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Katrina Paulson

Katrina Paulson

3 years ago

Dehumanization Against Anthropomorphization

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Bob Service

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."

Katherine Kornei

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.

Laura Sanders

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.

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Tanya Aggarwal

Tanya Aggarwal

3 years ago

What I learned from my experience as a recent graduate working in venture capital

Every week I meet many people interested in VC. Many of them ask me what it's like to be a junior analyst in VC or what I've learned so far.

Looking back, I've learned many things as a junior VC, having gone through an almost-euphoric peak bull market, failed tech IPOs of 2019 including WeWorks' catastrophic fall, and the beginnings of a bearish market.

1. Network, network, network!

VCs spend 80% of their time networking. Junior VCs source deals or manage portfolios. You spend your time bringing startups to your fund or helping existing portfolio companies grow. Knowing stakeholders (corporations, star talent, investors) in your particular areas of investment helps you develop your portfolio.

Networking was one of my strengths. When I first started in the industry, I'd go to startup events and meet 50 people a month. Over time, I realized these relationships were shallow and I was only getting business cards. So I stopped seeing networking as a transaction. VC is a long-term game, so you should work with people you like. Now I know who I click with and can build deeper relationships with them. My network is smaller but more valuable than before.

2. The Most Important Metric Is Founder

People often ask how we pick investments. Why some companies can raise money and others can't is a mystery. The founder is the most important metric for VCs. When a company is young, the product, environment, and team all change, but the founder remains constant. VCs bet on the founder, not the company.

How do we decide which founders are best after 2-3 calls? When looking at a founder's profile, ask why this person can solve this problem. The founders' track record will tell. If the founder is a serial entrepreneur, you know he/she possesses the entrepreneur DNA and will likely succeed again. If it's his/her first startup, focus on industry knowledge to deliver the best solution.

3. A company's fate can be determined by macrotrends.

Macro trends are crucial. A company can have the perfect product, founder, and team, but if it's solving the wrong problem, it won't succeed. I've also seen average companies ride the wave to success. When you're on the right side of a trend, there's so much demand that more companies can get a piece of the pie.

In COVID-19, macro trends made or broke a company. Ed-tech and health-tech companies gained unicorn status and raised funding at inflated valuations due to sudden demand. With the easing of pandemic restrictions and the start of a bear market, many of these companies' valuations are in question.

4. Look for methods to ACTUALLY add value.

You only need to go on VC twitter (read: @vcstartterkit and @vcbrags) for 5 minutes or look at fin-meme accounts on Instagram to see how much VCs claim to add value but how little they actually do. VC is a long-term game, though. Long-term, founders won't work with you if you don't add value.

How can we add value when we're young and have no network? Leaning on my strengths helped me. Instead of viewing my age and limited experience as a disadvantage, I realized that I brought a unique perspective to the table.

As a VC, you invest in companies that will be big in 5-7 years, and millennials and Gen Z will have the most purchasing power. Because you can relate to that market, you can offer insights that most Partners at 40 can't. I added value by helping with hiring because I had direct access to university talent pools and by finding university students for product beta testing.

5. Develop your personal brand.

Generalists or specialists run most funds. This means that funds either invest across industries or have a specific mandate. Most funds are becoming specialists, I've noticed. Top-tier founders don't lack capital, so funds must find other ways to attract them. Why would a founder work with a generalist fund when a specialist can offer better industry connections and partnership opportunities?

Same for fund members. Founders want quality investors. Become a thought leader in your industry to meet founders. Create content and share your thoughts on industry-related social media. When I first started building my brand, I found it helpful to interview industry veterans to create better content than I could on my own. Over time, my content attracted quality founders so I didn't have to look for them.

These are my biggest VC lessons. This list isn't exhaustive, but it's my industry survival guide.

Michael Salim

Michael Salim

3 years ago

300 Signups, 1 Landing Page, 0 Products

I placed a link on HackerNews and got 300 signups in a week. This post explains what happened.

Product Concept

The product is DbSchemaLibrary. A library of Database Schema.

I'm not sure where this idea originated from. Very fast. Build fast, fail fast, test many ideas, and one will be a hit. I tried it. Let's try it anyway, even though it'll probably fail. I finished The Lean Startup book and wanted to use it.

