Month: March 2024

A new study this week points to a potential transmission risk of Alzheimer’s disease. Researchers found evidence in mice that an inherited form of the neurological disorder can be passed on via bone marrow donation. While such a danger has yet to be confirmed in humans and likely to be infrequent if it can happen, the authors say more research has to be done to investigate the possibility.

The research was led by scientists from the University of British Columbia. They were interested in studying cells that produce something known as the amyloid precursor protein (APP)—proteins that seem to have several important functions but can also be turned into amyloid beta, a protein thought to play a driving role in causing Alzheimer’s disease. In those with Alzheimer’s, a misfolded and damaging version of amyloid beta accumulates in the brain, eventually forming into clumped-together deposits called plaques (a similar process occurs with the tau protein).

Most cases of Alzheimer’s are caused by multiple factors working together, such as age-related changes in the brain. But there are known inherited mutations that can make someone much more likely to develop it, usually at an earlier age than normal. Some of these mutations involve the gene that regulates APP production in cells. APP-producing cells aren’t just found in the brain, though, but throughout the body, including within our bone marrow. So the authors, led by immunologist Wilfred Jefferies, were curious about the potential of these outside cells to cause Alzheimer’s as well.

“We wondered, therefore, whether a familial form of Alzheimer’s disease could be initiated in a mouse after injection of the bone marrow from an afflicted mouse into the bloodstream of a normal mouse,” Jefferies told Gizmodo in an email.

The team first bred mice carrying a defective version of the APP gene found in humans, one that would ensure their development of Alzheimer’s. Then they transplanted bone marrow from these mice to two other groups of mice: mice with a normal APP gene and mice bred to have no APP gene at all. Following the transplantation, both groups of mice developed symptoms of cognitive impairment and clear signs of Alzhemer’s, such as plaque build-up in the brain. Those without the APP gene became sick quicker than expected, however, showing symptoms at six months old on average (both the original and normal APP-carrying mice began to show symptoms around nine months).

The findings, published Thursday in Stem Cell Reports, appear to demonstrate that “the mutated gene in the donor cells can transfer and cause” Alzheimer’s, Jefferies said. And while the mice without APP became sicker faster, the results suggest that even healthy individuals could be at risk from this route of infection.

Other scientists have found evidence that Alzheimer’s can be transmitted between people, though only under very rare and specific conditions, such as the donation of contaminated human growth hormone extracted from cadaver brains (a practice long since ended). And if there is a real transmission risk of familial Alzheimer’s via bone marrow transplantation, it’s likely to be low.

But based on their findings, the authors do “urge further investigation of this phenomenon,” Jeffries said. “We also advocate that human donors of blood, tissue, organ, and stem cells should be screened to prevent the inadvertent transfer of disease during blood product transfusions and cellular therapies.”

The authors plan to keep looking into the matter themselves. They would like to better understand exactly how these donated APP-producing stem cells, which can only turn into blood cells or platelets, not neurons, go on to trigger Alzheimer’s. They also hope to study whether other types of transplantation can transmit the disease or whether it’s possible to treat Alzheimer’s by transplanting normal cells to those afflicted with the condition; early animal trials involving stem cells have found some promising results for this approach.

There’s a new boss at a storied 47-year-old Formula 1 team, and he’s eager to shake things up. He’s been saying that the team is far behind its competition in technology and coordination. And Excel is a big part of it.

Starting in early 2023, Williams team principal James Vowles and chief technical officer Pat Fry started reworking the F1 team’s systems for designing and building its car. It would be painful, but the pain would keep the team from falling even further behind. As they started figuring out new processes and systems, they encountered what they considered a core issue: Microsoft Excel.

The Williams car build workbook, with roughly 20,000 individual parts, was "a joke," Vowles recently told The Race. "Impossible to navigate and impossible to update." This colossal Excel file lacked for information on how much each of those parts cost and the time it took to produce them, along with whether parts were already on order. Prioritizing one car section over another, from manufacture through inspection, was impossible, Vowles suggested.

