Samstag, 24. Februar 2018

Franz Fuchs

Angeblich soll jetzt ein neues Theaterstück über den Briefbomben-Attentäter Franz Fuchs aufgeführt werden. Ich befürchte das Schlimmste, nämlich, dass Franz Fuchs einseitig als Ausländerfeind dargestellt und die eigentliche Problematik ausgespart wird, nämlich die eines "zu Unrecht ausgeschlossenen" Hochbegabten. (Siehe:

Vielleicht sollte ich mehr über die Person Fuchsens recherchieren und mein eigenes Theaterstück über ihn verfassen.

Donnerstag, 22. Februar 2018

"Anything goes"

Poppers Erkenntnistheorie ist nicht ideal, Feyerabends aber auch nicht. "Anything goes" würde in der Realität dazu führen, dass derjenige mit der stärksten Machtposition Recht bekäme und nicht derjenige, der tatsächlich die Wahrheit spricht.

Popper's epistemology is not ideal, but neither is Feyerabend's. In reality, "Anything goes" would mean that the one with the strongest position of power would be right and not the one who actually speaks the truth.

Mittwoch, 21. Februar 2018

Adult puberty

After all, I have never gone through real puberty, a phase of adolescence in which one refuses to do what parents and teachers want from one, and rebelled openly. Even as a young adult, I have made every effort to maintain the appearance of always complying with what I thought was the official state doctrine. But in time I learned two things: Firstly, that it is of no use to me to be true to the line, because certain circles simply reject me because of my giftedness. Secondly, that what I thought was the official state doctrine was more in line with the Social Democratic Party, while at the Medical University the Christian Democratic Party was in charge and this party seemed to think differently about many things - another reason why I didn't benefit from being "true to the line". Consequently, I began to openly express my own opinion on the Internet. At first I thought I was provoking. But I found more and more agreement with my views. In the meantime, I have become accustomed to thinking freely, and I am no longer afraid of getting angry, nor do I believe that my remarks are really offensive. A certain circle of people has emerged who think about most things in a similar way as I do. I don't mess with these people, on the contrary. In Austria, there has even been a new political force in Parliament since 2013, with many of them belonging to it who have similar views as I do. The time is ripe for independent, critical thinking that puts the matter and not any personal feelings in the foreground. This was made possible by the internet and especially by Facebook. We are all most indebted to Mr Zuckerberg.

Translated with


Ich habe ja nie eine richtige Pubertät durchlebt, also eine Phase als Jugendlicher, in der man sich weigert, das zu tun, was Eltern und Lehrer von einem wollen, und offen rebelliert. Selbst als junger Erwachsener habe ich mich nach Kräften bemüht, nach außen stets den Anschein zu wahren, dem, was ich für die offizielle Staatsdoktrin hielt, zu entsprechen. Doch mit der Zeit bin ich auf zwei Dinge gekommen: Erstens, dass es mir nichts nützt, linientreu zu sein, weil gewisse Kreise mich schlicht und ergreifend wegen meiner Hochbegabung ablehnen. Zweitens, dass das, was ich für die offizielle Staatsdoktrin hielt, eher der Linie der sozialdemokratischen Partei entsprach, während an der Medizinischen Universität die christdemokratische Partei das Sagen hatte und diese Partei offenbar über viele Dinge anders dachte - ein weiterer Grund, warum es mir nichts nützte, "linientreu" zu sein. Folglich fing ich an, im Internet offen meine eigene Meinung zu vertreten. Anfangs glaubte ich, damit zu provozieren. Aber ich stieß mit meinen Ansichten immer mehr auf Zustimmung. Inzwischen habe ich mich daran gewöhnt, frei zu denken, und fürchte mich gar nicht mehr davor anzuecken, beziehungsweise glaube ich mittlerweile gar nicht mehr, dass meine Äußerungen wirklich Anstoß erregen. Es hat sich ein gewisser Personenkreis herauskristallisiert, der über die meisten Dinge ähnlich denkt wie ich. Bei diesen Leuten ecke ich keineswegs an, im Gegenteil. In Österreich gibt es seit 2013 sogar eine neue politische Kraft im Parlament, der viele angehören, die ähnlich ticken wie ich. Die Zeit ist reif für eigenständiges, kritisches Denken, das die Sache und nicht irgendwelche persönlichen Befindlichkeiten in den Vordergrund stellt. Möglich wurde dies vor allem durch das Internet und speziell durch Facebook. Wir alle sind Herrn Zuckerberg zu größtem Dank verpflichtet.

Dienstag, 20. Februar 2018

How high-flyers are disadvantaged

Austria was not always just the land of yodelers, folk rock' n' rollers and beer tent visitors. No, Austria was once also one of the world's leading scientific nations - you can think of names such as Sigmund Freud, Karl Popper, Kurt Gödel, Ludwig Boltzmann, Erwin Schrödinger, Konrad Lorenz or the von Mises brothers.

What these people have in common is that they mainly lived and worked before the Second World War. But how can it be explained that Austria has apparently not produced any comparable geniuses in the last seventy years?

Is it perhaps really due to the containment policy of the Christian Democratic education ministers (see the article "No Jew, no leftist, no positivist")? That the Christian Democrats wanted to maintain the status quo and suppress any progressive ideas?

Or is it due to the general hostility of the population towards the intellectual gifted, who are already called "nerds" as high school students and who are sometimes even oppressed by the teaching staff?

As the son of a teacher, I was in a privileged position during my time at grammar school. I always got the grades that matched my performance - these were usually very good grades - and no teacher really put me at a disadvantage. My girlfriend, on the other hand, who also has an intelligence quotient of more than 140, but comes from an "ordinary" family, has not forgotten how her life has been made difficult by so-called educators and how she herself has been confronted with horrendous accusations, such as that she is "asocial". (The term "asocial" is, by the way, Nazi terminology, see for example this article).

My friend and mentor, Dr. Uwe Rohr, used to say that we are living in a world dominated by ordinary people who design rules that are primarily geared to the needs of ordinary people. Uwe Rohr has identified the following three characteristics of normal talent:

1. Normal talented people want a regular income.
2. Normal talents have no revolutionary ideas.
3. Normal talented people don't always tell the truth.

Point one alone shows what ordinary people are all about: money, power and prestige. It is these three factors that motivate ordinary people to make a career. This also applies to a university career. After all, most university professors are naturally also normal talented. They are not interested in the pleasure of scientific work or a genuine interest in the subject, but in money, power and prestige. For these three factors they accept a hard, unfulfilled professional life, which is so hard and unfulfilled for them because they have no real interest in the subject and no pleasure in scientific work. Those students who show real enthusiasm for their subject and for science as such are perceived by them as a threat and are neglected or silenced as far as possible.

I can confirm from my own experience that gifted people are not celebrated as geniuses but rather disadvantaged in reality:

1. After I had put my personal homepage on the Internet at the beginning of my studies, which contained only truthful information (such as my grades in the Matura certificate, my attitude to study and to science and my expectations for my professional future), I got the most violent reactions in the guestbook, which ranged from false accusations ("You are the typical gay student" - I am straight!) up to absolutely unbelievable utterances ("Such people shouldn't exist").

2. At a summer school after the second year of my studies, a fellow student asked me if I was "the one with the website". She then said that I might be a "little genius", but she would imagine a doctor to be different. This little, insignificant fellow student wanted me to quite my studies. What a fool!

3. A colleague of mine wanted to receive tutoring in pharmacology and had already met with me to plan the lessons. But when she found out on the Internet that I have an intelligence quotient of over 150, she wrote to me that she didn't know I was so clever and now that she knew it, she was no longer interested.

4. When I applied to a research institute after my studies, although I had already introduced myself to the relevant people for several years and they had said that they had a good impression of me, I did not receive an answer for a few days. Then the head of the department I applied to wrote me, he saw that I was already celebrating my 29th birthday, and this institute would only employ people who were at most 28 years old. Obviously a flimsy reason, the real reason might have been that he was discouraged by the information about my intellectual abilities on my homepage.

5. I was invited to apply for a scholarship at the Vienna University of Technology and was invited to participate in an assessment center and give a presentation about myself. My application was finally rejected on the grounds that I had talked too much about my achievements and too little about my hobbies. I did indeed talk about my hobbies, but these are just things that normal people regard as intellectual "hard work", so they would not think of calling them hobbies.

I see the only possible solution to this situation as being that highly talented people would have to found a parallel society in which they are among themselves. Maybe even a state of their own. There are already efforts in this direction; one of the leading protagonists is Michael W. Ferguson.

The fact is: the way things are now, it cannot go on, and if a fruitful coexistence with ordinary people is not possible, the gifted will be forced to separate themselves and found their own political entity.

Translated with

Wie Hochbegabte benachteiligt werden

Österreich war nicht immer nur das Land der Jodler, der Volks-Rock'n'Roller und der Bierzelt-Besucher. Nein, Österreich war auch einmal eine der führenden Wissenschaftsnationen dieser Erde - man denke etwa an Namen wie Sigmund Freud, Karl Popper, Kurt Gödel, Ludwig Boltzmann, Erwin Schrödinger, Konrad Lorenz oder die Gebrüder von Mises.

Diesen Leuten ist gemeinsam, dass sie hauptsächlich vor dem Zweiten Weltkrieg lebten und wirkten. Wie kann man es sich aber erklären, dass Österreich in den letzten siebzig Jahren offenbar keine vergleichbaren Genies mehr hervorgebracht hat?

Liegt es vielleicht wirklich an der Containment-Politik der christdemokratischen Bildungsminister (siehe den Artikel "Kein Jude, kein Linker, kein Positivist")? Daran, dass die Christdemokraten den Status Quo aufrecht erhalten und das Aufkeimen jeglichen fortschrittlich anmutenden Gedankengutes im Keim ersticken wollten?

Oder liegt es an der allgemeinen Feindseligkeit der Bevölkerung gegenüber intellektuell Veranlagten, die schon in der Schule ein Lied davon singen können, als "Streber" beschimpft zu werden, und die teilweise auch vom Lehrpersonal niedergehalten werden?

