The Arrogance of the Academic

 Those in the Academy look at the folks who have not been properly indoctrinated as lesser creatures. After all, their high and mighty position makes them infallible and worth of being heeded. Take for example this Academic who states:

According to the recent NBC poll, among white voters, those with a college degree favor Harris by a margin of  21 points, while those without a college degree favor Trump by a margin of 28 points.

 Imputed in this statement is that college educated are smarter and they then choose the better candidate. Leaving aside the choice of a specific candidate this statement displays the arrogance of the academic. College, for many, is just a clear waste of time. Other than engineering or some sciences, college is just a mish mash of useless studies. From sociology, psychology, political history, modern literature, etc. Most os slanted studies of no useful benefit to mankind. In fact much is just indoctrination. Is is tough to indoctrinate organic chemistry or structural mechanics, but I leave that for another day.

Those without a college degree may frankly know more about reality than those with a degree. First they may have worked for the time those with a college degree were being indoctrinated. Second, they may have learned by doing, not by being told what to do.

Thus the above statement should be interpreted in a more broader context. Why the difference? Not because they are smarter or dumber, but because perhaps the indoctrination did or did not occur.

This is the problem with today's academics. They make a statement hoping to exude their brilliance yet fail to understand the complexity of its interpretation.

AI and Politics

 California has enacted what could be called the anti-AI law related to politics. It states in part:

The Legislature finds and declares all of the following:

(a)California is entering its first-ever generative artificial intelligence (AI) election, in which disinformation powered by generative AI will pollute our information ecosystems like never before. Voters will not know what images, audio, or video they can trust.

(b)In a few clicks, using current technology, bad actors now have the power to create a false image of a candidate accepting a bribe or a fake video of an elections official caught on tape saying that voting machines are not secure, or to generate the Governors voice telling millions of Californians their voting site has changed.

(c)In the lead-up to the 2024 presidential elections, candidates and parties are already creating and distributing deepfake images and audio and video content. These fake images or files can spread to millions of Californians in seconds and skew election results or undermine trust in the ballot counting process.

(d)The labeling information required by this bill is narrowly tailored to provide consumers with factual information about the inauthenticity of particular images, audio, video, or text content in order to prevent consumer deception.

(e)In order to ensure California elections are free and fair, California must, for a limited time before and after elections, prevent the use of deepfakes and disinformation meant to prevent voters from voting and to deceive voters based on fraudulent content. Accordingly, the provisions of this chapter are narrowly tailored to support California's compelling interest in protecting its free and fair elections.

 Now this is an example of what I was concerned about. It does not even define AI. It goes even further in calling it an AI election, yet we have no idea what AI is. If I were to use my Pentax and another a SONY camera, both pictures would be modified by the camera, Reality does not exist in an image, it is just a processed view of reality. Is that AI perhaps.

If someone wants to show their opponent in a less positive light, then by modifying an image, is that AI?

The above is a classic example of why Chevron made no sense. Who gets to decide the above terms? What is a free and fair election. 

Turley has a different slant but it supports in parallel my concerns. On the one hand is the free speech issue on the other hand is the grossly deficient use of terms which one suspects the Legislature of California is using.

 

Hidden Tax for Public Housing

 The State, namely the Taxpayers, subsidize public housing water and sewer. See NJ and town. Now consider a typical NJ town, say 5,000 homes. The water costs are about $30 per month plus sewer is $70 per month for a total of $100 per month per HH.

 Now assume low income housing is mandated, which it is and say 1,000 units mandated. Thus the subsidy is $1,200 per HH time 1,000 HH or $1.2 million. Now the 5,000 non subsidized will cost then each $240 per year added for the subsidy.

 BUT, there is a demand for water and sewer processing. If the water is from underground sources, there may be inadequate supply. This capital investments must be added on top of this. The same holds for sewer since the plant capacity must be expanded by more than 20%, a significant capital cost.

 This can easily result in a 35% to 50% “tax” on existing homeowners to support “low income” housing just for these two utilities. Then add on schools etc.

 Just a thought.

