More on Science

Laura Sanders
3 years ago
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.

Tomas Pueyo
2 years ago
Soon, a Starship Will Transform Humanity
SpaceX's Starship.
Launched last week.
Four minutes in:
SpaceX will succeed. When it does, its massiveness will matter.
Its payload will revolutionize space economics.
Civilization will shift.
We don't yet understand how this will affect space and Earth culture. Grab it.
The Cost of Space Transportation Has Decreased Exponentially
Space launches have increased dramatically in recent years.
We mostly send items to LEO, the green area below:
SpaceX's reusable rockets can send these things to LEO. Each may launch dozens of payloads into space.
With all these launches, we're sending more than simply things to space. Volume and mass. Since the 1980s, launching a kilogram of payload to LEO has become cheaper:
One kilogram in a large rocket cost over $75,000 in the 1980s. Carrying one astronaut cost nearly $5M! Falcon Heavy's $1,500/kg price is 50 times lower. SpaceX's larger, reusable rockets are amazing.
SpaceX's Starship rocket will continue. It can carry over 100 tons to LEO, 50% more than the current Falcon heavy. Thousands of launches per year. Elon Musk predicts Falcon Heavy's $1,500/kg cost will plummet to $100 in 23 years.
In context:
People underestimate this.
2. The Benefits of Affordable Transportation
Compare Earth's transportation costs:
It's no surprise that the US and Northern Europe are the wealthiest and have the most navigable interior waterways.
So what? since sea transportation is cheaper than land. Inland waterways are even better than sea transportation since weather is less of an issue, currents can be controlled, and rivers serve two banks instead of one for coastal transportation.
In France, because population density follows river systems, rivers are valuable. Cheap transportation brought people and money to rivers, especially their confluences.
How come? Why were humans surrounding rivers?
Imagine selling meat for $10 per kilogram. Transporting one kg one kilometer costs $1. Your margin decreases $1 each kilometer. You can only ship 10 kilometers. For example, you can only trade with four cities:
If instead, your cost of transportation is half, what happens? It costs you $0.5 per km. You now have higher margins with each city you traded with. More importantly, you can reach 20-km markets.
However, 2x distance 4x surface! You can now trade with sixteen cities instead of four! Metcalfe's law states that a network's value increases with its nodes squared. Since now sixteen cities can connect to yours. Each city now has sixteen connections! They get affluent and can afford more meat.
Rivers lower travel costs, connecting many cities, which can trade more, get wealthy, and buy more.
The right network is worth at least an order of magnitude more than the left! The cheaper the transport, the more trade at a lower cost, the more income generated, the more that wealth can be reinvested in better canals, bridges, and roads, and the wealth grows even more.
Throughout history. Rome was established around cheap Mediterranean transit and preoccupied with cutting overland transportation costs with their famous roadways. Communications restricted their empire.
The Egyptians lived around the Nile, the Vikings around the North Sea, early Japan around the Seto Inland Sea, and China started canals in the 5th century BC.
Transportation costs shaped empires.Starship is lowering new-world transit expenses. What's possible?
3. Change Organizations, Change Companies, Change the World
Starship is a conveyor belt to LEO. A new world of opportunity opens up as transportation prices drop 100x in a decade.
Satellite engineers have spent decades shedding milligrams. Weight influenced every decision: pricing structure, volumes to be sent, material selections, power sources, thermal protection, guiding, navigation, and control software. Weight was everything in the mission. To pack as much science into every millimeter, NASA missions had to be miniaturized. Engineers were indoctrinated against mass.
No way.
Starship is not constrained by any space mission, robotic or crewed.
Starship obliterates the mass constraint and every last vestige of cultural baggage it has gouged into the minds of spacecraft designers. A dollar spent on mass optimization no longer buys a dollar saved on launch cost. It buys nothing. It is time to raise the scope of our ambition and think much bigger. — Casey Handmer, Starship is still not understood
A Tesla Roadster in space makes more sense.
It went beyond bad PR. It told the industry: Did you care about every microgram? No more. My rockets are big enough to send a Tesla without noticing. Industry watchers should have noticed.
Most didn’t. Artemis is a global mission to send astronauts to the Moon and build a base. Artemis uses disposable Space Launch System rockets. Instead of sending two or three dinky 10-ton crew habitats over the next decade, Starship might deliver 100x as much cargo and create a base for 1,000 astronauts in a year or two. Why not? Because Artemis remains in a pre-Starship paradigm where each kilogram costs a million dollars and we must aggressively descope our objective.