Als Sohn einer Lehrerin war ich in meiner Zeit am Gymnasium in einer privilegierten Stellung. Ich bekam immer die Noten, die meinen Leistungen entsprachen - das waren meistens sehr gute Noten -, und wurde von keinem Lehrer wirklich benachteiligt. Meine Freundin hingegen, die ebenfalls einen Intelligenzquotienten von über 140 hat, aber aus einer "gewöhnlichen" Familie stammt, kann noch heute ein Lied davon singen, wie ihr von so genannten Pädagogen das Leben schwer gemacht worden und sie selbst mit aus der Luft gegriffenen Vorwürfen konfrontiert worden ist, wie etwa, dass sie "asozial" wäre. (Der Begriff "asozial" ist übrigens NS-Terminologie, siehe etwa diesen Artikel.)

Mein Freund und Mentor Dr. Uwe Rohr sprach davon, dass wir in einer Welt leben, die von Normalbegabten beherrscht wird, welche Regeln entwerfen, die wiederum in erster Linie an den Bedüfnissen von Normalbegabten ausgerichtet sind. Normalbegabung machte Uwe Rohr an folgenden drei Merkmalen fest:

1. Normalbegabte wollen ein regelmäßiges Einkommen.
2. Normalbegabte haben keine revolutionären Ideen.
3. Normalbegabte sagen nicht immer die Wahrheit.

Allein Punkt eins zeigt schon, worum es den Normalbegabten geht: nämlich um Geld, Macht und Prestige. Es sind diese drei Faktoren, welche Normalbegabte motivieren, Karriere zu machen. Das gilt auch für eine Hochschulkarriere. Denn selbstverständlich sind auch die meisten Universitätsprofessoren Normalbegabte. Ihnen geht es nicht um Freude am wissenschaftlichen Arbeiten oder um echtes Interesse am Fach, sondern um Geld, Macht und Prestige. Für diese drei Faktoren nehmen sie ein hartes, unerfülltes Berufsleben in Kauf, das für sie deswegen so hart und unerfüllt ist, weil sie kein echtes Interesse am Fach und keine Freude am wissenschaftlichen Arbeiten haben. Jene Studierenden, die tatsächlich Begeisterung für ihr Fach und für die Wissenschaft an sich zeigen, werden von ihnen als Bedrohung wahrgenommen und tunlichst vernachlässigt oder totgeschwiegen.

Dass Hochbegabte in der Realität nicht als Genies gefeiert, sondern benachteiligt werden, kann ich aus meiner eigenen Erfahrung bestätigen:

1. Nachdem ich zu Beginn meines Studiums meine persönliche Homepage ins Internet gestellt hatte, die nur wahrheitsgemäße Angaben enthielt (wie etwa meine Noten im Matura-Zeugnis, meine Einstellung zum Studium und zur Wissenschaft und meine Erwartungen an meine berufliche Zukunft), bekam ich im Gästebuch heftigste Reaktionen, die von falschen Anschuldigungen ("Du bist der typische schwule Student" - ich bin hetero!) bis hin zu absolut unglaublichen Äußerungen ("Solche Leute sollte es nicht geben") reichten.

2. Auf einer Summer School nach dem zweiten Studienjahr sprach mich eine Kommilitonin an, ob ich "derjenige mit der Website" sei. Sie sagte dann, ich sei wohl "ein kleines Genie", aber einen Arzt würde sie sich anders vorstellen. Diese kleine, unbedeutende Studienkollegin maß sich tatsächlich an, über mein Studium zu richten. Leute gibt's!

3. Eine Studienkollegin wollte von mir Nachhilfe im Prüfungsfach Pharmakologie erhalten und hatte sich mit mir bereits getroffen, um den Unterricht zu planen. Als die dann aber im Internet erfuhr, dass ich einen Intelligenzquotienten von über 150 habe, schrieb sie mir, sie hätte nicht gewusst, dass ich so gescheit bin, und jetzt, wo sie es wisse, habe sie kein Interesse mehr.

4. Als ich mich nach dem Studium an einem Forschungsinstitut bewarb, bekam ich, obwohl ich mich bereits einige Jahre den entsprechenden Personen vorgestellt hatte und sie bekundet hatten, einen guten Eindruck von mir zu haben, zuerst einige Tage lang keine Antwort. Dann schrieb mir der Abteilungsleiter, bei dem ich mich beworben habe, er habe gesehen, dass ich bereits meinen 29. Geburtstag gefeiert habe, und an diesem Institut würde man nur Personen anstellen, die höchstens 28 Jahre alt seien. Offensichtlich ein fadenscheiniger Grund, der wahre Grund dürfte wohl eher gewesen sein, dass ihn die Angaben zu meinen intellektuellen Fähigkeiten auf meiner Homepage abgeschreckt haben.

5. Ich wurde eingeladen, mich für ein Begabtenstipendium an der Technischen Universität Wien zu bewerben, und durfte an einem Assessment Center teilnehmen und dort eine Präsentation über meine Person halten. Meine Bewerbung wurde schließlich mit der Begründung abgelehnt, ich hätte zu viel über meine Leistungen und zu wenig über meine Hobbys gesprochen. Dabei habe ich sehr wohl über meine Hobbys gesprochen, nur handelt es sich bei diesen eben um Dinge, welche normale Menschen als intellektuelle "Schwerstarbeit" betrachten, bei denen es ihnen also nicht in den Sinn käme, sie Hobbys zu nennen.

Die einzige mögliche Lösung für diese Situation sehe ich darin, dass Hochbegabte eine Parallelgesellschaft gründen müssten, in der sie unter sich sind. Eventuell sogar einen eigenen Staat. Es gibt bereits Bestrebungen, die in diese Richtung gehen; einer der führenden Protagonisten ist Michael W. Ferguson.

Tatsache ist: So, wie es jetzt ist, kann es nicht weitergehen, und wenn ein fruchtbares Zusammenleben mit Normalbegabten nicht möglich ist, werden Hochbegabte eben gezwungen sein, sich zu separieren und ihr eigenes Süppchen zu kochen.

Freitag, 16. Februar 2018

Unmengen an Literatur zu Isoflavonen

Wenn man sich ein bisschen Zeit nimmt und im Netz recherchiert, findet man Unmengen an Literatur zu Isoflavonen, Adiol, dem Estrogen-Rezeptor β und anderen Dingen, über die mich Uwe unterrichtet hat. Die meisten Quellen sind durchaus positiv, also in Uwes Sinne. Es gibt auch kritische Stimmen, aber da scheinen kommerzielle Interessen vorzuliegen - objektiv scheinen sie mir nicht zu sein.

Insgesamt gesehen, zeigt sich, dass es bereits viele Produkte gibt, die auf Isoflavonen basieren. Uwe war jedoch der Meinung, dass diese Produkte im Allgemeinen zu niedrig dosiert seien und sich die eigentliche Wirkung in Bezug auf schwere seelische Störungen, Infektionskrankheiten und Krebs erst bei einer weit höheren Dosis entfalte.

