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Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
@NickAnderegg
Aug 6, 2024 • 30 tweets • 12 min read • Read on X
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THIS IS BIG. WOW. New paper in PLOS Pathogens has findings about:
- the effect of the SARS-CoV-2 spike protein on cardiac cells (and mitochondrial dysfunction!),
- a treatment to be investigated, and
- how this is NOT caused by mRNA vaccines!

Buckle up, we're diving in...

1/ Published August 5, 2024 in PLOS Pathogens: "SARS-CoV-2 spike-induced syncytia are senescent and contribute to exacerbated heart failure" "Author Summary In this paper, we directly linked SARS-2-S-triggered syncytium [fused cells] formation in the absence of infection with the ensuing induction of cellular senescence and its pathophysiological contribution to heart failure. We propose that both SARS-2-S expression and SARS-2-S protein internalization were sufficient to induce senescence in nonsenescent ACE2expressing cells. This is important because of the persistent existe...
[This paper is an uncorrected proof; it's been peer-reviewed, but not copyedited yet.]

A bit of background: syncytia (sin-sih-sha) are giant cells with multiple nuclei that form from the fusion of multiple cells. Viral infections are a common cause of syncytia.

2/
"Abstract SARS-CoV-2 spike protein (SARS-2-S) induced cell–cell fusion in uninfected cells may occur in long COVID-19 syndrome, as circulating SARS-2-S or extracellular vesicles containing SARS-2-S (S-EVs) were found to be prevalent in post-acute sequelae of COVID-19 (PASC) for up to 12 months after diagnosis. ... Here, we found that the senescent outcome of SARS-2-S induced syncytia exacerbated heart failure progression. We first demonstrated that syncytium formation in cells expressing SARS-2-S delivered by DNA plasmid or LNP-mRNA exhibits a senescence-like phenotype. Extracellular ...
NIH > National Library of Medicine Medical Subject Headings MeSH Descriptor Data 2024 Giant Cells (aka syncytia) Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. Entry Term(s): Giant Cells, Multinucleated; Multinucleated Giant Cells; Polykaryocytes; Syncytia; Syncytium;
The authors had two motivations for this study:

1. Cardiac complications are a major feature of COVID.
2. Patients with heart failure tend to experience very poor outcomes from COVID.

Really, it hasn't been entirely clear *how* COVID leads to heart failure... until now?

3/ "Introduction ...Although symptoms resulting from infection typically resolve within weeks, some individuals experience persistent symptoms following the acute phase of COVID-19, the so-called post-acute sequelae of COVID-19 (PASC) or long COVID [2–4]. SARS-CoV-2 infection predominantly offends the respiratory system. Currently, evidence has suggested cardiac complications as one of the important pathogenic features of COVID-19 [5,6]. More importantly, compared with patients without heart failure, those with diagnosed heart failure experienced a longer length of hospital stay, increas...
Syncytia form when the spike protein present on the surface of one cell makes contact with another cell.

This study went a step further by looking at how *extracellular* vesicles containing the spike protein can fuse cells... *without* active infection.

4/ "SARS-CoV-2 syncytium constitutes a hallmark of COVID-19-associated pathology and may potentially contribute to pathology by facilitating viral dissemination, cytopathy, immune evasion, and the inflammatory response [12]. ... In addition to mediate viral-cell fusion, the presence of SARS-2-S on the cell surface is sufficient to mediate cell-cell fusion, a mechanism called fusion from within (FFWI)[14,15]. The fusogenic activity of SARS-2-S is potent, as even undetectable amounts of SARS-2-S can cause cell-cell fusion [14]. In addition to mediating FFWI, viruslike particles or lipid ves...
Why do syncytia matter?

They're a potential route for the spike protein to cause damage even AFTER an active infection has subsided.

Like some other viruses, SARS-CoV-2 can cause cell senescence—which is when the cell replication cycle stops, and the cells degrades.

5/ "SARS-CoV-2 elicits the senescence of infected cells, similar to other viruses (virus-induced senescence, VIS). Cellular senescence is a state of stable cell cycle arrest characterized by ... induction of the lysosomal enzyme senescence-associated β-galactosidase (SA-β-gal) and activation of the senescence-associated secretory phenotype (SASP). SARS-CoV-2 infection triggers paracrine senescence and can lead to a hyperinflammatory environment and the onset of acute respiratory disease syndrome. ... Interestingly, isolated recombinant SARS-2-S protein has been shown to increase the SASP...
So before we dive into results, what is the headline?

