-due to this automation)?

3.    Will I learn something in the process that will make future automation easier?

It’s obvious to see that Q1 and Q2 determine whether the initial investments will be worth it. In general, Q3 is much more difficult to evaluate. In general, my person tendency has been that even if you don’t save much time, give it a shot. The answer to Q3 makes all the difference in the world. Suppose I’m operating at 90% efficiency right now (in the sense of Q1 and Q2 results), but due to this compromise, I can have 10% increased maximum efficiency in the future. This multiplies like compound interest and in several years, your 90% of maximal efficiency will be more than your 100% maximal efficiency if you hadn’t learned all that.

Spend time to learn things always. It might seem to take time and make you less effective, but it pays off at the end… 

Headache

Today, I'm getting some serious headache and I think it's due to the smells that I have been inhaling. I often get headaches due to perfumes or other strong smells like cleaning agents. I was wondering why... The most common reason seems to be that it's a mental overload. Basically, there's too much information to process. While this sounds plausible, I couldn't find any detailed studies on this hypothesis. My guess is that headache and sensory overload are two ideas that are both difficult to quantify and objectively determine.

multicellular organisms- Understanding the importance of surface area

One interesting question is why larger species are multicellular. Why can't there be human sized single cell organism. One plausible answer is that the surface area to volume ratio is significantly larger in multicellular organisms. Surface is where all the nutrient absorption occurs. The surface is where the cell contacts with the external medium. On the otherhand, the interior of the cell is where the nutrient consumption occurs. In some sense the nutrient need is proportional to the total . So to sustain a larger cell with higher volume, more surface is needed. That's were being multicellular comes in. Take 1 ball and divide it into two balls. The area increases. Do that again for the two balls and so forth. At the end, you have the same volume but increased surface area. If balls are difficult to visualize, think about painting blocks. Suppose you have a 3x3x3 block. Paint the surface. Separate the blocks into 27 separate blocks. Now, some surfaces are not painted. This thought experiment suggests that the surface area in the separated blocks. So, by being multicellular, organisms can increase the surface to volume ratio.

Observe. Ask why. Even if it doesn't get answered immediately, it changes how you think about the world. There are lots of stupid questions... but some of the seemingly stupid question may be the most important. No risk, no gain.

ref:
I think this is something I heard in one of my lectures but written with my own spin. No solid ref.

Vitamin C is Vitamin C...

You're looking to get some vitamin C supplements. There's a natural source and a synthetic source... What do you go for?
Many people tell me that they would rather buy the natural vitamin C even if it may be slightly more expensive. But how is the natural vitamin C actually different from the synthetic version?

As a chemist, there is no difference… That’s what one of my chemistry profs said in first year. The vitamin C molecule is a vitamin C molecule. Exactly same regardless of the previous history.

Think about how many atoms once forming Isaac Newton is part of your breakfast porridge… According to a redditor veryLittle, there will be around 10 million "Isaac Newton atoms" for every ounce of soup (The original post shows the calculation method in detail. link).

The world is made of molecules and the molecules that were once Isaac Newton are chemically no different from ones that were once Adolf Hitler. A human being is an emergent property. Just because all the components have property X, it does not mean that the overall structure has that property.

On a smaller level, all molecules are made of atoms. Depending on the rearrangement of atoms, the overall property of the molecule can change. When the atomic make up is the same, they are called isomers. A very interesting kind of isomers is enantiomers. Two molecules are enantiomeric if they are mirror images of each other. These molecules are interesting in that they have the same chemical properties but their actions in the body can be different. One common kind of enantiomer is amino acid. In our body, we only have the L version.

The next nature question might be how the enantiomer can act differently in our body. Before I describe the process in depth, it’s worth asking how compounds have an effect on our body. There are many ways, but the most general way is by binding to receptors. The binding event triggers other biological processes in our body and this is the effect that we notice.

When binding, the handedness matters.  Intuitively, it’s like a right-handed person using left handed tools or putting left hand gloves on your right hand. It just doesn’t fit well. 

At the end, it's the molecule that matters...

