In the modern world, physical appearance has a vital role in every phase of life. Hair on the scalp enhances your appearance and adds value to your look. However, a receding hairline makes your look age faster than you are. This can impact self-esteem and confidence which sometimes leads to depression.
Today, hair transplant is one of the most effective treatments for hair transplant one can look for. In this, Kolkata is becoming the hub for hair transplant, with clinics that offer affordable and tailor-made surgeries for patients with optimum care, a lot of hair loss patients prefer to take surgical treatments from the best hair transplant clinic in Kolkata.
https://preview.redd.it/am34ldph2hya1.png?width=1200&format=png&auto=webp&s=fa053304f00ed4048dfb0e2ee51eea029f01e544

What is Hair Transplant Surgery?

A hair transplant is a surgical procedure that involves moving hair follicles from a donor area (usually the back of the scalp) to a recipient area that is experiencing hair loss. The transplanted hair follicles then grow in their new location and result in a more full and natural-looking head of hair.
The hair transplant surgery is not limited to loss of hair from the scalp, this treatment is effective for eyelash loss, beard hair, and eyebrows. The treatment can take 8-10 weeks for recovery.

Types of Hair Transplant Surgery

There are two main types of hair transplant surgeries available in hair transplant clinic in Kolkata.

• Follicular Unit Transplantation (FUT): In this technique, a strip of scalp containing healthy hair follicles are removed from the donor area and then dissected under a microscope into individual follicular units. These units are then transplanted into the recipient area using tiny incisions. FUT is also commonly referred to as the "strip method."
• Follicular Unit Extraction (FUE): In this technique, individual hair follicles are extracted from the donor area one by one using a small punch tool. These follicles are then transplanted into the recipient area using tiny incisions. FUE is a less invasive method compared to FUT and leaves minimal scarring.

Number Of Sittings Required

On the basis of the severity of baldness, the hair transplant clinic in Kolkata, and your doctor will recommend the number of sitting required for hair transplant. A maximum of 4000-5000 follicles can be grafted into the scalp in one sitting. This process is known as the strip technique and if required then one can take the next session after 6 months.
However, in the FUE method, in single sitting 1500-2000 hairs can be implanted, so if the baldness is of larger size, you may need 2-3 sitting with an interval of 6 months.

Do Hair Transplants Last?

While considering a hair transplant from the best hair transplant clinic, one must think will they last?
Yes, hair transplants can last for a long time, and in many cases, they can be considered permanent. People undergoing hair loss treatment will have thicker hair after a successful hair transplant. However, you may need a "touch-up" appointment with your clinic to prevent the follicles from bending, or to fill in any follicle dies.

Conclusion

Dealing with problems related to severe hair loss must be taken care of under expert consultation. It is one of the effective options for anyone looking for a solution to hair thinning. Affordable hair transplant clinic assures confidence boost without costing hefty charges.

Introduction

Welcome to the pharmacology research guide.
I frequently get asked if I went to college to become adept in neuroscience and pharmacology (even by med students at times) and the answer is no. In this day and age, almost everything you could hope to know is at the touch of your fingertips.
Now don't get me wrong, college is great for some people, but everyone is different. I'd say it's a prerequisite for those looking to discover new knowledge, but for those whom it does not concern, dedication will dictate their value as a researcher and not title.
This guide is tailored towards research outside of an academy, however some of this is very esoteric and may benefit anyone. If you have anything to add to this guide, please make a comment. Otherwise, enjoy.

Table of contents

Beginners research/ basics
I - Building the foundation for an idea

• Sparking curiosity
• Wanting to learn

II - Filling in the gaps (the rabbit hole, sci-hub)

• Understand what it is you're reading
• Finding the data you want
• Comparing data

III - Knowing what to trust

• Understanding research bias
• Statistics on research misconduct
• Exaggeration of results
• The hierarchy of scientific evidence
• International data manipulation

IV - Separating fact from idea

• Challenge your own ideas
• Endless dynamics of human biology
• Importance of the placebo effect
• Do not base everything on chemical structure
• Untested drugs are very risky, even peptides
• "Natural" compounds are not inherently safe
• Be wary of grandeur claims without knowing the full context

Advanced research
I - Principles of pharmacology (pharmacokinetics)

• Basics of pharmacokinetics I (drug metabolism, oral bioavailability)
• Basics of pharmacokinetics II (alternative routes of administration)

II - Principles of pharmacology (pharmacodynamics)

• Basics of pharmacodynamics I (agonist, antagonist, receptors, allosteric modulators, etc.)
• Basics of pharmacodynamics II (competitive vs. noncompetitive inhibition)
• Basics of pharmacodynamics III (receptor affinity)
• Basics of pharmacodynamics IV (phosphorylation and heteromers)

Beginners research I: Building the foundation for an idea

Sparking curiosity:
Communities such as this one are excellent for sparking conversation about new ideas. There's so much we could stand to improve about ourselves, or the world at large, and taking a research-based approach is the most accurate way to go about it.
Some of the most engaging and productive moments I've had were when others disagreed with me, and attempted to do so with research. I would say wanting to be right is essential to how I learn, but I find similar traits among others I view as knowledgeable. Of course, not everyone is callus enough to withstand such conflict, but it's just a side effect of honesty.
Wanting to learn:
When you're just starting out, Wikipedia is a great entry point for developing early opinions on something. Think of it as a foundation for your research, but not the goal.
When challenged by a new idea, I first search "[term] Wikipedia", and from there I gather what I can before moving on.
Wikipedia articles are people's summaries of other sources, and since there's no peer review like in scientific journals, it isn't always accurate. Not everything can be found on Wikipedia, but to get the gist of things I'd say it serves its purpose. Of course there's more to why its legitimacy is questionable, but I'll cover that in later sections.

Beginners research II: Filling in the gaps (the rabbit hole, sci-hub)

