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Privacy coins. I have always been into coins that protect privacy online. With bitcoin (and most other coins), since the blockchain is public, it is relatively easy to figure out who’s got what. And if you send someone coins, they can look up your address and see how much more you have. If you wrote someone a check, would you want them to be able to look up how much you have in your account? I think not!

Zcash ($ZEC) is a prominent example and the zk-SNARKs used for privacy are quite clever, but privacy isn’t required by default, and a lot of their transactions aren’t kept private (well over 90% to the best of my understanding). In my opinion, Monero ($XMR) is much better. Monero uses ring signatures to scramble lots of transactions together, making it virtually impossible to figure out who is sending how much where. I’ve heard it explained as “you’ll never be able to figure out who farted in an elevator full of 30 people.”

XMR seems somewhat undervalued, as it was well over $350 back in 2017, but has only slowly crept back up to $225 or so after trading for years under $100. It is a good mining coin. They used to constantly try to avoid ASICs and stay a GPU coin by changing their algo every 6-12 months, but haven’t had too much trouble since switching to the CPU-favoring algorithm RandomX.

There are several minor players based on XMR’s protocol, like Wownero ($WOW), a funny privacy-focused meme project similar to Dogecoin in its branding. This is a smaller cap coin and is something of a test net for Monero. There are a few others like Bitcoin Private out there and PirateChain ($ARRR), but I’m not so informed about them.

Cardano ($ADA) — the new Coinbase Pro listing. This project has been on the books for years and has a substantial market cap, but really hasn’t done a whole lot. I’m not particularly enthusiastic about it, but Coinbase Pro listings generally pump a bit in price and are often work buying elsewhere before Coinbase Pro starts trading (3/18 in this case).

Hydra — Don’t know a ton about it, but KuCoin is offering insane ~180% annual interest yields on this coin through their flexible “soft staking” “Pool-X.” 10 are required at a minimum (~$180 worth) but this is quite the interest rate!

Saving gas — Gas prices these days are no joke, often costing you $30 or even more for relatively simple transactions on the Ethereum blockchain. While long-term solutions are currently being discussed, these fees are killer right now! If you want to save on your Eth gas fees, check out GasNow.org to see what times of the day throughout the week have the lowest average prices.

• Coinbase Pro is adding support for Sushi, MATIC, and SKL. They will go live for trading in a few days, once enough people deposit these coins on the exchange for them to have enough on-hand for trading (liquidity). These coins could pump significantly after trading opens, so buying them elsewhere beforehand could be a good move. However, all three are near all-time highs. Sushi was kind of a scam but has started to recover its reputation (it’s a token for SushiSwap, a decentralized DeFi exchange). The other two are ERC-20 tokens. Sushi can be bought on KuCoin, and the others on Uniswap, though MATIC is on Binance.US.
• Ethereum has committed to EIP-1559 in July. This is a protocol change (hard fork). They are going to stop paying miners high gas fees, and instead start burning them to help deflate the currency. They will allow for miner “tips” to be added to transactions when submitted. This may not reduce fees, and could leave many miners seeking greener pastures, which could reduce security and make the network more vulnerable to 51% attack. Or, it may succeed. Who knows?
• B20 is continuing to blow up and has nearly doubled since I first wrote about it. It’s a tokenized NFT exhibit (like an art museum).

Ahh, PCR, Kary Mullis’s Nobel Prize-worthy, LSD-inspired copy machine for DNA. He dreamed it up while driving down the Pacific Coast Highway, and now it’s used for everything from detecting SARS-CoV-2 to crime scene investigations to sequencing dinosaur DNA. Here are some tips I’ve picked up over the years:

• Set up a 50 µL reaction, then split it into two 25 µL reactions. Run one at T_m, the other at T_m – 5 ºC.
• Fool around with different DMSO concentrations. I have lately taken to using sulfolane (1-3%), an alternative to DMSO that may work better. Occasionally, sulfolane-DMSO mixtures have helped.
• Play around with primer designs. Use a G or C at the 3′ end when possible to anchor it down (the “GC clamp”). Use an online tool to check for pesky self-complementarity, and tweak the primers to keep the T_m values close together.
• Even if you don’t have fancy hot-start reagents, you can still manually hot-start a few PCR reactions at a time by adding the polymerase once the samples are up to temperature for the initial 98 ºC denaturation step. This is easier if you are adding the polymerase as a 5 or 10 µL solution in 1x buffer. (Hot start prevents annealing to off-target sequences in the important initial round of amplification. It also can improve yields and prevent primer dimerization).
• With the commonly-used Phusion high-fidelity polymerase, GC buffer works far better than HF buffer in my experience, despite the manufacturer’s recommendations to use HF first and GC only for difficult templates. Note that the error rate is twice as high for GC (9.5 x 10^-7 versus 4.4 x 10^-7 — a big relative change of 2.2-fold, but still small when the absolute rate is considered). The yield is much higher with GC buffer, and I sometimes don’t even get bands using HF..

A team led by Drs. Louis Falo and Andrea Gambotto at the University of Pittsburgh have reported a COVID-19 vaccine that is delivered on small patches with 100 soft plastic needles. The vaccine was generated using a fragment of the spike protein that coronaviruses use to bind receptors to get into cells. After the mice received the vaccine, serum from them was diluted 100-fold, and incubated on a plate coated in the COVID-19 spike protein fragment. The serum successfully detected the protein when the mice had been immunized for ≥ 2 weeks (it detected the protein on an ELISA plate coated with it). However, the following questions remain unclear:

• Are the antibodies generated using this vaccine actually capable of neutralizing the virus and preventing infection?
• Will a similar vaccine produce a useful antibody response in humans?

The COVID-19 work in this paper was tacked on at the end. The primary focus of this paper was on MERS vaccines, however. You may recall that MERS is another very dangerous coronavirus (34.4% case fatality rate). It hasn’t spread particularly far outside the Middle East, save for a 2015 outbreak in South Korea, and only 2,513 confirmed cases have been reported. However, the MERS virus still remains endemic in Saudi Arabia. There are long-term MERS experiments reported in this work (including a 55-week experiment showing the durability of the response to the vaccine), suggesting that this research has been underway for quite some time. It is likely that the work was begun when back when the MERS threat loomed large, prompting significant interest and funding in the work. Unfortunately, we tend to lose interest and stop funding important work when it’s not plastered all over the headlines we read, so the MERS work likely lost steam until the COVID-19 “money experiment” was tacked on to the end of this manuscript. In other news, we are still waiting for a Zika virus vaccine/treatment (though it will take several years even with lots of interest/money thrown at the problem)…

The researchers should be commended for their great speed in delivering these promising early results. The sequence of the COVID-19 spike protein has not been known for very long, and they were able to clone the gene into a plasmid (with and without an “RS09” peptide adjuvant tacked on), express and purify the protein from mammalian cells, characterize the protein, fabricate the vaccine, test it in mice, and run the ELISA. This was all done with a “skeleton crew” remaining at the University of Pittsburgh, which is almost entirely shut down save for a few research projects deemed to be essential.

The vaccine is certainly on an interesting platform. Dr. Falo’s start-up company, SkinJect, has been developing these patches for quite some time. The patch-based vaccine supposedly doesn’t hurt that much compared to metal needles. It doesn’t need to be refrigerated, is easy to manufacture quickly at a large scale (a small academic laboratory can put together a few hundred in short order), works after you sterilize it with gamma irradiation, and is easy to apply anywhere (you can immunize yourself). Based on the MERS data, the SkinJect platform raises a better antibody response than traditional injected vaccines, likely the intradermal delivery with a bit of inflammation provoked by the needles primes the immune system to respond effectively. It remains unclear how the COVID-19 patch-based would compare to a traditional injectable.

Ths was a impressive proof-of-concept rolled out in record time, but no one knows if the vaccine is actually effective, or if it will translate to humans. Still, these investigators are to be commended for their continued hard work and ingenuity at this difficult time.

Link to the paper (free of charge):
Kim, E. et al. “Microneedle array delivered recombinant coronavirus vaccines:
Immunogenicity and rapid translational development.” EBioMedicine (2020), https://doi.org/10.1016/j.ebiom.2020.102743.