Space agencies can deliver 100x more payload to space for the same budget with 100x lower costs and 100x higher transportation volumes. How can space economy saturate this new supply?
Before Starship, NASA supplied heavy equipment for Moon base construction. After Starship, Caterpillar and Deere may space-qualify their products with little alterations. Instead than waiting decades for NASA engineers to catch up, we could send people to build a space outpost with John Deere equipment in a few years.
History is littered with the wreckage of former industrial titans that underestimated the impact of new technology and overestimated their ability to adapt: Blockbuster, Motorola, Kodak, Nokia, RIM, Xerox, Yahoo, IBM, Atari, Sears, Hitachi, Polaroid, Toshiba, HP, Palm, Sony, PanAm, Sega, Netscape, Compaq, GM… — Casey Handmer, Starship is still not understood
Everyone saw it coming, but senior management failed to realize that adaption would involve moving beyond their established business practice. Others will if they don't.
4. The Starship Possibilities
It's Starlink.
SpaceX invented affordable cargo space and grasped its implications first. How can we use all this inexpensive cargo nobody knows how to use?
Satellite communications seemed like the best way to capitalize on it. They tried. Starlink, designed by SpaceX, provides fast, dependable Internet worldwide. Beaming information down is often cheaper than cable. Already profitable.
Starlink is one use for all this cheap cargo space. Many more. The longer firms ignore the opportunity, the more SpaceX will acquire.
What are these chances?
Satellite imagery is outdated and lacks detail. We can improve greatly. Synthetic aperture radar can take beautiful shots like this:
Have you ever used Google Maps and thought, "I want to see this in more detail"? What if I could view Earth live? What if we could livestream an infrared image of Earth?
We could launch hundreds of satellites with such mind-blowing visual precision of the Earth that we would dramatically improve the accuracy of our meteorological models; our agriculture; where crime is happening; where poachers are operating in the savannah; climate change; and who is moving military personnel where. Is that useful?
What if we could see Earth in real time? That affects businesses? That changes society?

Michael Hunter, MD
2 years ago
5 Drugs That May Increase Your Risk of Dementia
While our genes can't be changed easily, you can avoid some dementia risk factors. Today we discuss dementia and five drugs that may increase risk.
Memory loss appears to come with age, but we're not talking about forgetfulness. Sometimes losing your car keys isn't an indication of dementia. Dementia impairs the capacity to think, remember, or make judgments. Dementia hinders daily tasks.
Alzheimers is the most common dementia. Dementia is not normal aging, unlike forgetfulness. Aging increases the risk of Alzheimer's and other dementias. A family history of the illness increases your risk, according to the Mayo Clinic (USA).
Given that our genes are difficult to change (I won't get into epigenetics), what are some avoidable dementia risk factors? Certain drugs may cause cognitive deterioration.
Today we look at four drugs that may cause cognitive decline.
Dementia and benzodiazepines
Benzodiazepine sedatives increase brain GABA levels. Example benzodiazepines:
Diazepam (Valium) (Valium)
Alprazolam (Xanax) (Xanax)
Clonazepam (Klonopin) (Klonopin)
Addiction and overdose are benzodiazepine risks. Yes! These medications don't raise dementia risk.
USC study: Benzodiazepines don't increase dementia risk in older adults.
Benzodiazepines can produce short- and long-term amnesia. This memory loss hinders memory formation. Extreme cases can permanently impair learning and memory. Anterograde amnesia is uncommon.
2. Statins and dementia
Statins reduce cholesterol. They prevent a cholesterol-making chemical. Examples:
Atorvastatin (Lipitor) (Lipitor)
Fluvastatin (Lescol XL) (Lescol XL)
Lovastatin (Altoprev) (Altoprev)
Pitavastatin (Livalo, Zypitamag) (Livalo, Zypitamag)
Pravastatin (Pravachol) (Pravachol)
Rosuvastatin (Crestor, Ezallor) (Crestor, Ezallor)
Simvastatin (Zocor) (Zocor)
This finding is contentious. Harvard's Brigham and Womens Hospital's Dr. Joann Manson says:
“I think that the relationship between statins and cognitive function remains controversial. There’s still not a clear conclusion whether they help to prevent dementia or Alzheimer’s disease, have neutral effects, or increase risk.”
This one's off the dementia list.
