Amazon's Problems

 Amazon used to be dependable. But now:

1. Amazon Services LLC seems to be some entity that loses every package transported. It appears to be a logistics entity serving, I assume at exorbitant prices, third party vendors. In my opinion and in my experience this is one of the most grossly incompetent entities in shipping ever! If one sees this in a planned purchase my suggestion is run as fast as possible away from it!

2. Third party vendors are all over turning this into some type of bazaar where the buyer must beware! Especially for the ubiquitous Chinese products

3. What used to be at most 2 day deliveries is now almost 20% lost packages and one week deliveries. I am just 14 miles from the Newark Airport Center so distance it not a problem

 4. Remediation is near impossible

5. It appears that the old management team is gone replaced by God only knows what....

6. Tracking no longer works and is unreliable at best. The old delivery rules no longer apply and the information is generally grossly in error. 

7. It also appears in my opinion that Amazon "sells" something they do not have. The accept the order, represent that they have shipped it while they go about finding a way to meet the order. This may in my opinion almost be a bait and switch type of sale.

8. But the core problem in my opinion and in my experience is that Amazon tells you what the progress of the deliverable is when they know or should know that what they are representing is materially false. In fact it is a gross misrepresentation that the consumer relies upon and which is unachievable.

For higher end things I go directly to the manufacturer! Try it, it is cheaper, faster, more reliable.

The next step will be a Federal Trade Commission investigation on the basis of false advertising, gross misrepresentation, and so forth! I would not go any where near this stock!

Waking Up!

 The NY Times has a piece on the complexities of adding "green" power to the grid. They note:

In the largest grids, such as those in the Midwest or Mid-Atlantic, a regional operator manages the byzantine flow of electricity from hundreds of different power plants through thousands of miles of transmission lines and into millions of homes. Before a developer can build a power plant, the local grid operator must make sure the project won’t cause disruptions — if, for instance, existing power lines get more electricity than they can handle, they could overheat and fail. After conducting a detailed study, the grid operator might require upgrades, such as a line connecting the new plant to a nearby substation. The developer usually bears this cost. Then the operator moves on to study the next project in the queue.

 We have been arguing this for years. The current grid was never designed to work this way. Power companies have at best a 19th century mind set, central generating and tree and branch network. If a branch fails, too bad.

If the Greens demand all electric we will experience a horror show. The network will fail, it will lack capacity, and the costs will be unbelievable.

We had US Department of Energy people whose sole purpose is to regulate and pontificate. They lack any technical competence, except the weapons folks. No one has thought through this, and especially at the Secretary level we have just religious zealots which may very well result in total collapse.

Prostate Cancer and Chromatin Conformation

 

We just posted an interesting report on the impact of chromosome conformation on prostate cancer, PCa. The issued discussed is based upon some recent papers which discuss how the genes in the nucleus can get intermixed resulting in changes that lead to cancer or make an existing malignancy metastatic.

We seem to be finding new interactions by the month if not week. Worth a look.

Eliza vs ChatGPT

In the late 1960s a group at MIT AI Lab created a program called Eliza. It simulated a psychotherapist. It would ask you a question and then you would respond and then it may be something like, what do you mean by sad? 

It was human interaction. Simple but useful.

Some Details

Click Here

 I have noticed that many vendors seek to have a customer survey. Laudable but they do the "Click Here" routine. Namely they have the customer click on some URL that is not the company. Rule No 1 in computer safety, never click here anywhere! 

I try to explain that to folks. The Click Here is almost always from some other site. Possibly safe but why take the chance.

Curiouser and Curiouser

 The NY Times reports:

The top military commander overseeing North American airspace said Monday that some previous incursions by Chinese spy balloons during the Trump administration were not detected in real time, and the Pentagon learned of them only later. “I will tell you that we did not detect those threats, and that’s a domain awareness gap,” said Gen. Glen D. VanHerck, the commander of the Pentagon’s Northern Command. One explanation, multiple U.S. officials said, is that some previous incursions were initially classified as “unidentified aerial phenomena,” Pentagon speak for U.F.O.s. As the Pentagon and intelligence agencies stepped up efforts over the past two years to find explanations for many of those incidents, officials reclassified some events as Chinese spy balloons. It is not clear when the Pentagon determined the incidents involved Chinese spying. When the determination was made, officials kept the information secret to avoid letting China know their surveillance efforts were uncovered, the officials said.