Although cytokine storm has long been thought the cause of COVID-related cardiac issues, this study found that the SARS-CoV-2 spike protein "led to profound cardiac fibrosis without affecting baseline cariac function."

6/ "Here, we recommend that rescue of cardiac metabolism dysfunction should be taken into consideration in individuals during the acute or post-acute stage of SARS-CoV-2 infection. It should be noted that SARS-CoV-2 infection also induces new onset of multiple cardiovascular diseases and causes long-term cardiovascular sequelae in PACS patients. Cytokine storm was suggested to be a point of convergence in the pathophysiologic process between COVID-19 and heart failure. Here we found that SARS-2-S led to profound cardiac fibrosis without affecting baseline cardiac function. Further studies...
Moreover, they found a drug target that may be able to prevent "the downregulation of mitochondrial metabolism," and it has shown potential promise in treating heart failure overall.

It would treat the "increased risk of developing heart failure and sudden cardiac death"!

7/ "Previous studies have shown that small-molecule inhibition of WNK1 prevents the downregulation of mitochondrial metabolism and improves RV function and survival in pulmonary arterial hypertension. We found that WNK1 inhibition alleviated SARS-2-Saggravated heart failure and reduced serum cTnT and IL-1ß levels. cTnT is released into circulation during injury to cardiac myocytes(51]. Individuals with higher cTnT levels are at an increased risk of developing heart failure and sudden cardiac death. Therefore, through its metabolism-rescue and anti-inflammatory properties, WNK463 may have ...
Let's dive in to the results! I'm going to jump around a bit, because this paper is EXTENSIVE.

First up, when they cultured cells expressing the spike (S) protein and the ACE2 receptor in a 1:1 ratio, the cells started fusing within four hours. Basic premise confirmed!

8/ "...To explore whether SARS-2-S expression was sufficient to induce senescence..., we cocultured SARS-2-S (Wuhan-Hu-1)-expressing A549 cells with ACE2-expressing A549 cells at a 1:1 ratio (S1A and S1B Fig). Syncytial cells rapidly appeared at 4 h post coculture (hpc) and gradually grew in size, as indicated by microscopic analysis (Fig 1A). Notably, SARS-2-S-expressing syncytia (hereafter referred to as SARS-2-S syncytia) with enhanced SA-B-gal staining began to appear at 12 hpc, and the percentage of SA-B-gal-positive syncytia among SARS-2-S syncytia gradually increased during the fus...
In the cultures with SARS-2-S syncytia, the cells secreted more senescence-related cytokines, including IL-6, IL-8, and IL-2, compared to the cells exposed to a mutant spike protein that can't cause senesense!

They found similar syncytia formation in other cell types.

9/ "Real-time PCR (RT-qPCR) revealed significant transcriptional upregulation of senescenceassociated genes (Fig 1B). The upregulation was fusion specific, as SNF , S, ACE2 and SNF +ACE2 cells did not exhibit such upregulation (S1G Fig). Consistently, the conditioned medium of SARS-2-S syncytia at 48 hpc contained significantly more SASP-related cytokines, such as IL-6, IL-8, and IL-2, than that at 0 hpc compared to SARS-2-S NF mutant (Fig 1D). We found that higher increased levels in secreted proteins than mRNA levels of IL-6 and IL-8. This may be due to the continued expression and secr...
They also tested the spike from four Omicron variants (BA.1, BA.5, BA.2.75, BA.2.75.2). Previous work has found BA.1 has a 5x reduction in ability to fuse cells (compared to wild-type), but the others have a 1.2-1.7x reduction.

All formed syncytia, just a bit more slowly.

