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."

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.
Jack Burns
3 years ago
Here's what to expect from NASA Artemis 1 and why it's significant.
NASA's Artemis 1 mission will help return people to the Moon after a half-century break. The mission is a shakedown cruise for NASA's Space Launch System and Orion Crew Capsule.
The spaceship will visit the Moon, deploy satellites, and enter orbit. NASA wants to practice operating the spacecraft, test the conditions people will face on the Moon, and ensure a safe return to Earth.
We asked Jack Burns, a space scientist at the University of Colorado Boulder and former member of NASA's Presidential Transition Team, to describe the mission, explain what the Artemis program promises for space exploration, and reflect on how the space program has changed in the half-century since humans last set foot on the moon.
What distinguishes Artemis 1 from other rockets?
Artemis 1 is the Space Launch System's first launch. NASA calls this a "heavy-lift" vehicle. It will be more powerful than Apollo's Saturn V, which transported people to the Moon in the 1960s and 1970s.
It's a new sort of rocket system with two strap-on solid rocket boosters from the space shuttle. It's a mix of the shuttle and Saturn V.
The Orion Crew Capsule will be tested extensively. It'll spend a month in the high-radiation Moon environment. It will also test the heat shield, which protects the capsule and its occupants at 25,000 mph. The heat shield must work well because this is the fastest capsule descent since Apollo.
This mission will also carry miniature Moon-orbiting satellites. These will undertake vital precursor science, including as examining further into permanently shadowed craters where scientists suspect there is water and measuring the radiation environment to see long-term human consequences.
Artemis 1 will launch, fly to the Moon, place satellites, orbit it, return to Earth, and splash down in the ocean. NASA.
What's Artemis's goal? What launches are next?
The mission is a first step toward Artemis 3, which will lead to the first human Moon missions since 1972. Artemis 1 is unmanned.
Artemis 2 will have astronauts a few years later. Like Apollo 8, it will be an orbital mission that circles the Moon and returns. The astronauts will orbit the Moon longer and test everything with a crew.
Eventually, Artemis 3 will meet with the SpaceX Starship on the Moon's surface and transfer people. Orion will stay in orbit while the lunar Starship lands astronauts. They'll go to the Moon's south pole to investigate the water ice there.
Artemis is reminiscent of Apollo. What's changed in 50 years?
Kennedy wanted to beat the Soviets to the Moon with Apollo. The administration didn't care much about space flight or the Moon, but the goal would place America first in space and technology.
You live and die by the sword if you do that. When the U.S. reached the Moon, it was over. Russia lost. We planted flags and did science experiments. Richard Nixon canceled the program after Apollo 11 because the political goals were attained.
Large rocket with two boosters between two gates
NASA's new Space Launch System is brought to a launchpad. NASA
50 years later... It's quite different. We're not trying to beat the Russians, Chinese, or anyone else, but to begin sustainable space exploration.
Artemis has many goals. It includes harnessing in-situ resources like water ice and lunar soil to make food, fuel, and building materials.
SpaceX is part of this first journey to the Moon's surface, therefore the initiative is also helping to develop a lunar and space economy. NASA doesn't own the Starship but is buying seats for astronauts. SpaceX will employ Starship to transport cargo, private astronauts, and foreign astronauts.
Fifty years of technology advancement has made getting to the Moon cheaper and more practical, and computer technology allows for more advanced tests. 50 years of technological progress have changed everything. Anyone with enough money can send a spacecraft to the Moon, but not humans.
Commercial Lunar Payload Services engages commercial companies to develop uncrewed Moon landers. We're sending a radio telescope to the Moon in January. Even 10 years ago, that was impossible.
Since humans last visited the Moon 50 years ago, technology has improved greatly.
What other changes does Artemis have in store?
The government says Artemis 3 will have at least one woman and likely a person of color.
I'm looking forward to seeing more diversity so young kids can say, "Hey, there's an astronaut that looks like me. I can do this. I can be part of the space program.”
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Muhammad Rahmatullah
3 years ago
The Pyramid of Coding Principles
A completely operating application requires many processes and technical challenges. Implementing coding standards can make apps right, work, and faster.
With years of experience working in software houses. Many client apps are scarcely maintained.