First, you cannot "blame" Trump. The Generals blew it big time.

Second, the US has massive intel from the CIA to the NRO. NROs job is intel from the sky. It is a massive organization. Historically, I worked for two former heads, Joe Charyk and John McLucas, so I have a modest understanding. It is their job to do reconnaissance.  But guess they missed this one.

Third, NORAD does have a big role. They blew it also.

Fourth the TRIAD land based ICBMs should have threat identification and remediation systems. This one does not. 

Fifth, seeing a 200 foot diameter threat at 60K feet is really not a problem, if you are doing your job. The Generals did not do their jobs. 

Solution, simple, get new Generals and keep doing it every time the mess up. They may get to do it right if they cannot play golf at the Country Club.

And, by the way. perhaps they may want to tell the White House something.

Classroom Study

 The above example was done for my grandson's science class. Namely how large a balloon filled with helium was required to keep a pumpkin from smashing. Think ChiCom spy stuff and you just plug in the numbers!

Some New Approaches to Cancer Immunotherapy

 Cancer immunotherapy has had many advances over the past decade. However there still is a great number of new options becoming available. These options present the opportunity for targeting individual patients and their specific lesions. We listed a new paper discussing these for prostate cancer, PCa. PCa is a complex cancer to treat for a variety of reasons. Many cases present as relatively indolent in nature whereas there is a small number which are highly aggressive. Understanding and identifying them is still a work in progress.

However we see options for doing so by using PCa cell surface markers. Using them we than have a variety of immunotherapeutic approaches.We show some of these below. Namely we look at stem cells, progression cells, and the tumor micro-environment. For the cell targets we look for surface markers. Then we can use antibodies, immune cells and even viral attacks. Our recent result considers the first two.

Consider a cancer cell with the surface markers as shown below. This is quite common for PCa cells, especially stem cells. We thus can look at the approaches below. First identify and find markers on the stem cells. The choose a CAR approach with one of several immune cells and/or choose an antibody approach using what are called poly specific antibodies.

 Now antibodies, Ab, are common elements of the immune system. 

 

As shown above they have a collection of proteins linked so that at the short end they attach to the target cell surface marker and at the lower end to an immune system cell. The result is elimination of the target. Think COVID.  An example is below with an NK or natural killer cell. If a normal cell is found then it will have a surface marker MHC saying it is a good cell so do not do anything.

However if MHC is absent we get what we see below:

which results in an attack and elimination of the bad cell. 

Thus we rely upon these Ab to help direct the immune cells to kill the bad or cancer cells. There are two possible ways to do this. One is to create Ab to attach to the cell and then wait for immune cells to attack. Or we can create immune cells with the ligand which can attach to the cancer cell. These are CAR or chimeric cells.

The malignant prostate cell typically has these 4 if not more targets as shown below.

 

 

 

Likewise the interaction between the NK cell and the PCa cell results from interactions as shown below.

 

Now the basic principle we espouse is that if we demand a set of multiple targets s shown above, not just one, then we get better targeting and less bad consequences. Namely we get to eliminate just what we want. We show that graphically below:

Now we can use what we call polyspecific Ab as shown below:

This is a 4th generation CAR. We have three ligand attachment areas plus when all 3 are attached they activate the release of cytokines and kill the cancer cell. These types of poly Ab are relatively easy to make and if they do the full attachment their have limited morbidity. They go after just the cancer cells and no others.

Now we can use Ab alone. Below we show a poly Ab attaching to a cell and then activating an immune cell.

These approaches are all based upon existing protocols. The demand the ability to identify the cancer cell and then produce the CAR or Ab as noted.

Production can be complex and costly as we show below for a CAR:

However CAR-T is more costly than CAR-NK. CAR-NK has shown to be readily produced with less side effects. The down side is the CAR-NK cells last only two weeks whereas the CAR-T for several months. But overall cost may be much lower. In contrast the poly Ab may be quite easy to produce in volume as shown with many of the Ab on the market today. In fact a library of them may be made readily available.

