More on Science
Laura Sanders
4 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.
Michael Hunter, MD
3 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.
Katherine Kornei
3 years ago
The InSight lander from NASA has recorded the greatest tremor ever felt on Mars.
The magnitude 5 earthquake was responsible for the discharge of energy that was 10 times greater than the previous record holder.
Any Martians who happen to be reading this should quickly learn how to duck and cover.
NASA's Jet Propulsion Laboratory in Pasadena, California, reported that on May 4, the planet Mars was shaken by an earthquake of around magnitude 5, making it the greatest Marsquake ever detected to this point. The shaking persisted for more than six hours and unleashed more than ten times as much energy as the earthquake that had previously held the record for strongest.
The event was captured on record by the InSight lander, which is operated by the United States Space Agency and has been researching the innards of Mars ever since it touched down on the planet in 2018 (SN: 11/26/18). The epicenter of the earthquake was probably located in the vicinity of Cerberus Fossae, which is located more than 1,000 kilometers away from the lander.
The surface of Cerberus Fossae is notorious for being broken up and experiencing periodic rockfalls. According to geophysicist Philippe Lognonné, who is the lead investigator of the Seismic Experiment for Interior Structure, the seismometer that is onboard the InSight lander, it is reasonable to assume that the ground is moving in that area. "This is an old crater from a volcanic eruption."
Marsquakes, which are similar to earthquakes in that they give information about the interior structure of our planet, can be utilized to investigate what lies beneath the surface of Mars (SN: 7/22/21). And according to Lognonné, who works at the Institut de Physique du Globe in Paris, there is a great deal that can be gleaned from analyzing this massive earthquake. Because the quality of the signal is so high, we will be able to focus on the specifics.
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Alexander Nguyen
3 years ago
A Comparison of Amazon, Microsoft, and Google's Compensation
Learn or earn
In 2020, I started software engineering. My base wage has progressed as follows:
Amazon (2020): $112,000
Microsoft (2021): $123,000
Google (2022): $169,000
I didn't major in math, but those jumps appear more than a 7% wage increase. Here's a deeper look at the three.
The Three Categories of Compensation
Most software engineering compensation packages at IT organizations follow this format.
Minimum Salary
Base salary is pre-tax income. Most organizations give a base pay. This is paid biweekly, twice monthly, or monthly.
Recruiting Bonus
Sign-On incentives are one-time rewards to new hires. Companies need an incentive to switch. If you leave early, you must pay back the whole cost or a pro-rated amount.
Equity
Equity is complex and requires its own post. A company will promise to give you a certain amount of company stock but when you get it depends on your offer. 25% per year for 4 years, then it's gone.
If a company gives you $100,000 and distributes 25% every year for 4 years, expect $25,000 worth of company stock in your stock brokerage on your 1 year work anniversary.
Performance Bonus
Tech offers may include yearly performance bonuses. Depends on performance and funding. I've only seen 0-20%.
Engineers' overall compensation usually includes:
Base Salary + Sign-On + (Total Equity)/4 + Average Performance Bonus
Amazon: (TC: 150k)
Base Pay System
Amazon pays Seattle employees monthly on the first work day. I'd rather have my money sooner than later, even if it saves processing and pay statements.
The company upped its base pay cap from $160,000 to $350,000 to compete with other tech companies.
Performance Bonus
Amazon has no performance bonus, so you can work as little or as much as you like and get paid the same. Amazon is savvy to avoid promising benefits it can't deliver.
Sign-On Bonus
Amazon gives two two-year sign-up bonuses. First-year workers could receive $20,000 and second-year workers $15,000. It's probably to make up for the company's strange equity structure.
If you leave during the first year, you'll owe the entire money and a prorated amount for the second year bonus.
Equity
Most organizations prefer a 25%, 25%, 25%, 25% equity structure. Amazon takes a different approach with end-heavy equity:
the first year, 5%
15% after one year.
20% then every six months
We thought it was constructed this way to keep staff longer.
Microsoft (TC: 185k)
Base Pay System
Microsoft paid biweekly.
Gainful Performance
My offer letter suggested a 0%-20% performance bonus. Everyone will be satisfied with a 10% raise at year's end.
But misleading press where the budget for the bonus is doubled can upset some employees because they won't earn double their expected bonus. Still barely 10% for 2022 average.
