Xenobots, tiny living machines, can duplicate themselves.
Strange and complex behavior of frog cell blobs
A xenobot “parent,” shaped like a hungry Pac-Man (shown in red false color), created an “offspring” xenobot (green sphere) by gathering loose frog cells in its opening.
Tiny “living machines” made of frog cells can make copies of themselves. This newly discovered renewal mechanism may help create self-renewing biological machines.
According to Kirstin Petersen, an electrical and computer engineer at Cornell University who studies groups of robots, “this is an extremely exciting breakthrough.” She says self-replicating robots are a big step toward human-free systems.
Researchers described the behavior of xenobots earlier this year (SN: 3/31/21). Small clumps of skin stem cells from frog embryos knitted themselves into small spheres and started moving. Cilia, or cellular extensions, powered the xenobots around their lab dishes.
The findings are published in the Proceedings of the National Academy of Sciences on Dec. 7. The xenobots can gather loose frog cells into spheres, which then form xenobots.
The researchers call this type of movement-induced reproduction kinematic self-replication. The study's coauthor, Douglas Blackiston of Tufts University in Medford, Massachusetts, and Harvard University, says this is typical. For example, sexual reproduction requires parental sperm and egg cells. Sometimes cells split or budded off from a parent.
“This is unique,” Blackiston says. These xenobots “find loose parts in the environment and cobble them together.” This second generation of xenobots can move like their parents, Blackiston says.
The researchers discovered that spheroid xenobots could only produce one more generation before dying out. The original xenobots' shape was predicted by an artificial intelligence program, allowing for four generations of replication.
A C shape, like an openmouthed Pac-Man, was predicted to be a more efficient progenitor. When improved xenobots were let loose in a dish, they began scooping up loose cells into their gaping “mouths,” forming more sphere-shaped bots (see image below). As many as 50 cells clumped together in the opening of a parent to form a mobile offspring. A xenobot is made up of 4,000–6,000 frog cells.
Petersen likes the Xenobots' small size. “The fact that they were able to do this at such a small scale just makes it even better,” she says. Miniature xenobots could sculpt tissues for implantation or deliver therapeutics inside the body.
Beyond the xenobots' potential jobs, the research advances an important science, says study coauthor and Tufts developmental biologist Michael Levin. The science of anticipating and controlling the outcomes of complex systems, he says.
“No one could have predicted this,” Levin says. “They regularly surprise us.” Researchers can use xenobots to test the unexpected. “This is about advancing the science of being less surprised,” Levin says.
More on Science
Bob Service
3 years ago
Did volcanic 'glasses' play a role in igniting early life?
Quenched lava may have aided in the formation of long RNA strands required by primitive life.
It took a long time for life to emerge. Microbes were present 3.7 billion years ago, just a few hundred million years after the 4.5-billion-year-old Earth had cooled enough to sustain biochemistry, according to fossils, and many scientists believe RNA was the genetic material for these first species. RNA, while not as complicated as DNA, would be difficult to forge into the lengthy strands required to transmit genetic information, raising the question of how it may have originated spontaneously.
Researchers may now have a solution. They demonstrate how basaltic glasses assist individual RNA letters, also known as nucleoside triphosphates, join into strands up to 200 letters long in lab studies. The glasses are formed when lava is quenched in air or water, or when melted rock generated by asteroid strikes cools rapidly, and they would have been plentiful in the early Earth's fire and brimstone.
The outcome has caused a schism among top origin-of-life scholars. "This appears to be a great story that finally explains how nucleoside triphosphates react with each other to create RNA strands," says Thomas Carell, a scientist at Munich's Ludwig Maximilians University. However, Harvard University's Jack Szostak, an RNA expert, says he won't believe the results until the study team thoroughly describes the RNA strands.
Researchers interested in the origins of life like the idea of a primordial "RNA universe" since the molecule can perform two different functions that are essential for life. It's made up of four chemical letters, just like DNA, and can carry genetic information. RNA, like proteins, can catalyze chemical reactions that are necessary for life.
