The Geometry of Life

Long ago I heard about various bods trying to explore geometry as it relates to life. Now the research is getting interesting ... .

The basic idea of Dr. Andrulis' framework is that all physical reality can be modeled by a single geometric entity with life-like characteristics: the gyre. 

Cancer and Chromosomes - Again

Aneuploidy has been much neglected but is now gaining interest, possibly because after finding so many genetic alterations it has been realised that cancers are much more than about genes. There is one issue with this news release though. When they state:

"But in cancer, there are many cases of extra or missing chromosomes. Yet cancer cells thrive more effectively than other cells," Prof. Shamir says.


Yet in the paper I read the other day it was claimed that most cancer cells become senescent after 60-90 days(in their model at least). That makes sense because if a cell is being damaged or not working properly it will become senescent. Cancer cells don't thrive, the cancer stem cells may thrive, but even that is problematic. 

Cancer and Stem Cells

Ever wondered why a cancer treatment can so successfully reduce tumor size only to see it come back stronger than ever some months later? If you're prepared to investigate the mathematical model put forward in this paper then you'll have an interesting perspective on the challenge of cancer treatment and the realisation that modern cancer treatments are still missing a vital component in strategy.

Happy Dog.

Thorium and Climate Change

A friend of mine directed me to this TED talk. I have heard of the promise of thorium reactors and this talk by Kirk Sorensen is an excellent example of why we need to consider nuclear power for our future needs.




I do believe in AGW but I don't believe in props on sticks and shiny things facing the sky. These technologies have their place and will be important for our future energy needs but the current attempts to rely so much on these energy technologies is not only misguided it is a big mistake. We are planning to rely on environmentally contingent energy sources because we are convinced the environment is undergoing massive change. That does not make sense. We need energy sources that we have complete control over.

Because thorium is associated with nuclear people panic. It's that word thing again, too many people pay too much attention to words rather than meanings. Politicians use this to great effect the bastards. Thorium reactors, however, cannot melt down and the waste is very manageable. Recent designs in standard nuclear reactors has also led to the creation of meltdown proof reactors. The Chinese are the first nation to grid one of these new reactor designs.

Why thorium hasn't received more attention is beyond me. Except to say this: you cannot create fissile material with a thorium reactor. I don't think that is the major reason though, it is just typical of our species to fall into a mode of behavior and refuse to budge even when the evidence for change is overwhelming. Politicians use this to great effect the bastards.

We now cannot prevent climate change, it is already happening. We have to prepare for the future and if history is any guide the ability to harness and control energy is a key aspect of a civilisation's success. While I am an environmentalist I am also a realist. Human beings en masse will not change their behavior in time to prevent the ongoing environmental "degradation". ("Degradation" suggests some proper state for the earth. There isn't.) If we survive our civilisation will completely transform the ecology of this planet, and perhaps that last claim should be in the past tense. There is no balance, it is always changing, and as change agents we are Nature.

Listen to what Kirk Sorensen has to say. Because the whole climate change debate is largely driven by Green interests any type of nuclear power is off limits. Our future will demand nuclear power. If climate change is going to be as drastic as some of the alarmists claim then we're going to need huge amounts of manageable energy to address all the unexpected contingencies that will arise in the future. Controlled high energy sources, combined with automation, will enable us to transform the planet even further. We're going to do it because we've always done it and if you think you can stop it you are on the wrong planet.

House keeping and exercise

"House keeping" refers to an intra-cellular process that relates to the functions which involve removing excess and potentially dangerous molecules and detritus from the cell. It is crucial to cell function and survival. The main waste product that builds up is called lipofuscin, a set of lipids and proteins and lipoproteins that need regular removal before aggregation makes it too difficult to remove the same. Accumulation of lipofuscin can be taken as a marker of cell aging to developing strategies to maintain regular house keeping is very important because aggregates of molecules are extremely difficult to degrade.

For example, a key protein degradation pathway, the UPS pathway, has a severe limitation in that the organelle has a very narrow opening and hence will not allow aggregated proteins into the organelle to be digested. So it is essential we maintain UPS and the other key process mentioned in this article, autophagy, to maintain cellular health.