Wait no that's not true. The environment in which the molecule is at also matters. Phenophethalein is a very common pH indicator. It changes color depending on the pH of the environment. I remember doing a phenophthalein pH titration in highschool. I thought it was really cool at first, because color change is just cool... So the same molecule can exhibit different properties... in different environments... 

So to summarize, the the physiological and physicochemical properties of something depends on 1. the chemical composition, 2. the arrangement of atoms (isomers can have different effects), and 3. the environment in which the molecule is exposed to.

So... back to the original question. Is natural vitamin C different from a synthetic one? Maybe maybe not. The fact that it is natural or synthetic doesn't matter. However, natural vitamin C and synthetic vitamin C may contain different impurities. The extraction process for obtaining natural vitamin C is not perfect, so some other compounds may be existent and very low quantities. Similarly, the synthetic process introduces impurities that is not completely removed (just because 100.00000000...% is near impossible to achieve). Can this factor have any influence? I would say yes... for sure. In theory, it's possible. Whether it actually does is a different question altogether. Human studies suggest to difference apparently [1] and I would personally buy whatever is cheaper. But don't take my word for it. I need to do more readings to make sure.

[1] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847730/

DNA origami

As promised, today's topic will be DNA origami. Folding DNA into cool shapes.

I initially wanted to start with a very basic background information about DNA that would explain why DNA is very cool and unique, but I think for this post, I want to show the invention first.

 Figure 1. Shapes made of DNA origami. Adapted from [1]

These are tiny at around 100 nm in width. They are smaller than what your eyes can see and ethis is so small that you can't use typical light microscopes to see it. They used AFM which is an interesting device for visualizing topology (heights). Again, maybe a topic for another post.

All the folding patterns shown here are 2D but it could be expanded to make 3D shapes or containers. Even more interestingly, the box state (ex. open or closed) can be responsive to the environment. This is an amazing capability. Imagine if you can have these nanomachines in your body and it senses problems and unloads cargo (ex. medicine) in the appropriate location. You don't need to take medication when you feel sick. These can find out before you feel sick.

There has been some development focusing cancer treatment. One of the problems with cancer is that the cancer cells are a version of your own cell. Killing just cancer cells is very difficult with conventional drugs. What if these nanomachines can probe the entire body and find cancer cells and unload medicine only in that region. This idea of local drug delivery is a commonly used technique. Think about eye drops or eating Strepsils. The compounds in the eye drop mostly stay in the eye. For Strepsils, only your tongue/throat area is numb. This is due to local delivery. If the things in strepsils were applied to your arm, your arm would be numb.

These nanomachines can sense the presence of two biomarkers for cancer and unload medication in the area if both biomarkers are present. 

Figure 2. Nanorobot made of DNA. In pink are the cargo. Top left shows the geometry while closed. The blue and green boxes are highlighting the lock mechanisms.Adapted from [2].

This is conceptually very cool. Considering how there are mechanisms made of DNA that can act as logic gates, it is actually possible to make a more complex DNA based computer. At least in theory...for now. 

[1] Rothemund, P. W. K. Folding DNA to create nanoscale shapes and patterns. Nature 2006, 440, 297-302.

[2] Douglas, S. M.; Bachelet, I.; Church, G. M. A Logic-Gated Nanorobot for Targeted Transport of Molecular Payloads. Science 2012, 335, 831-834.

Soap in action

Your hands are greasy and you are trying to wash away the grease. You try to wash it with water, but you see droplets of water on your hand and it still feels oily. You use soap and problem solved. Why does soap work?