Mich persönlich interessiert an der ganzen Angelegenheit nur das Wissenschaftliche. Kommerzielle Ambitionen habe ich nicht. Ich lebe von meiner Arbeit als "Hirnwerker" in der Software-Industrie.
Very importantly, they report that 3b-Adiol is an anticarcinogen (for the technically inclined, a redifferentiating agent) that activates estrogen receptor beta, an anticarcinogenic estrogen receptor present in large numbers in the prostate gland. [...] The androgen derivative 5a-androstane-3b, 17b-diol [3b-Adiol] inhibits prostate cancer cell migration through activation of the estrogen receptor beta subtype. [...] For the really technically inclined, here are several “mechanisms of action” of 3b-Adiol, all of which come from stimulation of estrogen receptor beta:
- repression of VEGF-A (vascular endothelial growth factor A) expression 
- destabilization of HIF-1a (hypoxia-inducible factor 1a)
- reduction of “Snail1” (can’t identify this acronym) relocation from the cytoplasm to the nucleus of cancer cells
Fortunately, researchers are reporting possibilities for stimulating the natural endogenous biosynthesis of 3b-Adiol with natural substances which stimulate 3b-HSD and/or 17b-HSD, the enzymes that convert 5a-DHT into 3b-Adiol. But there’s a caution: Although these studies are theoretically promising, none of them have as yet actually measured “before and after” quantities of 3b-Adiol itself, but rather activity and/or quantity of the enzymes that “lead to” 3b-Adiol. Until this research has been done, the best alternative is measuring the “before and after” levels in individuals, especially individuals found to personally have low 3b-Adiol levels. (In my own practice, I’ve observed that several of the items below have been associated with improved 3b-Adiol levels in individuals, but it’s too early to report that any one is reliably associated with improvement in low 3b-Adiol levels.)
Let’s start with (no kidding) coconut oil and olive oil. In 2008 and 2009, researchers reported that these two oils, used separately, significantly stimulated the activity of 3b-HSD and 17b-HSD, as well as significantly raising testosterone levels in experimental animals, while grapeseed oil and soy oil did not have any significant effect.
Then there’s our old “male health” standby, zinc. Studies in male rats demonstrated that zinc deficiency decreased 3b-HSD activity. Zinc deficiency also was associated with a very significant reduction in testosterone itself.
Hypothyroidism and “subclinical” hypothyroidism are relatively common. Here’s another reason to be ever-vigilant for these problems: T3 stimulates 3b-HSD type 2. Although this might suggest that T3 may stimulate 3b-Adiol, there are as yet no publications exploring this possibility.
However, it’s easy enough to check in any one individual with lower than desirable 3b-Adiol.
3b-HSD also requires NAD (niacinamide adenine dinucleotide), but once again there are no studies yet linking NADH supplementation with improved levels of 3b-Adiol.
In a study of adrenal cell activity, lithium was reported to increase synthesis of 3b-HSD type 2. (Obviously the adrenals and testes are entirely different, but the 3b-HSD enzyme is the same enzyme in both areas).
Lastly (for now) all-trans retinoic acid (ATRA) has been shown to increase 3b-HSD type 2. As too much ATRA can become toxic, this one is available only by prescription.
We found that 3beta-Adiol not only inhibits PC3-Luc cell migratory properties, but also induces a broader anti-tumor phenotype by decreasing the proliferation rate, increasing cell adhesion, and reducing invasive capabilities in vitro. All these 3beta-Adiol activities are mediated by ERbeta and cannot be reproduced by the physiological estrogen, 17beta-estradiol, suggesting the existence of different pathways activated by the two ERbeta ligands in PC3-Luc cells.
Here, we provide evidence that 5-androsten-3b,17b-diol (ADIOL) functions as a selective modulator of estrogen receptor (ER)b to suppress inflammatory responses of microglia and astrocytes. ADIOL and a subset of synthetic ERb-specific ligands, but not 17b-estradiol, mediate recruitment of CtBP corepressor complexes to AP1-dependent promoters, thereby repressing genes that amplify inflammatory responses and activate Th17 T cells. Reduction of ADIOL or ERb expression results in exaggerated inflammatory responses to TLR4 agonists. Conversely, the administration of ADIOL or synthetic ERb-specific ligands that promote CtBP recruitment prevents experimental autoimmune encephalomyelitis in an ERb-dependent manner. These findings provide evidence for an ADIOL/ERb/CtBP-transrepression pathway that regulates inflammatory responses in microglia and can be targeted by selective ERb modulators.
ER-β is a potent tumor suppressor and plays a crucial role in many cancer types such as prostate cancer.
3β-Androstanediol, also known as 5α-androstane-3β,17β-diol, and often shortened to 3β-diol, is an endogenous steroid hormone. It is a 5α-reduced and 17β-hydroxylated metabolite of dehydroepiandrosterone (DHEA) as well as a 3β-hydroxylated metabolite of dihydrotestosterone (DHT). 3β-Diol is a selective, potent, high-affinity full agonist of the ERβ, and hence, an estrogen. It has higher affinity for this receptor than estradiol. In contrast to ERβ, 3β-diol does not bind to the androgen receptor (AR). 3β-Diol has been reported to also bind to ERα with low nanomolar affinity, with several-fold lower affinity relative to ERβ. It has approximately 3% and 7% of the affinity of estradiol at the ERα and ERβ, respectively. Unlike its 3α-isomer, 3α-androstanediol (3α-diol), 3β-diol does not bind to the GABAA receptor.
3β-Diol appears to be the endogenous ligand of ERβ in the prostate gland, and as a result of activation of the ERβ, 3β-diol has antiproliferative effects against prostate cancer cells. Through the ERβ, 3β-diol positively regulates oxytocin neurons and signaling in the paraventricular nucleus of hypothalamus (PVN), and has been found to have antidepressant, anxiolytic, cognitive-enhancing, and stress-relieving effects via this action. Androgens, including testosterone and dihydrotestosterone (DHT), are known to downregulate the hypothalamic-pituitary-adrenal axis, and this has been found to be due in part or full to their conversion into 3β-diol rather than to activation of the AR.
A determination of the circulating levels of 3β-diol in humans found concentrations of 239 ± 76 pg/ml and 82 ± 45 pg/ml of the compound in normal male and female serum, respectively.
3α-Androstanediol (often abbreviated as 3α-diol), also known as 5α-androstane-3α,17β-diol, is an endogenous inhibitory androstane neurosteroid and weak androgen, and a major metabolite of dihydrotestosterone (DHT). As a neurosteroid, it acts as a potent positive allosteric modulator of the GABAA receptor, and has been found to have rewarding, anxiolytic, pro-sexual, and anticonvulsant effects. As androgens such as testosterone and DHT are known to have many of the same effects as 3α-diol and are converted into it in vivo, it is thought that this compound may in part be responsible for said effects. Relative to its isomer 3β-androstanediol, which is a potent estrogen, 3α-androstanediol has substantially lower, though still significant affinity for the estrogen receptors, with a several-fold preference for ERβ over ERα. It has approximately 0.07% and 0.3% of the affinity of estradiol at the ERα and ERβ, respectively.
An orally active synthetic analogue of 3α-androstanediol, 17α-ethynyl-5α-androstane-3α,17β-diol (HE-3235, Apoptone), was formerly under investigation for the treatment of prostate cancer and breast cancer.
Androstenediol, or 5-androstenediol (abbreviated as A5 or Δ5-diol), also known as androst-5-ene-3β,17β-diol, is an endogenous weak androgen and estrogen steroid hormone and intermediate in the biosynthesis of testosterone from dehydroepiandrosterone (DHEA). It is closely related to androstenedione (androst-4-ene-3,17-dione).
Eine umfassende Auswertung der verfügbaren wissenschaftlichen Erkenntnisse hat keine Hinweise darauf ergeben, dass Isoflavone in Konzentrationen, die üblicherweise in Nahrungsergänzungsmitteln zu finden sind, für postmenopausale Frauen schädlich sind.
Isoflavone wirken als Phyto-SERMS
Der Begriff „Phyto-Östrogene“ ist in Zusammenhang mit Isoflavonen falsch gewählt, da Isoflavone – anders als Östrogene – ausschließlich am Östrogenrezeptor ß binden. Sie sind also besser als „selektive Rezeptor-Modulatoren“ oder „PhytoSERMs“ zu bezeichnen. Durch ihre spezifischen Eigenschaften entfalten sie einen Schutzeffekt gegenüber ungewollter Zellproliferation, da sie über die Wirkung des Östrogenrezeptor ß (ER-ß) eine antagonistische, antiproliferative und somit kontrollierende Wirkung auf den Östrogenrezeptor α (ER-α) ausüben.
Östrogen ist gleichsam das Schutz- und Schönheitshormon für die Frau. Das Wissen, dass Androgene aber eine ebenso hohe Bedeutung für das weibliche Wohlbefinden haben, ist leider nicht so weit verbreitet. Frauen merken dieses Fehlen aber schlagartig, nämlich dann, wenn menopausale Beschwerden eintreten. Sie vermuten dann oft, dass ihnen Östrogene fehlen, aber nicht so sehr, dass es eben auch an Androgenen mangeln könnte. Ein essenzieller Metabolit des Testosterons – 5alpha-Androstan3ß,17ß-diol (3ß-Adiol) – hat eine gleichwertig hohe Affinität zum ER-ß wie das physiologische Östradiol. Mit dem Beginn der Wechseljahre sinkt nicht nur Östrogen ab, sondern parallel dazu auch 3ß-Adiol. Dadurch kommt es zur Downregulierung des ER-ß und zum verstärkten Auftreten von Wechselbeschwerden, vorrangig Hitzewallungen mit gestörtem Temperaturempfinden. Isoflavone können nun annähernd gleichwertig zur Östrogenwirkung am ER-ß binden und zum Sistieren der Beschwerden beitragen. Die Aktivierung von ER-ß durch Östrogen, 3ß-Adiol oder auch durch Isoflavone bedeutet, dass Brust und Uterus vor einer überschießenden Proliferation geschützt sind, der Knochenabbau gebremst wird, das Herz-Kreislauf-System geschützt wird und vasomotorische Beschwerden der Wechseljahre hintangehalten werden.
Isoflavone sind sekundäre Pflanzenstoffe aus der Gruppe der Flavonoide, die strukturelle Ähnlichkeiten mit dem humanen 17β-Estradiol aufwiesen. Aus diesem Grund wurden Isoflavone zusammen mit weiteren pflanzlichen Substanzgruppen als „Phytoöstrogene“ bezeichnet und bei Beschwerden, die mit hormoneller Dysbalance assoziiert wurden, therapeutisch eingesetzt. Dieser übergeordnete Sammelbegriff hat sich in den letzten Jahren zwar etabliert, ist im Falle der Isoflavone nach aktuellem Wissenstand jedoch nicht richtig.
Bereits 1960 wurde der proliferativ wirkende Estrogenrezeptor-α (ER-α) entdeckt. Erst Jahre später (1996) fand die Arbeitsgruppe um Jan-Åke Gustafsson den Estrogenrezeptor-β (ER-β). Dieser hat eine antagonistische, antiproliferative Wirkung und kontrolliert ER-α. Beide Rezeptortypen finden sich in der weiblichen Brust, in den Ovarien und im Gehirn.
Isoflavone binden weitgehend selektiv an den ER-β. Sie sind also Phyto-SERMs – „pflanzliche selektive Estrogenrezeptor-Modulatoren“ mit antiproliferativer Wirkung, die den zelldifferenzierenden und wachstumsstimulierenden Effekten der ER-α-Aktivierung entgegenwirken.
Im Gegensatz dazu binden humane Östrogene und Phytoöstrogene aus Hopfen (8-Prenylnaringenin) und Sibirischem Rhabarber (Rhaponticin) sowohl am ER-α als auch am ER-β. Das Wirkprofil der Isoflavone ist also klar von dem des humanen 17β-Estradiols zu unterscheiden.
Körpereigenes 5α-Androsan-3β ,17β-diol [sic!] (3β-Adiol), ein Metabolit des Testosterons ohne anabole Wirkung, fungiert durch die hohe Affinität zum zellprotektiven ER-β als physiologischer Gegenspieler des 17β-Estradiols. Ab dem 2. Lebensjahr und über die Dauer der gebärfähigen Phase verlaufen die Spiegel von 3β-Adiol und 17β-Estradiol weitgehend parallel. Wechseljahresbeschwerden treten erst dann auf, wenn beide Hormone in der Perimenopause erheblich absinken.
Dadurch lässt sich auch der Wiederspruch erklären, warum es bei hohem Estradiolspiegel in der reproduktiven Phase der Frau zu keinem erhöhten Risiko für Brust- und Gebärmutterkrebs kommt. Der Abfall des 3β-Adiols geht mit einer Downregulation des ER-β einher. Dies führt im zentralen HPA-System (Hypophysen-Hypothalamus-Adrenocorticale-Achse) zu einer verminderten Stressresistenz, Verstimmungszuständen und einer gestörten Thermoregulation.
Isoflavone kompensieren über selektiven Agonismus am ER-β den Abfall des endogenen SERMs 3β -Adiol im HPA-System und vermindern so typische klimakterische Beschwerden wie u.a. Hitzewallungen oder Schweißausbrüche. Zudem üben sie über peripher exprimierte ER-β-Schutzeffekte auf das Brustgewebe aus.
Da sich der ER-β überwiegend in Gehirn, Knochen, Darm, Prostata und Gefäßen befindet, ergeben sich zusätzliche positive Effekte der Isoflavone auf das Skelett- und Herz-Kreislauf-System sowie den Urogenitaltrakt. Der Grund hierfür liegt unter anderem in einer Verstärkung der Vitamin-D-Synthese, Stimulierung der NO-Synthetase und Aromatasehemmung. Des Weiteren weisen Isoflavone auch antioxidative und zellschützende Effekte auf.
Phytoöstrogene sind keine Steroide. Trotzdem entfalten sie an den Östrogenrezeptoren eine, wenn auch eingeschränkte, Wirkung. Im Unterschied zu Steroidhormonen wirkt die pflanzliche Alternative nicht auf Brust- und Uterusgewebe. Phytoöstrogene bringen kein erhöhtes Herz-Kreislauf-Risiko mit sich und steigern auch das Krebsrisiko nicht, wie es Steroidhormone tun.
Soja-Isoflavone werden als "Phytoöstrogene" bezeichnet. Diese Bezeichnung ist irreführend, weil sich der Wirkmechanismus der Isoflavone von den typischen Östrogen-vermittelten Effekten klar unterscheidet. Isoflavone wirken nicht wie das Östrogen Estradiol, sondern eher wie Androstane – sie greifen modulierend in die komplexe Steuerung der hormonellen Effekte ein.
Vor etwa zehn Jahren hat die schwedische Arbeitsgruppe von Jan-Åke Gustafsson zusätzlich zu dem bereits bekannten Östrogenrezeptor einen weiteren Rezeptor entdeckt, der zur Unterscheidung des eigentlichen Östrogenrezeptors ER-α die Bezeichnung ER-β erhielt. Die Entdeckung des zweiten Östrogenrezeptors wurde gar mit einem Paradigmenwechsel in der Hormonbiologie gleichgesetzt und hat wesentlichen Einfluss auf die Krebsforschung und die Entwicklung neuer Wirkstoffe für die Behandlung von Krebs, Erkrankungen mit Ursprung im zentralen Nervensystem, Entzündungen oder Erkrankungen der Knochen und des Herz-Kreislauf-Systems – Organe, bei denen dem ER-β eine wesentliche protektive Rolle zukommen könnte.
In aktuellen Studien werden regelmäßig neue Funktionen und Zusammenhänge des Wechselspiels zwischen ER-α und ER-β erkannt. Während der klassische Östrogenrezeptor ER-α die Proliferation an Brust und Uterus und dadurch bedingt auch das Krebsrisiko fördert, hat der ER-β diesen Effekt nicht – diskutiert wird eher das Gegenteil, ein krebsprotektiver Effekt.
Derzeit wird intensiv an der Entwicklung selektiver ER-β-Agonisten geforscht. Strukturelles Vorbild war dabei Genistein – das Hauptisoflavon in Soja. Die Affinität von Genistein zu ER-β wurde bereits kurz nach der Entdeckung des neuen Rezeptors veröffentlicht. Heute können viele der epidemiologischen und klinischen Beobachtungen mit Soja zwanglos über die Effekte der Isoflavone am ER-β erklärt werden.
ER-β dient als Gegenspieler zu ER-α. Er hat im Organismus eine nachgeordnete Funktion und wird vor allem dann verstärkt exprimiert, wenn ER-α-vermittelte Prozesse aus dem Ruder laufen. ER-β könnte die Funktion einer "Notbremse" zukommen: Der Rezeptor wird durch hohe Estradiolkonzentrationen, wie sie z. B. in der Schwangerschaft vorliegen, aktiviert und trägt so zur Selbstlimitierung östrogener Effekte bei. Estradiol ist jedoch nicht das einzige Substrat dieses Rezeptors: Ein weiterer endogener Aktivator ist 5α-Androstan-3β,17β-diol (kurz: 3β-Adiol), ein Hormon, das bereits vor der Produktion von Östrogenen in der Pubertät im weiblichen Organismus nachweisbar aktiv ist. Die Hormonspiegel von 3β-Adiol gehen über die Dauer der gebärfähigen Phase mit denen von Estradiol parallel. Für beide Hormone sinken die Spiegel in den Wechseljahren erheblich ab. Das Auftreten von Wechseljahresbeschwerden korreliert nicht nur mit den erniedrigten Estradiol-, sondern auch mit den abgesenkten 3β-Adiolspiegeln.
Die bislang bekannten Zusammenhänge zwischen Estradiol und 3β-Adiol sowie den Rezeptoren ER‑α und ER-β können zwanglos einige scheinbare Widersprüche erklären, zum Beispiel die Frage, warum die hohen Estradiolspiegel der reproduktiven Phase der Frau nicht zu einem Anstieg des Risikos für Brust- und Gebärmutterkrebs führen, dagegen aber in den Wechseljahren die erniedrigten Hormonspiegel mit einem Anstieg der Krebshäufigkeit einhergehen.
Dieser Zusammenhang zwischen Estradiol und 3β-Adiol bzw. den Östrogenrezeptoren ER-α und ER-β ist wahrscheinlich auch einer der Hintergründe für die Hitzewallungen der Wechseljahre. Medikamentös werden diese Beschwerden durch Östrogengabe behandelt. Scheinbar paradox ist dagegen, dass übergewichtige menopausale Frauen, die über die Estradiolbiosynthese im Fettgewebe über höhere Estradiolspiegel verfügen als Normalgewichtige, dennoch stärker unter Hitzewallungen leiden. Ohne Berücksichtigung der Effekte von 3β-Adiol am ER-β wäre dies ein schwer erklärbares Phänomen. Tatsächlich ist bereits seit vielen Jahren bekannt, dass Hitzewallungen wie auch Depressionen (ebenfalls ein typisches Symptom der Wechseljahre) mit dem sogenannten HPA-System (der Hypophysen-Hypothalamus-Adrenocorticalen Achse, also dem Stresshormonsystem) in direktem Zusammenhang stehen. Dieses System wird, wie in einer aktuellen Arbeit dargestellt, über den ER-β gesteuert. Der eigentliche Bindungspartner ist 3β-Adiol, aber auch Estradiol kann bei ausreichender Konzentration den Effekt am ER-β auslösen. Dies erklärt, warum die Gabe von Östrogenen wie auch die Gabe anderer ER‑β-Agonisten wie Isoflavone gleichsinnig Hitzewallungen bekämpfen können – es erklärt aber auch, warum die Isoflavone nicht auch die dem Estradiol eigenen proliferationsfördernden Effekte ausüben.
Die Isoflavone aus Soja, insbesondere Genistein und Daidzein, wurden schon frühzeitig als selektive ER-β-Agonisten erkannt. So hat Genistein am ER-α nur 4% der Affinität von Estradiol, am ER-β dagegen 87%. Dieser Effekt wird in Anwesenheit auch kleiner Mengen an Estradiol (wie es auch im Organismus der Frau in den Wechseljahren der Fall ist) überadditiv verstärkt. Die mit typischen Sojazubereitungen zugeführten Isoflavonmengen reichen für eine Aktivierung des ER‑β, nicht aber des ER-α aus. Mit diesem Mechanismus stehen nicht nur die beobachteten Effekte der Isoflavone bei Wechseljahresbeschwerden, sondern auch die postulierte Senkung des Risikos hormonabhängiger Tumoren in den Wechseljahren im Zusammenhang.
Neben der Aktivierung des ER-β durch Isoflavone wird auch eine Reihe unabhängiger, Enzym-vermittelter Mechanismen diskutiert. So gibt es Hinweise darauf, dass Phytoöstrogene im Brustgewebe die Biosynthese von Estradiol aus Testosteron oder Estron hemmen können – ein in der Summe nicht sehr stark ausgeprägter Effekt, der aber möglicherweise bei Brustkrebs zu einer Verringerung des Proliferationsrisikos durch Soja-Isoflavone beiträgt.