Understand what it is you're reading:
Google, google, google! Do not read something you don't understand and then keep going. Trust me, this will do more harm than good, and you might come out having the wrong idea about something.
In your research you will encounter terms you don't understand, so make sure to open up a new tab to get to the bottom of it before progressing. I find trying to prove something goes a long way towards driving my curiosity on a subject. Having 50 tabs open at once is a sign you're doing something right, so long as you don't get too sidetracked and forget the focus of what you're trying to understand.
Finding the data you want:
First, you can use Wikipedia as mentioned to get an idea about something. This may leave you with some questions, or perhaps you want to validate what they said. From here you can either click on the citations they used which will direct you to links, or do a search query yourself.
Generally what I do is google "[topic] pubmed", as pubmed compiles information from multiple journals. But what if I'm still not getting the results I want? Well, you can put quotations around subjects you explicitly want mentioned, or put "-" before subjects you do not want mentioned.
So, say I read a source talking about how CB1 (cannabinoid receptor) hypo- and hyperactivation impairs faucets of working memory, but when I google "CBD working memory", all I see are studies showing a positive result in healthy people (which is quite impressive). In general, it is always best to hold scientific findings above your own opinions, but given how CBD activates CB1 by inhibiting FAAH, an enzyme that degrades cannabinoids, and in some studies dampens AMPA signaling, and inhibits LTP formation, we have a valid line of reasoning to cast doubt on its ability to improve cognition.
So by altering the keywords, I get the following result:
Example 1 of using google to your advantage
In this study, CBD actually impaired cognition. But this is just the abstract, what if I wanted to read the full thing and it's behind a paywall? Well, now I will introduce sci-hub, which lets you unlock almost every scientific study. There are multiple sci-hub domains, as they keep getting delisted (like sci-hub.do), but for this example we will use sci-hub.se/[insert DOI link here]. Side note, I strongly suggest using your browser's "find" tool, as it makes finding things so much easier.
Example of where to find a DOI link
So putting sci-hub.se/10.1038/s41598-018-25846-2 in our browser will give us the full study. But since positive data was conducted in healthy people and this was in cigarette users, it's not good enough. However, changing the key words again I get this:
Example 2 of using google to your advantage
Comparing data:
Now, does this completely invalidate the studies where CBD improved cognition? No. What it does prove, however, is that CBD isn't necessarily cognition enhancing, which is an important distinction to make. Your goal as a researcher should always to be as right as possible, and this demands flexibility and sometimes putting your ego aside. My standing on things has changed many times over the course of the last few years, as I was presented new knowledge.
But going back to the discussion around CBD, there's a number of reasons as to why we're seeing conflicting results, some of the biggest being:

1. Financial incentive (covered more extensively in the next section)
2. Population type (varying characteristics due to either sample size, unique participants, etc.)
3. Methodology (drug exposure at different doses or route of administration, age of the study, mistakes by the scientists, etc.)

Of course, the list does not end there. One could make the argument that the healthy subjects had different endogenous levels of cannabinoids or metabolized CBD differently, or perhaps the different methods used yielded different results. It's good to be as precise as possible, because the slightest change to parameters between two studies could mean a world of difference in terms of outcome. This leaves out the obvious, which is financial incentive, so let's segue to the next section.

Beginners research III: Knowing what to trust

Understanding research bias:
Studies are not cheap, so who funds them, and why? Well, to put it simply, practically everything scientific is motivated by the idea that it will acquire wealth, by either directly receiving money from people, or indirectly by how much they have accomplished.
There is a positive to this, in that it can incentivize innovation/ new concepts, as well as creative destruction (dismantling an old idea with your even better idea). However the negatives progressively outweigh the positives, as scientists have a strong incentive to prove their ideas right at the expense of the full truth, maybe by outright lying about the results, or even more damning - seeking only the reward of accomplishment and using readers' ignorance as justification for not positing negative results.
Statistics on research misconduct:
To give perspective, I'll quote from this source:

The proportion of positive results in scientific literature increased between 1990/1991 reaching 70.2% and 85.9% in 2007, respectively.

While on one hand the progression of science can lead to more accurate predictions, on the other there is significant evidence of corruption in literature. As stated here, many studies fail to replicate old findings, with psychology for instance only having a 40% success rate.
One scientist had as many as 19 retractions on his work regarding Curcumin, which is an example of a high demand nutraceutical that would reward data manipulation.
By being either blinded by their self image, or fearing the consequence of their actions, scientists even skew their own self-reported misconduct, as demonstrated here:

1.97% of scientists admitted to have fabricated, falsified or modified data or results at least once –a serious form of misconduct by any standard– and up to 33.7% admitted other questionable research practices. In surveys asking about the behavior of colleagues, admission rates were 14.12% for falsification, and up to 72% for other questionable research practices. Meta-regression showed that self reports surveys, surveys using the words “falsification” or “fabrication”, and mailed surveys yielded lower percentages of misconduct. When these factors were controlled for, misconduct was reported more frequently by medical/pharmacological researchers than others.
Considering that these surveys ask sensitive questions and have other limitations, it appears likely that this is a conservative estimate of the true prevalence of scientific misconduct.

Exaggeration of results:
Lying aside, there are other ways to manipulate the reader, with one example being the study in a patented form of Shilajit, where it purportedly increased testosterone levels in healthy volunteers. Their claim is that after 90 days, it increased testosterone. But looking at the data itself, it isn't so clear:
Data used as evidence for Shilajit increasing testosterone
As you can see above, in the first and second months, free testosterone in the Shilajit group had actually decreased, and then the study was conveniently stopped at 90 days. This way they can market it as a "testosterone enhancer" and say it "increased free testosterone after 90 days", when it's more likely that testosterone just happened to be higher on that day. Even still, total testosterone in the 90 days Shilajit group matched placebo's baseline, and free testosterone was still lower.
This is an obvious conflict of interest, but conflict of interest is rarely obvious. For instance, pharmaceutical or nutraceutical companies often conduct a study in their own facility, and then approach college professors or students and offer them payment in exchange for them taking credit for the experiment. Those who accept gain not only the authority for having been credited with the study's results, but also the money given. It's a serious problem.
The hierarchy of scientific evidence:
A semi-solution to this is simply tallying the results of multiple studies. Generally speaking, one should defer to this:
https://preview.redd.it/y1fuimqs3wxa1.jpg?width=356&format=pjpg&auto=webp&s=2d6780211e40b1af184013adbdc85dec504932bc
While the above is usually true, it's highly context dependent: meta-analyses can have huge limitations, which they sometimes state. Additionally, animal studies are crucial to understanding how a drug works, and put tremendous weight behind human results. This is because, well... You can't kill humans to observe what a drug is doing at a cellular level. Knowing a drug's mechanism of action is important, and rat studies aren't that inaccurate, such in this analysis:

68% of the positive predictions and 79% of the negative predictions were right, for an overall score of 74%

Factoring in corruption, the above can only serve as a loose correlation. Of course there are instances where animals possess a different physiology than humans, and thus drugs can produce different results, but it should be approached on a case-by-case basis, rather than dismissing evidence.
As such, rather than a hierarchy, research is best approached wholistically, as what we know is always changing. Understanding something from the ground up is what separates knowledge from a mere guess.
Also, while the above graph does not list them, influencers and anecdotes should rank below the pyramid. The placebo effect is more extreme than you'd think, but I will discuss it in a later section.
International data manipulation:
Another indicator of corruption is the country that published the research. As shown here, misconduct is abundant in all countries, but especially in India, South Korea, and historically in China as well. While China has since made an effort to enact laws against it (many undeveloped countries don't even have these laws), it has persisted through bribery since then.