However, RNA can cause headaches. No one has yet discovered a set of plausible primordial conditions that would cause hundreds of RNA letters—each of which is a complicated molecule—to join together into strands long enough to support the intricate chemistry required to kick-start evolution.
Basaltic glasses may have played a role, according to Stephen Mojzsis, a geologist at the University of Colorado, Boulder. They're high in metals like magnesium and iron, which help to trigger a variety of chemical reactions. "Basaltic glass was omnipresent on Earth at the time," he adds.
He provided the Foundation for Applied Molecular Evolution samples of five different basalt glasses. Each sample was ground into a fine powder, sanitized, and combined with a solution of nucleoside triphosphates by molecular biologist Elisa Biondi and her colleagues. The RNA letters were unable to link up without the presence of glass powder. However, when the molecules were mixed with the glass particles, they formed long strands of hundreds of letters, according to the researchers, who published their findings in Astrobiology this week. There was no need for heat or light. Biondi explains, "All we had to do was wait." After only a day, little RNA strands produced, yet the strands continued to grow for months. Jan Paek, a molecular biologist at Firebird Biomolecular Sciences, says, "The beauty of this approach is its simplicity." "Mix the components together, wait a few days, and look for RNA."
Nonetheless, the findings pose a slew of problems. One of the questions is how nucleoside triphosphates came to be in the first place. Recent study by Biondi's colleague Steven Benner suggests that the same basaltic glasses may have aided in the creation and stabilization of individual RNA letters.
The form of the lengthy RNA strands, according to Szostak, is a significant challenge. Enzymes in modern cells ensure that most RNAs form long linear chains. RNA letters, on the other hand, can bind in complicated branching sequences. Szostak wants the researchers to reveal what kind of RNA was produced by the basaltic glasses. "It irritates me that the authors made an intriguing initial finding but then chose to follow the hype rather than the research," Szostak says.
Biondi acknowledges that her team's experiment almost probably results in some RNA branching. She does acknowledge, however, that some branched RNAs are seen in species today, and that analogous structures may have existed before the origin of life. Other studies carried out by the study also confirmed the presence of lengthy strands with connections, indicating that they are most likely linear. "It's a healthy argument," says Dieter Braun, a Ludwig Maximilian University origin-of-life chemist. "It will set off the next series of tests."
Sam Warain
3 years ago
Sam Altman, CEO of Open AI, foresees the next trillion-dollar AI company
“I think if I had time to do something else, I would be so excited to go after this company right now.”
Sam Altman, CEO of Open AI, recently discussed AI's present and future.
Open AI is important. They're creating the cyberpunk and sci-fi worlds.
They use the most advanced algorithms and data sets.
GPT-3...sound familiar? Open AI built most copyrighting software. Peppertype, Jasper AI, Rytr. If you've used any, you'll be shocked by the quality.
Open AI isn't only GPT-3. They created DallE-2 and Whisper (a speech recognition software released last week).
What will they do next? What's the next great chance?
Sam Altman, CEO of Open AI, recently gave a lecture about the next trillion-dollar AI opportunity.
Who is the organization behind Open AI?
Open AI first. If you know, skip it.
Open AI is one of the earliest private AI startups. Elon Musk, Greg Brockman, and Rebekah Mercer established OpenAI in December 2015.
OpenAI has helped its citizens and AI since its birth.
They have scary-good algorithms.
Their GPT-3 natural language processing program is excellent.
The algorithm's exponential growth is astounding. GPT-2 came out in November 2019. May 2020 brought GPT-3.
Massive computation and datasets improved the technique in just a year. New York Times said GPT-3 could write like a human.
Same for Dall-E. Dall-E 2 was announced in April 2022. Dall-E 2 won a Colorado art contest.
Open AI's algorithms challenge jobs we thought required human innovation.
So what does Sam Altman think?
The Present Situation and AI's Limitations
During the interview, Sam states that we are still at the tip of the iceberg.
So I think so far, we’ve been in the realm where you can do an incredible copywriting business or you can do an education service or whatever. But I don’t think we’ve yet seen the people go after the trillion dollar take on Google.
He's right that AI can't generate net new human knowledge. It can train and synthesize vast amounts of knowledge, but it simply reproduces human work.