Fortsetzung der Introspektion

Auch wenn ich vor kurzem geschrieben habe, meinen "Seelenfrieden" gefunden zu haben, ist die Selbst-Analyse durch Introspektion noch nicht als abgeschlossen zu betrachten. Noch immer ist nicht restlos geklärt, wo nun tatsächlich meine Stärken liegen und mein Potenzial.

Interessant ist jedenfalls, dass ich schon 2013 wusste, dass mein IQ bei ungefähr 150 liegen dürfte, siehe dieses Blog-Posting. An dieser Einschätzung hat sich nicht viel geändert. Die allgemeine Intelligenz dürfte in der Tat etwas über Prozent-Rang 99,9 liegen.

Interessant sind auch meine Analysen aus dem Jahr 2005, wo ich unter anderem schrieb:
I do not claim to be an original thinker; I'm just smart enough to discover many concepts myself which means that I don't rely on other people's (teachers') assistance or the assistance of tools, such as books, to the same degree as others do. The speed of discovering concepts is certainly influencing intelligence, but so does the intensity of thinking about new concepts. Maybe I score that high on IQ tests just because I think so much.
Damals schätzte ich meinen IQ auf 145. Da habe ich meine tatsächliche kognitive Begabung wohl ein wenig unterschätzt - auch wenn ich auch heute noch von Zeit zu Zeit in Tests online im Bereich zwischen 140 und 145 abschneide, so übertreffe ich doch meistens deutlich die Marke 145.

Ein wichtiges Posting aus dem Jahr 2005 scheint mir auch dieses hier zu sein, worin ich schrieb:
I'm changing. The focus of my doing in the past was to gain attention and respect (or even admiration). In my days at school, I felt that I constantly had to prove myself. When I took the admission test to the Austrian high intelligence society and passed it in my first year at university, I finally felt that the proof that I was superior was there. Nevertheless I remained pushy: on the contrary, this trait increased as I now had the seemingly naive feeling of being predestinated to great success in my studies and in science, while my marks actually got worse since I wasn't naturally interested in memorizing the facts the medicine curriculum required at that stage. It was good to start computer science as it showed me the real significance of my talents (i.e. that I merely have an easy time with logics-related things compared to other students, while I'm not equally outstanding at memorizing facts). Meanwhile I accept not getting only A's. I'm not forcing myself any longer to study things perfectly that don't interest me much; I just study them as much as I believe it to be necessary to pass the exams. I've become a more relaxed and absolutely calm person.
Ich vermute, dass dieses Posting der Auslöser war, warum eine Studienkollegin ihr Interesse an mir verlor, weil sie offenbar deswegen von mir beeindruckt war, weil ich scheinbar immer alles perfekt lernte. Damit hat sie aber mein wahres Wesen und mein wahres Talent verkannt.