We believe that these techniques present great opportunities for change in dealing with this malignancy. However much of the above is still speculative depending on the results of clinical trials.

"Look Up!"

My mother sent me once to NYC to pick up shoes for my sister. The shoe store was in the Empire State Building and I was still in grammar school, 8th grade I believe. I managed to get from Staten Island to 34th street and up to street level. Unfortunately I had been given no address for the Empire State building by my mother. She was a classic New Yorker who thought that everyone knew where the building was. But 34th street is a long block and to me, an address was essential. 

Thus I walked around yet in classic New York fashion I refrained from asking anyone where the building was. Finally I took a few coins in my pocket, reserved only for a crisis,and called my mother. I asked her what was the address of the Empire State Building. Her answer stuck with me for the rest of my life, she said bluntly, "Look Up!" She then hung up the phone. So I looked up, and behold, there it was, just to my left and a few blocks down. Now off to the shoe store, but I had to remember my bread crumbs to return!

Well this applies to our recent ChiCom balloon as well, someone just looked up. Not that they were hiding anything. I recall that I even saw Sputnik as it flew by and monitored its beeps on my Hallicrafters short wave radio. But that is another story for another time!

The FAA and Airport Surface Traffic Control

 In the summer of 1974 I was asked if I wanted to take a group of minority students from Boston to work on a project I was to do at MIT Lincoln Labs. This group became the first MITES class of minority students. I took the group and the project was to develop an airport surface tracking system using data we gathered at Logan airport.

So day after day we drove a big yellow van labelled Discreet Air Beacon System, DABS. Apparently the painter could not spell Discrete or else he really meant we were to be discreet. But my big yellow truck did get a lot of attention.

We tested our systems at Logan and compared the results to the rather archaic system in place. What I learned in that project was that the FAA was one of the worst Government agencies ever. It was using WW II technology and techniques then some twenty years later, and frankly little has changed. 

The problem of ASTC is simple. Prevent collisions on the airport surface while maximizing traffic flow. The Hill recounts some of the recent near misses. Now some fifty years after my summer project I find that not much has changed. It appears that the troglodytes of the 70s have been replaced by the same team in the 20s. Perhaps worse!

More Thoughts on the Balloon

 The "balloon" has caused a bit of a stir. Almost everyone yelled "shoot it down". That in my opinion was destroying evidence. Now capturing the payload is not trivial but not impossible. We learned how to do that in the 60s! Yes folks, well before most of your parents were born! I was there then. X-15 and F104.

So why did the Government blow it to pieces. Either that was just a scam to put of the ChiComs or it was intentionally meant to destroy evidence. It did make for good TV but bad Intel.

The devices on-board held invaluable intel regarding sources and methods. Sources such as where did the technology come from and methods as to how it sent data back and forth. But now we will never know. The Government made sure of that.

How then could this be retrieved. Well at 60,000 feet an F22 can easily get there. Then it could "hook" a retrievable parachute to the device, assume we have a great pilot say from Edwards and then good 50 caliber shot to deflate the balloon. Down it come with GPS tracking in one piece. Off a carrier send a helo to retrieve and then examine. Simple but it requires competence not the correct pronouns. 

Perhaps that is why we never won a war with the Generals that we started with. Except Washington.

So what were both sides hiding?

Spy in the Sky

 There have been many vehicles that have been used to gather intelligence. Not just balloons, but tons. One I recall from the 60s was a satellite that photographed Soviet sites and then dropped the film to be picked up by an aircraft with a hook. Nicely called "the Hook". Then the SR-71, but initially called the RS-71, but due to President Johnson;s dyslexia introduced as the SR-71 and thus the name stuck.

In all cases the data gathered had to get back to the gatherer some how. Now how can this China balloon get stuff back to the mainland. Simple, spread spectrum it up to a satellite and then down to the processing site. Better yet it can also communicate to agents on the ground lots of stuff. 

All they need are good processing chips which thankfully we have designed and have given them! Yep, and most likely educated their technical people at our best institutions, where they were most likely supported by DoD funded research projects.

This story will make Pearl Harbor look patriotic. Remember Yamamoto was educated at Harvard. Want to see his replacement now part of the CCP, just look at the news sites of some of our top universities.