Comprehensive DD on $CTYX: The OTC Biotech Stock of the Decade That Is Being Slept On
[Connectyx (OTC-PINK: CTYX). Will change to Curative Biotechnology with ticker $CURB in Q1 2021.] I posted this on pennystocks yesterday. Full Disclosure: I have a $6k initial position in this stock at a cost average of $.06. The stock is now at $0.155 (as of 2/6/21) with my position at $15.5k and movement is just starting. I am not a financial advisor. I am simply a broke graduate student interested in investing and fucking retiring early. This post represents my personal views and should not be taken as financial advice. Do your own damn research and stop pumping your hard-earned cash into trending stocks on Reddit posts that are nothing but hype, rocket emojis, and a mob chat jerking each other off. Also, not a doctor! The medical content below should never be a substitute for professional medical advice. With that said, $CTYX is going to fucking Pluto 🚀🚀🚀🚀🚀🚀 🌑 Price Target: $0.5 by May 1, 2021; $1.25 - $3.00 (~10x) within 2 years with credible potential to be listed on NASDAQ. This company is absolutely solid on all sides: healthy financials, an experienced & reliable management team, favorable market conditions with a reasonable business model, a solid lineup of products in its pipeline, and many large announcements anticipated within the next 3 months. Simply put, there is extreme asymmetric upside. $CTYX or Connectyx was taken over by its current team led by CEO Paul Michaels around Feb 2020. Within a year, this CEO has kept every promise he's made and established the infrastructure for growth. The company specializes in bringing orphan drugs (more on this below) through clinical trials and then to market. Paul and his team have decades of experience in big pharma, biotech research, finance, and drug licensing/development (in-depth description in the Management Team section below). They've vetted 3 promising drug candidates in under a year and promised to start clinical trials by mid-2022. If any one of these pass phase 1/2 trials, the market cap grows by hundreds of millions. They also have a reasonable chance to obtain a Priority Review Voucher (PRV) from the FDA that is worth $100-$300M from their strategic picks. They have a clean balance sheet, acquired non-dilute bridge financing while putting these drugs through trials, and have plans of additional deals in the near future. Why orphan drugs? Orphan drugs are therapeutics that treat rare diseases (defined as illnesses affecting less than 200k Americans per year). From the Orphan Drug Act, there are multiple incentives given by the government to develop orphan drugs: (1) significant tax credits (2) longer market exclusivity after approval (3) waiver of certain FDA fees (4) easier & faster approval process. In 2019, the global orphan drug market is estimated to be valued at $151B. By 2027, this is projected to reach $340.84B (10% compounded annual growth). This the cornerstone of their business model. By gathering a group of experts, they can cheaply vet high potential candidates to add to their development pipeline and then commercialize them from reduced fees as well as fast-track benefits from the FDA. So why the hell is it call Connectyx? It is just the old name of a software services company which the team acquired. The company has filed for a name change that will be granted within the next 2 weeks to Curative Biotechnology Inc. with a new ticker $CURB. In addition, the CEO himself has hinted at an uplisting to $OTCQB (a certification upgrade from current pink sheet status), mergeacquisition announcements, and $100M in non-dilutive funding. The official FINRA announcement of the name change will be the catalyst for the additional news. Some quick notes about the charts. The 15x jump in the past couple of months is only the beginning. There is a clear trend of resistance breakthroughs and medium-term consolidation after each announcement. Volatility is low, the number of outstanding shares is small, and there is limited dilutive potential for an OTC. Let's dive deeper into this hidden gem. All-Star Management Team CEO Paul Michaels Curative BioTech lucked out with a CEO with 25 years of experience in investment banking with a focus on life sciences. Paul has an impressive record, starting as the Executive Vice President and board member of Global Capital Group (a Wall Street wealth management firm). He also got extensive experience in big Pharma through Inabata & Co. Ltd, a subsidiary of a large Japanese drug company, Sumitomo Chemical Group, which totaled $21.8B in revenue in 2013 and employs over 30k people. While serving as Inabata's CFO, Paul licensed American drugs (some from Gilead) for the Asian market. After, the guy helped create Nobelpharma, an orphan drug company, which licenses drugs for rare diseases and got over $35M in initial capital. In February 2020, Paul took over Connectyx (a software services company at the time) and made it an orphan drug company. It is extremely rare for pink-sheet companies to have such high-caliber, established talent as a leader: decades of experience with finance and leadership positions in multi-billion dollar pharmaceutical companies. He helped build up Inabata and Nobelpharam (both thriving today), and I am confident in his ability to do it again with Connectyx. VP Communications Pam Bisikirski Recently, Curative announced Pam as the new Vice President of Communications. She previously served as the director of marketing of National Vision for 21 years. National Vision ($EYE) is a huge optical retail, eye care, and eye-ware company that is trading near a $4B market cap on NASDAQ. Scientific Advisory Board Dr. Michael Grace [news] - Ph.D. in Biochemistry and BS in Chemistry from the University of Nebraska. 30 years of experience in BioPharma with top roles in names like Procter & Gamble, Schering-Plough, Bristol-Myers Squibb, NPS Pharma, and Advaxis Immunotherapies. Lead 6 products to registration and commercialization. Dr. Ronald Bordens [news] - Ph.D. in Biotechnology with over 26 publications and over 2000 citations. 40 years in biotech and big pharma in research & development. Had a fruitful 26-year career at Schering-Plough Research. Richard Garr [news] - Serves as Director and CEO as well as President of Neuralstem Inc. (now Seneca Biopharma, Inc. which is listed on NASDAQ as $SNCA) for 20 years. Advocate for right to try treatments in the US and Europe. Founded Access Hope CRO (contract research organization) which dedicates itself to this cause. Was founder and current Board Member of the First Star Foundation Mid-Atlantic chapter which focuses on ill children (including pediatric brain cancer). Robust Drug Pipeline Keep in mind this company became a biotech firm in Feb 2020 and they already have 3 drugs in the pipeline along with exclusive rights licenses. Insane. 1) IMT504 immune therapy to treat late-stage rabies. (11/23/2020 Announcement implies IMT504 rabies license deal is complete) Strategic relationship with Mid-Atlantic BioTherapeutics, Inc. announced on 8/27/2020. Acquired all rights for development of this patented immunotherapy to treat late-stage rabies (a disease with 100% fatality rate after the treatable period, [kills 59k](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613553/#:~:text=about this topic%3F-,Each year%2C rabies causes approximately 59%2C000 deaths worldwide%2C including approximately,of postexposure prophylaxis (PEP).).)) globally per year). Now, the value of this may not be in the drug approval itself (although passing trials would be a huge asset of course). The value is the potential in CTYX obtaining a Priority Review Voucher (PRV). These coupons are handed out by the FDA each year to incentivize research into rare diseases. Exercising the coupon means diminishing the approval process from 10 months to 6 after trials. Further, you can freely sell these on a secondary market to other companies! Historically, these have been sold between $100M to $300M each. If obtained, this is an instant 2x-6x increase to its current $50M market cap. There's more.. notice that the FDA has added Rabies to its PRV-eligible tropical diseases list. Currently, there is only a handful of rabies therapies being researched. This means there's actually a good chance of CYTX getting rewarded a voucher, despite the relatively low count of vouchers distributed annually. PRVs are also possible for all other drugs in the pipeline. 2) CURB906 monoclonal antibody cytotoxic conjugate for the treatment of Glioblastoma. (10/16/2020 NIH gives a grant of license for worldwide rights) The second license was filed near July 2020 for a novel monoclonal antibody conjugate to treat brain cancer. Glioblastomas are aggressive brain tumors with poor survival rates in children. Recent studies (e.g. s1, s2) have shown different combinations of chemo-therapy and antibody-drug conjugate (ADCs) therapeutics were effective in both mice and human models. ADCs are innovative methods that attach a cytotoxic compound (one meant to kill cancer cells) to an antibody that specifically attaches to certain cancer cell receptors, thus delivering therapies to their targets. There is great promise and lots of potential in these therapeutics. Exclusive Evaluation and Commercialization Option License Agreement with the National Cancer Institute (NCI) has been granted. 3) Metformin repurposed to treat retinal degeneration. (2/4/2021 NIH gives a grant of license for worldwide rights) This is probably the ace in the hole and the largest reason behind the recent stock surge. On 2/4/2021, CTYX announced they received an NIH grant for exclusive worldwide rights to adapt a diabetes drug, Metformin, to treat retinal degeneration. Not only is Metformin proven safe (it is a widely used drug to treat Type1 Diabetes since 1995), there are many studies (e.g. s1, s2, s3) that hint at its effectiveness for retinal diseases. The recently granted license not only covers pediatric retinal generation (in the form of Stargardt Disease), it covers treatment in adults as well and includes macular degeneration. This promising treatment potentially covers 2/3 of the US population (2/3 of Americans are pre-diabetic, 1/10 are diabetic, and 11 million have some form of macular degeneration; why care about diabetes? diabetes causes retinopathy). Huge Upcoming Announcements The announced name change is the opening of the flood gates for all upcoming news. Additional licenses, uplistings, and deals with be done under the new company name. Expect many of these announcements following FINRA approval. These are some forward-looking implications:
(Within 2 weeks) FINRA approval of name change to Curative Biotechnology Inc. and ticker $CURB.
(Within weeks of name change) Following the name change, there will be an uplisting to OTCQB. OTCQB is a tier up from Pink Sheets and must adhere to stricter management certifications, undergo annual audits, and are more stringent in their financial reporting. Connectyx is currently working to become fully reporting OTCQB; to that end, the Company appointed Jonathan D. Leinwand, PA as Legal Counsel.
(Within weeks of name change) Talk of multiple upcoming drugs (if the Metformin announcement was one of them, we should see at least one more).
(Within weeks of name change) Hints at $100M of non-dilutive funding for clinical trials.
(Within months of name change) Mergers, acquisitions, and partnerships with other firms for licensing and commercialization.
Downsides Before we get ahead of ourselves and dream about retiring in 3 months while riding this into space, we gotta ground ourselves and discuss the downsides. Remember: in life, there are no solutions, only tradeoffs. There are always downsides and risks. Risk 1) This is currently a pink sheet. That itself should make you more cautious because there is reduced regulation, more "flexible" rules, and less scrutiny/transparency. Risk 2) High risk, high reward. If all 3 drugs flop (assuming no additional therapeutics are added) and they don't get a PRV (priority review voucher), then this company is worthless. Granted, the chances are low, but still a possibility to consider. Risk 3) Share dilution and raising capital. Because clinical trials often require obscene amounts of capital (~$400M investment for normal drugs), there is a risk that managers might dilute the stock in order to raise money or to take profits in general. There are currently 322M outstanding shares with 1.1B authorized shares. Read the share disclosures, do the math, gauge the risks. Note that orphan drug trials are a lot less costly as well. Risks and unknowns are certainly there. However, the upside potential is too big to ignore. Buy at pennies, sell for dollars. Do the research and take advantage of any dips that might come on Monday from 2 days of green explosions. ------------------------------------------------------------ TL;DR.
You should fucking read it, because this Phoenix has a high probability of rising from ashes to become the OTC stock of the yeadecade with effortless 10x upside in the short-term.
$CTYX will change to $CURB (Curative BioTech) soon. Business strategy: (1) bring together financial experts, veterans in big pharma, accomplished biotech researchers, and world-class grant writers to vet orphan drugs (2) make deals and obtain licenses for these drugs to help get them through clinical trials (3) take advantage of special FDA benefits for orphan drug approval (faster approval process, fee waivers, etc) and commercialize them after with longer exclusive rights.
Finance: company has no problematic debt, clean sheets, non-dilutive funding, and a small number of outstanding shares for an OTC (322M).
Products: 3 promising drug candidates in the pipeline within a year. Multiple exclusive license grants approved by the NIH.
Upcoming Announcements: (1) name change (2) uplisting to $OTCQB from pink sheets (3) more non-dilutive funding (4) additional drug(s) in pipeline (5) mergers, acquisitions, and deals with other pharma companies.
Current market cap: $50M. Upside: (1) +$100M - $300M if awarded a priority review voucher (PRV) (2) +hundreds of millions in market cap if any of the 3 promising drugs goes past phase 2 ~end of 2022 (3) +millions in speculative capital if new drugs are announced in pipeline (4) potential future merger with large pharma or uplisting to NASDAQ (other biotech companies are listed with half the number of products).