Nur: Worin besteht dieses wahre Talent?

Zum einen dürfte die "logische Schärfe" bei mir stärker ausgeprägt sein als bei den meisten Menschen; ich komme seltener zu Fehlschlüssen. Ich habe im Informatik-Studium, wie im Posting aus dem Jahr 2013 erwähnt, aber auch einen Studienkollegen gehabt, der im rein logisch-deduktiven Denken ebenfalls Spitze war, doch in Intelligenztests insgesamt nur im Bereich der Normalbegabung abgeschnitten hat (zwischen 120 und 130). Das heißt, dass bei Intelligenztests auch noch eine weitere Sache eine Rolle spielt außer dem streng deduktiven Schlussfolgern. Offenbar handelt es sich um "induktives Räsonieren", um eine gewisse Phantasie, die man braucht, um Zusammenhänge zu erkennen, die weniger Begabten, also der Mehrheit der Bevölkerung, anscheinend verborgen bleiben. Das heißt, auch in diesem Bereich liege ich zumindest deutlich über dem Durchschnitt der Bevölkerung.

Zum anderen muss man aber auch bedenken, dass ich im "Equally Normed Numerical Derivation Test" (ENNDT) als Drittbester der Welt abgeschnitten habe, fast gleichauf mit dem Zweitbesten, einem Amerikaner, der international als einer der besten Denksportler des Planeten gilt. Angeblich sollen von den 86 Teilnehmern, von denen die allermeisten in diesem neuartigen, experimentellen Intelligenztest völlig versagt haben, viele einen IQ von 145 oder höher gehabt haben. Das heißt, dass ich offenbar zu allem Überfluss noch über Fähigkeiten verfüge, die selbst unter Personen mit extrem hoher Intelligenz selten sind. Man bedenke, dass jener Amerikaner, der mich nur knapp geschlagen hat, angeblich einen IQ von 192 haben soll!

Es stellen sich die Fragen: Was ist das für eine besondere Fähigkeit, über die ich verfüge? Und: Gibt es vielleicht noch weitere verborgene Talente, die in mir schlummern?

Ich vermute jedenfalls, dass mein Abschneiden im ENNDT mit meiner Begabung für algorithmisches Denken zu tun habe. Diese Denkweise scheint mir nämlich in diesem Test eine große Rolle zu spielen.

Ich habe heute ja die Biografie von Nikola Tesla gekauft und darin gelesen; er soll über die Fähigkeit verfügt haben, sich Dinge sehr genau bildlich vorzustellen. Das ist sicher ein Ausnahmetalent, das durch herkömmliche Intelligenztests nicht ermittelt werden kann. Ich bin nicht so der visuelle Typ; meine Denkweise ist extrem abstrakt. Deswegen habe ich auch kein allzu großes Interesse an Maschinen oder Mechanik, sehr wohl aber an Theorien. Es sieht nicht so aus, als wäre ich Tesla ähnlich. Aber es sind offenbar andere Dinge, die bei mir in höchst ungewöhnlicher Ausprägung vorliegen. Worum genau es sich handelt, ist noch zu ergründen. Die Analyse ist noch längst nicht abgeschlossen.

Why people make mistakes

A thought of mine that I have never read before:

It could be that in the sense of evolution it is intended that humans do not function one hundred percent perfectly like machines, but make mistakes occasionally - even if they have a lot of practice in one thing.

Only if you occasionally do things differently than you have practiced, new paths can be opened up.

This means, however, that people should consider it necessary to build machines that perform routine tasks, which always have to be carried out 100% perfectly.

Translated with

Warum Menschen Fehler machen

Ein Gedanke von mir, den ich bisher noch nirgendwo gelesen habe:

Es könnte sein, dass es im Sinne der Evolution gewollt ist, dass Menschen nicht hundertprozentig perfekt wie Maschinen funktionieren, sondern gelegentlich - auch, wenn sie viel Übung in einer Sache haben - Fehler machen.

Nur wenn man gelegentlich Dinge anders macht, als man es sich eingeübt hat, können neue Pfade erschlossen werden.

Das bedeutet aber, dass Menschen es als notwendig erachten sollten, Maschinen zu bauen, die Routine-Tätigkeiten übernehmen, welche immer zu 100% perfekt erledigt werden müssen.

Neuer Lesestoff

Again I've bought a couple of books ("Lesestoff"):
- Richard Lucius und Brigitte Loos-Frank: Biologie von Parasiten
- Lynn Margulis: Der symbiotische Planet - Wie die Evolution wirklich verlief (Original title: Symbiotic Planet)
- W. Bernard Carlson: Tesla - Der Erfinder des elektrischen Zeitalters (Original title: Tesla - Inventor of the Electrical Age)

Die beiden erstgenannten Bücher werden mir bei der Entwicklung meiner "Symbiontenkonversionstheorie" und der Niederschrift der Abhandlung über dieselbige zugute kommen!

Die Theorie, die Frau Margulis in ihrem Buch beschreibt, ist nicht mit der meinigen identisch, aber verwandt (jedoch sehr verschieden von meiner Theorie - meine Theorie ist keineswegs abgekupfert oder gar eine Kopie). Die beiden Theorien könnten als einander ergänzend betrachtet werden, sozusagen als "symbiotisch". Vielleicht werden beide Theorien zusammen unter dem Gesamtbegriff "Symbiosetheorie" in die Geschichte eingehen.

Ein sehr guter Einkauf! I am proud of myself!

Symbiont Conversion Theory

I've decided to rename my theory, which I previously called "Symbiosis Theory" (German: "Symbiosetheorie"), to "Symbiont Conversion Theory" (German: "Symbiontenkonversionstheorie"). The reason for this is that the late Lynn Margulis coined a (complementary) theory called "Serial Endosymbiont Theory" and this theory has all the right to be called "Symbiosis Theory" as well. In fact, "Symbiosis Theory" might, as soon as I've published my own theory and it has gained attention from the scientific community, become a common term encompassing both Margulis' "Serial Endosymbiont Theory" and my "Symbiont Conversion Theory".

So, I won't modify my previous blog postings about my theory, but keep in mind that what is called "Symbiosis Theory" in those postings is now to be known as "Symbiont Conversion Theory"!

Mittwoch, 14. Februar 2018

Metabolite profiling: from diagnostics to systems biology

Fernie et al. (2004): Metabolite profiling: from diagnostics to systems biology

This paper "define[s] the currently used metabolite-profiling technologies and detail[s] the main differences between these technologies".
Historically, the measurement of metabolites has mostly been achieved by spectrophotometric assays that can detect single metabolites, or by simple chromatographic separation of mixtures of low complexity. Over the past decade, however, methods that offer both high accuracy and sensitivity for the measurement of highly complex mixtures of compounds have been established. Reflecting differences in metabolite coverage, accuracy and instrumentation, several terms have been adopted to describe these methods - ranging from metabolic fingerprinting and metabolite profiling, to metabolomics and metabonomics. [...] Fundamentally, there are two different types of metabolic-profiling approaches: mass-spectrometry and NMR methodologies.
These technologies bear relevance to diagnostics, annotation of gene function and systems biology.
Metabolic profiles have been widely used, in conjunction with statistical tools, for diagnosis. One of the first examples of the use of metabolite profiling in diagnostics was the estimation of modes of action of various herbicides. [...]
Metabolite profiling provides direct functional information on metabolic phenotypes and indirect functional information on a range of phenotypes that are determined by small molecules; for example, stress tolerance or disease manifestations. Given this, metabolite profiling has potential as a tool for functional genomics. [...]
In addition to the incorporation of metabolite profiling in systems-biology initiatives, the measurement of many metabolites in parallel gives insights into the complex regulatory circuits that underpin metabolism.

Enzyme function prediction with interpretable models

Syed et al. (2009): Enzyme function prediction with interpretable models

The goal of the authors was "to develop a new tool for functional prediction" of enzymes. To achieve this goal, they did the following:
In order to define this mapping we collected a set of 453 features and properties that characterize proteins and are believed to be related to structural and functional aspects of proteins. We introduce a mixture model of stochastic decision trees to learn the set of potentially complex relationships between features and function. To study these correlations, trees are created and tested on the Pfam classification of proteins, which is based on sequence, and the EC classification, which is based on enzymatic function. The model is very effective in learning highly diverged protein families or families that are not defined on the basis of sequence. The resulting tree structures highlight the properties that are strongly correlated with structural and functional aspects of protein families, and can be used to suggest a concise definition of a protein family.
The motivation for this effort is that "[o]ne of the main challenges [of researchers] is to decipher the intricate network of cellular pathways that exist in each genome":
Understanding this network is the key to understanding the functional role of individual genes, and the genetic variation across organisms with respect to key processes and mechanisms that are essential to sustain life. Of special interest are metabolic pathways that consist mostly of enzymatic reactions and are responsible for nucleotide and amino acid synthesis and degradation, energy metabolism, and other functions. [...]
Since experimental verification of pathways is a time consuming and expensive process, there is a great interest in computational methods that can extend the existing knowledge about pathways to newly sequenced genomes.
The authors list a couple of methods for identification of candidate enzymes, all of which "require a set of candidates for each [pathway] hole. And while they can use the trivial candidate set consisting of all of the proteins in the subject organism, their performance is likely to significantly improve if the candidate sets are small and focused. [...] Producing effective mappings from genes to enzyme families is the focus of this chapter."