Public Health, Pandemics, and the Government

 In a recent article by the former head of the NIH, in the NY Times, the author notes:

 Future historians will judge the development of safe and effective mRNA vaccines for Covid in 11 months as one of the greatest medical achievements in human history. We felt that at last we were on a path to conquering this disease and stopping the terrible death toll. And to a major extent, that came true: Current estimates by the Commonwealth Fund, a nonprofit foundation supporting research on health care, are that more than three million lives were saved in the United States between December 2020 and November 2022 by Covid vaccines. If you were vaccinated, you might be one of them. I might be also. Yet ultimately more than 50 million adult Americans declined vaccination — even after the shots were made widely available at no cost. Though medicine and public health make poor bedfellows with politics, one’s political party was a strong predictor of resistance. So was religion, with white evangelical Christians (my own group) the most resistant of all. Public distrust, driven by social media, cable news and even some politicians, reflected a host of concerns: whether Covid-19 was real, whether it was really all that serious, whether the vaccines were rushed, whether there were common and serious side effects that had been hidden, whether the mRNA would alter the recipient’s DNA, and whether companies had skirted the rules about safety. More outlandish conspiracies also circulated on social media: that the vaccines contained microchips or cells from recently aborted fetuses, for example. People of faith were particularly hard hit by misinformation.

 The author then presents his “philosophical” version of “truth”. He states:

 What do we mean by truth anyway?

 Let’s consider a set of concentric circles that represent various levels of truth. At the center is what could be called the zone of necessary truth. Items in this zone consist of statements about a concrete reality that just has to be the way that it is. Those items would have to be true in any imaginable universe, and they don’t care how we feel. In this rather narrow zone, the main entries are from mathematics and possibly from the nature of time. ….

 Unfortunately this alleged layer of truth has been buffeted by the minds of mathematicians over the centuries. Non-Euclidian geometry just a simple example. He continues:

 The next circle out, which is the home for a much wider range of reality claims, is firmly established facts. These are conclusions that are overwhelmingly supported by evidence, but discerning them has required human observation. We can safely place here most scientific conclusions about objective reality that have been supported by multiple experimental approaches and sustained over many decades…

 The author asserts DNA as such an example. However how we perceive DNA today as compared to how it was perceived in 1953 is dramatically different. Science at this level is a continual battle of ideas. It is one of “on the one hand and then on the other” For example, what is cancer? In 1964 I read Watson’s book on the Gene. Now when I read the literature it is dramatically more complex.

 As we move further out from the center, we reach claims that are potentially true, but the evidence is currently insufficient to move them into the circle of firmly established facts. We can call this the zone of uncertainty. Here’s an example: Did mask mandates provide benefit to a community in reducing Covid transmission? One careful study in Bangladesh said yes, but other large-scale studies in the West have had difficulty documenting that — with a major reason being that compliance has been so uneven. On the other hand, many studies have shown personal benefit from consistent mask-wearing in reducing risk to individuals and their close contacts.

 This statement can be an example of how “politicians” mess things up. To answer the mask issue we must first understand how the disease is transmitted. Since COVID is a single stranded RNA virus, which attached to cells via an ACE2 membrane receptor, it may be just nano particle like. No one knows. If nano then masks of the typical variety are useless. Furthermore, viruses can enter the surface of the eye, go down the gland to the nose then from there anywhere. So must we wear eye protection as well. Nano masks and nano eye protection are not readily available. Level 2 bio-hazard facilities may have them but never saw them on the E train. This issue is still not resolved and the author unfortunately seems clueless and balmes the public for even raising the question.

 Going even farther out, we get into territory where facts and evidence are frankly scanty or just irrelevant. This is the zone of subjective opinion. Some examples: Tattoos are cool. Dogs make better pets than cats. Shoes with brown leather tops and thick white soles look really good on men (on this last one, opinions at my house do not match). Disagreements about topics in this zone do not threaten the order of things. In fact, they make our society richer and more interesting because people have different tastes.

 The above are opinions, not facts. I like blue not orange. Perhaps it is the genetic makeup of my limbic system.

 When disagreements arise about what is true, it is really important to assess which zone we are working in. Looking at our concentric circles, I think we can all accept that claims in the outermost zone are subjective, so it’s fine to disagree about those. But here’s the point I really want to emphasize: As you move inward to zones where there is more and more actual evidence, it becomes more and more important to track down that evidence, and not just say that everything is a matter of opinion. When you get to the solid foundation in the innermost two circles, these are matters of currently established truth that have to be true for everybody. Those facts don’t care how you feel, and they can’t be — and are not — a matter of opinion.

 Opinions are available to all. Truth may be very difficult to determine. COVID was a challenge. What was shown was that the arrogance of “experts” and politicians isolated the public in a lack of trust. In my opinion and my experience the political experts exuded gross arrogance and talked down to the public. The author is a physician and a scientist. That duplex lends itself to a certain mindset. In contrast I studied medicine and see myself fundamentally as an engineer. When using my engineering expertise to raise capital in a venture world, I could only succeed by understanding how to communicate with the investors, I had to get to their level of understanding, I had to convince them with facts, and avoided truths. For in a venture environment today’s truth may be tomorrow’s falsity. Think dotcom bust.

