Hitler’s Scientists by John Cornwell and recovery

A trip to the local Waldenbooks resulted in the purchase of a deeply discounted book, “Hitler’s Scientists”. Back problems due to an unscheduled dismount and impact with the cross-rail have resulted in much time for reading while my wife goes out riding leaving the dog and I to vegetate in the condo. The book’s content was a mystery. Would it be about Mengele and experiments in the concentration camps or the collaboration of other scientists with the Nazi regime? It has some of all this but also includes sections on the development of industrial chemistry, nuclear physics and quantum mechanics in the late 19th and early 20th century to provide background. Much of the book describes the forced exodus of Jewish scientists to England and the U.S. with the resulting negative impact on the Nazi nuclear bomb program. If Hitler had not thrown out his Jewish theoretical physicists he might have had the bomb first. In fact, the whole of theoretical physics was called, “Jewish physics”, in contrast to applied or Aryan physics. The book includes an excelled description of the development of the understanding of nuclear fission and the different discoveries that lead systematically to a practical atomic bomb. It is especially good at describing the personalities their historical context. My reading has included books on quantum mechanics and most recently Maxwell’s equations in an effort to better understand the development of these areas and how they have lead to modern theories of cosmology. So, what looked like a history of technology in the Third Reich turns out to also be an excellent exposition of the individuals and development of modern chemistry and physics.

A beautiful day in Southern Pines, Progeria and farnesyl transferase inhibitors

The sky is blue with white fluffy clouds floating by, the air warm with a gentle breeze and I sit in the condo writing this missive, constrained by back problems. This affliction still limits my mobility but things are improving with a reduced of use of opiates for pain amelioration. In reality, things are progressing faster than hoped. Part of the time has been used to further my reading on the disease Progeria and defects in the critical nuclear protein Lamin A. This nuclear wall structural protein could be very critical in aging. It may be that Progeria can be treated with farnesyl transferase inhibitors drugs that are currently in phase three clinical trials as cancer therapeutics. Farnesyl is a precursor of cholesterol and as a greasy lipid helps hold certain proteins on the cell or nuclear membrane. For lamin, A lack of removal of this lipid adduct causes the protein to clump on the nuclear membrane causing the symptoms of this disease that mimics premature aging. The big question is whether normal aging is at least partially the result of a similar defect and could be slowed or reduced by the use of farnesyl transferase inhibitors.
http://www.progeriaresearch.org/index.shtml

Progeria and life extension

Progeria is a rare disease that causes children to show severe signs of ageing very early in their short lives. A full description can be found at:

http://www.progeriaresearch.org/index.shtml

With support from the Progeria Research Foundation, Francis Collins of human genome fame identified the gene that is defective in afflicted individuals. It was a surprise. Instead of being a gene in energy metabolism, DNA repair, or autoimmune disease, the mutant gene turned out to be a gene for a structural protein found in the nucleus of the cell LMNA which produces a protein called Lamin A. In afflicted individuals the defective gene product or protein clumps on the nuclear cell membrane and distorts the nucleus impeding normal function. Just how this situation causes advanced aging in young individuals is not known but the defective protein, progerin, has been found to accumulate in cells of blood vessel walls in affected children’s. However, it may be that a pharmaceutical that can reverse some or all of the symptoms already exists!

Once formed many proteins undergo modification before they take on their normal function. The LMNA gene produces a protein called prelamin A that is subsequently modified by the addition of the lipid farnesyl, removal of some amino acids and the addition of a carboxymethyl group These modifications are subsequently removed by an enzyme, Ste24 (Zmpste24) that requires a specific binding site to do its thing. After all this modification the protein is ready to go to work stabilizing the cell nucleus. Because the mutant protein lacks the binding site that the Zlmpste24 enzyme requires, the modifications cannot be removed and the progerin clumps on the nuclear membrane.

This all sounds complicated but one can consider that the normal protein is packaged for transport to the nuclear membrane and once there unpackaged so that it can function normally. The mutant protein, progerin, is never taken out of the box.



