Saturday, August 16, 2025

From MIT -- mRNA -- August 16, 2025

Locator: 48876MRNA.

Link here

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No-Pain Gains
or
No Pain, No Gain

From recent issue of The New Yorker. Link here.

Fascinating. 

Nerve cells have ion channels. 

One thing nerve cells do is transmit pain.

The McGill Pain Questionnaire, developed in 1971, comprises seventy-eight words for pain.

To transmit nerve signals, nerve cell membranes have ion channels which open and close and in the process transmit the sensation of pain from the periphery of the body to the central nervous system, the brain. 

There are five kinds of ions that are involved in the nerve membrane ionic channels:

  • sodium
  • calcium
  • potassium
  • chloride
  • hydrogen

A NaV1.8 nerve blocker is a drug that inhibits the function of the Nav1.8 sodium channel, which is predominantly found in peripheral nerve cells involved in transmitting pain signals. By blocking this channel, these drugs can reduce or prevent the transmission of pain signals from the site of injury to the central nervous system, potentially offering relief from various types of pain, particularly neuropathic pain. 

In January, 2025, this year, suzetrigine, under the name Journavx, became the first new non-opioid painkiller in more than twenty years to receive FDA approval for acute-pain treatment.  

Journavx, suzetrigine, was developed by Vertex Pharmaceuticals. 


Bummer.

Link here.

Vertex stock nose-dived Tuesday after the biotech company said it wouldn't advance its next-generation pain drug into additional testing.

The decision follows a lackluster midstage study in which the drug, dubbed VX-993, missed its mark in patients with acute pain following a bunion removal. Vertex Pharmaceuticals (VRTX) said it won't run additional tests of VX-993 as a solo treatment for acute pain.

Further, following discussions with the Food and Drug Administration, Vertex said it doesn't see a path forward in acute pain treatment for its approved pain drug, suzetrigine (Journavx), as a treatment for broad neuropathic pain. Instead, the company will focus on diabetic neuropathy, a smaller 20% piece of the overall chronic pain market. The drug is already approved as a treatment for moderate to severe acute pain in adults.

The news "will likely dampen exuberance around how easily VRTX will be able to capture the broadest pain revenue opportunity," RBC Capital Markets analyst Brian Abrahams said in a report. Analysts had valued the pain opportunity at $25 billion.

On today's stock market, August 5, 2025, shares skidded 20.6% to 374.98. Vertex stock undercut its 50-day and 200-day moving averages, but remained within a consolidation with a buy point at 519.88, MarketSurge shows.

From wiki:

However, in clinical studies, suzetrigine (Journavx) no superiority over hydrocodone and paracetamol (acetaminophen) in terms of pain reduction was shown. 

The approval of Journavx was met with criticism from medical professionals, where its efficacy was deemed inferior to opioid analgesics. Moreover, there are no studies comparing suzetrigine with full-dose opioids, and its cost-effectiveness is disputed.

Most patients in clinical trials required rescue NSAID administration. An important drawback compared to opioids is that suzetrigine exhibits CYP3A4-mediated drug interactions and there is limited long-term data regarding its use.

After all that time, money, and resources, suzetrigine was no more effective than Tylenol.

Rambling: META's 4Q25 -- Santa Barbara ASIC Chips -- In-House -- August 16, 2025

Locator: 48875META.

It's hard to believe -- I posted this back in 2023:

Original Post 

These stories are tracked herehttps://themilliondollarway.blogspot.com/2020/11/quick-how-many-transistors-on-new-apple.html.

Link herehttps://blockworks.co/news/intel-bitcoin-mining-chip.US tech giant Intel has cooled on bitcoin mining after discontinuing its practically new Blockscale 1000 chip series.

The move comes about a year after Intel announced its standalone crypto mining chip, pegged to be more powerful and energy efficient than top-of-the-line ASICs [application-specific integrated circuit].

“As we prioritize our investments in IDM 2.0, we have end-of-lifed the Intel Blockscale 1000 Series ASIC while we continue to support our Blockscale customers,” Intel told Blockworks via email on Wednesday.

IDM 2.0 refers to Intel’s strategy of utilizing third-party foundries to manufacture products including graphics and chipsets.

Intel’s decision to axe its mining chips was first reported by tech outlet Tom’s Hardware, which noted the company often cites a focus on IDM 2.0 when it plans to tighten resources or pull out of businesses.

Intel had previously announced its Blockscale ASIC (application-specific integrated circuit) would ship in the third quarter of 2022, and named Argo Blockchain, Block (formerly Square), GRIID Infrastructure and Hive Blockchain as its first customers.

Hive Blockchain later touted Intel’s chips as playing an important role in improving the efficiency of its ASIC fleet.

But the company now anticipates it will cease taking orders for Blockscale in another five months and stop shipping the chip by April 20 next year, Reuters reported, citing a document on Intel’s website.