[https://pubchem.ncbi.nlm.nih.gov/periodic-table/png/Periodic_Table_of_Elements_w_Chemical_Group_Block_PubChem.png ] As with literally everything else, the most appropriate way to think about chemical bonding depends heavily on the context. Generally speaking, chemical bonds are when atoms stick together and require a significant energy input to be broken back apart. Lower energy states tend to be more stable, while higher energy states tend to be less stable. Energy is delivered to molecules mostly as heat, which means molecules colliding with each other and exchanging velocity and hence kinetic energy. Photon absorption is another possibility, but the mechanics behind it are more complicated and can only get in the way at the moment. So, chemical bonds can exist at temperatures between 0 kelvin (absolute zero, no atomic movement at all) and the conditions under which all electrons completely dissociate from the nuclei to form plasma. The strength of the bonds in question and the conditions in which they are located will determine the specifics, but obviously some chemical bonds are much more resistant to high temperature than others. Towards one end, you have compounds like hydrogen peroxide that are fully capable of spontaneously dissociating at room temperature and pressure. In about the middle you have substances like wood that will break bonds and combust under ambient conditions if supplied with an ignition source, and towards the other end you have things like concrete or rock that don’t usually burn very well. However and while combustion is a convenient, easily accessible reaction, I should note that many other reactions also exist, most of which are more complicated than applying heat in an oxygen atmosphere. Before we get there, I should repeat that chemical bonds “glue” positively charged nuclei together with negatively charged electron density. To have a chemical bond, the valence electrons and orbitals of the bonding atoms need to combine. At one extreme, an electron can be completely transferred from one atom to another, resulting in an ionic compound. The most popular example of an ionic compound is table salt, sodium chloride/NaCl/Na+ Cl-. As can be seen, the highly electronegative chlorine atom is able to completely remove one of the valence electrons on the sodium atom, which despite the resulting charges puts both atoms into a noble gas electron configuration and is hence energetically favorable. At the other extreme, we have bonding electron density being split completely equally between the two atoms. This only occurs when two of the same atom are bonded together (H2, O2, N2, some carbon-carbon bonds, etc) and makes intuitive sense because you would not expect either of two identical atoms in identical chemical environments to be more electronegative than the other. In between these two extremes is a spectrum of bond polarization, with electron density skewed to some extent or another to the more electronegative of the two atoms. Please note that the electronegativity values I linked in the previous post do not take into account any other bonds that influence electron distribution and hence the chemical environments around the atoms in the bond of interest, so that table should be used cautiously. From a bond strength perspective, maximizing the electron density between the two bonding atoms also maximizes the strength and minimizes the length of the bonds. To put it another way, increased electron density shields the positive charges on the nuclei from each other, allowing the nuclei to be closer together. Consequently, ionic bonds are very weak in the sense that the cations and anions can be easily pulled apart, and covalent bonds that distribute electron density evenly between two atoms are much more difficult to pull apart. For the next part, I will neglect the behavior of ionic compounds (also acids and bases, which behave similarly) to focus on covalent bonding. I am also going to neglect the polarization of covalent bonds towards more electronegative atoms because the distribution of the electron probability density inside the molecular bonding orbitals does not affect our understanding of how these orbitals form. With covalent bonds, there are two main bond types that are helpful to think about. In reality, what actually happens is that the atoms and their atomic orbitals combine to whichever state is accessible and lowest in energy, but the process of generating a set of molecular orbitals for each individual molecule is very labor intensive and does not add much to our understanding. So, to start out with let’s examine the main organic elements: carbon, oxygen, nitrogen, and hydrogen. Hydrogen is easy to deal with because it bonds with the 1s orbital only, and the 1s orbital is a sphere. The remaining three elements have both a spherical 2s orbital and three 2p orbitals that can participate in bonding, which makes things more complicated. In terms of shape, each p-orbital can be thought of as existing in a 3D cartesian coordinate system with the nucleus at the origin. Each orbital then has two lobes parallel to the x, y, or z axes, with a nodal plane (no electron density) oriented in the other two axes. As an example, the p_x orbital will have two lobes parallel to the x axis and no electron density on the yz plane. In practice, the result will look much more like a sphere cut in half than the balloon-shaped lobes usually depicted, but that’s not all that important. I should also mention that opposite lobes have opposite polarizations, and that a + polarized p-orbital lobe on one atom does not have bonding overlap with – polarized p-orbital lobes on other atoms but will have bonding overlap with + polarized p-orbital lobes on other atoms. This becomes important later on when we get into conjugated systems and can explain some oddball bonding behavior much later on. Anyway, I still haven’t introduced sigma and pi bonding, so let’s do that. Sigma bonds have the bonding orbitals located directly between the bonding atoms are as a result yield the strongest bonds. Pi bonds depend on the bonding overlap of p-orbitals above and below and/or to either side of the axis directly between the two atoms where a sigma bond would form. Pi bonds still put electron density in between the two nuclei and are still bonds, but cannot be as strong as a sigma bond. Since hydrogen has no valence p-orbitals, it cannot participate in pi bonding schemes, but carbon, nitrogen, and oxygen are all fully capable of donating one or two p-orbitals to pi bonds. If three or more atoms in a row all have p-orbitals in the same plane, the potential exists for all of those p-orbitals to combine into one conjugated pi system, which usually offers energy advantages compared to isolated pi bonds. There is quite a bit more complexity along these lines, but this is mostly dealt with in organic chemistry. Moving back to sigma bonds, I should first note that the number of bonds that an atom can form in most circumstances is equal to the number of unoccupied electron spaces in its valence shell. So, hydrogen can only form one bond before filling the 1s orbital, boron in theory should form five bonds but in practice is only capable of three with a completely empty p-orbital before running out of bonding volume around the small atom, carbon can form four bonds, nitrogen can form three bonds, oxygen can form two bonds, and fluorine can form one bond. During bonding, an atom will usually be thought of as “owning” a number of electrons equal to the number of its valence electrons (hydrogen one, boron three, carbon four, nitrogen five, oxygen six, fluorine seven). Due to orbital overlap, the electrons in the bonds that are in theory “owned” by the other atoms are also thought of as filling out the valence shell of the bonded atom, and in this manner the atoms in organic compounds can achieve electron configurations close to or equaling noble gas configurations despite all of the atoms in the molecule having fewer than the eight valence electrons required to actually be a noble gas or halogen anion. To put it another way, in the absence of bonding all of the atoms in organic chemistry are severely electron-deficient from a valence shell point of view, with bonding the valence shells can (mostly) all be filled without stacking a bunch of extra electrons (that don’t exist in the big picture – the number of protons and electrons is about equal) onto all of the atoms. This would also generate screamingly unstable accumulations of negative charge, so from an energy perspective bonding works out very well for most or all of the atoms involved. At this point, I have not said anything about how bonds are actually arranged in space around an atom with both s and p valence orbitals. In the 2 shell where most of organic chemistry happens, the 2s and 2p orbitals all occupy roughly the same volume, which brings us to orbital hybridization and lone pairs. With four valence orbitals, we expect to have four bonding/molecular orbitals, each located in a distinct volume. Having a spherical 2s orbital and three p-orbitals at right angles arranged around the same nucleus is not compatible with this, and is not how atoms participate in bonding. Instead, three bonding arrangements are possible: tetrahedral (sp^3), trigonal planar (sp^2), and linear (sp). In the sp^3 case, the 2s and all of the 2p orbitals combine to form four new orbitals, each with one part s-orbital character and three parts p-orbital character. The hybridized orbitals form bonds as far apart as physically possible, resulting in a uniform bond angle of 109.5 degrees and the tetrahedral configuration. Methane (CH4) is an example of a tetrahedral compound – the sp^3 orbitals on the carbon atom bond with the 1s orbitals on the hydrogens, resulting in a perfectly symmetrical arrangement of bonds around the carbon atom. Ammonia (NH3) is also an example of a tetrahedral compound, although you might not expect that on first inspection. More properly, I should write ammonia as :NH3, which is because a nitrogen atom “owns” five valence electrons and can form three bonds. In this case, the open electron spaces are filled by the three bonding hydrogen atoms, with three nitrogen electrons participating in these bonds. The remaining two valence electrons from the nitrogen occupy the nitrogen sp^3 not already bonding with a hydrogen atom, with the absence of another positively charged nucleus meaning that the lone pair will tend to repel the electron density in the N-H bonds, pushing the hydrogens closer together on one end of the molecule and distorting the ideal 109.5 degree bond angles. In a trigonal planar sp^2 bond scheme, one of the p-orbitals does not participate in hybridization and is free to participate in pi bonds with other atoms. The loss of one p-orbital means that there are only three hybrid orbitals, each with one part s character and two parts p character. The higher fraction of s character means that sp^2 orbitals will be lower in energy than sp^3 orbitals, although whether or not the sp^2 bond scheme is energetically favorable overall also depends on the chemical environment of the remaining non-hybridized p-orbital. Geometrically, the remaining p-orbital will tend to occupy all of the space apart from the nodal plane, pushing the other three bonds into the nodal plane at about 120 degree angles from each other. A linear sp bond scheme is quite similar to the sp^2 bond scheme, but with two p-orbitals not participating in hybridization. The s-orbital and remaining p-orbital generate two hybrid orbitals with one part s character and one part p character, so sp orbitals are the lowest in energy of any of the hybrid orbitals. With two p-orbitals at right angles taking up much of the available volume, the other bonds will default to the volume along the intersection of the nodal planes of both of the p-orbitals. Since the intersection of two planes is a line, linear bonds will tend to be 180 degrees apart. Once we start getting into larger third row elements or the d and f blocks, things become much more chaotic and complicated. With the organic bonding mostly described here sufficient to form the basis of all biological processes, you can probably imagine the idiosyncrasies exhibited by the heavier atoms, particularly if you view the d and f orbitals as depicted here (https://i.stack.imgur.com/K5EcA.jpg ). If you are wondering why heavy metal poisoning can be so damaging to human bodies, this is much of the reason why.
Vaccines On Demand, with Engineered Cells (+All the synthetic biology research this week)
On-Demand Vaccines for Bacterial Infections: A new study, published in Science Advances, describes a method to produce conjugate vaccines—which are used to prevent some of the leading causes of vaccine-preventable deaths, according to the World Health Organization—using ground up, freeze-dried bacteria. E. coli bacteria were first engineered to produce an antigen for a pathogenic microbe of choice. Then, the researchers ripped open the cells and added in a piece of DNA encoding a carrier protein, which attaches to those antigens and helps display them to the immune system. The team turned the whole mixture into a powder that could be transported and stored at room temperature. Then, to make a dose of vaccine, they just add water. The freeze-dried tube produces the vaccine, on demand, in about one hour. As a proof of concept, the researchers manufactured vaccines that protected mice against a disease-causing bacteria, Francisella tularensis. The work was authored by researchers at Northwestern University in Evanston, Illinois. Why It Matters: Most vaccines need to be stored at cold temperatures. This makes it difficult to transport them to parts of the world without a temperature-controlled supply chain. This study could help make vaccines accessible to a greater number of people. The technique is also very general; it can be used to make just about any conjugate vaccine that is on the market today. Conjugate vaccines are already used to prevent a lot of childhood diseases, including multiple types of bacterial meningitis, which killed an estimated 300,000 people in 2016. That’s according to a 2018 study30387-9/fulltext) in The Lancet Neurology. Cas13a Treats SARS-CoV-2 and Flu: DNA targeting CRISPR enzymes, including Cas9 and Cas12a, can manipulate genomes with ease. But there are also CRISPR proteins that target RNA, including the Cas13 ‘family.’ Since influenza and SARS-CoV-2 are both RNA-based viruses, Cas13 can be used to target, and chop up, their genetic material. For a new study, published in Nature Biotechnology, researchers at the Georgia Institute of Technology and Emory University, in Atlanta, used Cas13a to cut specific regions of the influenza and SARS-CoV-2 viruses. They first searched for guide RNAs that could cut these viruses in a cell culture model. Then, they packaged up an mRNA sequence encoding Cas13a, together with its ‘guides,’ and delivered them into mouse airways with a nebulizer (a device that converts liquid into a fine mist). In the mice, “Cas13a degraded influenza RNA in lung tissue efficiently when delivered after infection, whereas in hamsters, Cas13a delivery reduced SARS-CoV-2 replication and reduced symptoms.” Why It Matters: Vaccines are great for fending off diseases. But knocking out a respiratory infection—after it has already happened—is much more challenging. This study shows that a CRISPR-based system can be programmed to target viruses, and can be easily delivered into airways with a nebulizer. This approach could likely be used to target other types of respiratory infections in the future. Glucose Sensor Upgrade: For a new study, published in Nature Communications, researchers at the University of Toronto merged engineered cells with a standard glucose meter, expanding the number of molecules that can be measured with these common devices. Glucose test strips are typically coated with an enzyme, called glucose oxidase, that senses sugar and converts that signal into electricity. The researchers built a genetic circuit that can sense a wider array of molecules—like an antigen from a pathogenic microbe—and produce a commensurate amount of sugar. Standard glucose test strips can then be used to measure the concentration of those ‘sensed’ molecules in about an hour. The genetic circuit + glucose sensor combo was used to measure small molecules and synthetic RNAs, including “RNA sequences for typhoid, paratyphoid A and B, and related drug resistance genes” at attomolar concentrations. Why It Matters: The ongoing pandemic has highlighted the need for scalable, rapid testing. By leveraging a household technology—glucose sensors—to detect a wider range of molecules, perhaps this study could be an entryway for synthetic biology; a way to get engineered cells into the hands of more people. Open the Genetic Floodgates: There are many ways to “turn on” a single gene, but few options to do the same for many genes at once. The Cas12a protein, though, is uniquely suited to this purpose. For a new preprint, which was posted to bioRxiv and has not been peer-reviewed, researchers at the University of Edinburgh used a Cas12a protein from the bacterium, Francisella novicida, to activate six genetic targets at once. They encoded six crRNAs—nucleotide sequences that direct Cas12a to a genetic target—in a single piece of DNA, and swapped around their order to study how their position impacts the efficiency of gene editing. They found that the crRNA in the last position was produced in the lowest amount. Why It Matters: Researchers have been activating specific genes in cells for decades. But only recently—in the last few years—has ‘multiplexed’ activation become simple; routine even. This new preprint is important, in my opinion, because of the depth of its experiments. The team played with the order of crRNAs, as I’ve already written, but they also tested the synergism of crRNAs. In other words, can you turn a gene on at even higher levels if you target it with two crRNAs instead of one? (Yes.) CRISPR Clocks: The Cas9 protein cuts DNA at a steady pace. Cut…cut…cut, like a wobbly metronome. For a new study00014-3), published in Cell, researchers at the Yonsei University College of Medicine, in Seoul, Korea, used this “CRISPR clock” to record the timing of cellular events. They figured out how long it takes Cas9 to cut DNA (every DNA sequence takes a different amount of time to cut) and then sequenced the DNA to figure out the amount of time that had elapsed. The “clocks” were tested in HEK293T, a type of human liver cell, and also in mice. The clocks could be turned “on” by inflammation or heat. In one experiment, the researchers put cells with these clocks into mice, and then injected the animals with fat molecules that cause inflammation. They sequenced the cells, and found that they could determine the elapsed time, from genetic sequencing alone, with a mean error of just 7.6 percent. Why It Matters: Biological clocks are useful for many reasons. The researchers said that their CRISPR clocks could be used to record when a pre-cancerous cell is turned into a cancer cell, for example. Scientists could expose cells to toxins, for example, and then measure the amount of time that it takes for cancerous growth to begin. The CRISPR clocks could be used to study these effects inside of living cells. More Studies