A PNAS paper, (http://www.pnas.org_cgi_doi_10.1073_pnas.0503712102/ ), discusses what happens to mutant cells in culture when the addition of the lipid farnesyl is blocked. Farnesyl is added to the protein by the enzyme farnesyl transferase. Inhibitors of this enzyme have been developed as treatments for certain types of cancer. Application of enzyme inhibitor rac-R115777 significantly reversed abnormal nuclear morphology suggesting that they could be useful in treating Progeria.

In a subsequent study mice with Progeria were treated with a farnesyl transferase inhibitor and found to improve significantly. This provides significant hope for a treatment for children with Progeria.

The big question is whether these farnesyl transferase inhibitors will be useful in life extension in general. It may be that Progeria mimics aging but is caused by a different mechanism so that farnesyl transferase inhibitors will be of little utility for the rest of us. However, these finding points toward the status of these structural proteins as key factors in the aging process.

Unscheduled dismount

During a riding lesson on Saturday, I had an unplanned dismount over a jump. Some very nice pills were obtained but I will not be back in the saddle for a while. The weather has been cool but is warming up and Wendy’s riding is going well.

Another day in Southern Pines NC

Breakfast was sautéed bell pepper and sausage with plenty of Cholula hot sauce. This concoction really wakes you up. Next the horses were feed as usual and the pasture cleaned up followed by a return to the condo. I took off for my riding lesson that included a few passes over the jump swith some trouble picking up the correct lead at the canter after the jump. Sometimes Willy will do a flying lead change and sometimes he will not. After a quick run back to the condo and a shower I headed off to the Southern Pines Rotary meeting where I learned about the finances of Pinehurst NC from a town official. Did you know that Pinehurst has only been incorporated for 25 years while Southern Pines has been a town for over 100 years. Back at the condo Wendy took off to go riding but without companions as Gail was training her new horse and Pat was busy with other endeavors. On the driving range 140 balls zoomed out into the distance. Some were well hit but there is much room for improvement. After walking the dog another bike ride was enjoyed until it started to sprinkle and I returned to the condo. After my third shower of the day we are to head out for cocktails at a friends “Hunt Box” (a rather elegant home over a stable).

Cold Rainy Day

It rained most of the day but we all met for lunch at LuLu's in downtown Southern Pines. Harris was spirited back to the airport and the frigid North in the evening. I was left to fend for myself in the condo without transportation.

Genographic project, my ancestors and haplogroup L

The Genographic project (https://www3.nationalgeographic.com/genographic/index.html ) analyzed my DNA and put my parental origins in India. This is strange as my paternal line was thought to come from Northern Europe and I don’t look Indian. It is possible but my haplogroup “L” is rarely found out side of central India. They use small tandem repeats (STRs) of DNA as markers and there are a number of STRs on the Y chromosome. These STRs can vary in length and the differences in lengths can be compared to others around the world. Certain lengths of certain STRs are found more frequently in people from one region than from another. For example, STR DYS19 can have lengths of 10 to 19. These patterns can be used to show how and where one’s ancestors migrated out of Africa. However, the Genographic results listed my STR DYS389-2: as 16 but none of the databases I have consulted (such as http://ybase.org/shaplo.asp )lists a 389-2 with a length of 16. They are all above 20. I believe that the Genographic project made a mistake.

Tailgate at the point to point and steeplechase in Southern Pines

After bruising their bottoms on horseback in the morning the girls decided to go to the steeplechase sponsored by the local fox hunt. I had been helping Hans put in some paddock gate hardware. Such devices never quite fit but with some skilful use of a chain saw the post was shaped to accept the hardware. A frantic call to spur me on so that we would not be late for the races had me leave Hans at the end of his drive and rush to pickup the thrill seekers. It all worked out and we munched on chips and sipped wine as the horses went by our excellent position on the rail. These were the last races on this field as it will soon be developed. Next year the races are to be at the Carolina horse park. In the evening Harris prepared a feast of coq-au-vin at Gail’s new house and a good time was had by all.

From Lancaster MA to Southern Pines NC

Harris flew in and Wendy picked her up at the airport. Later in the day the two went riding in the Moss Foundation Followed by a dinner out of the entire group.