As this study highlights exercise is a good way to promote autophagy. So stop reading and go for a walk!

Chromosomes and Cancer

In my previous post, Cancer as a Metabolic Disease, I referenced an extensive review article that argues for a different etiology for cancer. Their argument is that it arises from mitochondrial dysfunction which in turn causes aneuploidy, the key focus of this recent research. As stated in the news release:

"The most common genetic change in cancer is the presence of an incorrect number of intact chromosomes within cancer cells -- a condition known as aneuploidy," 

 That remark is consistent with the claims of the earlier study. It is odd that only now is it beginning to receive more attention but that probably reflects the gene centric orientation of cancer research. It is tempting to think of these are competing paradigms but this is incorrect, the paradigms are complementary and together can provide a much better picture of what is happening in cancers. There is no single correct paradigm for understanding cancer. It can arise directly through specific mutations and through mitochondrial dysfunction. In the same way that cardiovsacular disease or neurodegeneration can arise through a number of risk factors, cancer can have multiple etiologies.

This suggests that those who propose magic bullets for cancer have completely misunderstood the nature of the pathology. Correct, they have. There are potentially many approaches to managing cancer, from increasing alkalinity to DCA, each cancer type may well respond to different strategies.

Cancer is NOT a single entity pathology!

Cancer as a Metabolic Disease

4/01/2012 5:33PM

Cancer as a Metabolic Disease(Review),
Thomas N. Seyfried, Laura M. Shelton
Nutrition & Metabolism, 2010, 7:7
Download the full paper here.

Abstract
Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless of cellular or tissue origin. In contrast to normal cells, which derive most of their usable energy from oxidative phosphorylation, most cancer cells become heavily dependent on substrate level phosphorylation to meet energy demands. Evidence is reviewed supporting a general hypothesis that genomic instability and essentially all hallmarks of cancer, including aerobic glycolysis (Warburg effect), can be linked to impaired mitochondrial function and energy metabolism. A view of cancer as primarily a metabolic disease will impact approaches to cancer management and prevention.

It is nice to know that at my age I can still perceive my stupidity. This review paper reminded of concepts and findings in relation to cancer that I had long ago read about but only as an interesting footnote. I haven't studied cancer, except to say that I read enough of it to know that it is a terribly difficult phenomena to understand and I'd rather conquer a galaxy cluster or two than waste my time reading anymore about it because that would constitute a larger waste of time. I like aiming high and MOO3 sucks so I'll read something, if only because over the last 6 months I have read findings that raise serious questions about cancer being a disease of the genome.

Schizophrenia, Depression, the Hippocampus, and Information

19/12/2011 4:46PM

A review of a Nature Reviews Neuroscience paper, and then I just sortta wonder off and babble incessantly ... .


Nature publications generates some high quality reviews that are great for catching up on the latest developments in a given area. I've always  had a bit of interest in the hippocampus so was pleased that Nature Reviews Neuroscience offered the extensive review article below for free(each month the Review series and I believe some other Nature journals offer free articles).

Article:  A pathophysiological framework of hippocampal dysfunction in ageing and disease
Authors:   Scott A. Small, Scott A. Schobel, Richard B. Buxton, Menno P. Witter and Carol A. Barnes
Journal: Nature Reviews Neuroscience, Oct 2011.

Abstract | The hippocampal formation has been implicated in a growing number of disorders, from Alzheimer’s disease and cognitive ageing to schizophrenia and depression. How can the hippocampal formation, a complex circuit that spans the temporal lobes, be involved in a range of such phenotypically diverse and mechanistically distinct disorders? Recent neuroimaging findings indicate that these disorders differentially target distinct subregions of the hippocampal circuit. In addition, some disorders are associated with hippocampal hypometabolism, whereas others show evidence of hypermetabolism. Interpreted in the context of the functional and molecular organization of the hippocampal circuit, these observations give rise to a unified pathophysiological framework of hippocampal dysfunction.