"When you start tracking now hundreds of 1000s of components through your organisation moving around, an Excel spreadsheet is useless," Vowles told The Race (which uses British spellings). Because of the multiple states each part could be in—ordered, backordered, inspected, returned—humans are often left to work out the details. "And once you start putting that level of complexity in, which is where modern Formula 1 is, the Excel spreadsheet falls over, and humans fall over. And that’s exactly where we are."

The consequences of this row/column chaos, and the resulting hiccups, were many. Williams missed early pre-season testing in 2019. Workers sometimes had to physically search the team’s factory for parts. The wrong parts got priority, other parts came late, and some piled up. And yet transitioning to a modern tracking system was "viciously expensive," Fry told The Race, and making up for the painful process required "humans pushing themselves to the absolute limits and breaking."

The devil you know strikes again

The idea that a modern Formula 1 team, building some of the most fantastically advanced and efficient machines on Earth, would be using Excel to build those machines might strike you as odd. F1 cars cost an estimated $12-$16 million each, inside a resource cap of about $145 million. But none of this really matters, and it actually makes sense, if you’ve ever worked IT at nearly any decent-sized organization.

Then again, it’s not even uncommon in Formula 1. When Sebastian Anthony embedded with the Renault team, he reported back for Ars in 2017 that Renault Sport Formula One’s Excel design and build spreadsheet was 77,000 lines long—more than three times as large as the Williams setup that spurred an internal revolution in 2023.

Every F1 team has its own software setup, Anthony wrote, but they have to integrate with a lot of other systems: Computational Fluid Dynamics (CFD) and wind tunnel results, rapid prototyping and manufacturing, and inventory. This leaves F1 teams "susceptible to the plague of legacy software," Anthony wrote, though he noted that Renault had moved on to a more dynamic cloud-based system that year. (Renault was also "a big Microsoft shop" in other areas, like email and file sharing, at the time.)

One year prior to Anthony’s excavation, Adam Banks wrote for Ars about the benefits of adopting cloud-based tools for enterprise resource planning (ERP). You adopt a cloud-based business management software to go "Beyond Excel." "If PowerPoint is the universal language businesses use to talk to one another, their internal monologue is Excel," Banks wrote. The issue is that all the systems and processes a business touches are complex and generate all kinds of data, but Excel is totally cool with taking in all of it. Or at least 1,048,576 rows of it.

Banks cited Tim Worstall’s 2013 contention that Excel could be "the most dangerous software on the planet." Back then, international investment bankers were found manually copying and pasting Excel between Excel sheets to do their work, and it raised alarm.

But spreadsheets continue to show up where they ought not. Spreadsheet errors in recent years have led to police doxxing, false trainee test failures, an accidental $10 million crypto transfer, and bank shares sold at sorely undervalued prices. Spreadsheets are sometimes called the "dark matter" of large organizations, being ever-present and far too relied upon despite 90 percent of larger sheets being likely to have a major error.

So Excel sheets catch a lot of blame, even if they’re just a symptom of a larger issue. Still, it’s good to see one no longer connected to the safety of a human heading into a turn at more than 200 miles per hour.

Have you ever worked on a hobby project where modifying and compiling the source code for a Linux-based emulator was possibly the easiest and most straightforward part of the whole thing?

Kevin Noki really, really wanted a functioning Macintosh Plus, complete with a functioning, auto-ejecting disk drive that it could boot from. The German maker already had a Mac Plus (1Mb) from eBay, but it had both a busted power supply and floppy drive. Rather than carve out the busted Plus’ one-of-a-kind internals and slap a Raspberry Pi in there like some DIY slacker, Noki went … a different path.

Noki 3D-printed his own Macintosh, the "Brewintosh." I would like you to consider what you think that last sentence means and then wipe your expectations clean. I have watched the entire 48-minute journey of Noki’s Brewintosh, which is both very soothing on some ASMR-adjacent gut level and also low-key maddening for the way it plays down all the individual accomplishments along the way. Any one of the Brewintosh’s pieces would be my entire weekend, and my spouse would not enjoy my mood while I was sunk into it.