Sign-On Bonus
Microsoft's sign-on bonus is a one-time payout. The contract can require 2-year employment. You must negotiate 1 year. It's pro-rated, so that's fair.
Equity
Microsoft is one of those companies that has standard 25% equity structure. Except if you’re a new graduate.
In that case it’ll be
25% six months later
25% each year following that
New grads will acquire equity in 3.5 years, not 4. I'm guessing it's to keep new grads around longer.
Google (TC: 300k)
Base Pay Structure
Google pays biweekly.
Performance Bonus
Google's offer letter specifies a 15% bonus. It's wonderful there's no cap, but I might still get 0%. A little more than Microsoft’s 10% and a lot more than Amazon’s 0%.
Sign-On Bonus
Google gave a 1-year sign-up incentive. If the contract is only 1 year, I can move without any extra obligations.
Not as fantastic as Amazon's sign-up bonuses, but the remainder of the package might compensate.
Equity
We covered Amazon's tail-heavy compensation structure, so Google's front-heavy equity structure may surprise you.
Annual structure breakdown
33% Year 1
33% Year 2
22% Year 3
12% Year 4
The goal is to get them to Google and keep them there.
Final Thoughts
This post hopefully helped you understand the 3 firms' compensation arrangements.
There's always more to discuss, such as refreshers, 401k benefits, and business discounts, but I hope this shows a distinction between these 3 firms.
Chris
3 years ago
What the World's Most Intelligent Investor Recently Said About Crypto
Cryptoshit. This thing is crazy to buy.
Charlie Munger is revered and powerful in finance.
Munger, vice chairman of Berkshire Hathaway, is noted for his wit, no-nonsense attitude to investment, and ability to spot promising firms and markets.
Munger's crypto views have upset some despite his reputation as a straight shooter.
“There’s only one correct answer for intelligent people, just totally avoid all the people that are promoting it.” — Charlie Munger
The Munger Interview on CNBC (4:48 secs)
This Monday, CNBC co-anchor Rebecca Quick interviewed Munger and brought up his 2007 statement, "I'm not allowed to have an opinion on this subject until I can present the arguments against my viewpoint better than the folks who are supporting it."
Great investing and life advice!
If you can't explain the opposing reasons, you're not informed enough to have an opinion.
In today's world, it's important to grasp both sides of a debate before supporting one.
Rebecca inquired:
Does your Wall Street Journal article on banning cryptocurrency apply? If so, would you like to present the counterarguments?
Mungers reply:
I don't see any viable counterarguments. I think my opponents are idiots, hence there is no sensible argument against my position.
Consider his words.
Do you believe Munger has studied both sides?
He said, "I assume my opponents are idiots, thus there is no sensible argument against my position."
This is worrisome, especially from a guy who once encouraged studying both sides before forming an opinion.
Munger said:
National currencies have benefitted humanity more than almost anything else.
Hang on, I think we located the perpetrator.
Munger thinks crypto will replace currencies.
False.
I doubt he studied cryptocurrencies because the name is deceptive.
He misread a headline as a Dollar destroyer.
Cryptocurrencies are speculations.
Like Tesla, Amazon, Apple, Google, Microsoft, etc.
Crypto won't replace dollars.
In the interview with CNBC, Munger continued:
“I’m not proud of my country for allowing this crap, what I call the cryptoshit. It’s worthless, it’s no good, it’s crazy, it’ll do nothing but harm, it’s anti-social to allow it.” — Charlie Munger
Not entirely inaccurate.
Daily cryptos are established solely to pump and dump regular investors.
Let's get into Munger's crypto aversion.
Rat poison is bitcoin.
Munger famously dubbed Bitcoin rat poison and a speculative bubble that would implode.
Partially.
But the bubble broke. Since 2021, the market has fallen.
Scam currencies and NFTs are being eliminated, which I like.
Whoa.
Why does Munger doubt crypto?
Mungers thinks cryptocurrencies has no intrinsic value.
He worries about crypto fraud and money laundering.
Both are valid issues.
Yet grouping crypto is intellectually dishonest.
Ethereum, Bitcoin, Solana, Chainlink, Flow, and Dogecoin have different purposes and values (not saying they’re all good investments).
Fraudsters who hurt innocents will be punished.