“It’s not going to cure cancer. It’s not going to add to the sum total of human scientific knowledge.”
But the key word is yet.
And that is what I think will turn out to be wrong that most surprises the current experts in the field.
Reinforcing his point that massive innovations are yet to come.
But where?
The Next $1 Trillion AI Company
Sam predicts a bio or genomic breakthrough.
There’s been some promising work in genomics, but stuff on a bench top hasn’t really impacted it. I think that’s going to change. And I think this is one of these areas where there will be these new $100 billion to $1 trillion companies started, and those areas are rare.
Avoid human trials since they take time. Bio-materials or simulators are suitable beginning points.
AI may have a breakthrough. DeepMind, an OpenAI competitor, has developed AlphaFold to predict protein 3D structures.
It could change how we see proteins and their function. AlphaFold could provide fresh understanding into how proteins work and diseases originate by revealing their structure. This could lead to Alzheimer's and cancer treatments. AlphaFold could speed up medication development by revealing how proteins interact with medicines.
Deep Mind offered 200 million protein structures for scientists to download (including sustainability, food insecurity, and neglected diseases).
Being in AI for 4+ years, I'm amazed at the progress. We're past the hype cycle, as evidenced by the collapse of AI startups like C3 AI, and have entered a productive phase.
We'll see innovative enterprises that could replace Google and other trillion-dollar companies.
What happens after AI adoption is scary and unpredictable. How will AGI (Artificial General Intelligence) affect us? Highly autonomous systems that exceed humans at valuable work (Open AI)
My guess is that the things that we’ll have to figure out are how we think about fairly distributing wealth, access to AGI systems, which will be the commodity of the realm, and governance, how we collectively decide what they can do, what they don’t do, things like that. And I think figuring out the answer to those questions is going to just be huge. — Sam Altman CEO
Nojus Tumenas
3 years ago
NASA: Strange Betelgeuse Explosion Just Took Place
Orion's red supergiant Betelgeuse erupted. This is astronomers' most magnificent occurrence.
Betelgeuse, a supergiant star in Orion, garnered attention in 2019 for its peculiar appearance. It continued to dim in 2020.
The star was previously thought to explode as a supernova. Studying the event has revealed what happened to Betelgeuse since it happened.
Astronomers saw that the star released a large amount of material, causing it to lose a section of its surface.
They have never seen anything like this and are unsure what caused the star to release so much material.
According to Harvard-Smithsonian Center for Astrophysics astrophysicist Andrea Dupre, astronomers' data reveals an unexplained mystery.
They say it's a new technique to examine star evolution. The James Webb telescope revealed the star's surface features.
Corona flares are stellar mass ejections. These eruptions change the Sun's outer atmosphere.
This could affect power grids and satellite communications if it hits Earth.
Betelgeuse's flare ejected four times more material than the Sun's corona flare.
Astronomers have monitored star rhythms for 50 years. They've seen its dimming and brightening cycle start, stop, and repeat.
Monitoring Betelgeuse's pulse revealed the eruption's power.
Dupre believes the star's convection cells are still amplifying the blast's effects, comparing it to an imbalanced washing machine tub.
The star's outer layer has returned to normal, Hubble data shows. The photosphere slowly rebuilds its springy surface.
Dupre noted the star's unusual behavior. For instance, it’s causing its interior to bounce.
This suggests that the mass ejections that caused the star's surface to lose mass were two separate processes.
Researchers hope to better understand star mass ejection with the James Webb Space Telescope.
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Hunter Walk
2 years ago
Is it bad of me to want our portfolio companies to generate greater returns for outside investors than they did for us as venture capitalists?
Wishing for Lasting Companies, Not Penny Stocks or Goodwill Write-Downs
Get me a NASCAR-style company-logoed cremation urn (notice to the executor of my will, theres gonna be a lot of weird requests). I believe in working on projects that would be on your tombstone. As the Homebrew logo is tattooed on my shoulder, expanding the portfolio to my posthumous commemoration is easy. But this isn't an IRR victory lap; it's a hope that the firms we worked for would last beyond my lifetime.