Basic research IV: Separating fact from idea

Challenge your own ideas:
Imagining new ideas is fun and important, but creating a bulletproof idea that will survive criticism is challenging. The first thing you should do when you construct a new idea, is try to disprove it.
For example, a common misconception that still lingers to this day is that receptor density, for example dopamine receptors, can be directly extrapolated to mean a substance "upregulated dopamine". But such changes in receptor density are found in both drugs that increase dopamine and are known to have tolerance (i.e. meth), or suppress it somehow (i.e. antipsychotics). I explain this in greater detail in my post on psychostimulants.
Endless dynamics of human biology:
The reason why the above premise fails is because the brain is more complicated than a single event in isolation. Again, it must be approached wholistically: there are dynamics within and outside the cell, between cells, different cells, different regions of cells, organs, etc. There are countless neurotransmitters, proteins, enzymes, etc. The list just goes on and on.
Importance of the placebo effect:
As you may already know, a placebo is when someone unknowingly experiences a benefit from what is essentially nothing. Despite being conjured from imagination, it can cause statistically significant improvement to a large variety of symptoms, and even induce neurochemical changes such as an increase to dopamine. The fact that these changes are real and measurable is what set the foundation for modern medicine.
It varies by condition, but clinical trials generally report a 30% response to placebo.
In supplement spheres you can witness this everywhere, as legacies of debunked substances are perpetuated by outrageous anecdotes, fueling more purchases, thus ultimately more anecdotes. The social dynamics of communities can drive oxytocinergic signaling which makes users even more susceptible to hypnotism, which can magnify the placebo effect. Astroturfing and staged reviews, combined with botted traction, is a common sales tactic that supplement companies employ.
On the other hand there's nocebo, which is especially common amongst anxious hypochondriacs. Like placebo, it is imagined, but unlike placebo it is a negative reaction. It goes both ways, which is why a control group given a fake drug is always necessary. The most common nocebos are headache, stomach pain, and more, and since anxiety can also manifest physical symptoms, those experiencing nocebo can be fully immersed in the idea that they are being poisoned.
Do not base everything on chemical structure:
While it is true that drug design is based around chemical structure, with derivatives of other drugs (aka analogs) intending to achieve similar properties of, if not surpass the original drug, this is not always the case. The pharmacodynamics, or receptor affinity profile of a drug can dramatically change by even slight modifications to chemical structure.
An example of this is that Piracetam is an AMPA PAM and calcium channel inhibitor, phenylpiracetam is a nicotinic a4b2 agonist, and methylphenylpiracetam is a sigma 1 positive allosteric modulator.
However, even smaller changes can result in different pharmacodynamics. A prime example of this is that Opipramol is structured like a Tricylic antidepressant, but behaves as a sigma 1 agonist. There are many examples like this.
I catch people making this mistake all the time, like when generalizing "racetams" because of their structure, or thinking adding "N-Acetyl" or "Phenyl" groups to a compound will just make it a stronger version of itself. That's just not how it works.
Untested drugs are very risky, even peptides:
While the purpose of pharmacology is to isolate the benefits of a compound from any negatives, and drugs are getting safer with time, predictive analysis is still far behind in terms of reliability and accuracy. Theoretical binding affinity does not hold up to laboratory assays, and software frequently makes radically incorrect assumptions about drugs.
As stated here, poor safety or toxicity accounted for 21-54% of failed clinical trials, and 90% of all drugs fail clinical trials. Pharmaceutical companies have access to the best drug prediction technology, yet not even they can know the outcome of a drug in humans. This is why giving drugs human trials to assess safety is necessary before they are put into use.
Also, I am not sure where the rumor originated from, but there are indeed toxic peptides. And they are not inherently more selective than small molecules, even if that is their intention. Like with any drug, peptides should be evaluated for their safety and efficacy too.
"Natural" compounds are not inherently safe:
Lack of trust in "Big Pharma" is valid, but that is only half of the story. Sometimes when people encounter something they know is wrong, they take the complete opposite approach instead of working towards fixing the problem at hand. *Cough* communism.
But if you thought pharmaceutical research was bad, you would be even more revolted by nutraceutical research. Most pharmaceuticals are derived from herbal constituents, with the intent of increasing the positive effects while decreasing negatives. Naturalism is a regression of this principle, as it leans heavily on the misconception that herbal compounds were "designed" to be consumed.
It's quite the opposite hilariously enough, as most biologically active chemicals in herbs are intended to act as pesticides or antimicrobials. The claimed anti-cancer effects of these herbs are more often than not due to them acting as low grade toxins. There are exceptions to this rule, like Carnosic Acid for instance, which protects healthy cells while damaging cancer cells. But to say this is a normal occurrence is far from the truth.
There are numerous examples of this, despite there being very little research to verify the safety of herbals before they are marketed. For instance Cordyceps Militaris is frequently marketed as an "anti-cancer" herb, but runs the risk of nephrotoxicity (kidney toxicity). The damage is mediated by oxidative stress, which ironically is how most herbs act as antioxidants: through a concept called hormesis. In essence, the herb induces a small amount of oxidative stress, resulting in a disproportionate chain reaction of antioxidant enzymes, leading to a net positive.
A major discrepancy here is bioavailability, as miniscule absorption of compounds such as polyphenols limit the oxidative damage they can occur. Most are susceptible to phase II metabolism, where they are detoxified by a process called conjugation (more on that later). Chemicals that aren't as restricted, such as Cordycepin (the sought after constituent of Cordyceps) can therefore put one at risk of damage. While contaminates such as lead and arsenic are a threat with herbal compounds, sometimes the problem lies in the compounds themselves.
Another argument for herbs is the "entourage effect", which catapults purported benefits off of scientific ignorance. Proper methodology would be to isolate what is beneficial, and base other things, such as benefits from supplementation, off of that. In saying "we don't know how it works yet", you are basically admitting to not understanding why something is good, or if it is bad. This, compounded with the wide marketability of herbs due to the FDA's lax stance on their use as supplements, is a red flag for deception.
And yes, this applies to extracts from food products. Once the water is removed and you're left with powder, this is already a "megadose" compared to what you would achieve with diet alone. To then create an extract from it, you are magnifying that disparity further. The misconception is that pharmaceutical companies oppose herbs because they are "alternative medicine" and that loses them business. But if that was the case then it would have already been outlawed, or restricted like what they pulled with NAC. In reality what these companies fight over the most is other pharmaceuticals. Creative destruction in the nutraceutical space is welcomed, but the fact that we don't get enough of it is a bad sign.
Be wary of grandeur claims without knowing the full context:
Marketing gimmicks by opportunists in literature are painstakingly common. One example of this is Dihexa: it was advertised as being anywhere from 7-10,000,000x stronger than BDNF, but to this day I cannot find anything that so much as directly compares them. Another is Unifiram, which is claimed to be 1,000x "stronger" than Piracetam.
These are egregious overreaches on behalf of the authors, and that is because they cannot be directly compared. Say that the concentration of Dihexa in the brain was comparable to that of BDNF, they don't even bind to the same targets. BDNF is a Trk agonist, and Dihexa is c-Met potentiator. Ignoring that, if Dihexa did share the same mechanism of action as BDNF, and bound with much higher affinity, that doesn't mean it's binding with 7-10,000,000x stronger activation of the G-coupled protein receptor. Ignoring that, and to play devil's advocate we said it did, you would surely develop downsyndrome.
Likewise, Unifiram is far from proven to mimic Piracetam's pharmacodynamics, so saying it is "stronger" is erroneously reductive. Piracetam is selective at AMPA receptors, acting only as a positive allosteric modulator. This plays a big role in it being a cognitive enhancer, hence my excitement for TAK-653. Noopept is most like Piracetam, but even it isn't the same, as demonstrated in posts prior, it has agonist affinity. AMPA PAMs potentiate endogenous BDNF release, which syncs closely with homeostasis; the benefits of BDNF are time and event dependent, which even further cements Dihexa's marketing as awful.