Before we think about how soap works, let's think about what happens when there is no soap. Think about mixing oil and water. They don't mix. Oil and water behave very differently compared to say alcohol and water. Most of you probably have never seen near pure alcohol, but when you mix alcohol and water... you don't see different parts to it. These parts are typically called phases. In the oil and water system, there are two phases - the oil phase and the aqueous (water) phase. Suppose you added salt and mixed it. You should still observe two phases. But taste the oil before and after. The salt preferentially goes into the aqueous phase and "avoids" the oil phase. Intuitively, this is because the two phases have  different capacity to interact with the salt molecule. Since water can interact more favorably, water dissolves the salt better. This is called partitioning. In a sense, this is why water and oil form two distinct phases (and are not miscible). Water doesn't dissolve completely in oil and oil doesn't dissolve completely in water. But, it should be noted that to some degree water does dissolve in the oil. When the two phases form, water is saturated* with oil and the oil is saturated with water. It might be a very very low concentration but there is some water in the oil phase and some oil in the water phase. *Saturation in chemistry means it has reached the thermodynamically maximum concentration. In more simple terms, more of it cannot dissolve. Think about adding a lot of sugar into water and leaving it for a really long time. The sugar crystals remain and there is no net dissolution of sugar crystals.

Okay, I think I was a little long winded, but the main point was that some things dissolve in certain phases - oil or water. Typically not both. But what if you had a thing that dissolves in water and connected it to something that dissolves in oil? You get an amphiphilic thing. It's like having a cat-dog. Half of it loves water and the other half loves oil. It's like a glue that brings the two things together. This amphiphilic thing called surfactant (ex. SDS) acts like a linker between water and oil and now the two different phases are no longer visible. When you wash your hands, the oil is washed away with the water because surfactants are helping the oil "attach" to the water.

Next time you see soap in water you know how things work in the molecular level. Surfactants are very interesting species (btw in chemistry, things like chemical entities are called species... I found this really weird and difficult at first but it's a very generic term referring to almost anything. The word "thing" doesn't sound scientific enough I guess). They can come together in very interesting ways. Think about adding special surfactant in a particular liquid and these surfactants build some very ordered and defined structure as shown in Figure 1. This process is called self-assembly.

Figure 1. adapted from http://www.rsc.org/chemistryworld/Issues/2003/July/amphiphiles.asp

Possibly, self-assembly is a interesting topic for tomorrow. DNA is also capable of undergoing self-assembly and there are some really cool research out there that try to build nano-machines using DNA as building blocks.

Haemoglobin and oxygen transport

I remember when I first learned about haemoglobin. I was amazed by the way it works. It's affected by many different factors to "sense" the environment and respond to it. Very different from the perfluorocarbon which carries oxygen by solubilizing it. For perfluorocarbons, oxygen solubility is maybe slightly dependent on the temperature, pressure, etc but not much on pH and some important chemical ques. Haemoglobin, however is sensitive to all these factors and changes its oxygen carrying ability accordingly. In addition, the carrying level changes drastically when in different concentrations of oxygen. As I will elaborate on later, this is important in improving the efficiency of oxygen transport.


Before I get explain the amazingness of haemoglobin, I will talk briefly about what it is. As you may be aware, this is a protein that has heme (figure 1) as its prosthetic group (AKA non amino acid component. The heme group is an iron chelator and the iron is what binds to the oxygen in a manner shown in Figure 2.

Figure 1

Figure 2 Oxygen binding with heme group within the crevice in haemoglobin

In our body actually, there are at least two different proteins that can bind oxygen: myoglobin and haemoglobin. However, haemoglobin is used as oxygen carriers and is in circulation while myoglobin is mostly used as oxygen storage and located in muscle tissue [1]. Why is that? The following oxygen binding curve (Figure 3) may provide some insight as to why. On the x-axis of the curve is the pO2 which represents the partial pressure of oxygen. Intuitively, this is referring the the amount of oxygen in the blood with higher numbers reflecting higher oxygen content. The y-axis is the fractional saturation which refers to the fraction of protein that is oxygen bound.
This graph is interesting for biochemists because of the shape of the haemoglobin's oxygen binding behaviour - it's sigmoidal, which means the slope of the curve is low at first, getting higher, and then lower. Oxygen binding behavior of myoglobin on the other hand is more "normal". As more oxygen binds, the the slope of the curve is decreased. Intuitively, the "oxygen binding ability" is decreased. However, it is important to note that there two different myoglobins - oxygen-bound and free. There are no kind of oxygen-bound (technically, there are myoglobins in the "transition" state, but it is assumed to be neglectable).