(Review) Transcription factor-based biosensor for dynamic control in yeast for natural product synthesis. Frontiers in Bioengineering and Biotechnology. Open Access. Link
A protein-based biosensor for detecting calcium by magnetic resonance imaging. bioRxiv. Open Access. Link
Fundamental Discoveries
A genome-wide screen in the mouse liver reveals sex-specific and cell non-autonomous regulation of cell fitness. bioRxiv. Open Access. Link
Photoactivatable CaMKII induces synaptic plasticity in single synapses. Nature Communications. Open Access. Link
Resolving phylogenetic and biochemical barriers to functional expression of heterologous iron-sulphur cluster enzymes. bioRxiv. Open Access. Link
Intercellular communication induces glycolytic synchronization waves between individually oscillating cells. PNAS. Open Access. Link
A comprehensive phenotypic CRISPR-Cas9 screen of the ubiquitin pathway uncovers roles of ubiquitin ligases in mitosis. Molecular Cell. Link00014-9)
Genetic Circuits
Ultrasensitive molecular controllers for quasi-integral feedback. Cell Systems. Link00035-1)
Genetic Engineering & Control
Small-molecule inhibitors of histone deacetylase improve CRISPR-based adenine base editing. Nucleic Acids Research. Open Access. Link
A piggyBac‐mediated transgenesis system for the temporary expression of CRISPCas9 in rice. Plant Biotechnology Journal. Link
Expanding the SiMPl plasmid toolbox for use with spectinomycin/streptomycin. bioRxiv. Open Access. Link
Joint universal modular plasmids (JUMP): a flexible vector platform for synthetic biology. Synthetic Biology. Open Access. Link
Medicine and Diagnostics
Engineering advanced logic and distributed computing in human CAR immune cells. Nature Communications. Open Access. Link
A thermostable, flexible RNA vaccine delivery platform for pandemic response. bioRxiv. Open Access. Link
Toolkit for quickly generating and characterizing molecular probes specific for SARS-CoV-2 nucleocapsid as a primer for future coronavirus pandemic preparedness. ACS Synthetic Biology. Link
Metabolic Engineering
An artificial self-assembling nanocompartment for organising metabolic pathways in yeast. bioRxiv. Open Access. Link
Transport engineering for improving production and secretion of valuable alkaloids in Escherichia coli. bioRxiv. Open Access. Link
Autophagy‐inducing peptide increases CHO cell monoclonal antibody production in batch and fed‐batch cultures. Biotechnology and Bioengineering. Link
Quorum sensing-mediated protein degradation for dynamic metabolic pathway control in Saccharomyces cerevisiae. Metabolic Engineering. Link
(Review) Synthetic biology approaches to enhance microalgal productivity. Trends in Biotechnology. Open Access. Link00004-4)
A biological route to conjugated alkenes: Microbial production of hepta-1,3,5-triene. ACS Synthetic Biology. Open Access. Link
(Review) Yeast-based biosynthesis of natural products from xylose. Frontiers in Bioengineering and Biotechnology. Open Access. Link
New Technology
Synthetic protein quality control to enhance full-length translation in bacteria. Nature Chemical Biology. Link
Scalable characterization of the PAM requirements of CRISPR–Cas enzymes using HT-PAMDA. Nature Protocols. Link
A platform for post-translational spatiotemporal control of cellular proteins. Synthetic Biology. Open Access. Link
An all-to-all approach to the identification of sequence-specific readers for epigenetic DNA modifications on cytosine. Nature Communications. Open Access. Link
Protein Engineering
Computation-guided optimization of split protein systems. Nature Chemical Biology. Link
Efficient Lewis acid catalysis of an abiological reaction in a de novo protein scaffold. Nature Chemistry. Link
Periplasmic expression of SpyTagged antibody fragments enables rapid modular antibody assembly. Cell Chemical Biology. Link00011-8)
Systems Biology and Modelling
A MATLAB toolbox for modeling genetic circuits in cell-free systems. Synthetic Biology. Open Access. Link
Enzyme kinetics of CRISPR molecular diagnostics. bioRxiv. Open Access. Link
Potential landscapes, bifurcations, and robustness of tristable networks. ACS Synthetic Biology. Link
Modeling of copy number variability in Pichia pastoris. Biotechnology and Bioengineering. Link
Comprehensive DD on $CTYX: The OTC Biotech Stock of the Decade That Is Being Slept On
[Connectyx (OTC-PINK: CTYX). Will change to Curative Biotechnology with ticker $CURB in Q1 2021.] Full Disclosure: I have a $6k initial position in this stock at a cost average of $.06. The stock is now at $0.155 (as of 2/6/21) with my position at $15.5k and movement is just starting. I am not a financial advisor. I am simply a broke graduate student interested in investing and fucking retiring early. This post represents my personal views and should not be taken as financial advice. Do your own damn research and stop pumping your hard-earned cash into trending stocks on Reddit posts that are nothing but hype, rocket emojis, and a mob chat jerking each other off. Also, not a doctor! The medical content below should never be a substitute for professional medical advice. With that said, $CTYX is going to fucking Pluto 🚀🚀🚀🚀🚀🚀 🌑 Price Target: $0.5 by May 1, 2021; $1.25 - $3.00 (~10x) within 2 years with credible potential to be listed on NASDAQ. This company is absolutely solid on all sides: healthy financials, an experienced & reliable management team, favorable market conditions with a reasonable business model, a solid lineup of products in its pipeline, and many large announcements anticipated within the next 3 months. Simply put, there is extreme asymmetric upside. $CTYX or Connectyx was taken over by its current team led by CEO Paul Michaels around Feb 2020. Within a year, this CEO has kept every promise he's made and established the infrastructure for growth. The company specializes in bringing orphan drugs (more on this below) through clinical trials and then to market. Paul and his team have decades of experience in big pharma, biotech research, finance, and drug licensing/development (in-depth description in the Management Team section below). They've vetted 3 promising drug candidates in under a year and promised to start clinical trials by mid-2022. If any one of these pass phase 1/2 trials, the market cap grows by hundreds of millions. They also have a reasonable chance to obtain a Priority Review Voucher (PRV) from the FDA that is worth $100-$300M from their strategic picks. They have a clean balance sheet, acquired non-dilute bridge financing while putting these drugs through trials, and have plans of additional deals in the near future. Why orphan drugs? Orphan drugs are therapeutics that treat rare diseases (defined as illnesses affecting less than 200k Americans per year). From the [Orphan Drug Act](https://www.wikiwand.com/en/Orphan_Drug_Act_of_1983#:~:text=The Orphan Drug Act of,residing in the United States.)), there are multiple incentives given by the government to develop orphan drugs: (1) significant tax credits (2) longer market exclusivity after approval (3) waiver of certain FDA fees (4) easier & faster approval process. In 2019, the global orphan drug market is estimated to be valued at $151B. By 2027, this is projected to reach $340.84B (10% compounded annual growth). This the cornerstone of their business model. By gathering a group of experts, they can cheaply vet high potential candidates to add to their development pipeline and then commercialize them from reduced fees as well as fast-track benefits from the FDA. So why the hell is it call Connectyx? It is just the old name of a software services company which the team acquired. The company has filed for a name change that will be granted within the next 2 weeks to Curative Biotechnology Inc. with a new ticker $CURB. In addition, the CEO himself has hinted at an uplisting to $OTCQB (a certification upgrade from current pink sheet status), mergeacquisition announcements, and $100M in non-dilutive funding. The official FINRA announcement of the name change will be the catalyst for the additional news. Some quick notes about the charts. The 15x jump in the past couple of months is only the beginning. There is a clear trend of resistance breakthroughs and medium-term consolidation after each announcement. Volatility is low, the number of outstanding shares is small, and there is limited dilutive potential for an OTC. Let's dive deeper into this hidden gem.
All-Star Management Team
CEO Paul Michaels Curative BioTech lucked out with a CEO with 25 years of experience in investment banking with a focus on life sciences. Paul has an impressive record, starting as the Executive Vice President and board member of Global Capital Group (a Wall Street wealth management firm). He also got extensive experience in big Pharma through [Inabata & Co. Ltd's](https://www.wikiwand.com/en/Inabata_%26_Co.,_Ltd.)), a subsidiary of a large Japanese drug company, Sumitomo Chemical Group, which totaled $21.8B in revenue in 2013 and employs over 30k people. While serving as Inabata's CFO, Paul licensed American drugs (some from Gilead) for the Asian market. After, the guy helped create Nobelpharma, an orphan drug company, which licenses drugs for rare diseases and got over $35M in initial capital. In February 2020, Paul took over Connectyx (a software services company at the time) and made it an orphan drug company. It is extremely rare for pink-sheet companies to have such high-caliber, established talent as a leader: decades of experience with finance and leadership positions in multi-billion dollar pharmaceutical companies. He helped build up Inabata and Nobelpharam (both thriving today), and I am confident in his ability to do it again with Connectyx. VP Communications Pam Bisikirski Recently, Curative announced Pam as the new Vice President of Communications. She previously served as the director of marketing of National Vision for 21 years. National Vision ($EYE) is a huge optical retail, eye care, and eye-ware company that is trading near a $4B market cap on NASDAQ. Scientific Advisory Board Dr. Michael Grace [news] - Ph.D. in Biochemistry and BS in Chemistry from the University of Nebraska. 30 years of experience in BioPharma with top roles in names like Procter & Gamble, Schering-Plough, Bristol-Myers Squibb, NPS Pharma, and Advaxis Immunotherapies. Lead 6 products to registration and commercialization. Dr. Ronald Bordens [news] - Ph.D. in Biotechnology with over 26 publications and over 2000 citations. 40 years in biotech and big pharma in research & development. Had a fruitful 26-year career at Schering-Plough Research. Richard Garr [news] - Serves as Director and CEO as well as President of Neuralstem Inc. (now Seneca Biopharma, Inc. which is listed on NASDAQ as $SNCA) for 20 years. Advocate for right to try treatments in the US and Europe. Founded Access Hope CRO (contract research organization) which dedicates itself to this cause. Was founder and current Board Member of the First Star Foundation Mid-Atlantic chapter which focuses on ill children (including pediatric brain cancer).
Robust Drug Pipeline
Keep in mind this company became a biotech firm in Feb 2020 and they already have 3 drugs in the pipeline along with exclusive rights licenses. Insane. 1) IMT504 immune therapy to treat late-stage rabies. (11/23/2020 Announcement implies IMT504 rabies license deal is complete) Strategic relationship with Mid-Atlantic BioTherapeutics, Inc. announced on 8/27/2020. Acquired all rights for development of this patented immunotherapy to treat late-stage rabies (a disease with 100% fatality rate after the treatable period, [kills 59k](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613553/#:~:text=about this topic%3F-,Each year%2C rabies causes approximately 59%2C000 deaths worldwide%2C including approximately,of postexposure prophylaxis (PEP).).)) globally per year). Now, the value of this may not be in the drug approval itself (although passing trials would be a huge asset of course). The value is the potential in CTYX obtaining a Priority Review Voucher (PRV). These coupons are handed out by the FDA each year to incentivize research into rare diseases. Exercising the coupon means diminishing the approval process from 10 months to 6 after trials. Further, you can freely sell these on a secondary market to other companies! Historically, these have been sold between $100M to $300M each. If obtained, this is an instant 2x-6x increase to its current $50M market cap. There's more.. notice that the FDA has added Rabies to its PRV-eligible tropical diseases list. Currently, there is only a handful of rabies therapies being researched. This means there's actually a good chance of CYTX getting rewarded a voucher, despite the relatively low count of vouchers distributed annually. PRVs are also possible for all other drugs in the pipeline. 2) CURB906 monoclonal antibody cytotoxic conjugate for the treatment of Glioblastoma. (10/16/2020 NIH gives a grant of license for worldwide rights) The second license was filed near July 2020 for a novel monoclonal antibody conjugate to treat brain cancer. Glioblastomas are aggressive brain tumors with poor survival rates in children. Recent studies (e.g. s1, s2) have shown different combinations of chemo-therapy and antibody-drug conjugate (ADCs) therapeutics were effective in both mice and human models. ADCs are innovative methods that attach a cytotoxic compound (one meant to kill cancer cells) to an antibody that specifically attaches to certain cancer cell receptors, thus delivering therapies to their targets. There is great promise and lots of potential in these therapeutics. Exclusive Evaluation and Commercialization Option License Agreement with the National Cancer Institute (NCI) has been granted. 3) Metformin repurposed to treat retinal degeneration. (2/4/2021 NIH gives a grant of license for worldwide rights) This is probably the ace in the hole and the largest reason behind the recent stock surge. On 2/4/2021, CTYX announced they received an NIH grant for exclusive worldwide rights to adapt a diabetes drug, Metformin, to treat retinal degeneration. Not only is Metformin proven safe (it is a widely used drug to treat Type1 Diabetes since 1995), there are many studies (e.g. s1, s2, s3) that hint at its effectiveness for retinal diseases. The recently granted license not only covers pediatric retinal generation (in the form of Stargardt Disease), it covers treatment in adults as well and includes macular degeneration. This promising treatment potentially covers 2/3 of the US population (2/3 of Americans are pre-diabetic, 1/10 are diabetic, and 11 million have some form of macular degeneration; why care about diabetes? diabetes causes retinopathy).
Huge Upcoming Announcements
The announced name change is the opening of the flood gates for all upcoming news. Additional licenses, uplistings, and deals with be done under the new company name. Expect many of these announcements following FINRA approval. These are some forward-looking implications:
(Within 2 weeks) FINRA approval of name change to Curative Biotechnology Inc. and ticker $CURB.
(Within weeks of name change) Following the name change, there will be an uplisting to OTCQB. OTCQB is a tier up from Pink Sheets and must adhere to stricter management certifications, undergo annual audits, and are more stringent in their financial reporting. Connectyx is currently working to become fully reporting OTCQB; to that end, the Company appointed Jonathan D. Leinwand, PA as Legal Counsel.
(Within weeks of name change) Talk of multiple upcoming drugs (if the Metformin announcement was one of them, we should see at least one more).
(Within weeks of name change) Hints at $100M of non-dilutive funding for clinical trials.
(Within months of name change) Mergers, acquisitions, and partnerships with other firms for licensing and commercialization.
Downsides
Before we get ahead of ourselves and dream about retiring in 3 months while riding this into space, we gotta ground ourselves and discuss the downsides. Remember: in life, there are no solutions, only tradeoffs. There are always downsides and risks. Risk 1) This is currently a pink sheet. That itself should make you more cautious because there is reduced regulation, more "flexible" rules, and less scrutiny/transparency. Risk 2) High risk, high reward. If all 3 drugs flop (assuming no additional therapeutics are added) and they don't get a PRV (priority review voucher), then this company is worthless. Granted, the chances are low, but still a possibility to consider. Risk 3) Share dilution and raising capital. Because clinical trials often require obscene amounts of capital (~$400M investment for normal drugs), there is a risk that managers might dilute the stock in order to raise money or to take profits in general. There are currently 322M outstanding shares with 1.1B authorized shares. Read the share disclosures, do the math, gauge the risks. Note that orphan drug trials are a lot less costly as well. Risks and unknowns are certainly there. However, the upside potential is too big to ignore. Buy at pennies, sell for dollars. Do the research and take advantage of any dips that might come on Monday from 2 days of green explosions. ------------------------------------------------------------ TL;DR.
You should fucking read it, because this Phoenix has a high probability of rising from ashes to become the OTC stock of the yeadecade with effortless 10x upside in the short-term.
$CTYX will change to $CURB (Curative BioTech) soon. Business strategy: (1) bring together financial experts, veterans in big pharma, accomplished biotech researchers, and world-class grant writers to vet orphan drugs (2) make deals and obtain licenses for these drugs to help get them through clinical trials (3) take advantage of special FDA benefits for orphan drug approval (faster approval process, fee waivers, etc) and commercialize them after with longer exclusive rights.
Finance: company has no problematic debt, clean sheets, non-dilutive funding, and a small number of outstanding shares for an OTC (322M).
Products: 3 promising drug candidates in the pipeline within a year. Multiple exclusive license grants approved by the NIH.
Upcoming Announcements: (1) name change (2) uplisting to $OTCQB from pink sheets (3) more non-dilutive funding (4) additional drug(s) in pipeline (5) mergers, acquisitions, and deals with other pharma companies.
Current market cap: $50M. Upside: (1) +$100M - $300M if awarded a priority review voucher (PRV) (2) +hundreds of millions in market cap if any of the 3 promising drugs goes past phase 2 ~end of 2022 (3) +millions in speculative capital if new drugs are announced in pipeline (4) potential future merger with large pharma or uplisting to NASDAQ (other biotech companies are listed with half the number of products).