Before going into details, the authors introduce the EC hierarchy:
Traditionally, enzymes have been organized into a a systematic, hierarchical classification scheme devised by the IUB Enzyme Commission [EC]. The EC number of an enzyme has the form A.B.C.D, where the first digit A indicates the enzyme's major functional family: oxidoreductase, transferase, hydrolase, lyasase, isomerase, or ligase. The second digit B places the enzyme in a functional subfamily, the third into a sub-subfamily, and so on. For example, the EC number designates enzymes which are oxidoreductase (the first digit) that act on the aldehyde or oxo group of donors (the second digit) and have oxygen as an acceptor (the third digit). In this case, the last digit specifies the particular reaction that is catalyzed by this family of enzymes.
The difficulty in assigning the correct EC number lies in the fact that "in many cases sequences have diverged to the extent that their common ancestry cannot be detected even with the most powerful sequence comparison algorithms". However, "[s]ince structure is more conserved than sequence, structural similarity can suggest functional similarity even when sequences have diverged beyond detection". Therefore, "approaches based on alternate representation of proteins" have been devised:
Instead of traditional sequence or structural alignment techniques, several groups have proposed comparison algorithms that rely on an alternative representation of proteins. These representations are usually derived from sequence motifs (i.e. short patterns), simple physio-chemical properties that can easily be computed from sequence, or annotations that are independent of sequence but can be found in databases for many proteins, e.g. subcellular location.
Algorithms used for this purpose include Naive Bayes, Decision Trees, Nearest Neighbor and Support Vector Machines.

The authors decided not only to consider sequence and structure but also "[f]eatures such as the domain content, subcellular location, tissue specificity, pairwise interactions and expression profiles" and in this way developed "a method to predict the function of a protein based on basic biochemical properties augmented with (partial) data available from database records of biological properties that may hint at the biological context of the protein" with the goal being "to identify the most relevant and informative features and combination of features that best characterize protein families (e.g. enzyme families), and to create a model for each protein family that can be used for classification and function prediction". For this, they introduced "a mixture model of stochastic decision trees".
Each family is modeled by a collection of decision trees that capture the salient features that are common to the members of the family. Our choice of the model was motivated by the nature of the data. Decision trees are useful when the data is nominal, i.e. when there is no natural notion of similarity or even ordering between objects. Such is the case for some of the attributes we associate with proteins, for example, tissue specificity and subcellular location. These attributes rule out the use of many other popular machine learning models, such as Support Vector Machines. Other attractive aspects of decision trees are robustness to errors both in classification and attribute values. Moreover, decision trees can be used when some of the data is missing, and this is often the case with database attributes.
In addition, the authors "converged to a locally optimal learning strategy by conducting a rough greedy search over the space of decision tree learning algorithms".

The paper concludes with the following remark:
There are several modifications that may improve performance. One modification that we are considering is to modify the pruning algorithm and switch from a local approach to a global approach (where all nodes are considered before deciding on the node to be pruned). Another modification would be to assign probabilities to attribute values, since for some nominal attributes it is possible to quantify the likelihood of the different values. Clearly, integration of other features can refine the models, and finally, boosting techniques can also help to improve the performance.

Ein Problem aus der Kombinatorik

Da ich in diesem Blog so wenig über Mathematik schreibe, habe ich mir gedacht, ich poste hier meine Lösung zu einem Problem aus der Kombinatorik, das mir am 1. Februar 2018 gestellt worden ist. Das Problem lautete:
20 people work in an office, and the boss is about to select six people at random to form a committee. What are the chances that Albert and Bilbert both end up on that committee?
Die Lösung:
Zu Ihrer Frage: Ich werde sie gleich für den allgemeinen Fall beantworten. Für Ihren speziellen Fall gilt: 
n := 20
k := 6
p := 2 
Es gibt insgesamt n choose k Möglichkeiten, wie man aus einer Gesamtmenge von n Personen Gruppen mit k Mitgliedern bilden kann (siehe Wikipedia, Stichwort "Binomialkoeffizient"). Uns interessiert, wie viele von diesen Möglichkeiten die p angegebenen Personen beinhalten. Dazu rechnen wir aus, wie viele Möglichkeiten mindestens eine dieser p Personen nicht beinhalten, und subtrahieren diesen Wert von n. Wie viele Möglichkeiten beinhalten genau eine bestimmte dieser p Personen nicht? Ganz einfach: (n - 1) choose k. Diesen Wert müssen wir mit p multiplizieren, um alle p Personen abzudecken. Nun gibt es (n - p) choose k Möglichkeiten, wie Gruppen zu k Personen gebildet werden können, ohne dass auch nur eine der p genannten Personen darin vorkommt. Diese Anzahl müssen wir mit p - 1 multiplizieren und von p * ((n - 1) choose k) abziehen, um alle "Duplikate" zu eliminieren (denn diese Möglichkeiten sind in jeder Menge von (n - 1) choose k Möglichkeiten "enthalten", wir haben sie also (p - 1)-mal zu oft gezählt). 
Das ergibt als Formel:
1 - (p * ((n - 1)! / (k! * (n - 1 - k)!) - ((p - 1) * (n - p)! / (k! * (n - p - k)!)) / (n! / (k! * (n - k)!)) 
In Ihrem speziellen Fall lautet das Ergebnis:
1 - (54264 - 18564) / 38760 = 1 - 35700 / 38760 = 1 - 35 / 38 = ca. 8% 
Ich muss sagen: kein triviales Beispiel. Es hat mich einiges an Zeit
und Energie gekostet, diese Lösung zu finden. Danke für die

Samstag, 10. Februar 2018

Chemical space and biology

Dobson (2004): Chemical space and biology

In the abstract, the author states that chemical space "encompasses all possible small organic molecules, including those present in biological systems" and the exploration of this space has "greatly enhanced our understanding of biology" and has "led to the development of many of today's drugs". "The discovery of new bioactive molecules, facilitated by a deeper understanding of the nature of the regions of chemical space that are relevant to biology, will advance our knowledge of biological processes and lead to new strategies to treat disease."
The simplest living organisms can function with just a few hundred different types of such molecule, and fewer than 100 account for nearly the entire molecular pool. Moreover, it seems that the total number of different small molecules within our own bodies could be just a few thousand. So, it is clear that, at least in terms of numbers of compounds, 'biologically relevant chemical space' is only a minute fraction of complete 'chemical space'[.]
What is important is that biological molecules "are packed together to an extraordinary degree within cells":
A space-filling representation of a typical cell illustrates how molecular species are crowded together in its complex organizational structure. Such 'molecular crowding' is likely to be important in many facets of biological chemistry. For example, binding affinities and the rates of self-assembly can change by orders of magnitude as a result of this phenomenon. Crowding is therefore an important factor to consider when using data derived from in vitro studies in dilute solution to understand processes taking place in vivo.
The author mentions that "[t]echniques such as X-ray crystallography, nuclear magnetic resonance (NMR) and mass spectrometry have already revolutionized our understanding of the structure and function of biological molecules" and there are new techniques to come, such as "cryoelectron tomography".

Regarding drug discovery:
[W]ith the immense developments in combinatorial methods over the past decade or so, huge arrays of new molecules can be produced in relatively short periods of time. Together with rapid screening methods, the drug-discovery process has been moving into uncharted territory; seemingly endless numbers of potentially active compounds are becoming available. As our knowledge of even the most complex aspects of biology at a molecular level expands, we can increasingly use rational arguments in the design of potential therapies and of new molecules that are promising to test or screen. [...] [T]he examination of molecules in silico for their ability to bind to specific targets already plays an important part in screening strategies, although such 'virtual screening' approaches have yet to achieve their full potential in the drug-discovery process.
Also, natural compounds from bacteria or other microorganisms might serve as the basis of new drugs:
Remarkably, however, it has been estimated that only 0.1% of all bacterial strains - the richest source of new biological molecules - has been cultured and analysed. Thus, as Clardy and Walsh discuss in this issue, there is a vast harvest of new natural products, perhaps running to millions of new compounds, waiting to be gathered from previously unexplored strains of living organisms (mainly bacteria, plants and fungi). Moreover, there are now opportunities to manipulate nature's 'production lines', for example, by using mutagenesis and gene shuffling to induce microorganisms to create new biologically active molecules, and hence to generate large libraries of new 'natural products'.
There is also a paragraph about "chemical genetics":
Using small molecules to probe biological systems is now often described as 'chemical genetics' or 'chemical genomics'. As well as the issues of diversity and specificity, cells may have evolved mechanisms to protect some of their most vital proteins from interference by small, extraneous molecules. Another major issue in chemical genetics concerns the quality of the data that are generated using various assay technologies; screening the same biological target with three different types of assay was recently found to give a set of hits that is consistent from assay to assay in only about 30% of cases.
DNA and RNA are becoming increasingly interesting, as well as oligosaccharides:
[V]arious RNA technologies are currently generating a great deal of interest. That RNA molecules play an important part in biological chemistry is well established, notably as the catalytic ribozymes that are involved in many important biological reactions, not least protein synthesis. Moreover, RNA interference (RNAi), in which synthetic RNA fragments are designed to interfere with the normal expression of specific genes, is becoming an important tool for exploring gene function[.] [...] Furthermore, members of a previously neglected class of molecules, the oligosaccharides, are emerging as biological tools, now that efficient methods for sequencing and synthesizing these complex molecules are being developed.
The authors conclude:
A rich array of data on the effects of small molecules on biological systems is accumulating, mainly from large-scale screening exercises[.] Analysis of such databases, using the types of computational method pioneered by the flourishing bioinformatics community, should lead to major advances, both in our understanding of biological chemistry and in our ability to identify promising therapeutic compounds and therapeutic targets. [...] With increasingly diverse, reliable and accessible databases of information about the effects of new chemical compounds on specific biochemical processes, we shall be able to understand much more about the nature of biologically relevant chemical space. In addition, we shall learn more about the types of compound that might make good drugs by analysing the behaviour of a much wider range of small molecules than the miserly number used by our bodies for so many purposes — from generating energy to building arsenals of macromolecules. In this regard, among the most exciting recent developments are efforts to generate public databases of chemical information, and the establishment by the US Government of Molecular Libraries Screening Centers. The latter initiative is designed to give public-sector researchers access to an initial library of around 500,000 small molecules for use in probing a diverse range of biological systems. These compounds may lead to new research tools and could aid the development of new drugs or the discovery of new applications for existing ones (see NIH Molecular Libraries Initiative).