Free Will, the Law, and other Meanderings.

I do get carried away. The below arose from a FB discussion. Normally I stay away from these debates but thought Sergio was worthy of a considered reply. No time to proof. Sorry about that.

6/10/2011 12:19AM


You're a good chap Sergio and worthy of a considered reply. I've done my best but it is well past midnight and work beckons ...

Warning! I have an unusual approach to these questions, my thinking very much informed by online discussions long ago with Frank Lefever and a few others. I am an iconoclast. One of my key epistemological heuristics is this: if many brilliant people have been trying to resolve issues over many decades, let alone centuries, then, in the absence of new information, I have no chance of developing any further insights and so will direct my attention elsewhere.

No time to proof this. Sorry.

1. I don't entertain free will, I am to blame for my actions.

I don't entertain free will because it provides no explanatory power. The great power of human cognition arises when we ask the questions that provide us with further insight into the relevant matter. Mathematicians refer to this as "fertility". So even an abstract idea can be useful but it must have fertility. This is why in science there is the insistence that ideas should be falsifiable. If we cannot prove or disprove idea how can we ever know if it is true? We still cannot say with certainty that free will is existent yet we continue on our way. Most people who don't believe in free will do not fall into antinomianism, the belief that they cannot be responsible for their actions. This was a big issue with the Calvinist doctrine of predestination, many christians arguing that to believe God elects us "before the beginning of time"(Eph chapter 1 I think) is to invite moral anarchy. It doesn't. We far too often think about behavior being driven by thoughts. Now without venturing into radical behaviorism and its view that even thinking is behavior, a view I find favourable but wonder if it is just semantics, it is perfectly clear to me that my thoughts are but one aspect of how my behavior is formed. In fact I would argue that our thoughts about how other people perceive our behavior and our anticipation of the potential consequences of that perception is a far more powerful modulator of our behavior than our preferred philosophical position.

2. Neuroscience and Cognition.

The great fuss about how neuroscience is deepening our understanding of behavior is a fancy. Modern neuroscience is like a hunter gatherer looking for the first time at a car and seeing the wheels turn, thinks, the wheels make the car go forward. He sees the wheels, but the wheels do not move the car, the engine does. He cannot see the engine. Modern neuro-imaging is only seeing the wheels. It may even be worse than that, it may only be seeing the dust kicked up by the wheels. Even in recent months some long held assumptions about the classic model of neural function have been very much demolished. If you read enough of the literature, if you keep reading, you soon come across experiments that make a mockery of textbook explanations of neural function. There are deep and very difficult philosophical questions here, many of which revolve around Information Theory. That is a long and difficult road, I went down the road on a fast motorcycle, turned out the first corner was a decreasing radius turn and I'm still licking my wounds ... .

3. Blame is a reinforcer

If I am speeding down the road and without intention, quite unconsciously, I will still receive a speeding ticket and no amount of pleading will prevent that. If I unintentionally kill someone I will still be charged with manslaughter. That we know that breaking the law can have serious personal repercussions reinforces lawful behavior. Whether I break the law intentionally or unintentionally does not alter the fact that I broke the law. Unintentional breaking of the law may mitigate liability but it does not get me off the hook. So the linkage between "freely choosing" and "blaming" is not consistent. We blame people as a way of modulating their behavior and the behavior of others. Irrespective of my willing I am culpable for my actions. Even in cases of known psychopathology the pathology is at best a mitigating factor, it does get people off the hook and nor should it. The law is about much more than personal responsibility, it is very much about establishing reinforcement contingencies to maintain social order. The Law can never be a conceptually and philosophically consistent system. The Law is very much a response to the problem arising from the vagaries of human behavior and the environment. It is primarily driven by the need to maintain social order, not be a neat and tidy system of thought. In short, the world is messy so the Law will always be messy.

Obviously, the concept of free will is not a critical determinant of the legitimacy of our legal system.