Why are these programs "barely maintainable"? If we're used to coding concepts, we can probably tell if an app is awful or good from its codebase.
This is how I coded much of my app.
Make It Work
Before adopting any concept, make sure the apps are completely functional. Why have a fully maintained codebase if the app can't be used?
The user doesn't care if the app is created on a super server or uses the greatest coding practices. The user just cares if the program helps them.
After the application is working, we may implement coding principles.
You Aren’t Gonna Need It
As a junior software engineer, I kept unneeded code, components, comments, etc., thinking I'd need them later.
In reality, I never use that code for weeks or months.
First, we must remove useless code from our primary codebase. If you insist on keeping it because "you'll need it later," employ version control.
If we remove code from our codebase, we can quickly roll back or copy-paste the previous code without preserving it permanently.
The larger the codebase, the more maintenance required.
Keep It Simple Stupid
Indeed. Keep things simple.
Why complicate something if we can make it simpler?
Our code improvements should lessen the server load and be manageable by others.
If our code didn't pass those benchmarks, it's too convoluted and needs restructuring. Using an open-source code critic or code smell library, we can quickly rewrite the code.
Simpler codebases and processes utilize fewer server resources.
Don't Repeat Yourself
Have you ever needed an action or process before every action, such as ensuring the user is logged in before accessing user pages?
As you can see from the above code, I try to call is user login? in every controller action, and it should be optimized, because if we need to rename the method or change the logic, etc. We can improve this method's efficiency.
We can write a constructor/middleware/before action that calls is_user_login?
The code is more maintainable and readable after refactoring.
Each programming language or framework handles this issue differently, so be adaptable.
Clean Code
Clean code is a broad notion that you've probably heard of before.
When creating a function, method, module, or variable name, the first rule of clean code is to be precise and simple.
The name should express its value or logic as a whole, and follow code rules because every programming language is distinct.
If you want to learn more about this topic, I recommend reading https://www.amazon.com/Clean-Code-Handbook-Software-Craftsmanship/dp/0132350882.
Standing On The Shoulder of Giants
Use industry standards and mature technologies, not your own(s).
There are several resources that explain how to build boilerplate code with tools, how to code with best practices, etc.
I propose following current conventions, best practices, and standardization since we shouldn't innovate on top of them until it gives us a competitive edge.
Boy Scout Rule
What reduces programmers' productivity?
When we have to maintain or build a project with messy code, our productivity decreases.
Having to cope with sloppy code will slow us down (shame of us).
How to cope? Uncle Bob's book says, "Always leave the campground cleaner than you found it."
When developing new features or maintaining current ones, we must improve our codebase. We can fix minor issues too. Renaming variables, deleting whitespace, standardizing indentation, etc.
Make It Fast
After making our code more maintainable, efficient, and understandable, we can speed up our app.
Whether it's database indexing, architecture, caching, etc.
A smart craftsman understands that refactoring takes time and it's preferable to balance all the principles simultaneously. Don't YAGNI phase 1.
Using these ideas in each iteration/milestone, while giving the bottom items less time/care.
You can check one of my articles for further information. https://medium.com/life-at-mekari/why-does-my-website-run-very-slowly-and-how-do-i-optimize-it-for-free-b21f8a2f0162

cdixon
3 years ago
2000s Toys, Secrets, and Cycles
During the dot-com bust, I started my internet career. People used the internet intermittently to check email, plan travel, and do research. The average internet user spent 30 minutes online a day, compared to 7 today. To use the internet, you had to "log on" (most people still used dial-up), unlike today's always-on, high-speed mobile internet. In 2001, Amazon's market cap was $2.2B, 1/500th of what it is today. A study asked Americans if they'd adopt broadband, and most said no. They didn't see a need to speed up email, the most popular internet use. The National Academy of Sciences ranked the internet 13th among the 100 greatest inventions, below radio and phones. The internet was a cool invention, but it had limited uses and wasn't a good place to build a business.
A small but growing movement of developers and founders believed the internet could be more than a read-only medium, allowing anyone to create and publish. This is web 2. The runner up name was read-write web. (These terms were used in prominent publications and conferences.)