![a little boy planting a dollar bill in the ground and pouring a watering can out on it, digital art [DALL-E]](https://storage.googleapis.com/int3grity/posts/V62hkReDx56S/images/vMwzqrYeXaYnUIMXAdTY9)
Venture investors too often take credit or distance themselves from startups based on circumstances. Successful companies tell stories of crucial introductions, strategy conversations, and other value. Defeats Even whether our term involves Board service or systematic ethical violations, I'm just a little investment, so there's not much I can do. Since I'm guilty, I'm tossing stones from within the glass home (although we try to own our decisions through the lifecycle).
Post-exit company trajectories are usually unconfounded. Off the cap table, no longer a shareholder (or a diminishing one as you sell off/distribute), eventually leaving the Board. You can cheer for the squad or forget about it, but you've freed the corporation and it's back to portfolio work.
As I look at the downward track of most SPACs and other tarnished IPOs from the last few years, I wonder how I would feel if those were my legacy. Is my job done? Yes. When investing in a business, the odds are against it surviving, let alone thriving and being able to find sunlight. SPAC sponsors, institutional buyers, retail investments. Free trade in an open market is their right. Risking and losing capital is the system working! But
We were lead or co-lead investors in our first three funds, but as additional VCs joined the company, we were pushed down the cap table. Voting your shares rarely matters; supporting the firm when they need it does. Being valuable, consistent, and helping the company improve builds trust with the founders.
I hope every startup we sponsor becomes a successful public company before, during, and after we benefit. My perspective of American capitalism. Well, a stock ticker has a lot of garbage, and I support all types of regulation simplification (in addition to being a person investor in the Long-Term Stock Exchange). Yet being owned by a large group of investors and making actual gains for them is great. Likewise does seeing someone you met when they were just starting out become a public company CEO without losing their voice, leadership, or beliefs.
I'm just thinking about what we can do from the start to realize value from our investments and build companies with bright futures. Maybe seed venture financing shouldn't impact those outcomes, but I'm not comfortable giving up that obligation.
Theresa W. Carey
3 years ago
How Payment for Order Flow (PFOF) Works
What is PFOF?
PFOF is a brokerage firm's compensation for directing orders to different parties for trade execution. The brokerage firm receives fractions of a penny per share for directing the order to a market maker.
Each optionable stock could have thousands of contracts, so market makers dominate options trades. Order flow payments average less than $0.50 per option contract.
Order Flow Payments (PFOF) Explained
The proliferation of exchanges and electronic communication networks has complicated equity and options trading (ECNs) Ironically, Bernard Madoff, the Ponzi schemer, pioneered pay-for-order-flow.
In a December 2000 study on PFOF, the SEC said, "Payment for order flow is a method of transferring trading profits from market making to brokers who route customer orders to specialists for execution."
Given the complexity of trading thousands of stocks on multiple exchanges, market making has grown. Market makers are large firms that specialize in a set of stocks and options, maintaining an inventory of shares and contracts for buyers and sellers. Market makers are paid the bid-ask spread. Spreads have narrowed since 2001, when exchanges switched to decimals. A market maker's ability to play both sides of trades is key to profitability.
Benefits, requirements
A broker receives fees from a third party for order flow, sometimes without a client's knowledge. This invites conflicts of interest and criticism. Regulation NMS from 2005 requires brokers to disclose their policies and financial relationships with market makers.
Your broker must tell you if it's paid to send your orders to specific parties. This must be done at account opening and annually. The firm must disclose whether it participates in payment-for-order-flow and, upon request, every paid order. Brokerage clients can request payment data on specific transactions, but the response takes weeks.
Order flow payments save money. Smaller brokerage firms can benefit from routing orders through market makers and getting paid. This allows brokerage firms to send their orders to another firm to be executed with other orders, reducing costs. The market maker or exchange benefits from additional share volume, so it pays brokerage firms to direct traffic.
Retail investors, who lack bargaining power, may benefit from order-filling competition. Arrangements to steer the business in one direction invite wrongdoing, which can erode investor confidence in financial markets and their players.