4. Childrens' behavior is not guided by their belief in free will.

In fact children rarely if ever consider themselves to be free willing agents. Children are not engaging into those types of cognitive behaviors, that type of operational function only really emerges, at best, post puberty. Often never! Children are amongst the first to proclaim, "Johnny made me do it!" Adults abandon that habit because it becomes socially unacceptable. Not because they delve into the philosophical arguments surrounding Free Will but because it is in their best interests not to blame others. Blaming ourselves, as much if not moreso than blame from others, is a strong contingency that modulates our behavior. Blaming is not about free will, it is about behavior modification. Arminianism, the theological school of thought in opposition to Calvinism, can eat my shorts. I have no interest in free will,  that I consciously decide to do something provides me with absolutely no insight into the causes of my behavior. As the experiments of Sperry and Gazzaniga make worryingly clear, we have this habit of rationalising the causes of our behavior. We provides reasons after the event but the work of those two great neuroscientists indicate that we appear to make up stories to explain our behavior. As that wonderful line made by Geoff Goldbloom in the movie "The Big Chill" goes: You can go for a week without sex but can you go for a week without a rationalisation? (Same meaning, closely to that, and dreadfully true.)

5. The history of Free Will

My understanding is that the prominence of this concept in our culture primarily derives from the post Reformation great theological debates. I actually like the Calvinist approach because John Calvin himself was very much about setting up Geneva through laws, education, democracy, and social control. With regard to the latter he was sometimes unforgivingly ruthless and cruel. Eastern cultures, with Buddhism being a prominent example, don't seem as preoccupied with this question. Mayahana and Zen Buddhism will even assert that "self" and "free will" are illusions. Said conclusions arose from extensive exercises in enhancing "self awareness", which as the previously mentioned neuroscientists and many others have indicated, is hopelessly insufficient for understanding the true causes of our behavior. This again comes back to the theme of radical behaviorism that thought is behavior. The thoughts we acquire from our culture, not from our cognition, may be closer to the primary causes of our interest in this question than any "rational" deliberation of the legitimacy of that mode of analysis.

6. Self Awareness.

Who was that Greek chap, Aristotle? Was he the one who carried on about the need for self awareness. What are we observing when we observe "the self"? Look closely, you are not looking at some whole or some entity within yourself, you are thinking about individual instances of your behavior and attempting to coalesce these individual fragments into some coherent whole. The most successful areas of psychology are not in the "Big Ideas" but rather in the attempts to modify specific behaviors. For decades the psychologists peddled self-esteem as the cure all for so many human problems. Bollocks, the research of Ray Baumeister, circa 2002, pretty much put that fancy to rest. There is not so much talk about self esteem these days. Why? The studies don't support the claim that changing one's view of one's self makes any significant difference. Nonetheless I do believe our self perception does have implications for our behavior but that brings us back to the radical behaviorist idea of thinking being behavior.

I prefer the advice of Baumeister. Want to change your behavior? Then focus on those behaviors you wish to change. Establish in your life the appropriate environmental contingencies, and by environment I include the people around you, and your behavior will change. That is why religious bodies are so successful at behavior modification: the creation of a social environment that establishes multiple reinforcers modify behavior to be in accordance with the group. As the studies of Milgram and Zimbardo illustrate, or for that matter the SS of the Nazis, or even just plain being in a war zone, our environment, and especially the people in that environment, are vastly more determinative of our behavior than our philosophy. I grant you there are rare exceptions but as numerous historical examples illustrate, even the most religious of people can become murderous assholes. Only last night I heard a philosopher state how during the rise of Japanese militarism the Buddhists were often fully on board with justifying the incredible cruelty that Japanese military government managed to engender during that period. And contrary to the popular view, the Japanese at that time were far more brutal than the Germans. But that's another story.

Self awareness is also important but it can also be crippling. I prefer the attitude of Albert Camus, "Forever shall I be a stranger to myself."(The Myth of Sisyphus). Or this wonderful line from the great American street writer Henry Miller ....

Even the psychic invalid throws away his crutches, in such moments [large external threat]. For him the greatest joy is to realise that there is something more important than himself. All his life he has turned on the spit of his own roasted ego. He made the fire with his own hands.

Sexus, page 337.