10/ "We next compared the senescence potential of four Omicron variants, SARS-2-SBA.1 , SARS-2-SBA.5 , SARS-2-SBA.2.75 , and SARS-2-SBA.2.75.2 , with that of SARS-2-S (S1C Fig). As reported, the Omicron BA.1 variant showed significantly weaker fusogenic activity than SARS-2-S [26] (5× reduction). The fusogenic capacity of BA.5 (1.2× reduction), BA.2.75 (1.7× reduction), and BA.2.75.2 (1.7× reduction) was modestly lower than that of SARS-2-S [27,28]. Notably, the percentage of SA-β-gal-positive syncytia was comparable to that of SARS-2-S, although they formed more slowly (Fig 1F and 1G). .....
Here's where it gets REALLY concerning: Extracellular vesicles—little packets, emitted by cells, containing a protein or some other type of small molecule—have been found carrying the S protein in patients' blood long after initial infection...

11/ "SARS-2-S delivery by EVs or mRNA confers the ability to trigger syncytial senescence Since SARS-2-S was shown to be incorporated into extracellular vesicles circulating in patient blood [29], we then asked if SARS-2-S protein internalization by S-EVs has the ability to trigger syncytium formation and cell senescence in an FFWO-dependent manner. To this end, we first used ultracentrifugation to purify EVs from the supernatant of HeLa- or SARS-2-Sexpressing HeLa cells and confirmed their identity by probing for exosome markers and the EVs were normalized by NTA (S2A-S2C Fig). We next l...
...and they found that these extracellular vesicles, once taken up by a cell, can cause the cell to fuse to another ACE2-expressing cell.

The fused cells then showed signs of senescence (including increased transcription of TNF, IL6, IL8, and CDKN1A genes).

Not great!

12/ "SARS-2-S delivery by EVs or mRNA confers the ability to trigger syncytial senescence ... These cells fused with cells expressing ACE2 at 8 hpc, as indicated by the appearance of multinucleated cells (Fig 2A). Importantly, the fused cells exhibited enhanced SA-ß-gal and p21 staining, with increased transcription of the TNF, IL6, IL8 and CDKN1A genes (Fig 2B), features that are typical of senescence."
What about the mRNA vaccines—they produce a spike protein, so can they also cause this problem? Nope!

The spike design used in the vaccines has a couple of tweaks to make it more stable, and those changes prevent it the vaccine-based spike protein from causing cell fusion!

13/ "Since COVID-19 mRNA vaccines, including Pfizer and Moderna, express S protein antigen by delivering SARS-2-S mRNA, we next asked whether SARS-2-SwT and S-protein-based vaccine (SARS-2-Sv) delivered in the form of encoding mRNA would trigger syncytium formation and cell senescence (S3A Fig). Previous study indicated, compared to SARS-2-SwT, two prolines were added to stabilize the structure's prefusion shape of S-protein in COVID-19 vaccine, this mutation greatly reduces cell fusion of COVID-19 vaccine. ... ... We did not observe syncytial cells formation, signs of senescence and sign...
To be really sure that the S protein can cause this type of syncytial senescence to occur in real organs, they injected mice with a virus that causes them to express human ACE2 in their livers.

When injected with the wild S protein, it induced senescence in their livers!

14/ "Finally, we explored whether cell senescence related to SARS-2-S-mediated cell fusion would also occur in vivo. To this end, we injected AAV-hACE2 constructs into the tail veins of 8-week-old C57BL/6] mice to drive mainly hepatic hACE2 expression. Four weeks later, we intramuscularly administered a single dose of S-mRNA-LNP or LNP to hACE2-expressing mice and examined the induction of senescence. Immunohistochemical analysis revealed robust SARS-2-S expression and the increased appearance of multinucleated cells with at least four nuclei in the livers of S-mRNA-LNP-treated mice compar...
Next up, they looked at mitochondrial regulation.

Long story story, MAVS (mitochondrial antiviral signaling) proteins, which detect foreign double-stranded RNA, cause mitochondrial senescence in response to the SARS-2-S syncytia.