Comprehensive DD on $CTYX: The OTC Biotech Stock of the Decade That Is Being Slept On
[Connectyx (OTC-PINK: CTYX). Will change to Curative Biotechnology with ticker $CURB in Q1 2021.] Full Disclosure: I have a $6k initial position in this stock at a cost average of $.06. The stock is now at $0.155 (as of 2/6/21) with my position at $15.5k and movement is just starting. I am not a financial advisor. I am simply a broke graduate student interested in investing and fucking retiring early. This post represents my personal views and should not be taken as financial advice. Do your own damn research and stop pumping your hard-earned cash into trending stocks on Reddit posts that are nothing but hype, rocket emojis, and a mob chat jerking each other off. Also, not a doctor! The medical content below should never be a substitute for professional medical advice. With that said, $CTYX is going to fucking Pluto 🚀🚀🚀🚀🚀🚀 🌑 Price Target: $0.5 by May 1, 2021; $1.25 - $3.00 (~10x) within 2 years with credible potential to be listed on NASDAQ. This company is absolutely solid on all sides: healthy financials, an experienced & reliable management team, favorable market conditions with a reasonable business model, a solid lineup of products in its pipeline, and many large announcements anticipated within the next 3 months. Simply put, there is extreme asymmetric upside. $CTYX or Connectyx was taken over by its current team led by CEO Paul Michaels around Feb 2020. Within a year, this CEO has kept every promise he's made and established the infrastructure for growth. The company specializes in bringing orphan drugs (more on this below) through clinical trials and then to market. Paul and his team have decades of experience in big pharma, biotech research, finance, and drug licensing/development (in-depth description in the Management Team section below). They've vetted 3 promising drug candidates in under a year and promised to start clinical trials by mid-2022. If any one of these pass phase 1/2 trials, the market cap grows by hundreds of millions. They also have a reasonable chance to obtain a Priority Review Voucher (PRV) from the FDA that is worth $100-$300M from their strategic picks. They have a clean balance sheet, acquired non-dilute bridge financing while putting these drugs through trials, and have plans of additional deals in the near future. Why orphan drugs? Orphan drugs are therapeutics that treat rare diseases (defined as illnesses affecting less than 200k Americans per year). From the [Orphan Drug Act](https://www.wikiwand.com/en/Orphan_Drug_Act_of_1983#:~:text=The Orphan Drug Act of,residing in the United States.)), there are multiple incentives given by the government to develop orphan drugs: (1) significant tax credits (2) longer market exclusivity after approval (3) waiver of certain FDA fees (4) easier & faster approval process. In 2019, the global orphan drug market is estimated to be valued at $151B. By 2027, this is projected to reach $340.84B (10% compounded annual growth). This the cornerstone of their business model. By gathering a group of experts, they can cheaply vet high potential candidates to add to their development pipeline and then commercialize them from reduced fees as well as fast-track benefits from the FDA. So why the hell is it call Connectyx? It is just the old name of a software services company which the team acquired. The company has filed for a name change that will be granted within the next 2 weeks to Curative Biotechnology Inc. with a new ticker $CURB. In addition, the CEO himself has hinted at an uplisting to $OTCQB (a certification upgrade from current pink sheet status), mergeacquisition announcements, and $100M in non-dilutive funding. The official FINRA announcement of the name change will be the catalyst for the additional news. Some quick notes about the charts. The 15x jump in the past couple of months is only the beginning. There is a clear trend of resistance breakthroughs and medium-term consolidation after each announcement. Volatility is low, the number of outstanding shares is small, and there is limited dilutive potential for an OTC. Let's dive deeper into this hidden gem. All-Star Management Team CEO Paul Michaels Curative BioTech lucked out with a CEO with 25 years of experience in investment banking with a focus on life sciences. Paul has an impressive record, starting as the Executive Vice President and board member of Global Capital Group (a Wall Street wealth management firm). He also got extensive experience in big Pharma through [Inabata & Co. Ltd's](https://www.wikiwand.com/en/Inabata_%26_Co.,_Ltd.)), a subsidiary of a large Japanese drug company, Sumitomo Chemical Group, which totaled $21.8B in revenue in 2013 and employs over 30k people. While serving as Inabata's CFO, Paul licensed American drugs (some from Gilead) for the Asian market. After, the guy helped create Nobelpharma, an orphan drug company, which licenses drugs for rare diseases and got over $35M in initial capital. In February 2020, Paul took over Connectyx (a software services company at the time) and made it an orphan drug company. It is extremely rare for pink-sheet companies to have such high-caliber, established talent as a leader: decades of experience with finance and leadership positions in multi-billion dollar pharmaceutical companies. He helped build up Inabata and Nobelpharam (both thriving today), and I am confident in his ability to do it again with Connectyx. VP Communications Pam Bisikirski Recently, Curative announced Pam as the new Vice President of Communications. She previously served as the director of marketing of National Vision for 21 years. National Vision ($EYE) is a huge optical retail, eye care, and eye-ware company that is trading near a $4B market cap on NASDAQ. Scientific Advisory Board Dr. Michael Grace [news] - Ph.D. in Biochemistry and BS in Chemistry from the University of Nebraska. 30 years of experience in BioPharma with top roles in names like Procter & Gamble, Schering-Plough, Bristol-Myers Squibb, NPS Pharma, and Advaxis Immunotherapies. Lead 6 products to registration and commercialization. Dr. Ronald Bordens [news] - Ph.D. in Biotechnology with over 26 publications and over 2000 citations. 40 years in biotech and big pharma in research & development. Had a fruitful 26-year career at Schering-Plough Research. Richard Garr [news] - Serves as Director and CEO as well as President of Neuralstem Inc. (now Seneca Biopharma, Inc. which is listed on NASDAQ as $SNCA) for 20 years. Advocate for right to try treatments in the US and Europe. Founded Access Hope CRO (contract research organization) which dedicates itself to this cause. Was founder and current Board Member of the First Star Foundation Mid-Atlantic chapter which focuses on ill children (including pediatric brain cancer). Robust Drug Pipeline Keep in mind this company became a biotech firm in Feb 2020 and they already have 3 drugs in the pipeline along with exclusive rights licenses. Insane. 1) IMT504 immune therapy to treat late-stage rabies. (11/23/2020 Announcement implies IMT504 rabies license deal is complete) Strategic relationship with Mid-Atlantic BioTherapeutics, Inc. announced on 8/27/2020. Acquired all rights for development of this patented immunotherapy to treat late-stage rabies (a disease with 100% fatality rate after the treatable period, [kills 59k](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613553/#:~:text=about this topic%3F-,Each year%2C rabies causes approximately 59%2C000 deaths worldwide%2C including approximately,of postexposure prophylaxis (PEP).).)) globally per year). Now, the value of this may not be in the drug approval itself (although passing trials would be a huge asset of course). The value is the potential in CTYX obtaining a Priority Review Voucher (PRV). These coupons are handed out by the FDA each year to incentivize research into rare diseases. Exercising the coupon means diminishing the approval process from 10 months to 6 after trials. Further, you can freely sell these on a secondary market to other companies! Historically, these have been sold between $100M to $300M each. If obtained, this is an instant 2x-6x increase to its current $50M market cap. There's more.. notice that the FDA has added Rabies to its PRV-eligible tropical diseases list. Currently, there is only a handful of rabies therapies being researched. This means there's actually a good chance of CYTX getting rewarded a voucher, despite the relatively low count of vouchers distributed annually. PRVs are also possible for all other drugs in the pipeline. 2) CURB906 monoclonal antibody cytotoxic conjugate for the treatment of Glioblastoma. (10/16/2020 NIH gives a grant of license for worldwide rights) The second license was filed near July 2020 for a novel monoclonal antibody conjugate to treat brain cancer. Glioblastomas are aggressive brain tumors with poor survival rates in children. Recent studies (e.g. s1, s2) have shown different combinations of chemo-therapy and antibody-drug conjugate (ADCs) therapeutics were effective in both mice and human models. ADCs are innovative methods that attach a cytotoxic compound (one meant to kill cancer cells) to an antibody that specifically attaches to certain cancer cell receptors, thus delivering therapies to their targets. There is great promise and lots of potential in these therapeutics. Exclusive Evaluation and Commercialization Option License Agreement with the National Cancer Institute (NCI) has been granted. 3) Metformin repurposed to treat retinal degeneration. (2/4/2021 NIH gives a grant of license for worldwide rights) This is probably the ace in the hole and the largest reason behind the recent stock surge. On 2/4/2021, CTYX announced they received an NIH grant for exclusive worldwide rights to adapt a diabetes drug, Metformin, to treat retinal degeneration. Not only is Metformin proven safe (it is a widely used drug to treat Type1 Diabetes since 1995), there are many studies (e.g. s1, s2, s3) that hint at its effectiveness for retinal diseases. The recently granted license not only covers pediatric retinal generation (in the form of Stargardt Disease), it covers treatment in adults as well and includes macular degeneration. This promising treatment potentially covers 2/3 of the US population (2/3 of Americans are pre-diabetic, 1/10 are diabetic, and 11 million have some form of macular degeneration; why care about diabetes? diabetes causes retinopathy). Huge Upcoming Announcements The announced name change is the opening of the flood gates for all upcoming news. Additional licenses, uplistings, and deals with be done under the new company name. Expect many of these announcements following FINRA approval. These are some forward-looking implications:
(Within 2 weeks) FINRA approval of name change to Curative Biotechnology Inc. and ticker $CURB.
(Within weeks of name change) Following the name change, there will be an uplisting to OTCQB. OTCQB is a tier up from Pink Sheets and must adhere to stricter management certifications, undergo annual audits, and are more stringent in their financial reporting. Connectyx is currently working to become fully reporting OTCQB; to that end, the Company appointed Jonathan D. Leinwand, PA as Legal Counsel.
(Within weeks of name change) Talk of multiple upcoming drugs (if the Metformin announcement was one of them, we should see at least one more).
(Within weeks of name change) Hints at $100M of non-dilutive funding for clinical trials.
(Within months of name change) Mergers, acquisitions, and partnerships with other firms for licensing and commercialization.
Downsides Before we get ahead of ourselves and dream about retiring in 3 months while riding this into space, we gotta ground ourselves and discuss the downsides. Remember: in life, there are no solutions, only tradeoffs. There are always downsides and risks. Risk 1) This is currently a pink sheet. That itself should make you more cautious because there is reduced regulation, more "flexible" rules, and less scrutiny/transparency. Risk 2) High risk, high reward. If all 3 drugs flop (assuming no additional therapeutics are added) and they don't get a PRV (priority review voucher), then this company is worthless. Granted, the chances are low, but still a possibility to consider. Risk 3) Share dilution and raising capital. Because clinical trials often require obscene amounts of capital (~$400M investment for normal drugs), there is a risk that managers might dilute the stock in order to raise money or to take profits in general. There are currently 322M outstanding shares with 1.1B authorized shares. Read the share disclosures, do the math, gauge the risks. Note that orphan drug trials are a lot less costly as well. Risks and unknowns are certainly there. However, the upside potential is too big to ignore. Buy at pennies, sell for dollars. Do the research and take advantage of any dips that might come on Monday from 2 days of green explosions. ------------------------------------------------------------ TL;DR.
You should fucking read it, because this Phoenix has a high probability of rising from ashes to become the OTC stock of the yeadecade with effortless 10x upside in the short-term.
$CTYX will change to $CURB (Curative BioTech) soon. Business strategy: (1) bring together financial experts, veterans in big pharma, accomplished biotech researchers, and world-class grant writers to vet orphan drugs (2) make deals and obtain licenses for these drugs to help get them through clinical trials (3) take advantage of special FDA benefits for orphan drug approval (faster approval process, fee waivers, etc) and commercialize them after with longer exclusive rights.
Finance: company has no problematic debt, clean sheets, non-dilutive funding, and a small number of outstanding shares for an OTC (322M).
Products: 3 promising drug candidates in the pipeline within a year. Multiple exclusive license grants approved by the NIH.
Upcoming Announcements: (1) name change (2) uplisting to $OTCQB from pink sheets (3) more non-dilutive funding (4) additional drug(s) in pipeline (5) mergers, acquisitions, and deals with other pharma companies.
Current market cap: $50M. Upside: (1) +$100M - $300M if awarded a priority review voucher (PRV) (2) +hundreds of millions in market cap if any of the 3 promising drugs goes past phase 2 ~end of 2022 (3) +millions in speculative capital if new drugs are announced in pipeline (4) potential future merger with large pharma or uplisting to NASDAQ (other biotech companies are listed with half the number of products).