Riding and cycling

Yesterday I had a riding lesson and then cycled 18 miles. The major problem was the hills. Even with 21 gears they can be pretty tough. Today I had another riding lesson and did some jumps. It has been several years since I did a jump course but it all came back and felt comfortable. My wife still has her cold but went riding anyway. When I returned she was asleep on the ground next to the trailer. Some people are really dedicated to riding. Tomorrow Harris comes for several days of riding and viewing the three day event and point to point scheduled for this weekend in Southern Pines.

A great party followed by a ride on Slick Willy

Last night Wendy prepared her fabulous chicken in onion sour cream sauce for a party at Gail’s with Pat and Hans in attendance. We set out on the deck enjoying the evening while talking and looking at the horses. Earlier I helped or watched Hans remove a window from his commercial property in downtown Southern Pines. With this experience an extraction of a problematic window at home may be possible. Today after feeding the horses I drove off the Fox Catcher Farm for a lesson on my old pal Slick Willy. He may not have remembered me from last year but the adventure went well and my arthosopically enhanced knee seemed to operate well. Tomorrow will tell more. In the afternoon Wendy walked Gidget and I rode my new bike in the reservoir park. The trail is interesting as there are many twists and turns and many very young or very old hikers to avoid. Thai food was enjoyed for dinner. Tomorrow Hans and I are off to Beneteau to watch them build sailboats.

The Zen of bicycle maintenance

It was a beautiful day with temperatures in the 80s. We fed the horses and I fitted my GPS to the handlebars of the birthday gift Schwinn. Hopefully, this device will reduce the experiences of going around in circles as in this area there are few straight roads. On one foray across Rt one down Young’s road things didn’t feel quite right. A quick inspection revealed a back tire that was flat on one side, the side next to the pavement. As this is a mountain bike I often ride on the side of the road in the grass. Unfortunately, this area is often littered with broken glass, a piece of which impacted my rear tire. The bike was walked back to the condo and the instruction manual consulted. In the “changing the tire” section, the manual instructed one to remove the wheel but gave not hit as to how this can be done successfully. The rear wheel has many attachments including breaks, gears and chain derailing mechanisms. After much searching a wheel removal section was discovered in the middle of something else and the extraction successfully accomplished. However, the tool kit for the bike was not robust enough to loosen the axel bolts so another trip to WalMart was required to purchase a 15 mm open-end wrench. You can’t buy just one. I now own a number of wrenches that I don’t need. The 15mm wrench worked and the wheel was extracted from the frame. Next the inner tube was pulled out with some other specialty tools and a new inner tube containing green goo to eliminate unexpected flatness was inserted. It all went smoothly. My wife’s 12 volt air pump did an excellent job of providing 55 lbs of inflation and off I went.

In the evening we enjoyed an excellent dinner at the condo next door talking about golf, horses and the meaning of life.

Leaving Virginia for Southern Pines

I got up early as Keith and Martin were driving to North to pick up a Norwich Terrier puppy. We wish them good luck with the new addition to their family.

I took the long way home through Norfolk down along the shore seeing Virginia Beach and then heading inland along Albemarle sound. In 2005 I joined Keith and Martin in their Bristol 48 for the first part of their trip down the inland waterway to the Bahamas. When I arrived back in Southern Pines Gail, Wendy and I went out for a dinner of prime rib. The future will have to include significant exercise to compensate for all the food I consumed over the last few days.

Touring Norfolk’s port, the battleship USS Wisconsin and Nauticus

In the morning Keith and I journeyed into Norfolk over the bridge and through the tunnel among all the Navy ships. The harbor is a very impressive sight. An Aegis cruiser was entering the port accompanied by a fire boat with plumes of water streaming from its water cannons. We parked near the shore and walked to the impressive Nauticus site at the National Maritime Center http://www.thenmc.org/ . This includes the battleship USS Wisconsin. Nauticus is a combination maritime and science museum. It is very well done with a combination of old fashioned museum and computer displays. The most impressive was the mock-up of the Aegis control room where a moderator demonstrates the different armaments. Then each seat has a control panel and one is asked to select the correct response to a threat in real time. It is not as easy as it sounds, especially when more than one threat presents itself at one time. For the finale everything comes in at once and the ship blows up. After this excitement we toured the battleship Wisconsin. However, unlike the battleship North Carolina in Wilmington one can’t go inside as the ship is still commissioned and could be pulled back into service as it was in the first Gulf War. After our tour we met Martin at a Marina filled with sailboat for an elegant dinner.