Figure 3 oxygen binding curve for myoglobin and haemoglobin

This funny shape has been explained through the concept of cooperative binding... a topic for another post perhaps. Here, however, we can easily understand the consequence of lower slope. The binding level between tissues and lungs change drastically. To be an effective oxygen carrier, it should load oxygen (high binding to oxygen) in the lungs (~100 torr O2) and unload in the tissues (~25 torr O2).
Haemoglobin's binding level changes from ~0.95 -> 0.4, which in a very simple model implies that around 0.55 oxygen molecules are transported (in actuality, it may not be that simple because the flow is continuous etc... I will introduce a few other interesting complexities). This is incontrast to myoglobin which holds tightly to the oxygen molecule both in the lung environment and tissue environment... unable to unload anything.

That's not all. Haemoglobin's binding changes depends on pH level as shown in figure 4. This is important in the body since pH near cells that are consuming oxygen rapidly is lower. This is because respiration releases carbon dioxide and decreases pH (increases H+ content) via a process shown figure 5. Effectively, this helps hamoglobin "unload" the cargo even farther and more importantly, preferentially to locations where oxygen is in most need.

Figure 4. pH dependence of haemoglobin's oxygen binding 

Figure 5. carbon dioxide mediated pH decrease.

Also, the carbon dioxide can reversibly react with some side chain of haemoglobin to form carbamate group. This stabilized the oxygen-unbound (deoxyhaemoglobin) further aiding in the unloading process. Equally importantly, haemoglobin also helps transport carbon dioxide back to the lungs where it would be expelled.

Perfluorocarbon is interesting? Sure, but haemoglobin is amazing. There are a lot more interesting features that control oxygen binding and the more mathematical model inclined readers should look up cooperative binding models. Maybe I will post something in the future.

refs:
[1] http://jeb.biologists.org/content/207/20/3441.full
[2] General biochemistry text (ex. Biochemistry by Voet and Voet; Biochemistry by Stryer, Tymoczko, and Berg)

liquid breathing - perfluorocarbons

People can't breathe underwater. People can't breathe in most liquids. But it's not the liquid nature that prevents one from breathing from it. Air is just a medium from which we get our oxygen and theoretically, it does not need to be gas. It's called liquid breathing.

However, the solubility of oxygen in water at atmospheric conditions is 40 mg/L [1]. That means if you inhale 6 L/min, which is a typical rate of volume of air inhaled and exhaled at rest (parameter called respiratory minute volume)[2], at most you can 240 mg of oxygen. It is important to realize that this value is the maximum amount since not all of the oxygen can be extracted. 240 mg is not sufficient anyhow to sustain a person at rest.
Let's do a quick calculation:
VO2 (oxygen consumption) at rest is 3.5 ml/min/kg. For a 70 kg person (typical standard weight for medical stuff... Most "nominal" values are based on a 70 kg adult), this is 245 ml of oxygen. 245 ml to mg conversion can be done as follows using the ideal gas law:
PV = nRT
n = PV/RT
n * [MW] = PV/RT * [MW]
m = PV/RT * [MW]
P: pressure, V: volume, n = number of moles of it, R: ideal gas constant, T: temperature in kelvin.

P = 1 atm, V: 0.245 L, MW = 32 g/mol, T = 23 + 273 = 293 K, 0.08206 L atm mol¯¹ K¯¹.

m = 1 * 0.245 / (0.08206 * 293) *32 = 0.326 g = 326 mg

So, we need at least 326 mg of oxygen every minute, which cannot be supplied by water.

Are there other liquids with high oxygen solubility? What about perfluorocarbons? APF-140HP [4] is a mixture of isomers of certain C10 (meaning it has 10 carbons) has oxygen solubility of 49 ml O2/100ml. That's a maximum of around 2940 ml of oxygen in 1 min (assuming 6L/min inhalation).