[https://pubchem.ncbi.nlm.nih.gov/periodic-table/png/Periodic_Table_of_Elements_w_Chemical_Group_Block_PubChem.png ] or [https://ptable.com/#Properties ] If we are going off the Lewis definition of acids as electron pair acceptors and bases as electron pair donors, the problems of ion solubility (mostly H+ and OH- ions) can be appropriately distanced from the actual behavior of hydronium (H3O+) or hydroxide (OH-) complexes in water. In other words, we first ask what species exist in what concentrations in the solution of interest, then what will happen between the different species. However, we cannot completely separate the Brønsted-Lowry and Lewis definitions due to Le Chatelier’s principle, which would state that the presence of the products of dissociation tend to prevent additional dissociation events. However, if product ions start being consumed in other reactions, the effective result is to shift the equilibrium back towards the starting materials, and additional dissociation events will then become energetically favorable. The result of this is that the behavior of chemical reactions is best contemplated holistically and with a full set of executive functionality instead of being taught as a series of disconnected fragments that imply the existence of a much higher level of precision than is actually ever possible and must be stitched together by students working without the benefit of fully developed brains. As I go through the process of writing out this series of posts, I am getting the definite impression that the progress that has been made in our understanding of atoms and orbitals has mostly obsoleted the way that general chemistry is currently taught, and that the current state of teaching is centered around exams to the detriment of the students. My general chemistry education also had far too much emphasis on the Brønsted-Lowry definition of acids and bases instead of treating these as equilibrium problems. So and before we go any farther, let’s get pH out of the way. A lowercase “p” denotes the mathematical operation of taking the negative log of a quantity for some reason, so pH is actually the negative (base 10) log of H where H is the ionic activity of “H+” in the solution of interest. As it turns out, this is actually the activity of hydronium complexes instead of lone protons, but unless you are trying to visualize what is actually happening in the solution the two can be treated as equivalent. Of course, if you’ve gotten so obsessed with applying equations to chemical processes that you are willing to ignore the three-dimensional picture, you’re probably also not doing anything of value, but anyway. In most cases, pH can be calculated with the concentration of hydronium in moles per liter instead of a more rigorous activity measurement, so in other words pH is mostly equal to -log([H3O+]). [I should also note that the difference between the concentration of hydronium and the concentration of protons is not particularly significant in acid-base problems because the protons in water will either react with other species or form hydronium. If you are calculating the concentration of protons in water at any given time, you are also calculating the concentration of hydronium.] If you’re willing to get pedantic there is a nearly infinite amount of additional complexity that can be brought in here, but I’m not emotionally invested in this and see no reason to care. Proceeding with pH=-([H3O+]), you may notice that we are only calculating the acidity of our solution and not the basicity. However, due to the spontaneous dissociation/autoionization of water, acidity and basicity are closely related to each other. In a volume of water, the multiplication product of the concentrations in moles per liter of hydronium/H3O+ and hydroxide/OH- is a constant. At 25 degrees Celsius, this constant (Kw) is equal to 1.0x10^-14, and Kw=[H3O+]*[OH-]. In this notation scheme, the square brackets denote concentration in moles per liter, and square brackets are usually but not always moles per liter. In any case, the reason to care is that the assumptions here mostly hold true once we start adding additional chemical species to the volume of water we started with. As the number of ions in solution increase, other issues start to arise, but mostly what you need to remember is that this is a simplified model and not an absolute definition of what is happening on the molecular level. Where this model is valuable is in relating the concentration of hydronium to the concentration of hydroxide (both in moles per liter) in a mostly reliable manner, which means that if we know a value for one at a given time we can calculate the value of the other one. So, if you have a concentration of hydroxide and you want to know the pH, you can use Kw to calculate the concentration of hydronium, then take the negative base 10 log of the result to get to pH. The addition of the logarithm allows the comparison of numbers with vastly different orders of magnitude but also brings quite a bit of confusion. In any case, using these assumptions we can define interrelated pH and pOH scales to measure acidity and basicity as the density of hydronium and hydroxide in solution. You may notice that this aligns well with the Lewis definitions, although we are not considering any other possible Lewis acids or bases. Once you get into organic chemistry and start trying to do reactions, having a trace amount of ions in your reaction mixture doesn’t get you anywhere, and all of the assumptions as previously defined get thrown out of the window. At high concentrations of ions/high ionic activities (which are mostly equivalent concepts), we get back to the idiosyncratic and non-intuitive behavior that we expect to see in chemistry. These conditions also favor the Lewis definitions, and if it seems like I am being a bit heavy-handed in mentioning the advantages of teaching the Lewis definitions to students as early as possible you would be quite correct. Fully embracing the Lewis definitions will require the more neurotic or tradition-bound individuals among the chemical community to let go of literally centuries of work that turns out not to be valid, but as before I have no particular emotional investment in Brønsted-Lowry and would much prefer to be taught the concepts in a way that actually makes sense. In my list of topics I am supposed to cover acid-base equilibrium, which in the context of water (aqueous solutions) is how hydronium and hydroxide move into and out of solution. First looking at “HA” or a proton donor, we can either have the acidic proton attached to the conjugate base or not. The Lewis basic strength of “A-” determines how tightly the H+ is bonded and therefore how accessible it is to the surrounding water molecules. If the H+ is bonded too tightly, there is no chance of a water molecule ever removing it, and the compound is probably not going to be participating in any aqueous acid-base reactions. At this point I am really wanting to bring in some more organic chemistry concepts and talk about an example like ethanol (CH3CH2OH) as a compound with three distinct types of protons in three different chemical environments, with the hydrogen on the oxygen end (Eth-OH) as well as the two lone pairs on the oxygen being the most interesting electron pair acceptors and donors, but the current general chemistry syllabus as defined by the American Chemical Society (ACS) prevents this. Moving on to “BOH” in water, the strength of the bond between “B+” and hydroxide is also going to be important. As an example, the hydroxl group on ethanol has essentially no chance of being removed in an aqueous solution unless something quite energetic/violent happens, but the hydroxl proton can be stripped off or another proton can bond to one of the lone pairs on oxygen depending on the reaction conditions. In the context of this post, I am basically trying to get into a decent position to talk about buffers. These are modeled by the Henderson Hasselbalch equation and are usually a combination of a weakly proton-donating “HA” with the “A-” part of that molecule paired with a positively charged counterion (counter-cation possibly). As an example cation, let’s choose sodium (Na+), which is a terrible electron pair acceptor because it is already in a noble gas valence electron configuration and adding electrons will be destabilizing. So, we can basically ignore the sodium ions unless we are interested in the total ionic activity for some reason, and at the same time the charges all balance out. If we select the correct “A-” and adjust the relative amounts of “HA” and “NaA”, we end up with a mixture that starts out at a pH that can be predicted via calculation. This is normal when adding proton or hydroxide donors to water, but where buffers are different is the ability to absorb proton or hydroxide inputs without the pH changing much. This is because of the presence of both protonated “HA” and deprotonated “A-” and is useful in situations were the molecules under study cannot tolerate large pH swings, which usually means proteins and other biological molecules. Selecting a buffer requires the concept of the constant of acidic dissociation (Ka) and the negative log of the same (pKa), but between this and Henderson Hasselbalch equation you should have plenty of keywords to play with. I am also supposed to be covering titrations here, but since these are as obsolete as Brønsted-Lowry and really shitty to have to carry out in the lab I’m not going to bother.
[https://pubchem.ncbi.nlm.nih.gov/periodic-table/png/Periodic_Table_of_Elements_w_Chemical_Group_Block_PubChem.png ] or [https://ptable.com/#Properties ] In the last 14 posts, I have attempted to present the main points/useful information from a whole academic year of general chemistry. A significant fraction of the material taught in general chemistry is obsolete, but I am also skipping over any of the information that is actually beneficial to have somewhat memorized, all of the math, etc. Generally speaking, people don’t seem to have much trouble retaining information that is useful to them, so unless you’re having to pass a series of exams I would not worry about any of the details if you don’t want to. Maintaining a degree of rigor and intellectual honesty is important, but at the same time knowing a theory should enhance your understanding of the real world instead of detracting from it. In any case, we have atomic nuclei with positively charged protons and non-charged neutrons surrounded by somewhat amorphous clouds of negatively charged electron density generated by a discrete number of negatively charged electrons moving around at high speed. How nuclei, orbitals, and electrons interact is chemistry, and given the complexity in chemical reactions that is evident (particularly in biology) it should come as no surprise that the behavior of electrons, elements, and molecules is also extremely complex. We as a species have spent many centuries of unified time and uncountable person-millennia of effort grappling with aspects of the complexity of chemical behavior, before discovering relatively recently that everything is derived from quantum mechanics and none of the simple mathematical models are particularly valid. The discovery of quantum mechanics started in the early 1900s to the 1920s or so in the physics community and has led to a progressive series of major improvements in the way we think about the world that is still underway. The information gained has led to our disastrous exploration of nuclear fission in heavy elements but also to the development of much more potent instrumentation, semiconductors, computers, and a better, if not necessarily more comforting, understanding of the universe that we live in. Looking at chemistry specifically, our goal as a species needs to be to do as little chemistry as possible while still ensuring our survival. Where chemical reactions are unavoidable, we need to take care to ensure that the resulting waste is as non-toxic, biodegradable, and/or easily denaturable as possible. Simple molecules such as carbon dioxide can cause problems when emitted in bulk, and more complex molecules tend to be nastier in much lower quantities and concentrations (eg polychlorinated biphenyls/PCBs). As creatures with cellular machinery that is mostly made of organic molecules, we are going to be most interested in organic reactions despite our historical inability to make much sense of the complicated electronics and molecular orbitals of organic reactions. Unfortunately, this means that we will not be able to skip as many of the details, and if I want to try for complete coverage I would expect to see a few tens of posts. The main difference between general and organic chemistry is that a significant fraction (possibly even most) of the general chemistry material is obsolete and/or irrelevant, while the majority of organic chemistry material is both important and relevant. So this may take a while, and I’m going to wish that I still had access to the ChemDoodle software that is set up for organic structures. On ubuntu linux, the GChemPaint program seems similar and is free, and I guess that I’m about to find out how well that it works. I will do my best to relate concepts back to the mental picture of how chemical compounds interact that you are hopefully building up as I introduce them, but as always things are usually going to be messy. The list of high level topics in organic chemistry as defined by my undergraduate study guide is as follows: structure, bonding, intermolecular forces of organic molecules, acids and bases in organic reactions, nomenclature, isomers, principles of kinetics and energy in organic reactions, preparation and reactions of (alkenes, alkynes, aldehydes, ketones, alcohols, sulfides, carboxylic acids, amines, aromatic compounds), organic reaction mechanisms, principles of conjugation and aromaticity, and spectroscopy. I have not yet decided if this is the order in which I would like to present these concepts, but hopefully you can see that this is a large amount of material. As a final note, organic chemistry is mostly the chemistry of hydrogen, carbon, nitrogen, and oxygen with trace quantities of several other elements participating at times. Organic molecules are interesting both because of the wide range of properties and behaviors that they exhibit and also because of our desire to understand our biology, and we are studying mainly the chemistry of the 1s, 2s, and 2p valence orbitals in small atoms.
It's my first week in OChem and I'm stuck on a homework problem. The problem asks to rank the basicity of 4 different compounds given in the form of bond-line structures. We are given 3 attempts to solve the problem correctly, of which I have used 2. On my first attempt, I took the completely wrong approach (used acid rules). On my second attempt, I figured out the chemical formulas and then researched the pKas of their conjugate acids to figure out which is the strongest. This still didn't seem to be right, although I think my approach is on the right track. The pKas for the conjugate acids for these specific structures are not provided in the textbook. I've never heard analogous structures in this context and could not find a chemistry definition online, so I'm not quite sure what that means. The order displayed in the screen shot below is my most recent attempt. I would appreciate any help. https://preview.redd.it/ak8zd5b7brc61.png?width=1372&format=png&auto=webp&s=70ee3353540a2e304c64ca1cccf0c9cbae89eefd
[Discussion] Hepatic Metabolism of Oral AAS, Hepatotoxicity, and Liver Support
I know this is a long write up, the first half is biochemistry and what happens on a cellular level. The second half is more pertaining to the average AAS user, including a deeper dive into liver functioning tests and liver support. I highly recommend at least reading the second half, especially the Liver Support section. Hepatotoxicity is a word that is frequently thrown around, everyone’s heard it, everyone thinks they know what it is, but once you ask something beyond surface level, you get a whole lot of conflicting answers. Let’s dive into it. Overview/Background/General Information/What the fuck actually happens? Drug Metabolism: The human body identifies almost all drugs as foreign substances and subjects them to various chemical processes to make them suitable for elimination. Drug metabolism is typically split into two phases: Phase 1 (oxidation via Cytochrome P450, reduction, and hydrolysis) tends to increase water solubility of the drug and can generate metabolites. Phase 2 further increases water solubility of the drug, inactivating metabolites, thus preparing it for excretion.
Aside: There has been a lot of questions regarding using high dose psoralens (from grapefruit juice/extract) to inhibit the activity of Cyp3A4 (and the Cyp450 family in general) or consuming large quantities of chargrilled meat to induce the activity Cyp450. DO NOT purposely do this in an attempt to increase the bioavailability of oral steroids. The Cyp450 family is incredibly important enzyme family that is involved in the metabolism (both activation and degradation depending) of statins, oral contraceptives, acetaminophen, anti-depressants, beta-blockers, antiarrhythmic agents, and many, many more. This can cause SEVERE adverse effects.
Example: Acetaminophen (Tylenol) is often seen as hepatotoxic, it is not. One of the metabolites, NAPQI, is. Under normal conditions, NAPQI is produced in incredibly minor amounts. Alcohol induces Cyp450 enzyme family, which increases the breakdown of Tylenol into NAPQI, causing intensive acute liver damage which can often be fatal in high doses. In short, don’t nurse your hangover with Tylenol, use Advil instead… or better of just don’t drink alcohol.
17α-Alkylated Anabolic Steroids. These AAS contain a methyl or ethyl group on the C17α position, allowing for oral activation. This modification allows the drug to survive hepatic metabolism, limiting the amount of steroid that is broken down, allowing for more drug to reach the bloodstream. Without this modification, the drug is completely broken down by the liver, never reaching systemic circulation. This initial process is called First Pass Metabolism. First pass metabolism: After a drug is swallowed, it is absorbed by the digestive system and enters the hepatic portal system. It is carried through the portal vein into the liver before it reaches the rest of the body. The liver metabolizes many drugs, sometimes to such an extent that only a small amount of active drug emerges from the liver to the rest of the circulatory system. This first pass through the liver may greatly reduce the bioavailability of the drug. Some oral steroids have a very low bioavailability due to first pass metabolism, thus injectable versions may be used to prevent the initial breakdown, effectively increase bioavailability and reducing liver stress.
Aside: There have been questions regarding sublingual administration of oral AAS in order to bypass first pass metabolism. In short, very few drugs can be properly absorbed sublingually, Nitroglycerin is a prime example. AAS, although can be manufactured for sublingual absorption it requires a specific method of delivery (sublingual tablets, strips, or sprays for example), which are difficult to obtain and manufacture; it’s not as simple as placing some powder under your tongue. Other drawbacks exist of sublingual administration such as tooth decay and difficulty in dose management.
Anavar: The exception to the rule: The oral bioavailability of oxandrolone is 97%. The drug is metabolized primarily by the kidneys and to a lesser extent by the liver. Oxandrolone is the only AAS that is not primarily or extensively metabolized by the liver, and this is thought to be related to its diminished hepatotoxicity relative to other AAS. For this reason, there is no reason to ever use injectable anavar (unless poking yourself that often is your kink, no judgement).
[aside: not all drugs are orally active, in fact the majority are inactive. For example, codeine (inactive) will be converted into the active form, Morphine, within the liver via Cyp450 enzymes]
In the case of oral AAS, hepatic metabolism can convert an active drug into its inactive form; C17α methylation prevents this. Why is this modification known to be hepatotoxic? The primary enzyme that normally breaks down hormonal steroids (such as endogenous DHEA, testosterone, estradiol, etc) is 17β-Hydroxysteroid dehydrogenase, 17β-HSD, (and to a minor extent the Cyp450 family) which can no longer break down the methylated drug, thus the liver finds an alternative route for metabolism. The actual specific process is still relatively unknown, but involves a variety of oxidation reactions, inducing an increase of free oxygen radicals within the hepatocytes (liver cells), causing cell death due to oxidative stress. There is another hypothesis which involves the presence of androgen receptors within the liver. The C17α methylated oral steroid, that is no longer properly broken down, will bind to these receptors, causing a drastic increase of androgenic activity within the liver, leading to hepatoxicity. In my opinion, it is a mixture of both. Many studies show a direct correlation between the androgenic effect of the oral steroid and the amount of hepatoxicity. The exact link between the two is yet to be determined. In general, the greater the affinity of C17α methylated oral steroid for the androgen receptor, the more hepatoxicity occurs.
Hepatotoxicity is an overlying term: the specifics related to AAS use are Cholestasis (blockage of biliary flow), Steatosis (accumulation of fatty lipids within the liver), Zonal Necrosis (hepatocyte death within a specific zone of the liver), and Peliosis Hepatitis (vascular lesions leading to liver enlargement).
Aside: Steatosis (fatty liver) has been an observed adverse effect of Nolvadex and Raloxifene
Cholestasis is a condition where bile cannot flow from the liver to the duodenum. It is the most common condition resulting from oral AAS use. In short, bile is continuously produced but cannot leave the liver, causing build up, backflow, and eventually hepatocyte death. Differential symptoms of cholestasis include but are not limited to pruritus (itchiness), jaundice (yellowing of the skin and whites of the eyes), pale stool, and dark urine. Liver Functioning Tests: What do they mean and why are they relevant? AST: Aspartate Transaminase: This alone is not a good indication of liver damage. AST is found in abundance within both cardiac and skeletal muscle. An elevated AST value can be caused by something as minor as weightlifting. ALT: Alanine Transaminase: ALT is found specifically within the liver and is released into the plasma when significant liver stress, including hepatocyte death, occurs. An elevated value is of concern.
Aside: general rule of thumb (not always true) if both elevated are elevated and if AST>ALT in a ratio of 2:1, suspect alcohol/drug induced damage. If both values are elevated and if ALT>AST in a ratio of 2:1, suspect viral hepatitis.