But Noki, over what he reports as "months," essentially works backward from 2024, using every kind of maker tool and skill to get back to a working 1986 Mac. Not just "classic Mac OS on a properly sized AliExpress monitor," mind you. We are talking a properly sized, colored, and textured box, which takes wall power, swallows 3.5-inch disks, works with both telephone-cord and ADB Apple keyboards and mice, has a screen dimmer, and makes the startup sound (the beep, not the chord). It’s not a "loving" tribute, it’s uncanny and potentially unnerving.

If you wanted a non-historic but ultra-authentic Mac like Noki’s, this is the somehow-not-exhaustive list of 29 things for which you would have to have the tools, skills, and patience:

• Meticulously measuring every single surface and angle of a Macintosh Plus
• Re-create those measurements and model them in AutoDesk Fusion 360
• Print the Mac case in four parts using a modified Ender-3 with gray PLA filament
• Apply one-part plastic filler and sand down the planes where the case pieces would join
• Drill registration holes in the case parts for metal pin connectors
• Use cyanoacrylate (CA) glue to join pieces and repeatedly sand every part with 3D layers showing
• Spray-paint both a primer and final beige color on the outward-facing parts
• Use a vinyl cutter to protect the case parts that should be smooth
• Apply textured clear-coat to replicate the Mac’s rough texture
• Disassemble a 10-inch screen that was a thrift-store find
• Replace the screen’s CCFL with LED lighting
• Rewire and solder a dimmer knob onto the screen to create a dimming control
• De-solder and modify a laptop charging brick to make a power assembly
• Modify a powered USB hub and its AC adapter
• Dye a physical power switch to match its proper case color
• Use WAGO connectors to connect power components safely
• Disassemble a $13 thin client computer and replace its power jack with an XT60
• Wire in a resistor to make that power supply work with an outside adapter
• Replace the thin client’s power button with an Arduino-controlled relay
• Build a front keyboard and mouse connector out of a Teensy USB dev board, RJ11 jack, and TMK keyboard firmware.
• Solder and wire in an internal speaker
• Rebuild a USB floppy drive reader with an Arduino-controlled stepper motor (that you coded) to eject disks from software controls
• Built an ADB peripheral board with a KiCAD design, a Teensy board, and an Arduino Pro Micro
• Configure an ATtiny85 to control mainboard and screen power, and play the startup sound
• Build a modified Mini vMac emulator inside a Linux system
• Design your own Brewintosh raised-text stereotype and apply foil to it with a laminator
• Create custom-designed Brewintosh multicolor stickers, print them, apply UV resin for a glossy finish, and cure them
• Design and print a replica sticker of the original Mac’s back panel
• Record yourself doing all these things and edit them into an engaging video.

I didn’t include the smaller ("smaller") things Noki 3D-printed in that list because I respect your scroll fingers. You also have to design and accurately print at least 12 other components. That list includes the feet in resin, a screen board holder, an inner frame, power assembly cover, power cabling routing box, audio jack holder, USB port and SD card holder, internal speaker chassis, disk drive stepper motor attachment, manual disk eject, the brightness control dial, and probably a dozen tiny things Noki doesn’t even mention.

I am not actually suggesting anybody with a biologically limited lifespan attempt what Noki has done here. If you tackled each component and 3D-printed part as individual weekend projects, it adds up to more than 40 weeks. Mind you, printing the 3D parts alone took 48 hours, according to Noki. But even that spread presumes that you’re starting from the obvious familiarity Noki has with all his printers, cutters, and tools. He doesn’t include any mistakes or missteps in his video, but you just know in your heart that you would reach a certain point in the assembly and realize that something just doesn’t fit at all, so you must go back and do it, and possibly two or three other whole things, again.

Watching this video did a number on me. Seeing the astounding number of skills on display, paired with the Steven Jobs-like attention to detail, can be overwhelmingly intimidating or simply affirming and wonderful, depending on how you take it in. Someone in the YouTube comments points out a little bit that Noki himself doesn’t even mention in his subtitle text: that the monitor stays off until the vMac emulator has started and produced the tiny smiling Mac icon. All of that, just to get to the point where you can play 3D chess or use MacPaint in a little beige time machine.