15/
"These data suggest the involvement of RIG-I, the primary sensor of nonself-derived dsRNA [this means it detects double-stranded RNA of a foreign-source (e.g. from a virus)], in functional MAVS aggregation in SARS-2-S syncytia." --- "SARS-2-S syncytia provoke the formation of functional MAVS aggregates ...We then focused on mitochondrial antiviral signalling adaptor protein (MAVS), a mitochondrial adaptor protein that links the cytoplasmic RNA sensor RIG-I to its downstream signalling molecules by forming well-ordered prion-like aggregates. .... Furthermore, MAVS aggregat...
"Fig 3. SARS-2-S syncytia induce the RIG-I-dependent formation of functional MAVS aggregates. Confocal microscopic images of MAVS and mitochondria in A549 cells infected with VSV or A549 cells cocultured for the indicated times. Red, MitoTracker staining for mitochondria; green, MAVS staining; blue, DAPI staining. A magnified view of the boxed region is also shown. Scale bars represent 10 um (whole image) and 1 um (magnified)."
Jumping ahead a bit, they found that "senescent SARS-2-S syncytia exhibit [shrunken] morphology, leading to the activation of WNK1," which is a molecule involved in regulating cell senesence.

It is activated by the fused cells losing their volume.

16/ "...Previous study indicated that with-no-lysine (WNK) kinasel is a molecular crowding sensor that undergoes cell shrinkage-dependent phase separation to restore cell volume, the shrinkage of senescent SARS-2-S syncytia made us wonder whether WNK1 was activated [41]. Notably, we observed a significant shift of WNK1 from a diffuse to punctate distribution in senescent SARS-2-S syncytia of A549 and AC16 cells (Fig 5E-5I), but not in those cells treated with palbociclib (Fig 5J-5M). This phase behaviour appeared as early as 12 hpc in AC16 cells (Fig 5E). Accordingly, WNK1-triggered SPAK p...
They found WNK1 activation led to significantly decreased "mitochondrial oxidative capacity of the cocultured cardiomyocyte"

But "inhibition of WNK1 via WNK463 [which prevents down-regulation of metabolic enzymes] was sufficient to rescue impaired mitochondrial respiration"

17/ "So, we try to study energy metabolism of cardiomyocytes syncytia whether dependent on WNK1 activation [42,43]. We next explored the possibility that senescent SARS-2-S syncytia in cardiomyocytes with WNK1 activation might contribute to impaired metabolism in the setting of heart dysfunction. Compared to non-fusion controls, the mitochondrial oxidative capacity of the cocultured cardiomyocytes was significantly decreased at 48 hpc as indicated by reduced basal respiration, ATP-linked respiration, spare respiratory, and maximal respiration (Fig 6A and 6B). In addition, these senescent c...
Jumping ahead again, we're getting to the headline experiments.

They administered the SARS-2-S protein to some mice that express the human ACE2 receptor, and syncytia formed, as expected.

18/ "Senescent SARS-2-S syncytia exacerbated heart failure To assess whether senescent SARS-2-S syncytium stimulates heart dysfunction in vivo, K18-hACE2 mice were administered with pseudovirus expressing BA.5 spike (SARS-2-Spp) intravenously. Mice were euthanized on the fifth day.... The results showed that the presence of cardiomyocyte syncytia in the hearts of mice infected with the SARS2-SpP. Additionally, fluorescence staining showed that cellular senescence in syncytia expressing the S protein. On the eighth day post administered, mice were performed heart function tests, then eutha...
They concluded that "SARS-2-S promotes fibrosis without causing baseline cardiac abnormalities," and in the mice with pre-existing heart failure, it "exacerbated heart failure progression"

"fibrosis without causing baseline cardiac abnormalities"... not great!

19/ "Functional analysis of hearts, including ejection fraction (EF), fractional shortening (FS), left ventricular internal dimension at end diastole (LVID;d), left ventricular internal dimension at end-systole (LVID;s), as well as serum brain natriuretic peptide (BNP) levels between the two groups were also comparable. Thus, SARS-2-S promotes fibrosis without causing baseline cardiac abnormalities during 7 observational days. We then repeated the above experiment with intraperitoneally (i.p.) injected isoproterenol (ISO) to assess the impact of SARS-2-Spp on cardiac function in mice with ...
Finally, they examined if WNK1 inhibition can "alleviate heart failure exacerbated by SARS-2-S through rescuing metabolic dysfunction." They found positive results, "further supporting the notion that senescent SARS-2-S syncytia contribute to exacerbated heart failure."