ALP: Alkaline Phosphatase: ALP is found within the hepatobiliary ducts. An elevated value is commonly indicative of obstruction and bile buildup, signifying cholestasis. GGT: Gamma-glutamyl Transferase: GGT is an enzyme that is found in many organs throughout the body, with the highest concentrations found in the liver. GGT is elevated in the blood in most diseases that cause damage to the liver or bile ducts. 5’-nucleotidase: The concentration of 5’-nucleotidase protein in the blood is often used as a liver function test in individuals that show signs of liver problems. ALP can be elevated due to both skeletal disorders and hepatic disorders. 5’-nucleosidase is elevated ONLY with hepatic stress, not skeletal, thus allowing for differentiation.
Putting it all together: Cholestasis can be suspected when there is an elevation of both 5'-nucleotidase and ALP enzymes. Normally GGT and ALP are anchored to membranes of hepatocytes and are released in small amounts in hepatocellular damage. In cholestasis, synthesis of these enzymes is induced, and they are made soluble. GGT is elevated because it leaks out from the bile duct cells due to pressure from inside bile ducts. As hepatocyte damage continues, ALT, AST, and unconjugated bilirubin will begin to rise. In short: Initial liver stress causes 5’-nucleiotidase and ALP to rise, shortly after GGT rises, then finally AST and ALT rise. Thus, with only AST and ALT values, it is difficult to determine the cause and extent of hepatic damage. Liver Support: NAC/TUDCA/Liv52 NAC: N-Acetyl Cystein NAC is a prodrug of L-cysteine, a precursor of the biological antioxidant glutathione which is able to reduce free radicals within the body. Free radicals, which as discussed above, are associated with causing extensive hepatocyte damage due to the oxidative breakdown of C17α methylated AAS. In addition to its antioxidant action, NAC acts as a vasodilator by facilitating the production and action of nitric oxide. This property is an important mechanism of action in the prophylaxis of contrast-induced nephropathy and the potentiation of nitrate-induced vasodilation.
Aside: NAC has been constantly used as an adjunct to multiple neurological disorders including Parkinson’s, Huntington’s, Multiple Sclerosis, Cerebral Ischemia, Alzheimer’s and MANY more due to the potent free radical trapping effect which prevent mitochondrial dysfunction.
Multiple studies have constantly showed NAC decreasing liver functioning tests and improving liver function and mitigating cholestasis. NAC had the ability to vastly improve markers of kidney function and was actually able to even double the rate of sodium excretion, indicating that NAC is may be useful in preventing water retention. In short, NAC has a vast number of benefits, including hepatoprotective (liver), nephroprotective (kidney), and neuroprotective (neural), and anti-inflammatory effects that have been constantly demonstrated thru literature. Moreover, NAC can and should be used for year-round support since the adverse effects are incredibly mild. There is absolutely NO reason to not be taking NAC.
TUDCA: Tauroursodeoxycholic acid TUDCA is a bile acid taurine conjugate form of UDCA. As discussed above, during cholestasis, bile builds up, creating backflow and inducing hepatocyte death thru apoptosis. Apoptosis, or programmed cell death, is largely influenced by the mitochondria. If the mitochondria are distressed, they release the molecule cytochrome C. Cytochrome C initiates enzymes called caspases to propagate a cascade of cellular mechanisms to cause apoptosis. TUDCA prevents apoptosis with its role in the BAX pathway. BAX, a molecule that is translocated to the mitochondria to release cytochrome C, initiates the cellular pathway of apoptosis. TUDCA prevents BAX from being transported to the mitochondria, effectively inhibiting hepatocyte death. Furthermore, TUDCA aids in the processing of toxic bile acids into less toxic forms, resulting in decreased liver stress, further preventing hepatocyte death. Moreover, TUDCA aids in the transport of bile from the liver into the duodenum, effectively unblocking the build up causing cholestasis. Finally, TUDCA has been proven to be an effective treatment for the necro-inflammatory effects of Hepatitis. Study after study has shown that TUDCA greatly improves liver enzyme values. Why do we recommend only using TUDCA with hepatotoxic oral steroids? The idea is that TUDCA induces liver damage when there is no hepatotoxicity present… but after reading the above, does that make sense? It does not. I could not find any literature showing that TUDCA induces liver toxicity. The recommendation instead is due to the negative effects of TUDCA on cholesterol values. TUDCA has been shown to greatly decrease HDL levels when taken for extended periods of time. The idea is, if you have a healthy functioning liver, there is no reason to take TUDCA for long periods of time since all you’re doing is decreasing HDL values. That being said, after doing the research and seeing the vast benefits of TUDCA (included bellow, not a comprehensive list), I am beginning to change my perspective on TUDCA use with only hepatotoxic oral AAS. In short, TUDCA prevents hepatocyte death, enhances hepatocyte function, exhibits anti-inflammatory effects on the liver, neutralizes toxic bile, and prevents bile build up that was caused by the alternative metabolism of C17α methylated AAS. ***THERE IS NO EVIDENCE THAT I HAVE COME ACROSS THAT SHOWS THAT TUDCA ITSELF INDUCES LIVER DAMAGE WHEN USED WITHOUT HEPATOTOXIC DRUGS**\* TUDCA has a variety of other benefits outside the liver, but I will not go into them this time. In short:
Increasing glucose-induced insulin release via the cAMP/PKA pathway, increasing insulin sensitivity.
Relieving endoplasmic reticulum (ER) stress. The ER makes sure proteins are folded properly.
Reducing programmed cell death (apoptosis) in healthy cells. TUDCA prevents the molecule BAX from reaching the mitochondria. BAX causes mitochondria to release cytochrome C, which causes enzymes (caspases) to initiate apoptosis.
Inactivating Bcl-2-associated death promoter (BAD), a molecule involved in apoptosis.
Removing toxic bile acids from the liver and preventing them from damaging liver cells
Exhibits neuroprotective effects via the inhibition of NF-kB
Preserve photoreceptor function and increases retinal health by increasing rd10
Liv52 Liv52 is an herbal liver support. There have been medical studies conducted on Liv.52 in recent years, many of which involve its ability to protect the liver from damage by alcohol or other toxins. Liv52 has been shown to exhibit antiperoxidative function, antioxidant effects, anti-inflammatory, diuretic effects and neutralization of toxic products within the liver. “The results demonstrated that the patients treated with Liv-52 for 6 months had significantly better child-pugh score, decreased ascites, decreased serum ALT and AST. We conclude that Liv-52 possess hepatoprotective effect in cirrhotic patients. This protective effect of Liv-52 can be attributed to the diuretic, anti-inflammatory, anti-oxidative, and immunomodulating properties of the component herbs.”
“Liv.52 enhanced the rate of absorption of ethanol and rapidly reduced acetaldehyde levels, which may explain its hepatoprotective effect on ethanol-induced liver damage.”
“Liv.52 administration reduced the deleterious effects of ethanol. The concentration of acetaldehyde in the amniotic fluid of ethanol-consuming animals was 0.727 microgram/ml. Liv.52 administration lowered it to 0.244 microgram/ml. The protective effect of Liv.52 could be due to the rapid elimination of acetaldehyde.”
That being said, there is conflicting research on Liv52. The studies either show hepatoprotective function or no effect, positive or negative. “There was no significant difference in clinical outcome and liver chemistry between the two groups at any time point. There were no reports of adverse effects attributable to the drug. Our results suggest that Liv.52 may not be useful in the management of patients with alcohol induced liver disease.”
In short, Liv52 can be used if you have the additional funds, it is not the end-all-be-all but can be used as an adjunct. It is an incredibly cheap drug thatmayimprove liver function and exhibit hepatoprotective effects. IT SHOULD IN NO WAY YOUR ONLY LIVER SUPPORT MEDICATION, but there is nothing wrong with using it.
F | 31 | 453.59 kg | 82.1 kg | 409.3 Wilks | 2020 RPS Fall Throwdown at Rivercity Barbell, Dayton, KY
tl;dr summary: almost bombed, totaled 1000, Pretzel puts on a show of ovarian fortitude. This is going to be long, in part because I like to go back and read these to reflect on what I learned every meet, and because when I was a noob I needed more experienced lifters to tell me literally everything that could possibly happen on meet day so I could mentally prepare myself. I'm also going to be pretty transparent about the things I had going on in my non-lifting life leading into this meet, because October is ADHD Awareness Month, and because the longer I've been in the sport, the more I understand how real life shows up on the platform. It's important to remain cognizant of what you're overcoming, on and off the platform. Skip about halfway down for the actual lifting. Videos of all 9 attempts are split between IG and imgur links, included below. BACKGROUND This was meet number six for me, my third in wraps and my second in the 181 class. Since my last meet in November 2019, I have been working with Lones Green (calloused hands), training conjugate. He has been great to work with, willing to make adjustments where my body demands it (for instance, dealing with elbow tendinitis) and willing to push me where I need it. He's been calling for this total (a little higher tbh) since I registered for a meet in May 2020, which obviously didn't happen. His style is based in conjugate, with traditional max effort and dynamic effort days, with a lot of training volume. Once I got acclimated to the volume, I loved it. I get a wide range of accessories to address weak points and build up my strong points, and it's generally just a fun way to lift. It's built incredible work capacity which kept me comparatively fresh by the time it was time to deadlift and built the ability to both rep out big weight and smoke new PR singles pretty regularly. I've also stayed healthy, which in this sport is a minor miracle. I plan to continue with this style as long as Lones wants to keep coaching and my body holds up. Leading into this meet, I had a lot of personal life things going on. Some were very positive, but some were fairly traumatic, and either way, it's a big emotional/mental/spiritual demand while also prepping for a meet. I moved in with my boyfriend at the end of August, which has been great! He has been a champ all the way through, and really is the MVP of this story. But telling my family went really, really poorly, and feeling that kind of rejection from the most important people in my life was one of the most painful things I've ever felt. Things have settled there, but it was really rough for a while. I also don't really recommend moving at six weeks out during the busiest work week of the entire year, but sometimes it be like that. The other thing was getting assessed, diagnosed, and then trying a medication for ADHD. I'm a 31 (relatively) accomplished attorney, and had no idea until quarantine that the constant feeling of "I'm lazy and why can't I cope like everyone else" wasn't normal. While it's a relief to know what the problem is, and to know that there are options to address my deficits, it's also crushing to find out that I have struggled against my own brain chemistry for 31 years and had no idea, and just spent that time beating myself up instead. There is an intense grieving process that goes with the diagnosis. I don't want to be this way, but here we are, and now it's time to fight, this time with all the correct information. I'm about five weeks into my first shot at medication, and it has not gone super well, but I know I have other options and I'm hopeful those work a little better for me. Shoutout to adhd for being an amazing resource; if you're struggling too, or think this is something you may be coping with, that's the most supportive subreddit I've ever seen. I know that my real name is very easily connected with this account, and I don't care. I'm not ashamed I've been medicated for depression for 6 years, so I am not going to be ashamed of the ADHD either. I'm not the only attorney in the world with ADHD, and I won't hide if it helps someone else get help. Finally, ten days out from competing, two of the people that I've been closest to since I moved to this area completely iced me out. I don't want to doxx them and I'm not going to get into the dramatic details or try to make them look like the devil, but this sucked. A lot. I didn't want to let it shake me up, but these two are also competitors, and to do this to someone you purportedly care about right before competition is not an accident. I don't wish them ill and I know I'll be better in the long term without that kind of petty toxicity in my life, but wow, not having them cheering for me this time--out of nowhere--shook me up. A lot. It showed up on the platform. I wish I were strong enough to say it didn't, but I'll own my mental weakness here. However, this experience really highlighted all the people who are absolutely in my corner, and that has been a gift. okay enough of Pretzel's diary, let's lift. SQUAT (1/3) lol. Just lol. This was an all systems failure that I have never experienced on the platform and hope to never experience again. Guy wrapping me was outstanding and my bf was great at keeping me calm, but shew lawd 1/10 do not recommend. I didn't miss a single squat in training. I just shit the bed. 1st attempt: 390 all i can say is wtf. This is easy weight for me, and even though I had been training with an up call for weeks, I jumped the call, realized I jumped it, and did this bizarre 1.5 squat. I mean, WTF? It was light, so I jumped to 410 and tried to shake it off. 2nd attempt: 410 Narrator: She did not shake it off. At this point I was DISTRAUGHT. I hadn't ever missed a freaking opener, let alone stared bombing out in the face. These guys were on the way. 3rd attempt: 410, 10 lb PR. Absolutely not the weight I came for, but bf jumped in to back spot and we had a little Titanic moment. He told me when I walked up not to get a call, just squat because I know how to do that. Turns out yes I do. 3 whites, we're in the game. As I've said and will say repeatedly, I think his believing that I could do it popped me back up out of the hole, because I was mentally crushed by this lift. Lessons: I got way too amped beforehand. Less is more there. I may not use ammonia at all going forward, because it didn't help me here at all, and I didn't use it other than my deadlift opener the rest of the day. I need to approach the bar calm and confident, not WILDIN OUT. I also need to trust that I am actually capable of finding depth on my own, pretty easily, and not get so worked up on missing a rep on depth that I do stupid things like this. BENCH (2/3) I was cramping pretty good between attempts but this went okay. 1st: 175, old meet PR for a smokeshow. 2nd: 190, 15 lb platform PR. pretty blown away with how easily this went up. Really happy with this bench. 3rd: 200, just not quite. I'm proud of how I handled it, just wish I didn't get a back cramp when the weight came off my chest. I know it's going to be there next time, and I have some ideas on tweaking my arch and salt intake to mitigate the cramps that haunt me EVERY SINGLE MEET. DEADLIFT (3/3) Honestly, I was dead in the water at this point. I felt like the day was a failure, which is silly because I was going to get a PR total on my opener, but it wasn't what I wanted going in, and I couldn't get my head right. Fortunately, I got the greatest back slaps of all time from bf, who by this point should be able to add my lifts to his total, because he was carrying me. I have had a complex for years, honestly, about being a weak puller, and just didn't think I could pull off the 1k total I wanted resting on this lift. Well... 1st: 355, smoke. 2nd: 380, good, 5 lb PR over my last meet and heaviest thing I've ever pulled off the floor til about 7 minutes later. 3rd: 400. Three. White. Lights. 25 lb lifetime PR. I knew I HAD to get this pull to save my day. I failed a 425 pull with reverse bands six weeks out. I thought I had no shot. And then it moved like this. It didn't stick off the floor, I didn't catback, it just went up. I got my 1000, my 400 pull the first time I ever attempted it, and I cried profuse quantities of happy tears afterwards. TAKEAWAYS Overall, despite the incredibly crappy start, I went 6/9 and still pulled off a thousand freaking pound total with PRs across the board. That's a 50 lb overall PR. Six meets deep, PRs are not a given, and I am thrilled to still be posting big ones even on not-my-best day. That final pull honestly took all the sting out of my squats, which in training had been by FAR my strongest lift. I missed deadlifts all over the place in training and then holy hell did they show up when it counted. Deadlift, maybe you and I can be friends after all. According to the RPS, I'm a pro now, which is worth a lululemon athlete discount and not much else. I put up numbers I never thought were possible, and I'm set up for a ridiculous squat PR next go around (because no way am I repeating that nonsense). I wanted to break after those first two misses, and my people and my innate stubbornness wouldn't let me, and I am very thankful. The end. If you read this whole thing, you've been procrastinating too long. Get back to work.