Pay-for-order-flow criticism
It has always been controversial. Several firms offering zero-commission trades in the late 1990s routed orders to untrustworthy market makers. During the end of fractional pricing, the smallest stock spread was $0.125. Options spreads widened. Traders found that some of their "free" trades cost them a lot because they weren't getting the best price.
The SEC then studied the issue, focusing on options trades, and nearly decided to ban PFOF. The proliferation of options exchanges narrowed spreads because there was more competition for executing orders. Options market makers said their services provided liquidity. In its conclusion, the report said, "While increased multiple-listing produced immediate economic benefits to investors in the form of narrower quotes and effective spreads, these improvements have been muted with the spread of payment for order flow and internalization."
The SEC allowed payment for order flow to continue to prevent exchanges from gaining monopoly power. What would happen to trades if the practice was outlawed was also unclear. SEC requires brokers to disclose financial arrangements with market makers. Since then, the SEC has watched closely.
2020 Order Flow Payment
Rule 605 and Rule 606 show execution quality and order flow payment statistics on a broker's website. Despite being required by the SEC, these reports can be hard to find. The SEC mandated these reports in 2005, but the format and reporting requirements have changed over the years, most recently in 2018.
Brokers and market makers formed a working group with the Financial Information Forum (FIF) to standardize order execution quality reporting. Only one retail brokerage (Fidelity) and one market maker remain (Two Sigma Securities). FIF notes that the 605/606 reports "do not provide the level of information that allows a retail investor to gauge how well a broker-dealer fills a retail order compared to the NBBO (national best bid or offer’) at the time the order was received by the executing broker-dealer."
In the first quarter of 2020, Rule 606 reporting changed to require brokers to report net payments from market makers for S&P 500 and non-S&P 500 equity trades and options trades. Brokers must disclose payment rates per 100 shares by order type (market orders, marketable limit orders, non-marketable limit orders, and other orders).
Richard Repetto, Managing Director of New York-based Piper Sandler & Co., publishes a report on Rule 606 broker reports. Repetto focused on Charles Schwab, TD Ameritrade, E-TRADE, and Robinhood in Q2 2020. Repetto reported that payment for order flow was higher in the second quarter than the first due to increased trading activity, and that options paid more than equities.
Repetto says PFOF contributions rose overall. Schwab has the lowest options rates, while TD Ameritrade and Robinhood have the highest. Robinhood had the highest equity rating. Repetto assumes Robinhood's ability to charge higher PFOF reflects their order flow profitability and that they receive a fixed rate per spread (vs. a fixed rate per share by the other brokers).
Robinhood's PFOF in equities and options grew the most quarter-over-quarter of the four brokers Piper Sandler analyzed, as did their implied volumes. All four brokers saw higher PFOF rates.
TD Ameritrade took the biggest income hit when cutting trading commissions in fall 2019, and this report shows they're trying to make up the shortfall by routing orders for additional PFOF. Robinhood refuses to disclose trading statistics using the same metrics as the rest of the industry, offering only a vague explanation on their website.
Summary
Payment for order flow has become a major source of revenue as brokers offer no-commission equity (stock and ETF) orders. For retail investors, payment for order flow poses a problem because the brokerage may route orders to a market maker for its own benefit, not the investor's.
Infrequent or small-volume traders may not notice their broker's PFOF practices. Frequent traders and those who trade larger quantities should learn about their broker's order routing system to ensure they're not losing out on price improvement due to a broker prioritizing payment for order flow.
This post is a summary. Read full article here
Rachel Greenberg
3 years ago
The Unsettling Fact VC-Backed Entrepreneurs Don't Want You to Know
What they'll do is scarier.
My acquaintance recently joined a VC-funded startup. Money, equity, and upside possibilities were nice, but he had a nagging dread.
They just secured a $40M round and are hiring like crazy to prepare for their IPO in two years. All signals pointed to this startup's (a B2B IT business in a stable industry) success, and its equity-holding workers wouldn't pass that up.
Five months after starting the work, my friend struggled with leaving. We might overlook the awful culture and long hours at the proper price. This price plus the company's fate and survival abilities sent my friend departing in an unpleasant unplanned resignation before jumping on yet another sinking ship.