Database job bores me. Important! I get drowsy working on it. Someone must do it. I remember this happening once. I needed examples at the time. Something similar to Recall (my other project) that I can copy — or at least use as a reference.

Frequently googled. Many tabs open. The results were useless. I raised my hand and agreed to construct the database myself.

It resurfaced. I decided to do something.

Due Diligence

Lean Startup emphasizes validated learning. Everything the startup does should result in learning. I may build something nobody wants otherwise. That's what happened to Recall.

So, I wrote a business plan document. This happens before I code. What am I solving? What is my proposed solution? What is the leap of faith between the problem and solution? Who would be my target audience?

My note:

Note of the exact problem and solutions I’m trying to solve

In my previous project, I did the opposite!

I wrote my expectations after reading the book's advice.

“Failure is a prerequisite to learning. The problem with the notion of shipping a product and then seeing what happens is that you are guaranteed to succeed — at seeing what happens.” — The Lean Startup book

These are successful metrics. If I don't reach them, I'll drop the idea and try another. I didn't understand numbers then. Below are guesses. But it’s a start!

Metrics I set before starting anything

I then wrote the project's What and Why. I'll use this everywhere. Before, I wrote a different pitch each time. I thought certain words would be better. I felt the audience might want something unusual.

Occasionally, this works. I'm unsure if it's a good idea. No stats, just my writing-time opinion. Writing every time is time-consuming and sometimes hazardous. Having a copy saved me duplication.

I can measure and learn from performance.

Copy of the product’s What and Why’s

Last, I identified communities that might demand the product. This became an exercise in creativity.

List of potential marketing channels

The MVP

So now it’s time to build.

A MVP can test my assumptions. Business may learn from it. Not low-quality. We should learn from the tiniest thing.

I like the example of how Dropbox did theirs. They assumed that if the product works, people will utilize it. How can this be tested without a quality product? They made a movie demonstrating the software's functionality. Who knows how much functionality existed?

So I tested my biggest assumption. Users want schema references. How can I test if users want to reference another schema? I'd love this. Recall taught me that wanting something doesn't mean others do.

I made an email-collection landing page. Describe it briefly. Reference library. Each email sender wants a reference. They're interested in the product. Few other reasons exist.

Header and footer were skipped. No name or logo. DbSchemaLibrary is a name I thought of after the fact. 5-minute logo. I expected a flop. Recall has no users after months of labor. What could happen to a 2-day project?

I didn't compromise learning validation. How many visitors sign up? To draw a conclusion, I must track these results.

Landing page

Posting Time

Now that the job is done, gauge interest. The next morning, I posted on all my channels. I didn't want to be spammy, therefore it required more time.

I made sure each channel had at least one fan of this product. I also answer people's inquiries in the channel.

My list stinks. Several channels wouldn't work. The product's target market isn't there. Posting there would waste our time. This taught me to create marketing channels depending on my persona.

Statistics! What actually happened

My favorite part! 23 channels received the link.

Results across the marketing channels

I stopped posting to Discord despite its high conversion rate. I eliminated some channels because they didn't fit. According to the numbers, some users like it. Most users think it's spam.

I was skeptical. And 12 people viewed it.

I didn't expect much attention on a startup subreddit. I'll likely examine Reddit further in the future. As I have enough info, I didn't post much. Time for the next validated learning

No comment. The post had few views, therefore the numbers are low.

The targeted people come next.

I'm a Toptal freelancer. There's a member-only Slack channel. Most people can't use this marketing channel, but you should! It's not as spectacular as discord's 27% conversion rate. But I think the users here are better.

I don’t really have a following anywhere so this isn’t something I can leverage.

The best yet. 10% is converted. With more data, I expect to attain a 10% conversion rate from other channels. Stable number.

This number required some work. Did you know that people use many different clients to read HN?

Unknowns

Untrackable views and signups abound. 1136 views and 135 signups are untraceable. It's 11%. I bet much of that came from Hackernews.

Overall Statistics

The 7-day signup-to-visit ratio was 17%. (Hourly data points)

Signup to Views percentageSignup to Views count

First-day percentages were lower, which is noteworthy. Initially, it was little above 10%. The HN post started getting views then.