The imitation game - A computational chemical approach to recognizing life

Cronin et al. (2006): The imitation game - A computational chemical approach to recognizing life

The authors of this article "propose an approach to the recognition of 'living' artificial chemical systems based on chemical cells (chells) as a Gedankenexperiment that exploits a cellular imitation game. The conceptual implications of this Turing test–like method are discussed as a procedure for deciding whether an artificially constructed chemical system is or is not alive".

The Turing test had the effect that "the question 'Can machines think?' was replaced by 'Are there imaginable digital computers that would do well in the imitation game?'" and "has proven a remarkably effective concept that has continued since 1950 to provoke discussion in the fields of computer science, philosophy of the mind and cognitive science".

A researcher named Harel "proposed that a kind of Turing test could be used to assess the quality of computer models for systems biology" and the authors of this paper "believe that just such a touchstone is needed also in the field of artificial cellularity in particular and the recognition of life in general"; therefore they "propose to use a similar approach here, that of an 'imitation game' that could help answer the analogous question 'Are there artificial chemical systems that would do well in the cellular imitation game'".
[W]e are interested in the fact that the chell in question should be able to communicate with natural cells (directly or via a relay) in such a way that, as in the spirit of the original imitation game, it can be interrogated by the latter. In such a case, it is not necessary that the language used for interrogating the chell is universal, as was the case for human languages in the original Turing test. On the contrary, the language by which a chell is interrogated by the natural cell should be sufficiently sophisticated so as to appropriately distinguish between alternative outputs from realizable experiments. We envision that as our knowledge of both chells and natural cells increases, better and better experiments will be possible that will distinguish ever more detailed and finegrained hypothetical properties and features of living matter. In turn, this will give rise to richer and richer communication languages between the artificial and natural entities. [...]
[I]nterrogation could take place following any of a series of increasingly more complex and sophisticated mechanisms, starting perhaps with a relatively simple quorum-sensing type of language based on, for example, low molecular weight signaling molecules, and moving toward mechanical transduction, bio-film formation and swarming patterns of behavior. Even as simple a mechanism as quorum sensing offers enough flexibility by virtue of it being 'Turing complete' (that is, it offers the potential of generating any recursively enumerable language).
Regarding the question whether such a test can be implemented, the authors write:
Current technology would seem to severely limit the chances of implementing such an idealized cellular imitation test in the foreseeable future. It might, however, still be possible to define, with the help of the synthetic biology/artificial life, origins of life and astro/exobiology research communities, a practical realization that, although not following the details of a Turing test, would share its philosophy. We propose that such a practical realization might draw some inspiration from the highly successful critical assessment of protein structure prediction (CASP) program.

Powerful Modern/Future Concepts of Computing

Ray Kurzweil's seminal book "The Singularity Is Near" (from 2005) contains several passages describing concepts of computing that radically differ from the traditional Von Neumann approach. I would like to quote from two especially interesting passages, which deal with DNA Computing and Reversible Computing, respectively:

DNA Computing
DNA is nature's own nanoengineered computer, and its ability to store information and conduct logical manipulations at the molecular level has already been exploited in specialized "DNA computers." A DNA computer is essentially a test tube filled with water containing trillions of DNA molecules, with each molecule acting as a computer. The goal of the computation is to solve a problem, with the solution expressed as a sequence of symbols. [...] Here's how a DNA computer works. A small strand of DNA is created, using a unique code for each symbol. Each such strand is replicated trillions of times using a process called "polymerase chain reaction" (PCR). These pools of DNA are then put into a test tube. Because DNA has an affinity to link strands together, long strands form automatically, with sequences of the strands representing the different symbols, each of them a possible solution to the problem. Since there will be many trillions of such strands, there are multiple strands for each possible answer [...]. The next step of the process is to test all of the strands simultaneously. This is done by using specially designed enzymes that destroy strands that do not meet certain criteria. The enzymes are applied to the test tube sequentially, and by designing a precise series of enzymes the procedure will eventually obliterate all the incorrect strands, leaving only the ones with the correct answer. [...] There's a limitation, however, to DNA computing: each of the many trillions of computers has to perform the same operation at the same time (although on different data), so that the device is a "single instruction multiple data" (SIMD) architecture. [...] [I]t is not possible to program them [SIMD computers] for general-purpose algorithms, in which each computer is able to execute whatever operation is needed for its particular mission.
Ray Kurzweil, The Singularity Is Near, pp. 117 f.

Reversible Computing
Ultimately, organizing computation with massive parallel processing, as is done in the human brain, will not by itself be sufficient to keep energy levels and resulting thermal dissipation at reasonable levels. The current computer paradigm relies on what is known as irreversible computing, meaning that we are unable in principle to run software programs backward. [...] This act of erasing data generates heat and therefore requires energy. [...] Rolf Landauer showed in 1961 that reversible logical operations such as NOT (turning a bit into its opposite) could be performed without putting energy in or taking heat out, but that irreversible logical operations such as AND (generating bit C, which is a 1 if and only if both input A and B are 1) do require energy. In 1973 Charles Bennett showed that any computation could be performed using only reversible logical operations. A decade later, Ed Fredkin and Tommaso Toffoli presented a comprehensive review of the idea of reversible computing. The fundamental concept is that if you keep all the intermediate results and then run the algorithm backward when you've finished your calculation, you end up where you started, have used no energy, and generated no heat. Along the way, however, you've calculated the result of the algorithm.
Ray Kurzweil, The Singularity Is Near, pp. 130 f.

It is most likely that these two approaches can be combined together, resulting in massive SIMD processing power without dissipation of energy. That would be ideal for cryptocurrency mining, which is nowadays done using massive arrays of GPUs that generate a real lot of heat (that's why these mining farms are usually located in cold places such as Iceland or Russia).

Of course Kurzweil also writes about Quantum Computing, a concept I am a bit more familiar with already. It is true that Quantum Computing will, on the long run, be the greatest revolution of all.

Key Technologies

One thing is definite: Medicine, Computer Science and Physics are the Key Technologies of Our Time. If you have degrees in all three subjects, you are well prepared for making a major impact.

(I have degrees in Medicine and in Computer Science, but not in Physics. Perhaps I will obtain a degree in Physics one day as well.)

Uwe was right!

It is time for a review. I am collecting scientific papers on a regular basis and since 2016, when Uwe Rohr died, there have been several publications related to his hypotheses. Most of them confirm what he stated, so it is safe to say: "Uwe was right!"

Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap
Gandal et al. performed meta-analyses of transcriptomic studies covering five major psychiatric disorders and compared cases and controls to identify coexpressed gene modules. From this, they found that some psychiatric disorders share global gene expression patterns.
This is exactly what Uwe said: Severe mental diseases, no matter whether it is schizophrenia, bipolar disorder or other diseases such as autism, are induced by stress. Stress affects the steroidal hormone cascade, and this effectively alters gene expression.

Meditation and vacation effects have an impact on disease-associated molecular phenotypes
More recent systems biology approaches have identified gene regulatory networks associated with a diversity of biological processes, including immune and stress responses, and objectively linked them with disease or salutary states. [...] Chronic stress is associated with higher inflammation, shorter telomeres, and lower activity levels of telomerase, the cellular enzyme that elongates telomeric DNA. [...] One found that mindfulness-based and supportive expressive therapies were associated with telomere maintenance, compared with a ‘treatment as usual’ control group. A second study found that mindfulness-based stress reduction was associated with increases in telomerase after 3 months. Long-term mind–body interventions, including tai chi, yoga and meditation, have been associated with gene expression (GE) changes associated with inflammatory pathways as reviewed elsewhere. [...] One study compared GE changes in experienced versus novice meditators after one session. They found changes in both groups in inflammation, energy metabolism, mitochondrial function and telomere maintenance, but experienced meditators had greater changes. Another study comparing experienced meditators to novices after 8 hours of meditation examined GE changes specific to epigenetic regulatory enzymes. Changes were found only in the experienced meditators. Another study found threefold changes in GE in the immune cells after yoga versus a control movement program.
Chronic stress is associated with higher inflammation - that's exactly what Uwe said. Inflammation is the bad thing that the immune system uses to thwart infectious agents. However, it is a mistake to conclude that patients would benefit from suppressing the immune system altogether! That's the mistake Carl Djerassi made, according to Uwe. Djerassi synthesized cortisone which suppresses inflammation but also the immune system as such. By contrast, the adiols (androstanediol and androstenediol) only suppress inflammation, while they keep the immune system intact and even boost it. So said Uwe.

The role of glucocorticoid receptors in metabolic syndrome and psychiatric illness
Glucocorticoids (GCs) are involved in a large number of the physiological changes associated with metabolic syndrome and certain psychiatric illness. Although significance is often given to the concentration of GC, its biological action is determined by the activation of intracellular GC receptors (GR). Genetic polymorphisms of the GR and the large array of GR related cofactors can directly or indirectly affect the pathophysiology and evolution of these conditions. This review will discuss the effects of GR mutations on metabolic syndrome and psychotic depression. [...] Glucocorticoids (GCs) play an integral role in a wide array of physiological systems in the body, affecting lipid and glucose metabolism, immunosuppressive and anti-inflammatory reactions, growth, reproduction and brain function. [...] The resemblance of the symptoms and biochemical findings between Cushing’s syndrome and metabolic syndrome suggest that cortisol plays a central role in the pathogenesis and the evolution of both of these medical conditions. [...] It has long been hypothesized that the development of psychotic symptoms in Psychotic Depression (PD) is related to increased or dysregulated systemic cortisol levels, leading to increased dopamine levels and changes to dopamine metabolism, which potentially induce psychotic symptoms in susceptible individuals. Biologic findings in patients with PD related to elevated and dysregulated cortisol levels include high rates of nonsuppression on the DST, reduced diurnal fluctuation of cortisol, high plasma cortisol and ACTH levels, and increased excretion of 24 h urinary free cortisol. [...] A higher incidence of the 9b polymorphism has been linked with a lower frequency of hypomanic episodes in patients with bipolar disorder, suggesting a protective effect of this polymorphism. [...] FKBP5 SNPs have been linked to a variety of psychiatric disorders including dissociative symptoms after trauma, a predictor of PTSD development in children and adult. In addition, FKBP5 SNPs have been linked to recurrence of major depression and the response to antidepressants.
One of Uwe's stances was also that metabolic syndrome is not caused by obesity but by stress, or stress combined with obesity, but not by obesity alone. Stress is the thing that makes you sick, not a few extra pounds. This view is confirmed by this paper.