20/ "We then wanted to test if WNK1 inhibition by WNK463 can alleviate heart failure exacerbated by SARS-2-S through rescuing metabolic dysfunction. ... Therefore, WNK1 intervention can effectively protect the heart from exacerbated heart failure triggered by SARS-2-S. Additional, to further prove that senescence SARS-CoV-2 syncytia act as a central pathogenic principle provoking heart failure, we attempted to eliminate senescent cells or inhibit fusion by using the senolytic drug dasatinib or the anti-syncytial drug niclosamide. Intriguingly, the administration of dasatinib and niclosamid...
What do they conclude?

The S protein can contribute to heart failure. This is important for acute infections AND long-term complications, because the "persistence of circulating SARS-2-S protein ... increase the likelihood of cell-cell fusion in uninfected cells."

21/ "Discussion ... the SARS-2-S protein mediates fusion between the viral and cellular membranes during particle entry, fusion with uninfected cells and FFWO. ... Here, we directly linked SARS-2-S-triggered syncytium formation with ... its pathophysiological contribution to heart failure progression. We found that both SARS-2-S expression and SARS-2-S protein internalization were sufficient to induce senescence in non-senescent ACE2-expressing cells. In particular, mRNAs-SARS-2-S injection provoked pathways ... in vivo. This was not only important for acute SARS-CoV-2 infection, but the ...
They also note that syncytia expressed senescence-related cytokines, including TNF-alpha, IL-6, and IFN-gamma, among others, and these seem related to the metabolic regulation.

22/ "Nevertheless, we provide evidence of the contribution of RIG-I-MAVS to the regulation of SARS-2-S syncytium fate through TNFa. Using multiplex protein analysis, we identified a burst of SASP-related cytokines, including TNFa, IL-6, IFN-y, and others, in the hACE2 mouse model injected with SARS-2-S mRNA. Although the exact contribution of each cytokine to SARS-2-S syncytium survival and senescence remains unclear, we provide evidence that the central regulation of SARS-2-S syncytium survival and senescence may be dependent on TNFa. Previous studies reported that TNFR2 interacts with th...
And, importantly, the mRNA vaccines CANNOT cause cellular senescence using this mechanism, as they have a couple of mutations which "effectively inhibit the formation of syncytia, mitigate cellular senescence, and prevent the release of" senescence-relate signals.

23/ "Our results have also revealed that the S sequence derived from the COVID-19 mRNA vaccine which harbors mutations in two proline residues. These mutations effectively inhibit the formation of syncytia, mitigate cellular senescence, and prevent the release of SASP. This finding corroborates prior research, affirming that the unique design of the mRNA vaccine mitigates syncytia formation, thus enhancing its safety. Moreover, our findings emphasize the necessity of optimizing vaccine sequences to mitigate the risk of syncytia formation in vaccine design."
Because patients with heart failure show elevated ACE2 expression, while those with Long COVID exhibit "persistent circulating SARS-2-S and EVs harboring SARS-2-S," this combination "may increase the likelihood of syncytium formation."

24/ "With the progression of COVID-19, heart failure appears to be a potential hazard due to SARS-CoV-2 infection, chiefly in elderly patients with hypertension, ischaemic heart disease, and diabetes mellitus. Patients with basic heart failure disease showed elevated ACE2 expression, whereas patients with PACS exhibited persistent circulating SARS-2-S and EVs harbouring SARS-2-S. High ACE2 expression and long SARS-2-S duration may increase the likelihood of syncytium formation. Moreover, the pre-existing inflammatory environment with older age or with chronic disease, especially those with...
This is very much a basic research paper and doesn't have anything directly *usable* in clinical practice. However, it really illuminates the pathophysiology of cardiac complications of SARS-CoV-2 infection—EVEN ASYMPTOMATIC INFECTIONS.

Paper:

25/25journals.plos.org/plospathogens/…
AFAIK, it’s totally a non-issue with the non-mRNA vaccines, because they don’t even have a full spike protein.

And I think their statements about how mRNA vaccines with a different design could have more complications was a veiled reference to one of China’s vaccines

26/25
No idea what to do about denialism at this point, other than continuing to educate and hope it gets through!

That's the goal with my threads: Hopefully, they can help give people the knowledge and language they need to discuss the science directly!

27/25
At this point, it's a *potential* treatment that still needs further study, but it's a solid lead!