Advanced research I: Principles of pharmacology (Pharmacokinetics)

Basics of pharmacokinetics I (drug metabolism, oral bioavailability):
Compared to injection (commonly referred to as ip or iv), oral administration (abbreviated as po) will lose a fraction before it enters the blood stream (aka plasma, serum). The amount that survives is referred to as absolute bioavailability. From there, it may selectively accumulate in lower organs which will detract from how much reaches the blood brain barrier (BBB). Then the drug may either penetrate, or remain mostly in the plasma. Reductively speaking, fat solubility plays a large role here. If it does penetrate, different amounts will accumulate intracellularly or extracellularly within the brain.
As demonstrated in a previous post, you can roughly predict the bioavailability of a substance by its molecular structure (my results showed a 70% consistency vs. their 85%). While it's no substitute for actual results, it's still useful as a point of reference. The rule goes as follows:

10 or fewer rotatable bonds (R) or 12 or fewer H-bond donors and acceptors (H) will have a high probability of good oral bioavailability

Drug metabolism follows a few phases. During first pass metabolism, the drug is subjected to a series of enzymes from the stomach, bacteria, liver and intestines. A significant interaction here would be with the liver, and with cytochrome P-450. This enzyme plays a major role in the toxicity and absorption of drugs, and is generally characterized by a basic modification to a drug's structure. Many prodrugs are designed around this process, as it can be utilized to release the desired drug upon contact.
Another major event is conjugation, or phase II metabolism. Here a drug may be altered by having a glutathione, sulfate, glycine, or glucuronic acid group joined to its chemical structure. This is one way in which the body attempts to detoxify exogenous chemicals. Conjugation increases the molecular weight and complexity of a substance, as well as the water solubility, significantly decreasing its bioavailability and allowing the kidneys to filter it and excrete it through urine.
Conjugation is known to underlie the poor absorption of polyphenols and flavonoids, but also has interactions with various synthetic drugs. Glucuronidation in particular appears to be significant here. It can adaptively increase with chronic drug exposure and with age, acting almost like a pseudo-tolerance. While it's most recognized for its role in the liver and small intestines, it's also found to occur in the brain. Nicotine has been shown to selectively increase glucuronidation in the brain, whereas cigarette smoke has been shown to increase it in the liver and lungs. Since it's rarely researched, it's likely many drugs have an effect on this process. It is known that bile acids, including beneficial ones such as UDCA and TUDCA stimulate glucuronidation, and while this may play a role in their hepatoprotection, it may also change drug metabolism.
Half life refers to the time it takes for the concentration of a drug to reduce by half. Different organs will excrete drugs at different rates, thus giving each organ a unique half life. Even this can make or break a drug, such as in the case of GABA, which is thought to explain its mediocre effects despite crossing the BBB contrary to popular belief.
Basics of pharmacokinetics II (alternative routes of administration):
In the event that not enough of the drug is reaching the BBB, either due to poor oral bioavailability or accumulation in the lower organs, intranasal or intraperitoneal (injection to the abdomen) administration is preferred. Since needles are a time consuming and invasive treatment, huge efforts are made to prevent this from being necessary.
Sublingual (below the tongue) or buccal (between the teeth and cheek) administration are alternative routes of administration, with buccal being though to be marginally better. This allows a percentage of the drug to be absorbed through the mouth, without encountering first pass metabolism. However, since a portion of the drug is still swallowed regardless, and it may take a while to absorb, intranasal has a superior pharmacokinetic profile. Through the nasal cavity, drugs may also have a direct route to the brain, allowing for greater psychoactivity than even injection, as well as faster onset, but this ROA is rarely applicable due to the dosage being unachievable in nasal spray formulations.
However, due to peptides being biologically active at doses comparatively lower than small molecules, and possessing low oral bioavailability, they may often be used in this way. Examples of this would be drugs such as insulin or semax. The downside to these drugs, however, is their instability and low heat tolerance, making maintenance impractical. However, shelf life can be partially extended by some additives such as polysorbate 80.
Another limitation to nasal sprays are the challenges of concomitant use, as using multiple may cause competition for absorption, as well as leakage.
Transdermal or topical usage of drugs is normally used as an attempt to increase exposure at an exterior part of the body. While sometimes effective, it is worth noting that most molecules to absorb this way will also go systemic and have cascading effects across other organs. Selective targeting of any region of the body or brain is notoriously difficult. The penetration enhancer DMSO may also be used, such as in topical formulations or because of its effectiveness as a solvent, however due to its promiscuity in this regard, it is fundamentally opposed to cellular defense, and as such runs the risk of causing one to contract pathogens or be exposed to toxins. Reductively speaking, of course.

Advanced research II: Principles of pharmacology (Pharmacodynamics)