Web 2 concepts included letting users publish whatever they want ("user generated content" was a buzzword), social graphs, APIs and mashups (what we call composability today), and tagging over hierarchical navigation. Technical innovations occurred. A seemingly simple but important one was dynamically updating web pages without reloading. This is now how people expect web apps to work. Mobile devices that could access the web were niche (I was an avid Sidekick user).
The contrast between what smart founders and engineers discussed over dinner and on weekends and what the mainstream tech world took seriously during the week was striking. Enterprise security appliances, essentially preloaded servers with security software, were a popular trend. Many of the same people would talk about "serious" products at work, then talk about consumer internet products and web 2. It was tech's biggest news. Web 2 products were seen as toys, not real businesses. They were hobbies, not work-related.
There's a strong correlation between rich product design spaces and what smart people find interesting, which took me some time to learn and led to blog posts like "The next big thing will start out looking like a toy" Web 2's novel product design possibilities sparked dinner and weekend conversations. Imagine combining these features. What if you used this pattern elsewhere? What new product ideas are next? This excited people. "Serious stuff" like security appliances seemed more limited.
The small and passionate web 2 community also stood out. I attended the first New York Tech meetup in 2004. Everyone fit in Meetup's small conference room. Late at night, people demoed their software and chatted. I have old friends. Sometimes I get asked how I first met old friends like Fred Wilson and Alexis Ohanian. These topics didn't interest many people, especially on the east coast. We were friends. Real community. Alex Rampell, who now works with me at a16z, is someone I met in 2003 when a friend said, "Hey, I met someone else interested in consumer internet." Rare. People were focused and enthusiastic. Revolution seemed imminent. We knew a secret nobody else did.
My web 2 startup was called SiteAdvisor. When my co-founders and I started developing the idea in 2003, web security was out of control. Phishing and spyware were common on Internet Explorer PCs. SiteAdvisor was designed to warn users about security threats like phishing and spyware, and then, using web 2 concepts like user-generated reviews, add more subjective judgments (similar to what TrustPilot seems to do today). This staged approach was common at the time; I called it "Come for the tool, stay for the network." We built APIs, encouraged mashups, and did SEO marketing.
Yahoo's 2005 acquisitions of Flickr and Delicious boosted web 2 in 2005. By today's standards, the amounts were small, around $30M each, but it was a signal. Web 2 was assumed to be a fun hobby, a way to build cool stuff, but not a business. Yahoo was a savvy company that said it would make web 2 a priority.
As I recall, that's when web 2 started becoming mainstream tech. Early web 2 founders transitioned successfully. Other entrepreneurs built on the early enthusiasts' work. Competition shifted from ideation to execution. You had to decide if you wanted to be an idealistic indie bar band or a pragmatic stadium band.
Web 2 was booming in 2007 Facebook passed 10M users, Twitter grew and got VC funding, and Google bought YouTube. The 2008 financial crisis tested entrepreneurs' resolve. Smart people predicted another great depression as tech funding dried up.
Many people struggled during the recession. 2008-2011 was a golden age for startups. By 2009, talented founders were flooding Apple's iPhone app store. Mobile apps were booming. Uber, Venmo, Snap, and Instagram were all founded between 2009 and 2011. Social media (which had replaced web 2), cloud computing (which enabled apps to scale server side), and smartphones converged. Even if social, cloud, and mobile improve linearly, the combination could improve exponentially.
This chart shows how I view product and financial cycles. Product and financial cycles evolve separately. The Nasdaq index is a proxy for the financial sentiment. Financial sentiment wildly fluctuates.
Next row shows iconic startup or product years. Bottom-row product cycles dictate timing. Product cycles are more predictable than financial cycles because they follow internal logic. In the incubation phase, enthusiasts build products for other enthusiasts on nights and weekends. When the right mix of technology, talent, and community knowledge arrives, products go mainstream. (I show the biggest tech cycles in the chart, but smaller ones happen, like web 2 in the 2000s and fintech and SaaS in the 2010s.)

Tech has changed since the 2000s. Few tech giants dominate the internet, exerting economic and cultural influence. In the 2000s, web 2 was ignored or dismissed as trivial. Entrenched interests respond aggressively to new movements that could threaten them. Creative patterns from the 2000s continue today, driven by enthusiasts who see possibilities where others don't. Know where to look. Crypto and web 3 are where I'd start.