 For a scientist, however, especially one under the rubric of the Government, they speak ex Cathedra. The arrogance of the scientist isolated the citizens and led to islands of disbelief. This article has no self doubt, just a continuation of the attitude of “truth” is theirs and if you fail to accept it you are anathema!

The author talks of efficacy. He alleges that the mRNA vaccine has high efficacy. In reality we face moving targets. Namely the virus mutates continuously. Secondly, the mRNA vaccine does NOT prevent infection, frankly no vaccine does. It just primes the immune system through B cells antibodies, T cells and the rest of the adaptive immune response. It does not prevent transmission. It takes days to get the primed immune system to react, and during that time we have the possibility to transmit.  These are complex issues, dealing with an moderate understanding of the immune system. Political science types seem to fail to understand that 99.999% of the people are clueless! Thus when they make dicta to be obeyed, and find out that the extreme dicta are not TRUTH, they lose all confidence. Once lost never regained!

Quality

 Quality is important. The Japanese learned that exceptional well. From tin toys to high quality photographic equipment and highly reliable cars. If it is made in Japan it would be the best.

Now for Chinese goods, the same is not there. They are cheap, but as the saying goes you get what you pay for. I have been observing this over the past few years with Amazon purchases. The latest was a clock. Looked good on line but when delivered it was a disaster, and in this case an expensive one. The numbers on the face were wrong to start with, the clock face was askew, and the ability to adjust the time required medical instruments to get to the change control! 

Now the list goes on. Buy batteries from a Chinese source and you have no idea if they are knock off. I have another clock, looks great but burns through batteries every 3 weeks. 

Does the American consumer want quality or just to be able to buy more junk. I suspect quality will become a real issue. Think Yugos.

Polyspecific Antibodies

 Five years ago I wrote a Technical Note on Poly-sspecific antibodies. Simply stated these complex antibodies could bind to multiple surface markers on a cancer cell as well as attaching to an immune cell, thus facilitating an aggressive immunotherapeutic response targeted specifically to the cancer cell. 

A recent paper in Nature Cancer,  details how these PSAb have been developed and are being used in multiple myeloma. The author notes:

To create the components of the new trispecific antibody, ISB 2001, the authors selected high-affinity antibody Fab fragments (the region of an antibody that gives antigen specificity) directed against both CD38 and BCMA, two well-validated targets in the MM therapeutics landscape3,5. The two anti-tumor Fab fragments were combined into a single trispecific antibody molecule with a Fab fragment directed against the T cell activation antigen CD3. A Fab fragment with medium-low affinity for CD3 was used because this was previously shown to help improve the balance between TCE efficacy and safety6,7. The anti-CD38 Fab fragment was additionally selected to recognize an epitope distinct from that recognized by daratumumab. This was done to avoid potential dampening of the activity of ISB 2001 in patients with r/r MM who have been recently treated with a daratumumab-based regimen. In addition, Carretero-Iglesia et al.4 generated an array of monospecific and bispecific control molecules. Together, these make for exceptionally well-controlled experiments from which the reader and fellow scientists can easily draw conclusions. The CD3, CD38 and BCMA Fab fragments were combined with an antibody Fc fragment that was mutated to retain its ability to extend the antibody in vivo half-life while preventing it from  interacting with IgG Fc receptors, thereby minimizing target-binding-independent T cell activation. Here, the spatial configuration of the Fab fragments was found to be crucial for optimal activity. Placing either of the tumor-targeting Fab fragments close to the CD3 Fab (meaning on the same antibody heavy chain) resulted in greater potency than did distal positioning (on the other heavy chain). In the trispecific setting, having the BCMA tumor-binding Fab positioned between the Fc fragment and the CD3 Fab was optimal for cytotoxicity (Fig. 1). As CD38 has a broader expression profile than BMCA (CD38 is more often expressed on non-tumor cells), placing the CD38 Fab in the less-active distal position resulted in reduced on-target off-tumor T cell activation, with the promise of maximizing the therapeutic window. Avidity (the combined binding strength in antibody–antigen complexes) is fundamental to antibody functional responses8. By mixing antibodies directed against multiple epitopes on a given antigen, high-avidity immune complexes may be formed that are characterized by tightened binding and increased activity toward cells expressing the antigen. In engineered antibodies, a covalent linkage between Fab fragments directed against distinct epitopes and/or distinct antigens may be used to generate bi- or multispecific antibodies with novel functions9. These ‘obligate bi- or multispecific antibodies’ may also benefit from higher activity due to avidity binding, an effect we might therefore call ‘obligate avidity’. 

 Namely the techniques we explored half a decade ago are making an entry into a significant malignancy with some hope of establishing a total remission.