Basics of pharmacodynamics I (agonist, antagonist, allosteric modulators, receptors, etc.):
What if I told you that real antagonists are actually agonists? Well, some actually are. To make a sweeping generalization here, traditional antagonists repel the binding of agonists without causing significant activation of the receptor. That being said, they aren't 100% inactive, and don't need to be in order to classify as an antagonist. Practically speaking, however, they pretty much are, and that's what makes them antagonists. Just think of them as hogging up space. More about inhibitors in the next section.
When you cause the opposite of what an agonist would normally achieve at a G-coupled protein receptor, you get an inverse agonist. For a while this distinction was not made, and so many drugs were referred to as "antagonists" when they were actually inverse agonists, or partial inverse agonists.
A partial agonist is a drug that displays both agonist and antagonist properties. A purposefully weak agonist, if you will. Since it lacks the ability to activate the receptor as much as endogenous ligands, it inhibits them like an antagonist. But since it is also agonizing the receptor when it would otherwise be dormant, it's a partial agonist. An example of a partial agonist in motion would be Tropisetron or GTS-21. While these drugs activate the alpha-7 nicotinic receptor, possibly enhancing memory formation, they can also block activation during an excitotoxic event, lending them neuroprotective effects. So in the case of Alzheimer's, they may show promise.
A partial inverse agonist is like a partial agonist, but... Inverse. Inverse agonists are generally used when simply blocking an effect isn't enough, and the opposite is needed. An example of this would be Pitolisant for the treatment of narcolepsy: while antagonism can help, inverse agonism releases more histamine, giving it a distinct advantage.
A positive allosteric modulator (PAM) is a drug that binds to a subunit of a receptor complex and changes its formation, potentiating the endogenous ligands. Technically it is an agonist of that subunit, and at times it may be referred to as such, but it's best not to get caught up in semantics. PAMs are useful when you want context-specific changes, like potentiation of normal memory formation with AMPA PAMs. As expected, negative allosteric modulators or NAMs are like that, but the opposite.
There are different types of allosteric modulators. Some just extend the time an agonist is bound, while others cause the agonist to function as stronger agonists. Additionally, different allosteric sites can even modulate different cells, so it's best not to generalize them.
Receptors themselves also possess varying characteristics. The stereotypical receptors that most people know of are the G-coupled variety (metabotropic receptors). Some, but not all of these receptors also possess beta arrestin proteins, which are thought to play a pivotal role in their internalization (or downregulation). They have also been proposed as being responsible for the side effects of opioid drugs, but some research casts doubt on that theory.
With G-coupled protein receptors, there are stimulatory (cAMP-promoting) types referred to as Gs, inhibitory types (Gi) and those that activate phospholipase C and have many downstream effects, referred to as Gq.
There are also ligand-gated ion channels (ionotropic receptors), tyrosine kinase receptors, enzyme-linked receptors and nuclear receptors. And surely more.
Basics of pharmacodynamics II (competitive vs. noncompetitive inhibition):
"Real" antagonists (aka silent antagonists) inhibit a receptor via competition at the same binding site, making them mutually exclusive. Noncompetitive antagonists bind at the allosteric site, but instead of decreasing other ligands' affinity, they block the downstream effects of agonists. Agonists can still bind with a noncompetitive antagonist present. Uncompetitive antagonists are noncompetitive antagonists that also act as NAMs to prevent binding.
A reversible antagonist acutely depresses activity of an enzyme or receptor, whereas the irreversible type form a covalent bond that takes much longer to dislodge.
Basics of pharmacodynamics III (receptor affinity):
Once a drug has effectively entered the brain, small amounts will distribute throughout to intracellular and extracellular regions. In most cases, you can't control which region of the brain the drug finds itself in, which is why selective ligands are used instead to activate receptors that interact desirably with certain cells.
At this stage, the drug is henceforth measured volumetrically, in uMol or nMol units per mL or L as it has distributed across the brain. How the drug's affinity will be presented depends on its mechanism of action.
The affinity of a ligand is presented as Kd, whereas the actual potency is represented as EC50 - that is, the amount of drug needed to bring a target to 50% of the maximum effect. There is also IC50, which specifically refers to how much is needed to inhibit an enzyme by 50%. That being said, EC50 does not imply "excitatory", in case you were confused. Sometimes EC50 is used over IC50 for inhibition because a drug is a partial agonist and thus cannot achieve an inhibition greater than 40%. EC50 can vary by cell type and region.
Low values for Kd indicate higher affinity, because it stands for "dissociation constant", which is annoyingly nonintuitive. It assumes how much of a drug must be present to inhibit 50% of the receptor type, in the absence of competing ligands. A low value of dissociation thus represents how associated it is at small amounts.
Ki is specifically about inhibition strength, and is less general than Kd. It represents how little of a substance is required to inhibit 50% of the receptor type.
So broadly speaking, Kd can be used to determine affinity, EC50 potency. For inhibitory drugs specifically, Ki can represent affinity, and IC50 potency.
Basics of pharmacodynamics IV (phosphorylation and heteromers):
Sometimes different receptors can exist in the same complex. A heteromer with two receptors would be referred to as a heterodimer, three would be a heterotrimer, four a heterotetramer, and so on. As such, targeting one receptor would result in cross-communication between otherwise distant receptors.
One such example would be adenosine 2 alpha, of which caffeine is an antagonist. There is an A2a-D2 tetramer, and antagonism at this site positively modulates D2, resulting in a stereotypical dopaminergic effect. Another example would be D1-D2 heteromers, which are accelerated by chronic THC use and are believed to play an important role in the cognitive impairment it facilitates, as well as motivation impairment.
Protein phosphorylation is an indirect way in which receptors can be activated, inhibited or functionally altered. In essence, enzymatic reactions trigger the covalent binding of a phosphate group to a receptor, which can produce similar effects to those described with ligands. One example of this would be Cordycepin inhibiting hippocampal AMPA by acting as an adenosine 1 receptor agonist, while simultaneously stimulating prefontal cortex AMPA receptors by phosphorylating specific subunits.

Hey Apes, Crux here.
I’m here to talk about what I call the Citadel Empire: the network of business entities built by, and the people surrounding, the now infamous Kenneth Cordele Griffin.
https://preview.redd.it/cg2ar1c19nxa1.jpg?width=800&format=pjpg&auto=webp&s=1ed1273eb8225b14e73e35e2f95bea87850a3119
It’s a tangled web. I will recap some prior DD’s, show you a few new pieces of information I’ve found, and talk about some bigger issues that I have become aware of through this research.

Original DD

I became very interested in Ken Griffin’s companies when a post by “behavior girl” on "Aviation Backed Securities" revealed a company owned by Ken, KP Holdings LLC, which his private jet was registered to. I wanted to see what else was in the public record, and I started digging.
I will not rehash all my posts in detail here; each has been an evolution of my research to understand Ken Griffin’s businesses. My first posts in August 2021 began with developing a network map of the Citadel Empire, and I figured out Ken Griffin was a butterfly lover and maintained a family office, despite the internet claiming otherwise (check the pinned posts on my profile, it was in another sub).
I continued digging. I began researching Ken’s real estate deals and I found Citadel was taking new loans from major banks, just like they had in the 2008 financial crisis.
Things got spicier. I discovered Ken gave £1M to a member of the UK Parliament through shell companies, which is potentially a crime under the Foreign Corrupt Practices Act (FCPA), a law which prohibits US citizens and companies from bribing foreign government officials for their benefit.
I even found a household manager Ken Griffin employed, linking him with Leslie Wexner and Mort Zuckerman, two fellow billionaires implicated in Jeffrey Epstein’s sordid affairs. They’re being subpoenaed in the US Virgin Islands v. JP Morgan lawsuit. Source 1. Source 2.
Earlier this year I posted a list of 500+ entities linked to Ken Griffin, all from public records. In compiling this list I found that the structure of the Citadel Empire has changed since I started my investigation over 18 months ago.