3. Dementia and anticholinergic drugs
Anticholinergic drugs treat many conditions, including urine incontinence. Drugs inhibit acetylcholine (a brain chemical that helps send messages between cells). Acetylcholine blockers cause drowsiness, disorientation, and memory loss.
First-generation antihistamines, tricyclic antidepressants, and overactive bladder antimuscarinics are common anticholinergics among the elderly.
Anticholinergic drugs may cause dementia. One study found that taking anticholinergics for three years or more increased the risk of dementia by 1.54 times compared to three months or less. After stopping the medicine, the danger may continue.
4. Drugs for Parkinson's disease and dementia
Cleveland Clinic (USA) on Parkinson's:
Parkinson's disease causes age-related brain degeneration. It causes delayed movements, tremors, and balance issues. Some are inherited, but most are unknown. There are various treatment options, but no cure.
Parkinson's medications can cause memory loss, confusion, delusions, and obsessive behaviors. The drug's effects on dopamine cause these issues.
A 2019 JAMA Internal Medicine study found powerful anticholinergic medications enhance dementia risk.
Those who took anticholinergics had a 1.5 times higher chance of dementia. Individuals taking antidepressants, antipsychotic drugs, anti-Parkinson’s drugs, overactive bladder drugs, and anti-epileptic drugs had the greatest risk of dementia.
Anticholinergic medicines can lessen Parkinson's-related tremors, but they slow cognitive ability. Anticholinergics can cause disorientation and hallucinations in those over 70.
5. Antiepileptic drugs and dementia
The risk of dementia from anti-seizure drugs varies with drugs. Levetiracetam (Keppra) improves Alzheimer's cognition.
One study linked different anti-seizure medications to dementia. Anti-epileptic medicines increased the risk of Alzheimer's disease by 1.15 times in the Finnish sample and 1.3 times in the German population. Depakote, Topamax are drugs.
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Caspar Mahoney
2 years ago
Changing Your Mindset From a Project to a Product
Product game mindsets? How do these vary from Project mindset?
1950s spawned the Iron Triangle. Project people everywhere know and live by it. In stakeholder meetings, it is used to stretch the timeframe, request additional money, or reduce scope.
Quality was added to this triangle as things matured.
Quality was intended to be transformative, but none of these principles addressed why we conduct projects.
Value and benefits are key.
Product value is quantified by ROI, revenue, profit, savings, or other metrics. For me, every project or product delivery is about value.
Most project managers, especially those schooled 5-10 years or more ago (thousands working in huge corporations worldwide), understand the world in terms of the iron triangle. What does that imply? They worry about:
a) enough time to get the thing done.
b) have enough resources (budget) to get the thing done.
c) have enough scope to fit within (a) and (b) >> note, they never have too little scope, not that I have ever seen! although, theoretically, this could happen.
Boom—iron triangle.
To make the triangle function, project managers will utilize formal governance (Steering) to move those things. Increase money, scope, or both if time is short. Lacking funds? Increase time, scope, or both.
In current product development, shifting each item considerably may not yield value/benefit.
Even terrible. This approach will fail because it deprioritizes Value/Benefit by focusing the major stakeholders (Steering participants) and delivery team(s) on Time, Scope, and Budget restrictions.
Pre-agile, this problem was terrible. IT projects failed wildly. History is here.
Value, or benefit, is central to the product method. Product managers spend most of their time planning value-delivery paths.
Product people consider risk, schedules, scope, and budget, but value comes first. Let me illustrate.
Imagine managing internal products in an enterprise. Your core customer team needs a rapid text record of a chat to fix a problem. The consumer wants a feature/features added to a product you're producing because they think it's the greatest spot.
Project-minded, I may say;
Ok, I have budget as this is an existing project, due to run for a year. This is a new requirement to add to the features we’re already building. I think I can keep the deadline, and include this scope, as it sounds related to the feature set we’re building to give the desired result”.
This attitude repeats Scope, Time, and Budget.
Since it meets those standards, a project manager will likely approve it. If they have a backlog, they may add it and start specking it out assuming it will be built.
Instead, think like a product;
What problem does this feature idea solve? Is that problem relevant to the product I am building? Can that problem be solved quicker/better via another route ? Is it the most valuable problem to solve now? Is the problem space aligned to our current or future strategy? or do I need to alter/update the strategy?
A product mindset allows you to focus on timing, resource/cost, feasibility, feature detail, and so on after answering the aforementioned questions.
The above oversimplifies because
Leadership in discovery
Project managers are facilitators of ideas. This is as far as they normally go in the ‘idea’ space.