This affects founders. This affects VC-backed companies (and all businesses). This affects anyone starting, buying, or running a business.
Here's the under-the-table approach that's draining VC capital, leaving staff terrified (or jobless), founders rattled, and investors upset. How to recognize, solve, and avoid it
The unsettling reality behind door #1
You can't raise money off just your looks, right? If "looks" means your founding team's expertise, then maybe. In my friend's case, the founding team's strong qualifications and track records won over investors before talking figures.
They're hardly the only startup to raise money without a profitable customer acquisition strategy. Another firm raised money for an expensive sleep product because it's eco-friendly. They were off to the races with a few keywords and key players.
Both companies, along with numerous others, elected to invest on product development first. Company A employed all the tech, then courted half their market (they’re a tech marketplace that connects two parties). Company B spent millions on R&D to create a palatable product, then flooded the world with marketing.
My friend is on Company B's financial team, and he's seen where they've gone wrong. It's terrible.
Company A (tech market): Growing? Not quite. To achieve the ambitious expansion they (and their investors) demand, they've poured much of their little capital into salespeople: Cold-calling commission and salary salesmen. Is it working? Considering attrition and companies' dwindling capital, I don't think so.
Company B (green sleep) has been hiring, digital marketing, and opening new stores like crazy. Growing expenses should result in growing revenues and a favorable return on investment; if you grow too rapidly, you may neglect to check that ROI.
Once Company A cut headcount and Company B declared “going concerned”, my friend realized both startups had the same ailment and didn't recognize it.
I shouldn't have to ask a friend to verify a company's cash reserves and profitability to spot a financial problem. It happened anyhow.
The frightening part isn't that investors were willing to invest millions without product-market fit, CAC, or LTV estimates. That's alarming, but not as scary as the fact that startups aren't understanding the problem until VC rounds have dried up.
When they question consultants if their company will be around in 6 months. It’s a red flag. How will they stretch $20M through a 2-year recession with a $3M/month burn rate and no profitability? Alarms go off.
Who's in danger?
In a word, everyone who raised money without a profitable client acquisition strategy or enough resources to ride out dry spells.
Money mismanagement and poor priorities affect every industry (like sinking all your capital into your product, team, or tech, at the expense of probing what customer acquisition really takes and looks like).
This isn't about tech, real estate, or recession-proof luxury products. Fast, cheap, easy money flows into flashy-looking teams with buzzwords, trending industries, and attractive credentials.
If these companies can't show progress or get a profitable CAC, they can't raise more money. They die if they can't raise more money (or slash headcount and find shoestring budget solutions until they solve the real problem).
The kiss of death (and how to avoid it)
If you're running a startup and think raising VC is the answer, pause and evaluate. Do you need the money now?
I'm not saying VC is terrible or has no role. Founders have used it as a Band-Aid for larger, pervasive problems. Venture cash isn't a crutch for recruiting consumers profitably; it's rocket fuel to get you what and who you need.
Pay-to-play isn't a way to throw money at the wall and hope for a return. Pay-to-play works until you run out of money, and if you haven't mastered client acquisition, your cash will diminish quickly.
How can you avoid this bottomless pit? Tips:
Understand your burn rate
Keep an eye on your growth or profitability.
Analyze each and every marketing channel and initiative.
Make lucrative customer acquisition strategies and satisfied customers your top two priorities. not brand-new products. not stellar hires. avoid the fundraising rollercoaster to save time. If you succeed in these two tasks, investors will approach you with their thirsty offers rather than the other way around, and your cash reserves won't diminish as a result.
Not as much as your grandfather
My family friend always justified expensive, impractical expenditures by saying it was only monopoly money. In business, startups, and especially with money from investors expecting a return, that's not true.
More founders could understand that there isn't always another round if they viewed VC money as their own limited pool. When the well runs dry, you must refill it or save the day.
Venture financing isn't your grandpa's money. A discerning investor has entrusted you with dry powder in the hope that you'll use it wisely, strategically, and thoughtfully. Use it well.