We have been getting a lot of confusion and questions on the color of Curowhite on our Facebook page, so I figured I would make a post here to address it. I am sure some people here are curious as well. To start, one of the major questions we have been getting is whether Curowhite is bleached to get rid of the color. I think many people are unaware of just how color works, which is why many people immediately jump to what they have experienced before. Many people have seen how chlorine bleach gets rid of color, so they fall back to that. I'll go through the details to clear things up. What is color? Well color is simply our eyes interpreting the wavelengths of light being reflected back to us from an object. If an object is white, that means that the entire spectrum of visible light is being reflected back to our eyes. If we were to take out part of that spectrum before it reflected back to our eyes, we would see it as a specific color. In curcumin's case, we take out the blue hues, which means our eyes see the curcumin as orange. If we remove all wavelengths, we see black. It's all just our eyes interpreting the wavelengths of light being reflected back to us by objects. So why is curcumin orange? Well from a chemistry perspective, color arises from the presence of a chromophores. Chromophores are parts of a molecule that form a conjugated pi system, which are made up of double carbon-carbon bonds. When you have a conjugated pi system in a molecule, they are able to capture photons as they pass. Since they are capturing some photons, they are absorbing some of the wavelengths of visible light, leading to only part of the spectrum being reflected back to our eyes. That's how color is made. Parts of the molecule are able to capture certain photons as they pass. Lengthening a conjugated system with more unsaturated bonds in a molecule will tend to absorb longer wavelengths of light. So the number of double carbon-carbon bonds in the conjugated pi system in a molecule will dictate which wavelengths are absorbed, and consequently which wavelengths are able to reflect back to our eyes. Chromophores are also how most HPLCs and UPLCs "see" the molecules they are assaying. They have UV detectors on them, which are measuring the reflectance off the analytes. The same goes for UV-VIS machines. So why is Curowhite white? Well Curowhite is made by converting the curcuminoids in tumeric into tetrahydro curcuminoids, hexahydro curcuminoids and octahydro curcuminoids through a process called hydrogenation. This breaks the double carbon-carbon bonds on the central hydrocarbon chain in the curcuminoids. This breaks the conjugated pi system, which no longer allows photons to be captured as they pass. This means that the hydrogenated curcuminoids in Curowhite will reflect back the entire spectrum of visible light, not absorb the blue hues like normal curcuminoids would. Here is an image I made to illustrate. So you can see that the process of hydrogenating the curcuminoids removes the conjugated pi system, which removes the color! So how does chlorine bleach remove color? Well it does that through oxidation. It attacks the chromophores in a molecule by oxidizing them. It's a different process, but he concept is the same. You are removing the double carbon-carbon bonds in a conjugated pi system, which stops the molecules ability to capture photons as they pass. Bleaching is not used in the production of Curowhite, and the hydrogenation process of the curcuminoids actually improves their bioavailability and effects compared to normal curcuminoids. It's actually a really ingenious process. Curowhite also then encases the hydrogenated curcuminoids in a cyclodextrin, which improves bioavailability even more, and makes it water soluble. So that is how they make a curcuminoid product that is white and water-soluble!
Although rankings should be taken with a grain of salt, USNWR ranks them #7 out of national LACs, #1 in undergraduate teaching out of LACs, #8 in writing, #14 in study abroad, and #18 in undergraduate research. Niche ranks them #10 for international relations, #17 for environmental science, #19 for global studies, #21 for religious studies, #23 for film and photography, and #25 for history and chemistry.
Typically, LACs tend to invoke the thought of the humanities and social sciences. Although Carleton is well known for their programs in the humanities and social sciences, they also are well known for their STEM abilities, in particular for computer science and math. You can read more about this here.
Carleton has a really unique academic year calendar, known as the 3/3 Calendar. It essentially uses a trimestequarter system where a term is only 10 weeks. However, in those 10 weeks, you generally enroll in three six-credit courses making it possible for you to take more courses all together over the course of the school year while focusing deeper on the courses you're taking for that term. You can read more about 3/3 here, and check out an example with the 2020-2021 schedule here.
Student-faculty ratio of 9:1 with 69.8% of courses having fewer than 20 students.
You can register for courses at St. Olaf College nearby as a Carleton student. This means that there's a lot of different academic subjects that are open to you, and you can even take courses in Norwegian.
Meets full demonstrated need of all accepted students, including internationals. (On a sidenote, their need based financial aid is also really exceptional.)
Offers Engineering programs in conjugation with WashU. They offer a 3-2 and a 4-2 engineering program where one receives a BA and a BS; a 4-2 where one receives a BA and a MS; and a 3-3 and a 4-3 where one receives a BA, BS, and MS.
Located in Northfield, Minnesota, so you're less than an hour from Minneapolis, a really nice city!
Because of Carleton's study abroad programs and connections with many international organizations, Carleton is well known for international relations!
Carleton publishes the outcomes of students after graduation, and the outcomes are really interesting! A lot of students attend really great graduate schools and work in many different careers. You can check the graduate schools they attend and the employment opportunities they get within each major as well!
I hope this helped! Best of luck! I truly hope all the seniors on A2C get into their top choices this winter and spring! Have a nice day!
Part I: Destiny's Main Logo is the Y-Goblet & How it's chemical cocktails reveal everything (The OXA Machine + Way Way More) (Ultra Extreme Deep Lore)
Preface: ///////// Ghost Fragment: Darkness 3 - From Toland The Shattered https://www.ishtar-collective.net/cards/ghost-fragment-darkness-3#toland-the-shattered I drive myself to the edge of madness trying to explain the truth. It's so simple. Elegant like a knife point. It explains - this is not hyperbole, this is the farthest thing from exaggeration - EVERYTHING. But you lay it out and they stare at you like you've just been exhaling dust. Maybe they're missing some underlying scaffold of truth. Maybe they are all propped on a bed of lies that must be burned away. Why does anything exist? No no no no no don't reach for that word. There's no 'reason'. That's teleology and teleology will stitch your eyelids shut. Why do we have atoms?Because atomic matter is more stable than the primordial broth. Atoms defeated the broth. That was the first war. There were two ways to be and one of them won. And everything that came next was made of atoms. Atoms made stars. Stars made galaxies. Worlds simmered down to rock and acid and in those smoking primal seas the first living molecule learned to copy itself. All of this happened by the one law, the blind law, which exists without mind or meaning.It's the simplest law but it has no worshippers here (out there, though, out there - !) HOW DO I EXPLAIN IT it's so simple WHY DON'T YOU SEE (Clue in Book Confessions Entry III to Toland mentioning The Blind Law of Atoms aka WHY CAN'T WE SEE) Book Confessions: Entry III https://www.ishtar-collective.net/entries/entry-iii#book-confessions We are all losing hope, but as long as we are still losing it, then it has not run out. Psions are said to have no sense of humor, because humor comes from the unexpected, and we are clairvoyant. Well, we were not clairvoyant enough to expect the coup, so I suppose we must be blind enough to retain a sense of humor, and I can still laugh at our predicament: the loyal retinue of the Curious Emperor, the Emperor of Joyous Excess, marooned in absolute nothingness. The Scientist: Freeborn Otzot, Psion Savanthttps://www.destinypedia.com/Cabal_Booklet Centuries after we destroyed thePsions' clairvoyantOXA Machine, word reached me that it had been rebuilt on the moon ofBrand. The Evocate-General sent her ships to bomb the moon. In my imperial forgiveness, I stopped her ships. I asked myself: who but a true genius could reconstruct the OXA? Who but a Psion who craved the OXA's power to see the unseen? Surely we could use that mind! I invited the builder to join me at a fete in her honor. She was called Otzot, freeborn Psion, and she glowed with the power of her thoughts. She said, "Is this not Calus's new Empire, an empire of achievement? Can't the Psions grow fat in thought, as you grow fat with power?" I said, you have a deal! I name you Imperial Dreamer, and you will have all that you need. All of us are stronger when we join hands in song - Cabal and Psion, Sindû and Clipse, Arkborn and all the others. If only I could have sensed her thoughts, as she so ably sensed mine. When I moved to free the indentured Psions, I threatened Otzot's superior status as a freeborn. She joined the conspiracy against me. She used the OXA to transmit messages in secret - the military's plans for their coup. Otzot must die. She can sense the hostility and focus of an assassin. Somehow you must reach her undetected. Approach her in joy and trust, as I once did. Then you have hope. https://youtu.be/GuJuRp98OuM?t=421 The end of The Insight Terminus Strike, were Otzot is being tracked by a reflection of Maya Sundaresh#12 from the Ishtar Collective on what the OXA Machine is and the information it contains. The Sundaresh Experiment 13-R https://www.ishtar-collective.net/entries/the-sundaresh-experiment-13-r#maya-sundaresh Ishtar Collective research led to places unexpected, unexplored, and in some cases unsanctioned. Esi: Is that… radiolarian fluid?! Sundaresh: Close the bulkhead, Chioma. Esi: Where did you even— Sundaresh: The excesses from Shim's siphons were just being discarded. This is better. Esi: And you're using it as, what? A propellant? Sundaresh: A coolant. If the Vex decide to simulate things in physical space such that we can experience them natively, we must understand more than just their physiology. We are too focused on the abstract and the theoretical and the simulated, love. We are scientists, yes, but Humans also make tools. Esi: That meditation sim really had an effect on you. Sundaresh: Hush. Esi: A ship built with repurposed Ishtar construction materials, integrating Vex technology almost as an afterthought. Sundaresh: You disapprove. Esi: The last time I questioned an idea like this, it ended up saving us from simulation purgatory. I would be a fool to disapprove.Sundaresh: Then come here and let's celebrate. --------------------------------------------------------------------------------------------------------------------------------------------------------- Introduction to the Chemicals and Atomic Structures that make up the Universe in Destiny (What the Light and Darkness actually are) !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!PAY SPECIAL ATTENTION TO BOLDED ITALICS!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! (Thread Theme and Inspiration for this detective work) : ) https://youtu.be/oUen2-zLDG8 Part I: The OXA Machine - OXA (definition) - indicating that a chemical compound contains oxygen, used esp to denote that a heterocycliccompound is derived from a specified compound by replacement of a carbonatom with an oxygen atom https://www.collinsdictionary.com/dictionary/english/oxa (from above in greater detail) https://en.wikipedia.org/wiki/Heterocyclic_compound Heterocyclic Compounds - A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s).[1]Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and applications of these heterocycles.[2] Examples of heterocyclic compounds include all of the nucleic acids, the majority of drugs,most biomass (cellulose and related materials), and many natural andsynthetic dyes**.** 59% of US FDA-approved drugs contain nitrogen heterocycles Although heterocyclic chemical compounds may be inorganic compounds or organic compounds, most contain at least one carbon. While atoms that are neither carbon nor hydrogen are normally referred to in organic chemistry as heteroatoms, this is usually in comparison to the all-carbon backbone. But this does not prevent a compound such as borazine (which has no carbon atoms) from being labelled "heterocyclic". IUPAC recommends the Hantzsch-Widman nomenclature for naming heterocyclic compounds. Heterocyclic compounds can be usefully classified based on their electronic structure.The saturated heterocycles behave like the acyclic derivatives. Thus, piperidine and tetrahydrofuran are conventional amines and ethers, with modified steric profiles. Therefore, the study of heterocyclic chemistry focuses especially on unsaturated derivatives, and the preponderance of work and applications involves unstrained 5- and 6-membered rings. Included are pyridine, thiophene, pyrrole, and furan. Another large class of heterocycles are fused to benzene rings, which for pyridine, thiophene, pyrrole, and furan are quinoline, benzothiophene, indole, and benzofuran, respectively. Fusion of two benzene rings gives rise to a third large family of compounds, respectively the acridine, dibenzothiophene, carbazole, and dibenzofuran. The unsaturated rings can be classified according to the participation of the heteroatom in the conjugated system, pi system. Heterocyclic Compounds Can Have up to 9 Atom Rings (I think this another clue with 9 entries in this lore book, plus the actual Nine. merely a clue that were on the right track) All of the items that Match places into the Y-Goblet in the entries of the Confessions Lore book are derivitives of a OXA-Heterocyclic Compound as explained in detail below History of Heterocyclic Chemistry The history of heterocyclic chemistry began in the 1800s, in step with the development of organic chemistry. Some noteworthy developments:[6] Piperidine https://en.wikipedia.org/wiki/Piperidine this chemical in real life is used to make PCP or angel dust the illegal drug, but since it's part of the OXA machine's actual molecular mechinations, it inferrs the examination of the way Ghost mentions how insanely aggressive Psions are in Psionic Potential mission on Mars when talking about their behavior. Much like being on that drug. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 1818: Brugnatelli isolatesalloxanfromuric acid - Alloxan https://en.wikipedia.org/wiki/Alloxan sometimes referred to as alloxan hydrate, refers to the organic compound with the formula OC(N(H)CO)2C(OH)2. It is classified as a derivative ofpyrimidine. The anhydrous derivative (OC(N(H)CO)2CO is also known as well as a dimeric derivative. These are some of the earliest known organic compounds. They also exhibit a variety of biological activities. - Pyrimidine https://en.wikipedia.org/wiki/Pyrimidine In March 2015,NASA Amesscientists reported that, for the first time, complexDNAandRNAorganic compoundsoflife, includinguracil,cytosineandthymine, have been formed in the laboratory underouter spaceconditions, using starting chemicals, such as pyrimidine, found inmeteorites. Pyrimidine, likepolycyclic aromatic hydrocarbons(PAHs), the most carbon-rich chemical found in theuniverse, may have been formed inred giantsor ininterstellar dustand gas clouds. (Interstellar dust hmmm, very very interesting eh : ) ) (Book Confesssions: Entry III) https://www.ishtar-collective.net/entries/entry-iii#book-confessions I think he feels small. Most of the universe is nothing, and he is nothing to it. This scar in our galaxy was cut long before he was born. I drew the Y-goblet in the dirt of a garden today. I used my finger, not my mind, so that no one would feel it. My faith was exterminated long before my people met the Cabal, in a way so total and vicious that I do not think a people without psionics could understand the pain. My ancestors were the strongest secret-keepers in the universe. I know this because they survived long enough to give birth to me. I don't know how they did it, because every time I look another Psion in the face I see the Y-goblet, the holy cup into which our minds were poured. What if Calus knows I'm losing my faith in him? What if I'm the poison that makes him wilt? (The Strongest Secret Keepers were the prehistoric Psions, the link to Savathun's ploy from Truth to Power) (Truth to Power: Thank You) https://www.ishtar-collective.net/entries/thank-you#book-truth-to-power "With this tribute, I shall undertake a mighty work. A real humdinger of a scheme. I'm going to refinance my entire existence. I'm going to move from an existential economy based on the accumulation of violence to an existential economy based on the accumulation of secrets and the tribute of failing-to-understand-me. I shall name this tribute of failing-to-understand IMBARU, for it shall be as formless as the mist." Imbaru - means enchantment / Dul - a little town called Josefuv Dul in the Czech Republic Dul means loop Josefuv is czech for Josef which means may God increase God Loop Josefuv Dul aka Trostland https://en.wikipedia.org/wiki/Josef%C5%AFv_D%C5%AFl_(Jablonec_nad_Nisou_District)) http://josefuvdul.eu/wp-content/uploads/MG_5002-1024x683.jpg http://josefuvdul.eu/ History Beginning in the year 1690, Maximilian II Emanuel populated the area with German immigrants. In 1701, the city of Karlsberg was founded by the Desfours family, who were known for the estates of Groß Rohosetz and Morchenstern. The new village was known for producing glass and crystal products.[4]#cite_note-josefuvdul-4) Karlsberg was divided into Untermaxdorf, Karlsberg and Josefsthal in 1827. Fifty years later Untermaxdorf and Antoniwald were incorporated. The Munich Agreement permitted Nazi Germany's Adolf Hitler to annex the area in 1938 into what he called the Sudetenland. Shortly thereafter Karlsberg was dissolved becoming Obermaxdorf and Antoniwald. Josefsthal and Untermaxdorf formed a new community named Iserwald. Following World War II, in 1945, the town returned to Czechoslovakia and the German inhabitants were expelled under the terms of Beneš decrees. Church The Josefův Důl church was built between 1862 and 1865 in a neo-gothic style. Its construction was partially funded by a lottery and 4000 gold pieces were collected. The ceremonial laying of the foundation stone was held in September 1862. The church tower is 45 metres (148 ft) high, the interior fittings house three valuable altar paintings by Wilhelm Kandler. https://en.wikipedia.org/wiki/Josef%C5%AFv_D%C5%AFl_(Jablonec_nad_Nisou_District)#/media/File:Kirche_Josefuv_Dul.jpg#/media/File:Kirche_Josefuv_Dul.jpg) Etymology: Joseph's valley,[1]#citenote-1) Joseph's Mine[[2]](https://en.wikipedia.org/wiki/Josef%C5%AFv_D%C5%AFl(Jablonec_nad_Nisou_District)#cite_note-2)Motto(s): The gateway to Jizera Mountains https://upload.wikimedia.org/wikipedia/commons/1/17/Josefuv_Dul_JN_CZ_CD_Class_810_in_1994.jpg Josefův Důl railway station https://en.wikipedia.org/wiki/Josef%C5%AFv_D%C5%AFl_dam Jusefuv Dul waterway dam https://en.wikipedia.org/wiki/Josef%C5%AFv_D%C5%AFl_dam#/media/File:Talsperre_Josefsthal_1.jpg hmmmm looks extremely familiar eh..... ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 1832: Dobereiner produces furfural (a furan) by treating starch with sulfuric acid ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 1834: Runge obtains pyrrole ("fiery oil") by dry distillation of bones Pyrrole https://en.wikipedia.org/wiki/Pyrrole History Pyrrole was first detected by F. F. Runge in 1834, as a constituent of coal tar.[6] In 1857, it was isolated from the pyrolysate of bone. Its name comes from the Greek pyrrhos (πυρρός, “reddish, fiery”), from the reaction used to detect it—the red color that it imparts to wood when moistened with hydrochloric acid Reactions and reactivity Due to itsaromatic character, pyrrole is difficult tohydrogenate, does not easily react as a diene in Diels–Alder reactions, and does not undergo usual olefin reactions. Its reactivity is similar to that of benzene and aniline, in that it is easy to alkylate and acylate. Under acidic conditions, pyrrolespolymerizeeasily, and thus manyelectrophilicreagents that are used in benzene chemistry are not applicable to pyrroles. In contrast, substituted pyrroles (includingprotectedpyrroles) have been used in a broad range of transformations (Book Confessions: Entry III) https://www.ishtar-collective.net/entries/entry-iii#book-confessions By the mind of Match. Upon the Leviathan, resigned to its course. Today I fill the Y-goblet with powdered bone, so that my ancestors may dry their ink. My every thought and purpose for my Emperor, Calus, once sovereign. (Book Dust: The Bone) https://www.ishtar-collective.net/entries/the-bone#book-dust Ikora Rey makes it fly away. "You weren't after that bone. It was after you. Did you make a wish, Lavinia? Did you ask to know about the Nine?" She tries to explain that she didn't, that she only wanted to track the bone back to its source (Venus, hopefully), and to learn why the Nine needed the Ahamkara. "Why do you think the Nine needed Ahamkara?" Ikora asks, dangerously. "To make wishes," Lavinia pants. "Xûr didn't appear in the Tower until the end of the Great Ahamkara Hunt. Whatever they used to get from the Ahamkara..." She leaves it unsaid: maybe the Nine are now getting it from Guardians. Ikora rubs her brow. "I can't stop you. But if you keep looking, I can't protect you from the consequences." "Help me!" Lavinia begs. "There's something here! Something that connects everything, the Trials, and the Ahamkara, and the Guardians, and the Nine. There are things the Consensus knows about Ghaul's attack, things they haven't told us—" (Book Dust: The Gate) https://www.ishtar-collective.net/entries/the-gate#book-dust Lavinia swears and beats her suited fist against her helmet. She's trapped in Cocytus! The last time the Awoken trapped anyone here, those poor souls went utterly insane. The doomed crew of the Dead Orbit scout ship Sophia called this place A113, an innocent catalogue number; they had no idea that the gates aboard—once a Golden Age experiment—had been captured by the Hive deity Crota. Those gates consumed them all. Now Crota is gone, and Lavinia has gambled everything that the portals have fallen into other hands. Ahamkara make the unreal real—Calus's ship is surrounded by a halo of unreal dark matter, like a ring of probing hands, Guardians can manipulate reality itself—there is a pattern here, a story, and it leads to Cocytus, to what these gates might do. "Logs." She pages frantically through the observations left by the Awoken sentries once stationed here. Cocytus was abandoned when the Red Legion attacked, all its defenses scavenged to reinforce Vesta. "What came out of the gate? What did you see?" //EVENT 1 TIME 00:00:00 Portal 3 emitted a hydrogen nucleus. Over 72 hours, the emissions developed from diatomic hydrogen to nitrogen, carbon, oxygen, water, and simple organic molecules. At the 80-hour mark, a pellet of thick black hydrocarbon tar. Until 82:34:15, the gate emitted tar containing complex monomers and polymers— "Come on!" Lavinia barks, paging ahead. "Come on, damn you, give me something real! Give me the Nine!" //EVENT 1 TIME 524:03:11 Portal 3 emitted a living organism. Death was immediate. Autopsy team reports a spherical body, radius one point one meters, surfaced in hydrocarbon tar. Deep, evenly spaced "throats" converged on a central cavity perhaps intended to serve as lung and stomach. The body consists of an undifferentiated tissue of primitive cells. A basic spasm reflex forces air down the throats. Without enzymes to catalyze metabolism, the organism could not survive. Cell death occurred instantaneously throughout the mass. There were no provisions for self-repair or reproduction. Lavinia reads this again, horrified and fascinated. Something on the far side of the gate is learning to assemble atoms, molecules, even haphazard life... something from a world of darkness and dust, probing its way into our structured existence, trying to cobble together a message, an emissary, a body... The Nine are on the far side of this gate. She's sure of it. She's found them. A113 isn't just a Pixar meme Nihonium https://en.wikipedia.org/wiki/Nihonium Nihonium is a syntheticchemical element with the symbol) Nh and atomic number113. It is extremely radioactive; its most stable known isotope, nihonium-286, has ahalf-lifeof about 10 seconds. In the periodic table, nihonium is atransactinide element in the p-block. It is a member of period 7 and group 13 (boron group). Nihonium was first reported to have been created in 2003 by a Russian–American collaboration at theJoint Institute for Nuclear Research(JINR) inDubna, Russia, and in 2004 by a team of Japanese scientists at Riken in Wakō, Japan. The confirmation of their claims in the ensuing years involved independent teams of scientists working in the United States, Germany, Sweden, and China, as well as the original claimants in Russia and Japan. In 2015, the IUPAC/IUPAP Joint Working Party recognised the element and assigned the priority of the discovery and naming rights for the element to Riken, as it judged that they had demonstrated that they had observed element 113 before the JINR team did so. The Riken team suggested the name nihoniumin 2016, which was approved in the same year. The name comes from the common Japanese name for Japan (日本 nihon). Very little is known about nihonium, as it has only been made in very small amounts that decay away within seconds. The anomalously long lives of some superheavy nuclides, including some nihonium isotopes, are explained by the "island of stability" theory.Experiments support the theory, with the half-lives of the confirmed nihonium isotopes increasing from milliseconds to seconds asneutronsare added and the island is approached. Nihonium has been calculated to have similar properties to its homologues boron, aluminium, gallium, indium, and thallium. All but boron are post-transition metals, and nihonium is expected to be a post-transition metal as well. It should also show several major differences from them; for example, nihonium should be more stable in the +1 oxidation state than the +3 state, like thallium, but in the +1 state nihonium should behave more likesilverandastatine than thallium. Preliminary experiments in 2017 showed that elemental nihonium is not veryvolatile); its chemistry remains largely unexplored. The Aphelion are made of Nihonium when they attacked the Awoken on Bamberga (Book The Dreaming City: Bamberga) https://www.ishtar-collective.net/entries/bamberga#aphelion SUMMARY OF SBU APHELION INCIDENTS FOLLOWS BELOW. *** EVENT 2PAL-A :: OTDR-4-REL *** INFORMATION RECEIVED APR 09-18T02:29:45+00:00 FROM PALADIN NOLG, CONSIDERED SOBER, DEPENDABLE, NOT OF FANTASY. NOLG REPORTED "A GLOWING CREATURE" ON EXT OF HIS SHIP "RETRIBUTION" MOMENTS BEFORE ROUTINE NLS JUMP. "RETRIBUTION" FDR SHOWED RAD SPIKE (5 SIGMA) ON TEPC, CPDS, AND RAM. CPD SHOWED NO EFFECT. ON RECOMMENDATION OF K WADJ, NOLG WAS QUARANTINED UNDER TECHEUN SUPERVISION FOR 1 MONTH. "RETRIBUTION" DECOMMISSIONED, SET ADRIFT BEYOND REEF. A SAR FLEET FOUND THAT THE AMESTRIS WAS UNSAFE TO BOARD DUE TO RADIOACTIVE SURFACE CONTAMINATION. SAR DEPLOYED MULTIPLE CROW DRONES FOR INTERIOR SURVEY. NO EVIDENCE OF HULL BREACH WAS FOUND. NO EVIDENCE OF MALTECH DETONATION WAS FOUND. NO EVIDENCE OF HOSTILE ALIEN INTERFERENCE WAS FOUND. NO EVIDENCE OF INTERNAL SABOTAGE WAS FOUND. NO SURVIVORS WERE FOUND. AMESTRIS ABANDONED, SET ADRIFT BEYOND REEF. Important Cutscenes Below to connect this stuff: https://youtu.be/5HmV_mKzWmo https://youtu.be/2ehZORTn3MM (Sjur Eido, the only Awoken to survive an attack from The Aphelion) The Nine saved Sjur Eido by absorbing all the surrounding Helium-4 around her, since this is what the actual "Darkness" is has she explored Anthenaeum World X Aphelion (definition) - (astronomy) The point in the ellipticalorbit of a planet, comet, etc., where it is farthest from the Sun. https://en.wiktionary.org/wiki/aphelion
A conjugated system is a system of connected p-orbitals with delocalized electrons in compounds with alternating single and multiple bonds, which in general may lower the overall energy of the … 2.4 Conjugated Pi Bond Systems - Chemistry LibreTexts A conjugated system requires that there is a continuous array of "p" orbitals that can align to produce a π bonding overlap along the whole system. If a position in the chain does not provide a "p" orbital or if geometry prevents the correct alignment, then the conjugation is interupted (broken) and therefore lost at that point. Chemistry A chemical compound that has been formed by the joining of two or more compounds. [Latin coniugāre , coniugāt- , to join together : com- , com- + iugāre , to join (from iugum , yoke ; see yeug- in Indo-European roots ).] Three Types of Conjugates. (1) A conjugate refers to a compound formed by the joining of two or more chemical compounds. (2) In the Bronsted-Lowry theory of acids and bases, the term conjugate refers to an acid and base that differ from each other by a proton. conjugated. ( ˈkɒndʒʊˌɡeɪtɪd) adj. 1. (Chemistry) chem. a. (of a molecule, compound, or substance) containing two or more double bonds alternating with single bonds. b. (of a double bond) separated from another double bond by one single bond. 2. Conjugation occurs when p orbital on three or more adjacent atoms can overlap Conjugation tends to stabilize molecules. Allylic carbocations are a common conjugated system. The positive charge of a carbocation is contained in a P orbital of a sp2 hybridized carbon. This allows for overlap with double bonds. Conjugated definition is - formed by the union of two compounds or united with another compound. How to use conjugated in a sentence. A diene is a molecule that has two double bonds. If the molecule is also a hydrocarbon, it is called an alkadiene. When the double bonds are separated from each other by two or more single bonds, they are called isolated double bonds. Isolated double bonds undergo normal alkene reactions, revealing that no interaction occurs between them. Chemistry. of or noting two or more liquids in equilibrium with one another. (of an acid and a base) related by the loss or gain of a proton: NH 3 is a base conjugate to NH 4 +. NH 4 + is an acid conjugate to NH 3. Also con·ju·gat·ed. (of an organic compound) containing two or more double bonds each separated from the other by a single bond. Conjugate Acid Definition. Conjugate acids and bases are Bronsted-Lowry acid and base pairs, determined by which species gains or loses a proton. When a base dissolves in water, the species that gains a hydrogen (proton) is the base's conjugate acid. Acid + Base → Conjugate Base + Conjugate Acid.
This video is unavailable. Watch Queue Queue. Watch Queue Video shows what conjugate acid-base pair means. two molecular entities, one of which (the acid) can readily transfer a proton to the other (the base). Conjugate acid-base pair Meaning. How to ... Strong acids almost completely dissociate in water. They produce a weak conjugate base. Weak in this case means that the base produced rarely reacts with t... UV -vis spectroscopy in hindi for msc 3rd sem students chemistry "Chem with Fun Man, Can have fun, man!" If you would like to have more chemistry fun, and learn about cool science, subscribe to this channel to view the upcoming videos. Thanks for watching and ... In the Brønsted-Lowry definition of acids and bases, a conjugate acid-base pair consists of two substances that differ only by the presence of a proton (H⁺).... Kelly Greene Alice Chan Neelofer Karimyar. For the Love of Physics - Walter Lewin - May 16, 2011 - Duration: 1:01:26. Lectures by Walter Lewin. ACS interviews Bioconjugate Chemistry's Editor-in-Chief Claude F. Meares and Senior Editor Peter Senter at UC Davis during the on-campus celebration of the journal's 20th Anniversary. Watch as ...