- Inhibiting the *WNK1 molecule* with a *WNK463 molecule* is the new option uncovered here
- Two existing preventative drugs should be investigated

28/25

WNK1 inhibition (using WNK463) is the potential new drug target to investigate. Other drugs to investigate include: • the anti-syncytial drug niclosamide • the senolytic (drug that may selectively kill senescent cells) dasatinib as a protective measure against heart failure exacerbation triggered by the SARS-2-S protein.
Glad you asked, because I was conflating previous vector vaccines with ones under development!

It seems that Novavax and Janssen use the same STABILIZED spike protein as Pfizer and Moderna:

But oddly enough...

29/25
pubs.acs.org/doi/10.1021/ac…

Janssen: "a stabilized variant of the SARS-CoV-2 spike (S) protein."
...it seems that a bunch of Russian viral vector vaccines—and AstraZeneca—used the regular spike protein!?

So that kind of explains the issues with the AstraZeneca vaccine! Weird.

30/25 ncbi.nlm.nih.gov/pmc/articles/P…

AstraZeneca: "containing S protein gene of coronavirus"
CanSino, Gam-COVID-Vac, and Sputnik Light: "the SARS-CoV-2 protein S gene"

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More from @NickAnderegg

Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Sep 7
Let’s talk about systemic risk from negligent public health: Catastrophe doesn’t require population-wide illness.

The worst case isn’t sickness. Worst case is infrastructure collapse due to overstressed resources.

You know power plants need stable power to operate?

1/many “8. Performance of Nuclear Power Plants Affected by the Blackout On August 14, 2003, nine U.S. nuclear power plants experienced rapid shutdowns (reactor trips) as a consequence of the power outage. Seven nuclear power plants in Canada operating at high power levels at the time of the event also experienced rapid shutdowns. […]. Many non-nuclear generating plants in both countries also tripped during the event. Numerous other nuclear plants observed disturbances on the electrical grid but continued to generate electrical power without interruption. […] - The severity of the grid transient...
If there is a widespread disruption in the service area of, e.g., a nuclear power plant, it shuts down for safety. Massive blackouts like in 2003 or in Spain this year are caused by safety systems!

If too much trips out at once, it has a ripple effect across the grid
2/ Source: https://www.insurancejournal.com/news/international/2025/04/29/821703.htm Why Restarting a Power Grid After Massive Collapse Is So Hard April 29, 2025 by Rachel Morison and William Mathis It’s a worst case scenario that grid operators plan for but hope never to encounter. After one of the worst blackouts in Europe in more than a decade, electricity grid operators in Spain and Portugal are trying to get networks back up and running from the ground up. The initial estimate from grid operator Red Electrica was that restoring all power supply in Spain may take between six and 10 hour...
Frequency Factor So far, the only information about what caused the crisis was a comment from grid operator Red Electrica that the blackout was a result of “oscillation,” which suggests a disruption in the grid’s frequency or voltage — both crucial factors for maintaining stability. The frequency, which normally stays pretty steady around 50 hertz, is the heartbeat of the grid. Frequency monitoring specialist Gridradar said it identified a rapid movement in frequency just after noon in Spain — right before the blackout hit. Such oscillations can cause chain reactions that ultimately lead ...
In 2003, it took 2 days to fully restore most power. The infrastructure is 20 years older than it was back then and higher demand creates risk of cascading failure.

As of 2003, recommendations from blackouts in 1965, 1977, 1982, 1996, and 1998 had not been implemented.
3/ “Recommendations to Prevent or Minimize the Scope of Future Blackouts As reported in previous chapters, the blackout on August 14, 2003, was preventable. It had several direct causes and contributing factors, including: • Failure to maintain adequate reactive power support • Failure to ensure operation within secure limits • Inadequate vegetation management • Inadequate operator training • Failure to identify emergency conditions and communicate that status to neighboring systems • Inadequate regional-scale visibility over the bulk power system.”
“Further, as discussed in Chapter 7, after each major blackout in North America since 1965, an expert team of investigators has probed the causes of the blackout, written detailed technical reports, and issued lists of recommendations to prevent or minimize the scope of future blackouts. Yet several of the causes of the August 14 blackout are strikingly similar to those of the earlier blackouts. Clearly, efforts to implement earlier recommendations have not been adequate. Accordingly, the recommendations presented below emphasize comprehensiveness, monitoring, training, and enforcement of r...
“1. Market mechanisms should be used where possible, but in circumstances where conflicts between reliability and commercial objectives cannot be reconciled, they must be resolved in favor of high reliability. 2. Regulators and consumers should recognize that reliability is not free, and that maintaining it requires ongoing investments and operational expenditures by many parties. Regulated companies will not make such outlays without assurances from regulators that the costs will be recoverable through approved electric rates, and unregulated companies will not make such outlays unless th...
“3. Recommendations have no value unless they are implemented. Accordingly, the Task Force emphasizes strongly that North American governments and industry should commit themselves to working together to put into effect the suite of improvements mapped out below. Success in this area will require particular attention to the mechanisms proposed for performance monitoring, accountability of senior manage-ment, and enforcement of compliance with standards. 4. The bulk power systems are among the most critical elements of our economic and social infrastructure. Although the August 14 blackout ...
Read 20 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Sep 4
If Florida drops vaccine mandates, society is probably officially over. I really, really, really don’t think most people get that herd immunity is the only thing keeping measles from ripping through the population, and a measles infection wipes out all pre-existing immunity