Business Requirements collection in classic project delivery requires extensive upfront documentation.
Agile project delivery analyzes requirements iteratively.
However, the project manager is a facilitator/planner first and foremost, therefore topic knowledge is not expected.
I mean business domain, not technical domain (to confuse matters, it is true that in some instances, it can be both technical and business domains that are important for a single individual to master).
Product managers are domain experts. They will become one if they are training/new.
They lead discovery.
Product Manager-led discovery is much more than requirements gathering.
Requirements gathering involves a Business Analyst interviewing people and documenting their requests.
The project manager calculates what fits and what doesn't using their Iron Triangle (presumably in their head) and reports back to Steering.
If this requirements-gathering exercise failed to identify requirements, what would a project manager do? or bewildered by project requirements and scope?
They would tell Steering they need a Business SME or Business Lead assigning or more of their time.
Product discovery requires the Product Manager's subject knowledge and a new mindset.
How should a Product Manager handle confusing requirements?
Product Managers handle these challenges with their talents and tools. They use their own knowledge to fill in ambiguity, but they have the discipline to validate those assumptions.
To define the problem, they may perform qualitative or quantitative primary research.
They might discuss with UX and Engineering on a whiteboard and test assumptions or hypotheses.
Do Product Managers escalate confusing requirements to Steering/Senior leaders? They would fix that themselves.
Product managers raise unclear strategy and outcomes to senior stakeholders. Open talks, soft skills, and data help them do this. They rarely raise requirements since they have their own means of handling them without top stakeholder participation.
Discovery is greenfield, exploratory, research-based, and needs higher-order stakeholder management, user research, and UX expertise.
Product Managers also aid discovery. They lead discovery. They will not leave customer/user engagement to a Business Analyst. Administratively, a business analyst could aid. In fact, many product organizations discourage business analysts (rely on PM, UX, and engineer involvement with end-users instead).
The Product Manager must drive user interaction, research, ideation, and problem analysis, therefore a Product professional must be skilled and confident.
Creating vs. receiving and having an entrepreneurial attitude
Product novices and project managers focus on details rather than the big picture. Project managers prefer spreadsheets to strategy whiteboards and vision statements.
These folks ask their manager or senior stakeholders, "What should we do?"
They then elaborate (in Jira, in XLS, in Confluence or whatever).
They want that plan populated fast because it reduces uncertainty about what's going on and who's supposed to do what.
Skilled Product Managers don't only ask folks Should we?
They're suggesting this, or worse, Senior stakeholders, here are some options. After asking and researching, they determine what value this product adds, what problems it solves, and what behavior it changes.
Therefore, to move into Product, you need to broaden your view and have courage in your ability to discover ideas, find insightful pieces of information, and collate them to form a valuable plan of action. You are constantly defining RoI and building Business Cases, so much so that you no longer create documents called Business Cases, it is simply ingrained in your work through metrics, intelligence, and insights.
Product Management is not a free lunch.
Plateless.
Plates and food must be prepared.
In conclusion, Product Managers must make at least three mentality shifts:
You put value first in all things. Time, money, and scope are not as important as knowing what is valuable.
You have faith in the field and have the ability to direct the search. YYou facilitate, but you don’t just facilitate. You wouldn't want to limit your domain expertise in that manner.
You develop concepts, strategies, and vision. You are not a waiter or an inbox where other people can post suggestions; you don't merely ask folks for opinion and record it. However, you excel at giving things that aren't clearly spoken or written down physical form.

Alex Mathers
2 years ago
How to Produce Enough for People to Not Neglect You
Internet's fantastic, right?
We've never had a better way to share our creativity.
I can now draw on my iPad and tweet or Instagram it to thousands. I may get some likes.
With such a great, free tool, you're not alone.
Millions more bright-eyed artists are sharing their work online.
The issue is getting innovative work noticed, not sharing it.
In a world where creators want attention, attention is valuable.
We build for attention.
Attention helps us establish a following, make money, get notoriety, and make a difference.
Most of us require attention to stay sane while creating wonderful things.
I know how hard it is to work hard and receive little views.
How do we receive more attention, more often, in a sea of talent?
Advertising and celebrity endorsements are options. These may work temporarily.
To attract true, organic, and long-term attention, you must create in high quality, high volume, and consistency.
Adapting Steve Martin's Be so amazing, they can't ignore you (with a mention to Dan Norris in his great book Create or Hate for the reminder)
Create a lot.