Percentage of signups to views for the first 2 days

When traffic drops, the number reaches just around 20%. More individuals are interested in the connection. hn.algolia.com sent 2 visitors. This means people are searching and finding my post.

Percentage of signups after the initial traffic

Interesting discoveries

1. HN post struggled till the US woke up.

11am UTC. After an hour, it lost popularity. It seemed over. 7 signups converted 13%. Not amazing, but I would've thought ahead.

After 4pm UTC, traffic grew again. 4pm UTC is 9am PDT. US awakened. 10am PDT saw 512 views.

Signup to views count during the first few hours

2. The product was highlighted in a newsletter.

I found Revue references when gathering data. Newsletter platform. Someone posted the newsletter link. 37 views and 3 registrations.

3. HN numbers are extremely reliable

I don't have a time-lapse graph (yet). The statistics were constant all day.

  • 2717 views later 272 new users, or 10.1%

  • With 293 signups at 2856 views, 10.25%

  • At 306 signups at 2965 views, 10.32%

Learnings

1. My initial estimations were wildly inaccurate

I wrote 30% conversion. Reading some articles, looks like 10% is a good number to aim for.

2. Paying attention to what matters rather than vain metrics

The Lean Startup discourages vanity metrics. Feel-good metrics that don't measure growth or traction. Considering the proportion instead of the total visitors made me realize there was something here.

What’s next?

There are lots of work to do. Data aggregation, display, website development, marketing, legal issues. Fun! It's satisfying to solve an issue rather than investigate its cause.

In the meantime, I’ve already written the first project update in another post. Continue reading it if you’d like to know more about the project itself! Shifting from Quantity to Quality — DbSchemaLibrary

Scott Galloway

Scott Galloway

3 years ago

First Health

ZERO GRACE/ZERO MALICE

Amazon's purchase of One Medical could speed up American healthcare

The U.S. healthcare industry is a 7-ton seal bleeding at sea. Predators are circling. Unearned margin: price increases relative to inflation without quality improvements. Amazon is the 11-foot megalodon with 7-inch teeth. Amazon is no longer circling... but attacking.

In 2020 dollars, per capita U.S. healthcare spending increased from $2,968 in 1980 to $12,531. The result is a massive industry with 13% of the nation's workers and a fifth of GDP.

Doctor No

In 40 years, healthcare has made progress. From 73.7 in 1980 to 78.8 in 2019, life expectancy rose (before Covid knocked it back down a bit). Pharmacological therapies have revolutionized, and genetic research is paying off. The financial return, improvement split by cost increases, is terrible. No country has expense rises like the U.S., and no one spends as much per capita as we do. Developed countries have longer life expectancies, healthier populations, and less economic hardship.

Two-thirds of U.S. personal bankruptcies are due to medical expenses and/or missed work. Mom or Dad getting cancer could bankrupt many middle-class American families. 40% of American adults delayed or skipped needed care due to cost. Every healthcare improvement seems to have a downside. Same pharmacological revolution that helped millions caused opioid epidemic. Our results are poor in many areas: The U.S. has a high infant mortality rate.

Healthcare is the second-worst retail industry in the country. Gas stations are #1. Imagine walking into a Best Buy to buy a TV and a Blue Shirt associate requests you fill out the same 14 pages of paperwork you filled out yesterday. Then you wait in a crowded room until they call you, 20 minutes after the scheduled appointment you were asked to arrive early for, to see the one person in the store who can talk to you about TVs, who has 10 minutes for you. The average emergency room wait time in New York is 6 hours and 10 minutes.

If it's bad for the customer, it's worse for the business. Physicians spend 27% of their time helping patients; 49% on EHRs. Documentation, order entry, billing, and inbox management. Spend a decade getting an M.D., then become a bureaucrat.

No industry better illustrates scale diseconomies. If we got the same return on healthcare spending as other countries, we'd all live to 100. We could spend less, live longer and healthier, and pay off the national debt in 15 years. U.S. healthcare is the worst ever.

What now? Competition is at the heart of capitalism, the worst system of its kind.

Priority Time

Amazon is buying One Medical for $3.9 billion. I think this deal will liberate society. Two years in, I think One Medical is great. When I got Covid, I pressed the One Medical symbol on my phone; a nurse practitioner prescribed Paxlovid and told me which pharmacies had it in stock.