N.B. When first announcing its energy-efficient computing technology in Feb. 2022, Intel’s former graphics chief Raja Koduri said a custom compute group would be created within the company’s Accelerated Computing Systems and Graphics business unit.

N.B. However, Intel split the unit in December to focus on “critical growth engines” and Koduri returned to his previous position as Intel’s chief architect.

N.B. Not long after, Koduri left Intel to create an AI-focused software company, CEO Pat Gelsinger said on Twitter.

Intel signaled that it isn’t completely turning away from the bitcoin market. “We continue to monitor market opportunities,” the chipmaker said.

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Update: Posted August 16, 2025

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ASIC

An ASIC, which stands for Application-Specific Integrated Circuit, is a microchip designed for a specific task or application, rather than being a general-purpose processor like a CPU. Essentially, it's a chip optimized for a single, well-defined function, offering high performance and efficiency for that particular task. 

ASIC, wiki

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META

Now, look at this from Beth today.

This is an absolutely awful site with all the ads, but it provides a simplistic update of Meta and ASIC. Link here.

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What Caught My Attention: Cooling.

For my investment purposes, AI runs on:

  • concrete;
  • cooling;
  • natural gas; and,
  • copper.

In Beth's note above, the obvious question: who is taking care of / managing the cooling?

Ask ChatGPT:

When it comes to Meta’s cooling infrastructure for its proprietary ASIC-powered server platforms (such as the upcoming “Santa Barbara” AI servers), the company has partnered with SynMing Electronics to deliver specialized water-cooling components. These include highly customized cabinets, sidecars, and liquid-cooling hardware designed to handle the exceptionally high thermal demands (TDP >180 kW) of these next-gen servers.

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META's "Santa Barbara" AI Servers

Holy mackerel!

Link here.

There are a handful of trillion-dollar companies that have the "hammer" on AI / large data centers. A handful would mean around ten. 

META is probably among the top five. Maybe the top three. Maybe number one. 

From the link above:

Meta has placed an order for next-generation ASIC-powered AI servers with Taiwanese manufacturer Quanta Computer.

According to a report from Economic Daily News (EDN), Meta has ordered up to 6,000 racks and plans to start deploying the AI servers, code-named Santa Barbara, by the end of 2025.

The Santa Barbara servers will replace Meta’s existing Minerva servers, with the report adding that the next-generation servers will have a TDP (Thermal Design Power) of more than 180kW and require highly customized cabinets, sidecars, and water-cooling components, all of which will be supplied by Chenming Electronic Tech Corp.

The report further claims that Meta has partnered with Broadcom for the supply of the ASIC chips, while Quanta Computer is handling the final assembly of the servers. Citing “supply chain sources,” EDN said the social media firm has finalized design decisions related to two to three new ASIC AI servers, and will decide on the final design this quarter, before starting trial production in Q4 2025.

Since the start of the generative AI boom, Meta has sought to significantly expand its AI server infrastructure and in-house ASIC development. In February 2024, the company was seemingly on the hunt for ASIC engineers, posting job adverts seeking workers with expertise in architecture, design, and testing in Bangalore, India, and Sunnyvale, California.
Although the job adverts didn’t reference any specific project, Meta has its own custom AI chips in development. Dubbed the Meta Training and Inference Accelerator (MTIA), the chips have been in development since 2023, with the company hoping to deploy them in its own data centers in an effort to reduce its reliance on Nvidia.

So much more at the link.

Minerva?

Meta develops its Minerva servers internally through their Infrastructure Hardware Design team and partners with external companies for various components and manufacturing.

Specifically, Celestica is mentioned as a Joint Development Manufacturer (JDM) partner in the Minerva project. Additionally, reports indicate that Meta has partnered with Broadcom for the ASIC chips and Quanta Computer for the final assembly of the Minerva servers.

It's important to note that the Minerva servers are being replaced by Meta's next-generation servers, code-named Santa Barbara, with deployment expected to begin in late 2025. The Santa Barbara servers will also feature custom ASIC chips from Broadcom and final assembly by Quanta Computer.

Quanta Computer: dead money the last two years --

Broadcom, this one surprised me ... a market cap of almost $1.5 trillion.

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Disclaimer
Brief Reminder 

Briefly:

  • I am inappropriately exuberant about the Bakken and I am often well out front of my headlights. I am often appropriately accused of hyperbole when it comes to the Bakken.
  • I am inappropriately exuberant about the US economy and the US market.
  • I am also inappropriately exuberant about all things Apple. 
  • See disclaimer. This is not an investment site. 
  • Disclaimer: this is not an investment site. Do not make any investment, financial, job, career, travel, or relationship decisions based on what you read here or think you may have read here. All my posts are done quickly: there will be content and typographical errors. If something appears wrong, it probably is. Feel free to fact check everything.
  • If anything on any of my posts is important to you, go to the source. If/when I find typographical / content errors, I will correct them. 
  • Reminder: I am inappropriately exuberant about the Bakken, US economy, and the US market.
  • I am also inappropriately exuberant about all things Apple. 
  • And now, Nvidia, also. I am also inappropriately exuberant about all things Nvidia. Nvidia is a metonym for AI and/or the sixth industrial revolution.
  • I've now added Broadcom to the disclaimer. I am also inappropriately exuberant about all things Broadcom.
  • Longer version here.    