Eventually, your effort will gain traction.
Traction shows your work's influence.
Traction is when your product sells more. Traction is exponential user growth. Your work is shared more.
No matter how good your work is, it will always have minimal impact on the world.
Your work can eventually dent or puncture. Daily, people work to dent.
To achieve this tipping point, you must consistently produce exceptional work.
Expect traction after hundreds of outputs.
Dilbert creator Scott Adams says repetition persuades. If you don't stop, you can persuade practically anyone with anything.
Volume lends believability. So make more.
I worked as an illustrator for at least a year and a half without any recognition. After 150 illustrations on iStockphoto, my work started selling.
With 350 illustrations on iStock, I started getting decent client commissions.
Producing often will improve your craft and draw attention.
It's the only way to succeed. More creation means better results and greater attention.
Austin Kleon says you can improve your skill in relative anonymity before you become famous. Before obtaining traction, generate a lot and become excellent.
Most artists, even excellent ones, don't create consistently enough to get traction.
It may hurt. For makers who don't love and flow with their work, it's extremely difficult.
Your work must bring you to life.
To generate so much that others can't ignore you, decide what you'll accomplish every day (or most days).
Commit and be patient.
Prepare for zero-traction.
Anticipating this will help you persevere and create.
My online guru Grant Cardone says: Anything worth doing is worth doing every day.
Do.

Onchain Wizard
3 years ago
Three Arrows Capital & Celsius Updates
I read 1k+ page 3AC liquidation documentation so you don't have to. Also sharing revised Celsius recovery plans.
3AC's liquidation documents:
Someone disclosed 3AC liquidation records in the BVI courts recently. I'll discuss the leak's timeline and other highlights.
Three Arrows Capital began trading traditional currencies in emerging markets in 2012. They switched to equities and crypto, then purely crypto in 2018.
By 2020, the firm had $703mm in net assets and $1.8bn in loans (these guys really like debt).
The firm's net assets under control reached $3bn in April 2022, according to the filings. 3AC had $600mm of LUNA/UST exposure before May 9th 2022, which put them over.
LUNA and UST go to zero quickly (I wrote about the mechanics of the blowup here). Kyle Davies, 3AC co-founder, told Blockchain.com on May 13 that they have $2.4bn in assets and $2.3bn NAV vs. $2bn in borrowings. As BTC and ETH plunged 33% and 50%, the company became insolvent by mid-2022.
3AC sent $32mm to Tai Ping Shen, a Cayman Islands business owned by Su Zhu and Davies' partner, Kelly Kaili Chen (who knows what is going on here).
3AC had borrowed over $3.5bn in notional principle, with Genesis ($2.4bn) and Voyager ($650mm) having the most exposure.
Genesis demanded $355mm in further collateral in June.
Deribit (another 3AC investment) called for $80 million in mid-June.
Even in mid-June, the corporation was trying to borrow more money to stay afloat. They approached Genesis for another $125mm loan (to pay another lender) and HODLnauts for BTC & ETH loans.
Pretty crazy. 3AC founders used borrowed money to buy a $50 million boat, according to the leak.
Su requesting for $5m + Chen Kaili Kelly asserting they loaned $65m unsecured to 3AC are identified as creditors.
Celsius:
This bankruptcy presentation shows the Celsius breakdown from March to July 14, 2022. From $22bn to $4bn, crypto assets plummeted from $14.6bn to $1.8bn (ouch). $16.5bn in user liabilities dropped to $4.72bn.
In my recent post, I examined if "forced selling" is over, with Celsius' crypto assets being a major overhang. In this presentation, it looks that Chapter 11 will provide clients the opportunity to accept cash at a discount or remain long crypto. Provided that a fresh source of money is unlikely to enter the Celsius situation, cash at a discount or crypto given to customers will likely remain a near-term market risk - cash at a discount will likely come from selling crypto assets, while customers who receive crypto could sell at any time. I'll share any Celsius updates I find.
Conclusion
Only Celsius and the Mt Gox BTC unlock remain as forced selling catalysts. While everything went through a "relief" pump, with ETH up 75% from the bottom and numerous alts multiples higher, there are still macro dangers to equities + risk assets. There's a lot of wealth waiting to be deployed in crypto ($153bn in stables), but fund managers are risk apprehensive (lower than 2008 levels).
We're hopefully over crypto's "bottom," with peak anxiety and forced selling behind us, but we may chop around.
To see the full article, click here.