What We’ve Learned

Citadel has evolved since its founding by Ken Griffin in 1990, though the general structure of its two business lines, a hedge fund and a market maker, have been in place for over 15 years. Combined with Ken’s personal holdings this is the highest-level, most basic depiction of the Citadel Empire I could come up with:
https://preview.redd.it/b6rrzeuw9nxa1.png?width=634&format=png&auto=webp&s=171ceca4255ac9127f2507dafa17643f8e5595b7
Citadel Advisors (the hedge fund) is almost wholly owned by Ken Griffin. This ownership structure is disclosed in various corporate records filed with FINRA, the SEC, and elsewhere.
Let’s work from their Form ADV filed with FINRA. First, the “direct” owners:
https://preview.redd.it/5wfzxiyy9nxa1.png?width=1136&format=png&auto=webp&s=89de63e532071873d8295994ebea9ac4902df0c4
https://files.adviserinfo.sec.gov/IAPD/content/viewform/adv/Sections/iapd_AdvScheduleASection.aspx?ORG_PK=148826&FLNG_PK=03D2E09E000801CD029D8E4104433A21056C8CC0
And the “indirect” owners:
https://preview.redd.it/e4ovpn70anxa1.png?width=1122&format=png&auto=webp&s=ff2085053e0ba499e6411088b6512505bfa4a39d
https://files.adviserinfo.sec.gov/IAPD/content/viewform/adv/Sections/iapd_AdvScheduleBSection.aspx?ORG_PK=148826&FLNG_PK=03D2E09E000801CD029D8E4104433A21056C8CC0
This is how these two tables of word salad combine into one visual:
https://preview.redd.it/nkto4ys1anxa1.png?width=664&format=png&auto=webp&s=aad8eb449f7806cd8bea965b5cfd9e5e347881a5
Citadel Advisors is the portfolio manager to a series of funds, which in turn are feeder funds or pooled investment vehicles, which are made up of US-based LLCs, and offshore-based companies so foreign investors don’t get hit with US tax liabilities…
My eyes are glazing over just writing this, let’s move on.
Sidenote on “offshore” companies:
Having subsidiaries in “offshore” jurisdictions is not illegal; rather institutional investors and corporations have the resources to hire the best tax lawyers and accountants to do everything possible to legally minimize their taxes. A 2017 study found 73% of the Fortune 500 had subsidiaries in tax havens, holding over $2.6 trillion in accumulated profits offshore for tax purposes.
However, the use of tax havens to evade taxes and hide wealth from taxing authorities is becoming more widely known since the release of the Panama Papers, Luxembourg Leaks, and other investigations by the International Consortium of Investigative Journalists (ICIJ) and their partner news organizations.
Another aspect of Citadel Advisors I found interesting is their fee structure, which differs from the industry standard “2 & 20”, or 2% of assets (a management/overhead fee) and 20% of profit (performance fee).
Instead, Citadel Advisors charges more. The Wall Street Journal reported in 2009 that, prior to the financial crisis, the firm charged a 6-9% management fee, plus the 20% performance fee, plus another 0.25% fee for back office work performed by another Citadel subsidiary. It was reported in 2017 that “pass-through” fees were 5-10% of assets, plus the 20% performance fee.
Separate companies provide these “services” that are passed through as fees to the funds. For example, Citadel HF Management (Europe) LLP’s latest accounts filing in the UK show it charged $2 billion in service fees to related parties in 2022 for "investment management activities."
amounts are in thousands
Citadel Securities (the market maker) has a similar ownership structure as Citadel Advisors, with extra layers.
The firm’s profile on FINRA (https://files.brokercheck.finra.org/firm/firm\_116797.pdf) provides equally confusing disclosures, which I won’t post in full here.
https://preview.redd.it/c2k65sk9anxa1.png?width=492&format=png&auto=webp&s=7d10430f117b03dd3a386981533e6b18b0bc386c
Here is the ownership structure visualized:
https://preview.redd.it/cjksez3fanxa1.png?width=815&format=png&auto=webp&s=c7514fce8eb927c9d82871242d6fe7a21301efdb
I won’t dive further into Citadel Securities; there are further subsidiaries for Citadel Securities Americas, Citadel Securities Europe, clearing, back office services, etc.
Griffin’s Personal Holdings
This is where I find things get really interesting.
I mentioned KP Holdings LLC at the start of this post; it was my entry into the Citadel Empire.
At the end of 2022 Griffin converted KP Holdings LLC, an Oregon company, to KPRE Holdings LLC, a Delaware company.
https://preview.redd.it/75nu1nuganxa1.png?width=899&format=png&auto=webp&s=994817524e38c271d634d1766321c0eb2fb54ccf
KPRE Holdings’ most recent filing in Florida revealed a new authorized signatory.
https://preview.redd.it/n721nanianxa1.png?width=693&format=png&auto=webp&s=fd4f89414aab90e4d1c8db95047d0b2bed05f971
Very interesting! I have rarely seen anyone besides Gerald Beeson on Ken Griffin’s personal business filings. (Gerald Beeson joined Citadel in 1993 and currently serves as COO, everything I have seen points to him being Ken’s right-hand man).
Looking into Tom Waller, I found that not only did Ken Griffin’s Citadel displace Ray Dalio’s Bridgewater Associates in 2022 as the most successful hedge fund of all time, but Ken hired a 9-year veteran of the Dalio Family Office too.
https://preview.redd.it/woldb7c79nxa1.png?width=370&format=png&auto=webp&s=1ea502d2947fb6f65938a02c5a7b2821ac43f145
So, Ken is adding an official family office manager to his roster.
Ken structures his personal holdings similar to Citadel Advisors and Citadel Securities. There are several “top level” entities which hold similar types of assets.
For example, KPRE Holdings / KP Holdings is the “top level” entity which holds Ken Griffin’s real estate. A quick search of Florida’s business records show the many LLCs it holds. I won’t detail the underlying real estate held by these entities in this post.
https://preview.redd.it/53dk6mqlanxa1.png?width=604&format=png&auto=webp&s=307c568dd2396f4f15cc769b4ca2348f57cedb80
https://preview.redd.it/fjg9c5ymanxa1.png?width=616&format=png&auto=webp&s=b1e050c62fab21df1d763b8e4d8e1e8f746cedd5
Tip: Are you interested in checking out some of these records yourself? Search the Florida Division of Corporations records here: https://dos.myflorida.com/sunbiz/search/
Type kp holdings or kpre holdings into the “Officer / Registered Agent” search to get the results above. Note results may change over time as new filings are recorded.
https://preview.redd.it/ow8vrg6oanxa1.png?width=579&format=png&auto=webp&s=3942567f097bcd098b5097f9e88aeaf9442e5c9e
Ken’s jets are registered to KP Holdings and other personal entities - not any Citadel entities. I would assume Ken charges Citadel any time the company uses them. Part of those “pass-through” fees getting charged to mom ‘n pop pension fund holders that Ken is so, so, worried about.
Like Citadel Advisors and Citadel Securities, there are “service” companies used to manage the various personal assets.
GFS LLC (f/k/a Griffin Family Services LLC) is the primary service company Ken uses for US-based matters. This entity employs nannies, household managers, etc. Another entity, GFS II Limited, is based in the UK and appears to run the $120 million house Griffin owns in London.
Despite the apparent separation between business and personal, there is commingling. One example is the work a former Citadel IT executive describes in their LinkedIn bio (I won’t name them here).
https://preview.redd.it/4b5ylva99nxa1.png?width=655&format=png&auto=webp&s=0b6f7d9bf7b6a03c687cedc710511c5e5c2ace5a
So not only did this guy do work for Citadel and Griffin Family Services, but he also worked for:

• Anne Dias Griffin’s hedge fund
• Galaxie Financial, a company owned by Frank C. Meyer, who gave Ken his start in Chicago
• Ken and Anne’s charitable foundation
• Reboot Media (a/k/a Reboot Illinois), a political journalism website formed by Anne Dias in 2012 and sold in 2016
• GreenLeaf Funds (haven’t been able to confirm the relation to Citadel)

I wonder if mom ‘n pop pension fund investors were paying this person’s salary too?
Another fun fact: Griffin Family Services also charged over $230k to The Kenneth and Anne Griffin Foundation between 2013 and 2014. Hmm…
2013
2014
Source: https://projects.propublica.org/nonprofits/organizations/364747915
The attachments noted the payments to Griffin Family Services were “Reported as authorized under IRS announcement 2001-33.” Given the relatively small amount I’ve not dug into what this means, but thought it was interesting nonetheless.
The list goes on. My prior posts linked above, or in my profile, have many more details. Feel free to ask about any of them.
Here’s where the rubber really meets the road
I’ve learned a lot over the last 18 months. Not just about Ken Griffin, Citadel, or the markets, but about the massive influence the uber-wealthy exert on the world. Billionaires use their money to impact elections, change (or keep stagnant) regulations, and shape the mainstream media (MSM) narrative to keep public perception in their favor.
You’re probably saying right now, “No shit, Sherlock.”
The Citadel Empire is just one example of this influence, and in the rest of this post I will tie some of what I’ve found researching the Citadel Empire to the tactics used by billionaires to exert their influence.
I am always open to other points of view, feedback, and of course tips that can lead me down news rabbit holes. And I’ll leave some extra materials in the comments.

Why This Matters Today / How This Applies Today

A common criticism in my prior postings on Ken Griffin and the Citadel Empire is, “how does this apply to GME?”
This is a fair question, and my responses could have been better articulated so I will address that here.
Besides Ken Griffin’s obvious connection to GameStop through the House Financial Services Committee hearing, Citadel as a short seller of GME prior to the January 2021 squeeze, and Citadel Securities the designated market maker of GME, the Citadel Empire can be representative of, in my opinion, a far bigger issue.
Transparency in the United States’ stock markets is a focus of this subreddit. Transparency has an impact on not just the shareholders of GameStop, but all market participants (especially individual investors). Dark pools, naked short selling, fails to deliver, etc… i.e. price discovery. These are big issues, and I applaud individual investors in and outside this sub who advocate for change.
I am also an advocate for other transparency issues, which are more wide-ranging than the stock markets. I am speaking specifically of transparency (and lack thereof) around the world which leads to tax abuse, dark money political contributions and money laundering that enables worse crimes like human trafficking.
An elite class of billionaires control much of the world's resources. In 2020 it was found that just 2,153 billionaires have more wealth than 4.6 billion people on the planet. But this wealth inequality is hard to measure, due to the laws shielding disclosure of the true beneficial owners of companies across numerous jurisdictions around the world.
And in many instances the tactics used by these billionaires to acquire and hide these assets are legal. Does that bother you?
Tax Justice Network ranks the United States at the top of their Financial Secrecy Index, “a ranking of jurisdictions most complicit in helping individuals to hide their finances from the rule of law.” https://fsi.taxjustice.net/
Delaware is one of the worst offenders, “a state that has fewer than a million residents… But it has 1.6 million companies registered there...” Source.
Transparency is a real-time battle. Just last week the United States’ Federal Elections Commission voted to no longer confirm or deny even the existence of complaints anymore.
Political contributions by hedge funds are on the rise:
https://preview.redd.it/ug8z7wgf9nxa1.png?width=681&format=png&auto=webp&s=95afd903b59dcbe78b6c6cb26fea7b533b120234
This is just what is reported. Are there other “dark money” contributions also being made?
An example of dark money flowing into politics is Jeffrey Yass, who doesn’t get enough attention on this sub. In this post I dissected an article written by investigative journalist Nettanel Slyomovics published by Haaretz in March 2021, showing how Yass and his friends are behind the scenes and obscure their contributions to Israeli politics by abusing paperwork loopholes.
Billionaire Harlan Crow is wrapped up in a scandal involving Supreme Court Judge Clarence Thomas, who traveled with Crow on vacations and sold property to Crow, amongst other previously undisclosed transactions. (Crow is also reportedly a dual citizen of St. Kitts and Nevis, another tax and secrecy haven.)
Media control is another major issue. We’ve seen first hand the constant stream of “sell GameStop” articles, or more major breaking news stories from “reputable” news organizations like the Wall Street Journal that break stories on GameStop based on “a source familiar with the matter”, that happen to coincide with other, positive events for the company.
Last year The Guardian published a list of billionaires who “use their wealth in the hope of extending their political influence” though it has also been found that the 100 wealthiest US billionaires stay almost entirely silent on political issues, instead resorting to other means of “secret influence” like those discussed above. See more on this secret influence and “stealth politics” here.
Now you may be asking yourself, “Crux, this was supposed to be a post about Ken Griffin. Is he doing anything shady like this?”
I’m glad you asked. Let’s walk through a few stories and you can decide.
But first, let’s start with a quote from Griffin. In 2012 he told the Chicago Tribune’s Melissa Harris that the ultrawealthy “have an insufficient influence” on the political process.
In the interview he also “reveals how the fallout from the 2008 financial crisis changed his industry's relationship with government — and not to his liking.” Griffin has “responded by giving millions of dollars to candidates and political groups that support his belief in limited government.”
Ken’s interest in politics began even before his trading career started at Harvard in 1987. In 1985, then a senior at Boca Raton High School, Griffin attended a balanced-budget focused City Hall event which included a Q&A session with Florida's U.S. Senator Lawton Chiles. Griffin reportedly questioned Senator Chiles, “whether bonuses could be awarded to federal agencies spending less than their allotment.” Senator Chiles said it was a great idea but he would have to do some research. Griffin reportedly left disappointed; feeling the senator was unprepared and earlier budget exercise at the event “did nothing to increase Griffin's respect for our elected leaders.” Source from the Sun-Sentinel, including quotes from Griffin.
I was also able to clip from the print edition of Boca Raton News, another local news outlet that covered the event. Though the event was taped on C-Span it appears to have not been maintained by the National Archives.
https://preview.redd.it/28k6djnj9nxa1.png?width=666&format=png&auto=webp&s=ad18fa4f4a2d065cb9a79d88f483c4c6547e65f4
Did the 2008 financial crisis really change Griffin’s relationship with government?
- - -
Ken Griffin’s massive political donations are well publicized. Less well publicized is his long-running association with conservative like Charles and David Koch. In the 2012 interview linked above, Griffin disclosed he had contributed $1.5 million to the Koch’s organization Americans for Prosperity, and he “[has] tremendous respect for their intellectual and financial commitment to embracing a set of economic policies that will give us global competitiveness.”
A tactic used by the Koch network is to fund political think tanks that then produce research favorable to their point of view. It’s not just Kochs or conservatives, there are a host of these think tanks across the political spectrum.
And Griffin might be doing the same. In this post I detailed evidence that Ken may be forming his own “Griffin Catalyst” political think tank.
- - -
Griffin supported Bruce Rauner’s winning 2014 campaign for governor of Illinois, reportedly spending $5.5 million and giving free use of his private plane. Rauner was a client of Griffin’s at the time, investing in two Citadel funds:
https://preview.redd.it/4h7ux0hn9nxa1.png?width=517&format=png&auto=webp&s=a486bb81c63ddc77ef6f72fefd2caf84e6aa50f4
Source: https://www.documentcloud.org/documents/841890-gubernatorial-candidates-statements-of-economic
Rauner maintained his investments during his tenure as governor.
https://www.documentcloud.org/documents/4911720-Rauner-2018-Economic-Interest-Form
https://www.documentcloud.org/documents/4117223-Bruce-Rauner-Economic-Interest-2017
Is this a conflict of interest? Perhaps. At least it was disclosed. But does it make you uncomfortable?
- - -
The “revolving door” is an issue of regulators leaving the government to work directly for the companies they have regulated, as lobbyists for those companies, or for the law firms and other consultants who are hired by those companies. The issue has been covered somewhat on this sub, so I will show you only briefly how Citadel is a master of it.
Citadel hired Ben Bernanke, former chairman of the Federal Reserve, as a senior advisor in 2015. Janet Yellen, who Citadel paid $810,000 for speaking fees, is now Secretary of the Treasury. Yellen and Bernanke both currently serve on the Advisory Board of Yale’s Program on Financial Stability. Perhaps, through this relationship, Citadel can get some “early thinking” on Treasury’s agenda, or perhaps Bernanke can “suggest” agenda items of his own.
There are other examples of Citadel hiring regulators:

• Heath Tarbert, former CFTC Chairman and Chief Executive
• Daniel J. Grimm, former CFTC Senior Counsel to the Chairman
• Gregg Berman, former SEC Associate Director, Division of Trading and Markets
• Stephen Luparello, former SEC Director, Division of Trading and Markets

Probably nothing.
- - -
One company under Griffin’s personal umbrella is the generically named “Media Holdings LLC”. Though boring in name, this entity is anything but. Media Holdings LLC is the shell company through which Ken Griffin passed £1M to a member of the UK Parliament. The third person involved in this business is Sir Lynton Crosby, an Australian political strategist who now works in the UK and elsewhere, including through CT Group which he co-founded.
Crosby and CT Group are deep into UK politics. The Guardian reported in June 2022 that Crosby, “has been attending Boris Johnson’s 8.30am meetings in No 10, showing he is more involved in the prime minister’s decision making than previously thought.”
The next month Claire Rewcastle-Brown, who runs Sarawak Report, (she broke the 1MDB scandal) reported on Crosby’s plan for Boris Johnson to “pack the house of lords,” dubbed “Project Homer.”
The Guardian also reported in October 2022 that Mark Fullbrook, formerly of CT Group (when it was CTF Partners) still held a stake in the consulting firm while simultaneously working as chief of staff to Liz Truss, who took the PM role after Boris Johnson resigned. CT Group is no stranger to pushing misinformation through social media:

CT Group was also involved in a series of unbranded Facebook pages that appeared to be a grassroots campaign for a hard Brexit in 2019. The campaign, which involved spending up to £1m of money from an unknown source on Facebook adverts, helped push Theresa May out of power and sow the seeds for the election of Boris Johnson as prime minister.
The company has previously set up a network of websites that appeared to be independent news outlets but were actually lobbying fronts paid for by clients. Reuben Solomon, the CT Group employee who administered some of the apparent news pages, is now a special adviser to Truss and runs Downing Street’s digital campaigns.

All of this begs the question: what the fuck is Ken Griffin doing in business with these people?
- - -
Ken Griffin recently gave $300 million to Harvard, bringing his total donations to the private university to over $500 million. Interestingly, Harvard’s investigation into Jeffrey Epstein’s ties to the university found he was involved in the same Graduate School of Arts and Sciences which Ken just donated to.

As to Epstein’s appointment as a Visiting Fellow, the initial appointment occurred in 2005, before Epstein’s arrest. The Visiting Fellow designation is now, as it was in 2005, granted to an independent researcher registered with Harvard’s Graduate School of Arts and Sciences as a graduate research student.

Surely just a coincidence. But one has to wonder: what is the calculus going on in Ken’s head to make this specific donation, versus others? Is the renaming of the Graduate School of Arts and Sciences to the Harvard Kenneth C. Griffin Graduate School of Arts and Sciences worth $300 million?
Why does he want his name in the news about this donation at this time? Are there other ways $300 million could have supported the arts and sciences, besides an elite graduate program at Harvard?
Perhaps Griffin heard the negative publicity, as he just made a donation to his now local Miami-Dade College… for $20 million, or 1 / 15th the amount he gave Harvard.
- - -
There are wide range of topics around issues of transparency, and they go much deeper than what I can describe here.
I do not want to distract from our focus on GameStop or the important goals of market structure reform and creating an even playing field for individual investors. However, there are intertwining issues, led by the same elite billionaires, which I believe must be understood and considered in this massive, multi-dimensional chess game.
You may want to shout “CRIME!”, but what feels to us like crime is also the overly complex system of regulations with their esoteric exceptions and exemptions these people have set up that allows this to legally happen.
If this makes you feel uncomfortable then I hope you consider learning more, gathering facts, and shedding light on these systems that you feel are wrong.
Thank you for taking the time to read this and I look forward to this discussion.

First time poster.. sorry if this has already bean answered..
I was gifted this GF Tassajara. It had sat in a shed for years. Its steel frame and I don't see much rust... there is a little on various screws and such. What would you guys do to get it up to speed? My plan is to disassemble and grease everything up. Install new shift/brake cables and housing. Maybe some new brake pads, new chain, new saddle, and new tires. Everything looks stock except for the saddle. That is the short term plan and I think ill have around 150ish into it.
Long term... if it was yours would you modify it? I like 1 x drivetrains but it looks like I will need a rear wheel or a donor hub. Also, I am not sure this one would feel right with the typical gravel things.. drop bars and such, but I am not sure. I haven't really restored a bike before so I am not even sure what I am getting into... Thanks for your time! Hopefully this post can eventually help someone else as well.
https://preview.redd.it/vot5qv3ve9xa1.jpg?width=4032&format=pjpg&auto=webp&s=a520e883d31cb6feabf2adbeec0a916128de7a4e
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https://preview.redd.it/yl7qwyunf9xa1.jpg?width=4032&format=pjpg&auto=webp&s=9bebec53e5b93ef9df12831c82700cf3eff05727
https://preview.redd.it/8bfhnyunf9xa1.jpg?width=4032&format=pjpg&auto=webp&s=956652eb4e8fa132f5ca947df176409f007ad98f

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