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.
Sara_Mednick
3 years ago
Since I'm a scientist, I oppose biohacking
Understanding your own energy depletion and restoration is how to truly optimize
Hack has meant many bad things for centuries. In the 1800s, a hack was a meager horse used to transport goods.
Modern usage describes a butcher or ax murderer's cleaver chop. The 1980s programming boom distinguished elegant code from "hacks". Both got you to your goal, but the latter made any programmer cringe and mutter about changing the code. From this emerged the hacker trope, the friendless anti-villain living in a murky hovel lit by the computer monitor, eating junk food and breaking into databases to highlight security system failures or steal hotdog money.
Now, start-a-billion-dollar-business-from-your-garage types have shifted their sights from app development to DIY biology, coining the term "bio-hack". This is a required keyword and meta tag for every fitness-related podcast, book, conference, app, or device.
Bio-hacking involves bypassing your body and mind's security systems to achieve a goal. Many biohackers' initial goals were reasonable, like lowering blood pressure and weight. Encouraged by their own progress, self-determination, and seemingly exquisite control of their biology, they aimed to outsmart aging and death to live 180 to 1000 years (summarized well in this vox.com article).
With this grandiose north star, the hunt for novel supplements and genetic engineering began.
Companies selling do-it-yourself biological manipulations cite lab studies in mice as proof of their safety and success in reversing age-related diseases or promoting longevity in humans (the goal changes depending on whether a company is talking to the federal government or private donors).
The FDA is slower than science, they say. Why not alter your biochemistry by buying pills online, editing your DNA with a CRISPR kit, or using a sauna delivered to your home? How about a microchip or electrical stimulator?
What could go wrong?
I'm not the neo-police, making citizen's arrests every time someone introduces a new plumbing gadget or extrapolates from animal research on resveratrol or catechins that we should drink more red wine or eat more chocolate. As a scientist who's spent her career asking, "Can we get better?" I've come to view bio-hacking as misguided, profit-driven, and counterproductive to its followers' goals.
We're creatures of nature. Despite all the new gadgets and bio-hacks, we still use Roman plumbing technology, and the best way to stay fit, sharp, and happy is to follow a recipe passed down since the beginning of time. Bacteria, plants, and all natural beings are rhythmic, with alternating periods of high activity and dormancy, whether measured in seconds, hours, days, or seasons. Nature repeats successful patterns.
During the Upstate, every cell in your body is naturally primed and pumped full of glycogen and ATP (your cells' energy currencies), as well as cortisol, which supports your muscles, heart, metabolism, cognitive prowess, emotional regulation, and general "get 'er done" attitude. This big energy release depletes your batteries and requires the Downstate, when your subsystems recharge at the cellular level.
Downstates are when you give your heart a break from pumping nutrient-rich blood through your body; when you give your metabolism a break from inflammation, oxidative stress, and sympathetic arousal caused by eating fast food — or just eating too fast; or when you give your mind a chance to wander, think bigger thoughts, and come up with new creative solutions. When you're responding to notifications, emails, and fires, you can't relax.
Downstates aren't just for consistently recharging your battery. By spending time in the Downstate, your body and brain get extra energy and nutrients, allowing you to grow smarter, faster, stronger, and more self-regulated. This state supports half-marathon training, exam prep, and mediation. As we age, spending more time in the Downstate is key to mental and physical health, well-being, and longevity.
When you prioritize energy-demanding activities during Upstate periods and energy-replenishing activities during Downstate periods, all your subsystems, including cardiovascular, metabolic, muscular, cognitive, and emotional, hum along at their optimal settings. When you synchronize the Upstates and Downstates of these individual rhythms, their functioning improves. A hard workout causes autonomic stress, which triggers Downstate recovery.
By choosing the right timing and type of exercise during the day, you can ensure a deeper recovery and greater readiness for the next workout by working with your natural rhythms and strengthening your autonomic and sleep Downstates.
Morning cardio workouts increase deep sleep compared to afternoon workouts. Timing and type of meals determine when your sleep hormone melatonin is released, ushering in sleep.
Rhythm isn't a hack. It's not a way to cheat the system or the boss. Nature has honed its optimization wisdom over trillions of days and nights. Stop looking for quick fixes. You're a whole system made of smaller subsystems that must work together to function well. No one pill or subsystem will make it all work. Understanding and coordinating your rhythms is free, easy, and only benefits you.
Dr. Sara C. Mednick is a cognitive neuroscientist at UC Irvine and author of The Power of the Downstate (HachetteGO)
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Percy Bolmér
3 years ago
Ethereum No Longer Consumes A Medium-Sized Country's Electricity To Run
The Merge cut Ethereum's energy use by 99.5%.
The Crypto community celebrated on September 15, 2022. This day, Ethereum Merged. The entire blockchain successfully merged with the Beacon chain, and it was so smooth you barely noticed.
Many have waited, dreaded, and longed for this day.
Some investors feared the network would break down, while others envisioned a seamless merging.
Speculators predict a successful Merge will lead investors to Ethereum. This could boost Ethereum's popularity.