Amazon enables the company's vision. One Medical's stock is down to $10 from $40 at the start of 2021. Last year, it lost $250 million and needs cash (Amazon has $60 billion). ONEM must grow. The service has 736,000 members. Half of U.S. households have Amazon Prime. Finally, delivery. One Medical is a digital health/physical office hybrid, but you must pick up medication at the pharmacy. Upgrade your Paxlovid delivery time after a remote consultation. Amazon's core competency means it'll happen. Healthcare speed and convenience will feel alien.

It's been a long, winding road to disruption. Amazon, JPMorgan, and Berkshire Hathaway formed Haven four years ago to provide better healthcare for their 1.5 million employees. It rocked healthcare stocks the morning of the press release, but folded in 2021.

Amazon Care is an employee-focused service. Home-delivered virtual health services and nurses. It's doing well, expanding nationwide, and providing healthcare for other companies. Hilton is Amazon Care's biggest customer. The acquisition of One Medical will bring 66 million Prime households capital, domain expertise, and billing infrastructure. Imagine:

"Alexa, I'm hot and my back hurts."

"Connecting you to a Prime doctor now."

Want to vs. Have to

I predicted Amazon entering healthcare years ago. Why? For the same reason Apple is getting into auto. Amazon's P/E is 56, double Walmart's. The corporation must add $250 billion in revenue over the next five years to retain its share price. White-label clothes or smart home products won't generate as much revenue. It must enter a huge market without scale, operational competence, and data skills.

Current Situation

Healthcare reform benefits both consumers and investors. In 2015, healthcare services had S&P 500-average multiples. The market is losing faith in public healthcare businesses' growth. Healthcare services have lower EV/EBITDA multiples than the S&P 500.

Amazon isn't the only prey-hunter. Walmart and Alibaba are starting pharmacies. Uber is developing medical transportation. Private markets invested $29 billion in telehealth last year, up 95% from 2020.

The pandemic accelerated telehealth, the immediate unlock. After the first positive Covid case in the U.S., services that had to be delivered in person shifted to Zoom... We lived. We grew. Video house calls continued after in-person visits were allowed. McKinsey estimates telehealth visits are 38 times pre-pandemic levels. Doctors adopted the technology, regulators loosened restrictions, and patients saved time. We're far from remote surgery, but many patient visits are unnecessary. A study of 40 million patients during lockdown found that for chronic disease patients, online visits didn't affect outcomes. This method of care will only improve.

Amazon's disruption will be significant and will inspire a flood of capital, startups, and consumer brands. Mark Cuban launched a pharmacy that eliminates middlemen in January. Outcome? A 90-day supply of acid-reflux medication costs $17. Medicare could have saved $3.6 billion by buying generic drugs from Cuban's pharmacy. Other apex predators will look at different limbs of the carcass for food. Nike could enter healthcare via orthopedics, acupuncture, and chiropractic. LVMH, L'Oréal, and Estée Lauder may launch global plastic surgery brands. Hilton and Four Seasons may open hospitals. Lennar and Pulte could build "Active Living" communities that Nana would leave feet first, avoiding the expense and tragedy of dying among strangers.

Risks

Privacy matters: HIV status is different from credit card and billing address. Most customers (60%) feel fine sharing personal health data via virtual technologies, though. Unavoidable. 85% of doctors believe data-sharing and interoperability will become the norm. Amazon is the most trusted tech company for handling personal data. Not Meta: Amazon.

What about antitrust, then?

Amazon should be required to spin off AWS and/or Amazon Fulfillment and banned from promoting its own products. It should be allowed to acquire hospitals. One Medical's $3.9 billion acquisition is a drop in the bucket compared to UnitedHealth's $498 billion market valuation.

Antitrust enforcement shouldn't assume some people/firms are good/bad. It should recognize that competition is good and focus on making markets more competitive in each deal. The FTC should force asset divestitures in e-commerce, digital marketing, and social media. These companies can also promote competition in a social ill.

U.S. healthcare makes us fat, depressed, and broke. Competition has produced massive value and prosperity across most of our economy.

Dear Amazon … bring it.