1/3
Measles specifically infects the cells that are responsible for “remembering” which pathogens your body has encountered before. So they ALL get wiped out, and all you’re left with is cells that remember your measles infection and nothing else.

2/3
Every infection, vaccination, and other pathogenic exposure you’ve ever had? Your body no longer knows how to detect them after a measles infection. The only immunity you’ll be left with is immunity to measles. That’s it. Open season for every other pathogen encountered.

3/3
Read 8 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Jun 30
Can I say something? I have a BA in psych, a BPhil in linguistics, and went to grad school for cognitive psych. My research, including an undergrad fellowship, was on the cognitive relationship between written and spoken language…

Audiobooks are NO DIFFERENT than reading print.
In the last hour, there have been a dozen replies from people nitpicking the first tweet

The topic of discussion is "do audiobooks 'count' as reading?," and the answer is "Audiobooks are NO DIFFERENT than reading print."

Maybe read the thread before arguing with it? lmfao
And for all those people with indignant responses who want to nitpick every detail, the fact that so many people hold THIS exact view—that audiobooks are somehow “cheating”—is the ENTIRE point. It leads to people who would benefit from audiobooks depriving themselves the medium
Read 4 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Feb 1
Many people are asking for recommendations about what storage media to buy, so here's a buying guide from an experienced data hoarder (me)

The MOST IMPORTANT thing to know is that SOLID-STATE MEDIA IS NOT DURABLE. Flash drives, SSDs, SD cards, etc. are NOT long-term storage.

1/
That's not to say that it's impossible to use solid-state media for long-term storage. It's just that anything with durability guarantees gets prohibitively expensive quickly. Spinning hard drives—as well as DVDs and Blu-ray discs!—are your friend.

2/
- The way data is stored in solid-state media makes it much more susceptible to bit rot than other media.
- In a spinning hard drive, the moving parts are the most common point of failure.
- When you burn a DVD, that shit is fairly permanent.

3/
Read 42 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Jan 9
I wish people would understand that insurance underwriters have armies of actuaries calculating risks, and if an insurance company drops you, it's because things have changed in such a way that insuring you will take more out of the financial pool than you're putting in

1/
It sucks, but it's a direct result of the fact that humans are widely inhabiting locations that are rapidly becoming impossible to inhabit safely. If you can't find insurance for your home, it means there's a high likelihood you'll need to move soon anyway.

2/
You get insurance so that you can replace all of your stuff in the event of a disaster. When the insurance company effectively says "the risk of disaster is so high that insuring you would almost certainly cause us to lose a lot of money," it ALSO means your life is in danger

3/
Read 7 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Jan 5
So here’s the thing about some of the subtle neuro damage related to SARS-CoV-2 infection that I think a lot of people miss: some of the known deficits are correlated with things like impulsiveness and poor emotional control, so we might expect to see deficits there are well

1/
Consider how impatient people seem to be on the road in the last couple years relative to the 2010s, and I think we have a perfect example of where this is LIKELY already manifesting.

2/
This impact is particularly insidious for the person experiencing it, because poor impulse control, by definition, doesn’t really come on gradually. My biggest concern is how interactions under these circumstances will play out if this impact continues to become more common

3/
Read 15 tweets

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