Impact of stress response in development of first-episode psychosis in schizophrenia: An overview of systematic reviews

In this paper our publication "Model approach for stress induced steroidal hormone cascade changes in severe mental diseases" ( is cited. However, it was not evaluated since we dealt with various types of severe mental diseases, while this paper focused on schizophrenia only, so our publication was not considered relevant.

The role of stress-regulation genes in moderating the association of stress and daily-life psychotic experiences
Results: Unlike genetic variants, distal and proximal stressors were associated with PEs in both samples and were more strongly associated with PEs in the early-psychosis than in the non-clinical group. The RGS4 TA and FKBP5 CATT haplotypes interacted with distal stress, whereas the A allele of OXTR (rs2254298) interacted with proximal stress, increasing momentary levels of PEs in the early-psychosis group. No interactions emerged with COMT or BDNF variants. 
Conclusion: Individual differences in relevant stress-regulation systems interact with both distal and proximal psychosocial stressors in shaping the daily-life manifestation of PEs across the psychosis continuum.
All in all, one may conclude that we were obviously on the best way to uncovering the truth about severe mental diseases! Uwe was right!

Donnerstag, 8. Februar 2018

My Goals with Symbiosis Theory

My long-term goal with Symbiosis Theory is to create organisms, most of all humanoid organisms, that have an improved immune system. Instead of destroying and killing intruders, the immune system of this post-human species should educate the parasites and convert them into symbionts. This, of course, is only a long-term goal. It requires synthetic biology to reach a level that allows to create artificial immune systems. It also requires artificial life and computational systems biology to be far more developed than now, so that synthetic organisms can be simulated on a computer before the modifications are actually implemented, as otherwise the risk of making a mistake would be too big. This may sound more like science fiction than like science, but it actually is science. Moreover, this is only the long-term goal. The short-term goal is to make new treatments of cancer and infectious diseases possible by means of signalling cascades triggered by hormones and by modification of microorganisms using synthetically engineered bacteriophages that do not kill bacteria but rather alter their behaviour.

Terminology of Professions in Computer Science

In computer science, there are several different terms for what is more or less the same profession:
- programmer,
- software developer,
- software engineer,
- software architect,
- ...

Those who call themselves programmers usually have a low self-esteem and in most cases have not completed university-level education in computer science. As I have a Master's degree in computer science, using the term programmer would be an understatement, which is why I call myself a software developer. But there are some pretentious people who think the term software developer is not prestigious enough for them and so they call themselves software engineer or software architect. I am not so pretentious; for me, the term software developer suffices. I am satisfied with this designation.

Mittwoch, 7. Februar 2018

Motivation for Symbiosis Theory

There is a practical and an ethical motivation for the development of this theory. Some may dismiss the ethical dimension as being unimportant; after all, who empathizes with microorganisms, except perhaps some crazy people? Even if you dismiss the ethical component, Symbiosis Theory has a practical value: it is just too well-known a matter of fact that chemotherapy, radiation therapy and antibiotics have harmful side-effects which are better to be avoided. However, I personally also have deep ethical motivations. Already at a very young age, I taught myself respect for all forms of life. While I crushed ants as a toddler, I realized when I was four or five years old that these creatures are also living things and have a right to life. My mother would often crush flies or spiders with a handkerchief when they were annoying us. I always refused to do the same. Even in a practical course on genetics at medical school, I refused to kill a specimen of Drosophila melanogaster to obtain its DNA. Of course this made me unsuitable for most of experimental biomedical research. But not only that: When I was working as an assistant physician for a short while after completing my medical degree, my boss came to the conclusion that I was not suited for the profession of a physician because I obviously had inhibitions to infringe the physical integrity of human beings. That is how I finally ended up in earning my living as a software developer. Nonetheless I have not lost my interest in medical science and have spent a lot of time reading, reading, reading and thinking about what I have read. One of the results of this process is Symbiosis Theory.

Political Implications of Symbiosis Theory

Symbiosis Theory also has political implications. Just like Darwin's principle of natural selection can be transferred to political reality, which results in the concept of Social Darwinism (that itself is sometimes considered inhumane), Symbiosis Theory lays the foundation of a political concept that prefers integration of foreigners, no matter whether they are initially benevolent or hostile, instead of segregating and removing them from the country. Thus, Symbiosis Theory when applied to politics is a modern form of Social Darwinism, but a far more positive and humane one.

Introduction to Symbiosis Theory

The paper in which I will present my new scientific theory, Symbiosis Theory, is probably going to start with the following words:
Symbiosis Theory is a new, innovative scientific theory which states that microorganisms and cells commonly considered parasitic can be "educated" and transformed into symbionts. This is not just a hypothesis but a theory since there is already evidence that proves that this is possible. The motivation for developing this theory is the failure of classical approaches to therapy of cancer and infectious diseases that follow the paradigm "destroy and kill". Chemotherapy and radiation therapy have detrimental side effects on healthy, functional tissue, and antibiotics also harm benevolent cells. These negative side effects can be avoided by the new approach of treating parasitic diseases by converting the culprits into symbionts of which the human organism profits.
Another motivation for developing this theory is that some researchers have suggested bacteria and other microbes have certain rights themselves, comparable to the human rights. See for instance this paper: "Microbial rights?" by Charles S. Cockell

I won't be bored the next weeks and months!

Dienstag, 6. Februar 2018

About Skepticism and Pseudoskepticism

A Skeptics movement also exists here in Austria. I once attended a lecture delivered by members of this organization.

There is a website that deals critically with the Skeptics movement. It says:
Genuine skepticism is a virtue in science. Unfortunately, some self-proclaimed guardians of science are committed to conventional taboos against psychic phenomena, despite many promising lines of evidence. Although they call themselves skeptics, they are in truth fundamentalists who attack any challenge to their beliefs, even if it means contradicting the core scientific principles of paying attention to evidence and keeping an open mind. They assume psychic phenomena cannot exist, and remain ignorant of the relevant research. They are pseudoskeptics.
My opinion on this is: I reject dogmatic materialism since I reject dogmatism in general, and I reject pseudoskepticism such as the one described here. However, I also reject the views of many of the people who reject pseudoskepticism since they usually have religious motivations. I am not a follower of any traditional religion, and if I was supposed to declare myself in religious terms, I would be most likely to declare myself as being an atheist (a weak atheist, to be more precise).

Science is about the attempt to uncover truth. It will always remain an attempt with limited success, but an attempt worth making.

Freitag, 2. Februar 2018

Entwurf Studienplan Medizin (Bachelor)

Ich habe mir schon einige Male darüber Gedanken gemacht, wie man das Medizinstudium gestalten sollte, um gewisse Probleme zu lösen, die mit dem alten Studienplan, den ich absolviert habe, verbunden waren - zuletzt habe ich am 4. August 2017 darüber geschrieben ( Hier ein vielleicht noch etwas ausgereifterer Vorschlag:

Modul 1 (Dauer: 1 Semester)
Naturwissenschaftliche Grundlagen
Ziel: Grundkenntnisse der wichtigsten naturwissenschaftlichen Fächer, die für das Verständnis der Physiologie des Menschen eine Rolle spielen.
- VO + UE Chemie für Mediziner
- VO + UE Physik für Mediziner
- VO + SE Zellbiologie und Genetik für Mediziner

Modul 2 (Dauer: 2 Semester)
Körperbau und Funktion des Menschen
Ziel: Umfassende Kenntnisse über den Bau und die Funktionsweise des menschlichen Organismus.
- VO + UE Anatomie (2-semestrig)
- VO + UE Mikroskopische Anatomie und Histologie
- VO + UE Neuro- und Sinnesphysiologie
- VO + UE Vegetative Physiologie
- VO + UE Biochemie für Mediziner

Modul 3 (Dauer: 1 Semester)
Morphologie und Funktionsweise der Krankheiten
Ziel: Die Fähigkeit, Krankheiten aufgrund ihres äußeren Erscheinungsbild zu erkennen, und Verständnis der Mechanismen, die bei der Krankheitsentstehung eine Rolle spielen.
- VO + UE Pathologische Anatomie und Histologie
- VO + SE Funktionelle Pathologie
- VO + UE Medizinische Mikrobiologie

Modul 4 (Dauer: 1 Semester)
Pharmakologie und Toxikologie
Ziel: Umfassendes Verständnis der Wirkmechanismen der Medikamente und der Giftstoffe.
- VO + SE Pharmakologie und Toxikologie

Modul 5 (Dauer: 1 Semester)
Vertiefung und Bachelorarbeit
Ziel: Vertiefung in ein Fach der Wahl und Verfassen einer schriftlichen Arbeit.
- Ein Wahlfach, zum Beispiel VO + SE Immunologie
- SE Bachelorarbeit

Im anschließenden Masterstudium erfolgt dann die klinische Ausbildung. Die Pflichtfamulaturen sind ebenfalls erst im Masterstudium zu absolvieren.

Im Vergleich zum alten Medizinstudium N201 ist die Biologie deutlich abgespeckt, die Embryologie gestrichen, und es fehlen die Fächer Erste Hilfe, Psychologie und Radiologie (die man ins Masterstudium verschieben könnte, wohin sie aufgrund ihrer klinisch-praktischen Orientierung auch besser passen würden). Dafür ist eine verpflichtende Abschlussarbeit (Bachelorarbeit) als zusätzliche Anforderung hinzugekommen.

Besonders problematisch waren im alten Studium die Prüfungen. Für ein faires Prüfungssystem habe ich bereits vor einiger Zeit (am 11. Oktober 2017) folgenden Vorschlag präsentiert:

Meiner Meinung nach sollte es separate Prüfungen über die einzelnen Vorlesungen geben, jedoch wäre es zumindest nahe liegend, das positive Absolvieren sämtlicher Prüfungen eines Moduls zur Voraussetzung zu machen, zu einer Prüfung im nächsthöheren Modul antreten zu dürfen. Nicht zuletzt bauen die einzelnen Fächer aufeinander auf.