Today's negative financial sentiment reminds me of 2008. If we face a prolonged downturn, we can learn from 2008 by preserving capital and focusing on the long term. Keep an eye on the product cycle. Smart people are interested in things with product potential. This becomes true. Toys become necessities. Hobbies become mainstream. Optimists build the future, not cynics.
Full article is available here

Raad Ahmed
3 years ago
How We Just Raised $6M At An $80M Valuation From 100+ Investors Using A Link (Without Pitching)
Lawtrades nearly failed three years ago.
We couldn't raise Series A or enthusiasm from VCs.
We raised $6M (at a $80M valuation) from 100 customers and investors using a link and no pitching.
Step-by-step:
We refocused our business first.
Lawtrades raised $3.7M while Atrium raised $75M. By comparison, we seemed unimportant.
We had to close the company or try something new.
As I've written previously, a pivot saved us. Our initial focus on SMBs attracted many unprofitable customers. SMBs needed one-off legal services, meaning low fees and high turnover.
Tech startups were different. Their General Councels (GCs) needed near-daily support, resulting in higher fees and lower churn than SMBs.
We stopped unprofitable customers and focused on power users. To avoid dilution, we borrowed against receivables. We scaled our revenue 10x, from $70k/mo to $700k/mo.
Then, we reconsidered fundraising (and do it differently)
This time was different. Lawtrades was cash flow positive for most of last year, so we could dictate our own terms. VCs were still wary of legaltech after Atrium's shutdown (though they were thinking about the space).
We neither wanted to rely on VCs nor dilute more than 10% equity. So we didn't compete for in-person pitch meetings.
AngelList Roll-Up Vehicle (RUV). Up to 250 accredited investors can invest in a single RUV. First, we emailed customers the RUV. Why? Because I wanted to help the platform's users.
Imagine if Uber or Airbnb let all drivers or Superhosts invest in an RUV. Humans make the platform, theirs and ours. Giving people a chance to invest increases their loyalty.
We expanded after initial interest.
We created a Journey link, containing everything that would normally go in an investor pitch:
- Slides
- Trailer (from me)
- Testimonials
- Product demo
- Financials
We could also link to our AngelList RUV and send the pitch to an unlimited number of people. Instead of 1:1, we had 1:10,000 pitches-to-investors.
We posted Journey's link in RUV Alliance Discord. 600 accredited investors noticed it immediately. Within days, we raised $250,000 from customers-turned-investors.
Stonks, which live-streamed our pitch to thousands of viewers, was interested in our grassroots enthusiasm. We got $1.4M from people I've never met.
These updates on Pump generated more interest. Facebook, Uber, Netflix, and Robinhood executives all wanted to invest. Sahil Lavingia, who had rejected us, gave us $100k.
We closed the round with public support.
Without a single pitch meeting, we'd raised $2.3M. It was a result of natural enthusiasm: taking care of the people who made us who we are, letting them move first, and leveraging their enthusiasm with VCs, who were interested.
We used network effects to raise $3.7M from a founder-turned-VC, bringing the total to $6M at a $80M valuation (which, by the way, I set myself).
What flipping the fundraising script allowed us to do:
We started with private investors instead of 2–3 VCs to show VCs what we were worth. This gave Lawtrades the ability to:
- Without meetings, share our vision. Many people saw our Journey link. I ended up taking meetings with people who planned to contribute $50k+, but still, the ratio of views-to-meetings was outrageously good for us.
- Leverage ourselves. Instead of us selling ourselves to VCs, they did. Some people with large checks or late arrivals were turned away.
- Maintain voting power. No board seats were lost.
- Utilize viral network effects. People-powered.
- Preemptively halt churn by turning our users into owners. People are more loyal and respectful to things they own. Our users make us who we are — no matter how good our tech is, we need human beings to use it. They deserve to be owners.
I don't blame founders for being hesitant about this approach. Pump and RUVs are new and scary. But it won’t be that way for long. Our approach redistributed some of the power that normally lies entirely with VCs, putting it into our hands and our network’s hands.
This is the future — another way power is shifting from centralized to decentralized.