Therefore, complaining is useless.
Why not stop it? Repair rather than complain.
Regrettably, individuals today don't offer solutions.
Blind Areas for Mungers
As with everyone, Mungers' bitcoin views may be impacted by his biases and experiences.
OK.
But Munger has always advocated classic value investing and may be wary of investing in an asset outside his expertise.
Mungers' banking and insurance investments may influence his bitcoin views.
Could a coworker or acquaintance have told him crypto is bad and goes against traditional finance?
Right?
Takeaways
Do you respect Charlie Mungers?
Yes and no, like any investor or individual.
To understand Mungers' bitcoin beliefs, you must be critical.
Mungers is a successful investor, but his views about bitcoin should be considered alongside other viewpoints.
Munger’s success as an investor has made him an influencer in the space.
Influence gives power.
He controls people's thoughts.
Munger's ok. He will always be heard.
I'll do so cautiously.
Thomas Tcheudjio
3 years ago
If you don't crush these 3 metrics, skip the Series A.
I recently wrote about getting VCs excited about Marketplace start-ups. SaaS founders became envious!
Understanding how people wire tens of millions is the only Series A hack I recommend.
Few people understand the intellectual process behind investing.
VC is risk management.
Series A-focused VCs must cover two risks.
1. Market risk
You need a large market to cross a threshold beyond which you can build defensibilities. Series A VCs underwrite market risk.
They must see you have reached product-market fit (PMF) in a large total addressable market (TAM).
2. Execution risk
When evaluating your growth engine's blitzscaling ability, execution risk arises.
When investors remove operational uncertainty, they profit.
Series A VCs like businesses with derisked revenue streams. Don't raise unless you have a predictable model, pipeline, and growth.
Please beat these 3 metrics before Series A:
Achieve $1.5m ARR in 12-24 months (Market risk)
Above 100% Net Dollar Retention. (Market danger)
Lead Velocity Rate supporting $10m ARR in 2–4 years (Execution risk)
Hit the 3 and you'll raise $10M in 4 months. Discussing 2/3 may take 6–7 months.
If none, don't bother raising and focus on becoming a capital-efficient business (Topics for other posts).
Let's examine these 3 metrics for the brave ones.
1. Lead Velocity Rate supporting €$10m ARR in 2 to 4 years
Last because it's the least discussed. LVR is the most reliable data when evaluating a growth engine, in my opinion.
SaaS allows you to see the future.
Monthly Sales and Sales Pipelines, two predictive KPIs, have poor data quality. Both are lagging indicators, and minor changes can cause huge modeling differences.
Analysts and Associates will trash your forecasts if they're based only on Monthly Sales and Sales Pipeline.
LVR, defined as month-over-month growth in qualified leads, is rock-solid. There's no lag. You can See The Future if you use Qualified Leads and a consistent formula and process to qualify them.
With this metric in your hand, scaling your company turns into an execution play on which VCs are able to perform calculations risk.
2. Above-100% Net Dollar Retention.
Net Dollar Retention is a better-known SaaS health metric than LVR.
Net Dollar Retention measures a SaaS company's ability to retain and upsell customers. Ask what $1 of net new customer spend will be worth in years n+1, n+2, etc.
Depending on the business model, SaaS businesses can increase their share of customers' wallets by increasing users, selling them more products in SaaS-enabled marketplaces, other add-ons, and renewing them at higher price tiers.
If a SaaS company's annualized Net Dollar Retention is less than 75%, there's a problem with the business.
Slack's ARR chart (below) shows how powerful Net Retention is. Layer chart shows how existing customer revenue grows. Slack's S1 shows 171% Net Dollar Retention for 2017–2019.
Slack S-1
3. $1.5m ARR in the last 12-24 months.
According to Point 9, $0.5m-4m in ARR is needed to raise a $5–12m Series A round.
Target at least what you raised in Pre-Seed/Seed. If you've raised $1.5m since launch, don't raise before $1.5m ARR.
Capital efficiency has returned since Covid19. After raising $2m since inception, it's harder to raise $1m in ARR.
P9's 2016-2021 SaaS Funding Napkin
In summary, less than 1% of companies VCs meet get funded. These metrics can help you win.
If there’s demand for it, I’ll do one on direct-to-consumer.
Cheers!