What Has Changed Since The Merge
The merging transitions Ethereum mainnet from PoW to PoS.
PoW sends a mathematical riddle to computers worldwide (miners). First miner to solve puzzle updates blockchain and is rewarded.
The puzzles sent are power-intensive to solve, so mining requires a lot of electricity. It's sent to every miner competing to solve it, requiring duplicate computation.
PoS allows investors to stake their coins to validate a new transaction. Instead of validating a whole block, you validate a transaction and get the fees.
You can validate instead of mine. A validator stakes 32 Ethereum. After staking, the validator can validate future blocks.
Once a validator validates a block, it's sent to a randomly selected group of other validators. This group verifies that a validator is not malicious and doesn't validate fake blocks.
This way, only one computer needs to solve or validate the transaction, instead of all miners. The validated block must be approved by a small group of validators, causing duplicate computation.
PoS is more secure because validating fake blocks results in slashing. You lose your bet tokens. If a validator signs a bad block or double-signs conflicting blocks, their ETH is burned.
Theoretically, Ethereum has one block every 12 seconds, so a validator forging a block risks burning 1 Ethereum for 12 seconds of transactions. This makes mistakes expensive and risky.
What Impact Does This Have On Energy Use?
Cryptocurrency is a natural calamity, sucking electricity and eating away at the earth one transaction at a time.
Many don't know the environmental impact of cryptocurrencies, yet it's tremendous.
A single Ethereum transaction used to use 200 kWh and leave a large carbon imprint. This update reduces global energy use by 0.2%.
Ethereum will submit a challenge to one validator, and that validator will forward it to randomly selected other validators who accept it.
This reduces the needed computing power.
They expect a 99.5% reduction, therefore a single transaction should cost 1 kWh.
Carbon footprint is 0.58 kgCO2, or 1,235 VISA transactions.
This is a big Ethereum blockchain update.
I love cryptocurrency and Mother Earth.
Amelia Winger-Bearskin
3 years ago
Reasons Why AI-Generated Images Remind Me of Nightmares
AI images are like funhouse mirrors.
Google's AI Blog introduced the puppy-slug in the summer of 2015.
Puppy-slug isn't a single image or character. "Puppy-slug" refers to Google's DeepDream's unsettling psychedelia. This tool uses convolutional neural networks to train models to recognize dataset entities. If researchers feed the model millions of dog pictures, the network will learn to recognize a dog.
DeepDream used neural networks to analyze and classify image data as well as generate its own images. DeepDream's early examples were created by training a convolutional network on dog images and asking it to add "dog-ness" to other images. The models analyzed images to find dog-like pixels and modified surrounding pixels to highlight them.
Puppy-slugs and other DeepDream images are ugly. Even when they don't trigger my trypophobia, they give me vertigo when my mind tries to reconcile familiar features and forms in unnatural, physically impossible arrangements. I feel like I've been poisoned by a forbidden mushroom or a noxious toad. I'm a Lovecraft character going mad from extradimensional exposure. They're gross!
Is this really how AIs see the world? This is possibly an even more unsettling topic that DeepDream raises than the blatant abjection of the images.
When these photographs originally circulated online, many friends were startled and scandalized. People imagined a computer's imagination would be literal, accurate, and boring. We didn't expect vivid hallucinations and organic-looking formations.
DeepDream's images didn't really show the machines' imaginations, at least not in the way that scared some people. DeepDream displays data visualizations. DeepDream reveals the "black box" of convolutional network training.
Some of these images look scary because the models don't "know" anything, at least not in the way we do.
These images are the result of advanced algorithms and calculators that compare pixel values. They can spot and reproduce trends from training data, but can't interpret it. If so, they'd know dogs have two eyes and one face per head. If machines can think creatively, they're keeping it quiet.
You could be forgiven for thinking otherwise, given OpenAI's Dall-impressive E's results. From a technological perspective, it's incredible.
Arthur C. Clarke once said, "Any sufficiently advanced technology is indistinguishable from magic." Dall-magic E's requires a lot of math, computer science, processing power, and research. OpenAI did a great job, and we should applaud them.
Dall-E and similar tools match words and phrases to image data to train generative models. Matching text to images requires sorting and defining the images. Untold millions of low-wage data entry workers, content creators optimizing images for SEO, and anyone who has used a Captcha to access a website make these decisions. These people could live and die without receiving credit for their work, even though the project wouldn't exist without them.
This technique produces images that are less like paintings and more like mirrors that reflect our own beliefs and ideals back at us, albeit via a very complex prism. Due to the limitations and biases that these models portray, we must exercise caution when viewing these images.
The issue was succinctly articulated by artist Mimi Onuoha in her piece "On Algorithmic Violence":
As we continue to see the rise of algorithms being used for civic, social, and cultural decision-making, it becomes that much more important that we name the reality that we are seeing. Not because it is exceptional, but because it is ubiquitous. Not because it creates new inequities, but because it has the power to cloak and amplify existing ones. Not because it is on the horizon, but because it is already here.
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!