In 1966, Clark and Gollan showed that a mouse can live while breathing in the oxygen-saturated liquid perfluorocarbon. Perfluorocarbons are hydrocarbons whose hydrogens have been replaced with fluorines. Oxygen interactions with fluorines is very strong for reasons I will not get depth here. This was shown in a movie called The Abyss (clip) as an incompressible oxygen supply source (when deep underwater the gas compresses due to high pressure and as the diver moves up it decompresses and bursts... maybe more on that later).

There is another important potential application of perfluorocarbon: synthetic blood. Blood transplants have many potential problems - storage, diseases spread, compatibility, availability, etc. Synthetic blood is one way to overcome such problems. But just being able to supply oxygen is not sufficient reason for using them. In addition to efficacy, toxicity, storage, ease of use, reliable manufacturing method are criteria that must be fulfilled. At the time of a review article [5] (2010), there were no perfluorocarbon based synthetic blood substitute that satisfied all of the criteria adequately.

The other sought after route for design of synthetic blood is hemoglobin based. Apparently, there were no hemoglobin based synthetic blood in 2014 [6].

Tomorrow, I will post about haemoglobin and why they're amazing. Maybe will shed light as to why our blood is so amazing and synthetic blood is hard to make.

ref:
[1] http://www.lenntech.com/periodic/water/oxygen/oxygen-and-water.htm
[2] http://biomed.brown.edu/arise/resources/docs/Biopac%20Lesson%2012%20Respiration%20Apnea.pdf
[3] http://www.ncbi.nlm.nih.gov/pubmed/15223593
[4] http://fluoromed.com/products/perfluorodecalin.html
[5] http://www.ncbi.nlm.nih.gov/pubmed/20698841
[6] http://www.fda.gov/biologicsbloodvaccines/scienceresearch/biologicsresearchareas/ucm127061.htm
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191624/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC137239/

It's fishy

Today, I had some fish and so the question of the day is why are fish fishy? I meant have a strong odor.

Fishy smell is from a lot of different things but one of them is the trimethylamine oxide decomposition. Old fish smell more because the bacterial enzymes that attack the fish triggers an redox reaction.

Redox is an oxidation reduction pair. It's a class of reactions describing electron transfers. It's so important that one of my organic chem professors used to say that there are only two kinds of reactions: redox (oxidation-reduction pair) and not redox -_-. One commonly known redox reaction is the browning of apples. The apples oxidize and the oxygen in the air is reduced. Note that redox reactions must occur in pairs, because it's a TRANSFER of something. Nothing is lost or gained in the process. Some thing loses (and is oxidized) and another thing gains (and is reduced).

Back to fishy smells, trimethylamine oxide is decomposed via an enzyme mediated redox reaction into trimethylamine. It's the trimethylamine that is reduced (notice the loss of the oxygen group) smells fishy.

trimethylamine

trimethylamine oxide

Why do fish have trimethylamine oxide? Apparently it's a common metabolite in animals. Metabolites are substances that are produced during metabolism (biochemical processes occuring in the body for example during generation of energy from food). But in saltwater fish, it serves another interesting function. It's an osmolyte. Particularly in sharks that use urea as osmolyte, trimethylamine oxide also counters the denaturing effects. Osmosis is an interesting topic and I hope to cover it in the near future. In short, think of what happens when you put a cucumber in salt water. The water moves out. Why is that?

Often, lemon or other acidic things are added to fish dishes. This has a chemical basis. Trimethylamine can undergo an acid-base reaction and the trimethylamine is protonated (gains a proton to become positively charged). Due to this positive charge, it becomes less volatile (more difficult to go into gas phase) and thus is not readily detected by our nose.

Next time you eat fish, remember to use lemon or lime to enhance the flavors and think about the new level of understanding you have about this previously encountered event.

ref:
http://www.fao.org/docrep/v7180e/v7180e06.htm
http://www.southernfriedscience.com/?p=8659

Hello

Chemistry is a central science and it's in the core of a lot of phenomena observed everyday. Recently, I realized that my background in chemistry makes me think and understand things at a level that is different from people with "normal" level of understanding. I hope to explain interesting things that you see everyday in a more indepth way but also an intuitive way so that everyone can understand.
But at the end, I think it boils down to the model. Chemists have molecular level models which provide more detail in the understanding.