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Top Five Companies Among Consumer Electronics

The companies:

  • Apple
  • Samsung Electronics
  • Microsoft
  • Sony
  • Huawei

For me: there are only two for investing.

A Most Interesting List Of Ten -- August 16, 2025

Locator: 48874INVESTING.

Before we get started, this graphic:

Now, back to the interesting list of ten.

Link here.

We've talked about gas turbines before. See backstory.

The top ten:

  • Palantir: data mining, everywhere, especially in the US government, and more specifically, the military; the gold standard
  • GE Vernova: about the only natural-gas turbine manufactured in the US; competes with Siemens, Europe;
  • Newmont: gold mining
  • Seagate: data storage; US but "HQ" in Dublin, Ireland; second to none?
  • Western Digital: data storage, San Jose, CA; one of the world's largest hard drive manufacturers in the world;
  • NRG Energy: energy generation; "HQ" in Houston, Texas
  • EBay:
  • GE Aerospace:
  • Idexx: animal veterinary research

I think I've heard CNBC mention only one of those on a regular basis: Palantir.

Occasionally: GE Vernova. 

Maybe GE Aerospace but none of the rest are "ever" mentioned.

Amphenol: electrical and fiber optic connectors; coaxial cables.

My Favorite Chart -- August 16, 2025

Locator: 48873MMF.

Money market fund assets. Updated two days ago. Link here.


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Movie Night Tonight


The original with Aussie dialogue. No dubbing.

1979.

Backstory is amazing.
 
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TV Series Later

Mash.

Starting with season 1, episode 1.

The episodes were produced by 20th Century Fox Television for the CBS network and aired from September 17, 1972, to February 28, 1983. The series, which covered a three-year military conflict, spanned 251 episodes, including the 2.5 hour finale over 11 seasons.

Me?

  • 1969: graduated from high school.
  • 1973: graduated from college. Mash, first full season, 1972 - 1973.
  • 1977: graduated from medical school. 
  • 1980: completed three years of residency.
  • 1983: first full military tour. Mash, final season ends, 1983.

Amazing, Mash was exactly contemporaneous with my medical training ad first Air Force tour as a physician. I probably did not miss (m)any episodes. 

Hard to believe: Mash takes place in 1950. North Korea -- 75 years of worthlessness. Korean War Armistice signed July 23, 1953.

Investing -- How Many Of These Were Around When I Started Investing In 1984? Posted August 16, 2025

Locator: 48872INVESTING.

Link here.

How many of these were available when I started investing in 1984?

2Q25 updates for Drunkenmiller, link here:


Coal, link here:

Public School Education -- August 16, 2025

Locator: 48871EDUCATION.

Nationally, link here, as of February, 2025:

Across the United States, federal, state, and local governments provide $878.2 billion or $17,700 per pupil to fund K-12 public education.

Williston school district; link here. Webpage here.

  • Williston Basin School District #7
  • "revenue": $88 million
  • budget: $87 million
  • surplus: $1 million
  • number of students: 5,235 students
  • $88 million / 5,235 = $16,810 / student

Trump Setbacks -- August 16, 2025

Locator: 48870ARCHIVES.

This past week has to be one of the worst weeks for Trump since his re-election. Nothing seemed to go right.

  • bookends:
    • extends tariff decision on China for another 90 days;
    • red carpet treatment for Putin resulted in nothing and set a record for shortest international summit ever;
      • doesn't even take questions at end of summit; 
      • apparently a "Biden-in-the-headlights" moment -- what the hell just happened? 
      • my wife's hunch: from the get-go, SecState Rubio knew this was a non-starter and told Trump to "get out [of Alaska now]” before Trump is sucked into an even bigger trap
        • Rubio knew from the get-go that Putin was not interested in talking;
        • it was all about the photo-op: a shaking of hands with President Trump
  • Intel boondoggle sits at the top of my "craziness list"; 
    • first he wants the Chinese-connected CEO to exit stage left
    • then he suggests he may take a stock position in Intel; says CEO is right man for right job
  • DC setback on something that seemed so obvious -- fighting crime; cleaning up DC
  • more states than ever are now planning massive gerrymandering to counter Trump's Texas proposal to gain five GOP seats
    • good news: The NYT says the GOP nationally has more to gain than the Democrats 
    • exhibit A: there are "no" GOP districts in California north of San Francisco or south of Legoland
      • there may be three GOP districts between Los Angeles and San Francisco 
      • California has 52 US congressional districts.

Many more weeks like this and the mid-term elections could be a disaster.