Visit to Keith and Martin

Today I drove from Southern Pines Mobjack VA to visit old friends from Groton who moved to a beautiful house with water on three sides and a 17-slip marina in the back yard. We talked and toured the new marina and enjoyed a fantastic meal. They are great cooks. Their property consists of a main house, a new cottage and a room over the garage re-done as an office with all sorts of computers. A marina building is under construction. This is going to be quite a facility.

Happy birthday to me

The day was taken up by horse feeding, golf, consulting, bike riding, golf, feeding horses, drinking and eating. Not a bad day. For three days I will be in Virginia visiting friends.
All the best to everyone

Computer problems, bikes and horses

This morning I got up and turned on the computer with no results. It couldn’t find the hard drive. After about an hour with a couple of local geeks (really good guys) the defect was repaired with no loss of data. I tried the computer “recovery disk” which began with the warning “all data will be lost”. What is one to recover from? Thank goodness for local geeks to compensate for the degenerate manufactures.

I did some more riding on my new Schwinn Sidewinder hoping to regain my endurance and strength. The process went well but I have still more to do to get back in shape. Hopefully, when the biking goes well I will move to horses. Our friend Gail bought a new gated horse that I will ride as things improve.

Pat and Hans' new place in Southern Pines

Pat and Hans are building a new house on 1 acre in Southern Pines next to the Foundation riding trails. They have brought down a trailer from MA for temporary housing until their new house is finished. Half the land is fenced and occupied by the horse they brought down from Massachusetts. We met there last night for a celebration around a small fire on the newly seeded pasture. There could be a bare spot. Unfortunately, no one brought any marshmallows so we had to settle for wine. The temperature was below freezing although a day before the temp was in the high 70s. The nights may be cool in Southern Pines this time of year but it warms up into the 50s during the day.

How to go to the Moon the right way

There is finally a new moon program and it is worthy of support but I worry about the goal. Hopefully, it will not be another look around and go home program. The goal set by President Kennedy was wrong! His goal was to send men to the moon and bring them back alive. This was a $200 billion publicity stunt in today’s dollars. There is immense physical wealth to be gained from permanent access to the Moon. IT is made of stuff and has ample solar energy available as well as being a much safer location for the use of nuclear energy than the Earth. With today’s technology we need only dirt and energy to make everything we need. There are trillions of dollars of new wealth to be gained form utilizing the moon. Everything we do on the Earth hurts it while everything we do on the Moon is an improvement. It would have been so much better to have followed up on the original Moon program rather than develop the space station.

In the first Moon program we should have established a permanent base first and then looked around. Supplies could have been sent ahead so that the astronauts wouldn’t have to carry all their supplies with them. This would have required being able to hit the same general spot more than once and perhaps such precision was difficult with the technology available at that time. We are going back using updated versions of the systems employed 40 years ago. These include expendable rockets with even the lunar lander being a bigger version of the original units. They are designed backwards. The rocket is on the bottom so that the crew and cargo are on the top. For the larger new unit this means that the astronauts will have to climb down a rather long ladder to reach the surface. Not falling will be one of the major challenges of the process. Carrying down materials to the surface will be even more difficult. The rockets should be on the sides or top so that the cargo will be close to the surface and can be deposited in a way similar to that used for ship containers today.

What we really need is a reusable orbiter that works. The shuttle should have been canned long ago and a new orbiter using knowledge gained from the shuttle created. A new orbiter with the capacity of a 747 freighter should come from a contest in which the winner receives 50 billion dollars when the orbiter has proven its practicality. It would be designed and built with venture and private money. The prize would minimize the commercial risk to make such an investment attractive. The prize money would be to cover the design costs and those of the first unit(s). Then purpose is to create an industry selling orbiters whose per unit cost is a few billion dollars to businesses and other countries. If we don’t do this soon we may loose the talent and infrastructure that would make such a program possible. The economic good news is that many nations around the world are becoming more prosperous with the bad news being that they are now very effective competitors. As a country we need something to sell that will not be done cheaper and better in a few years in China and India. The U.S. needs an effective space program.

Warm weather in Southern Pines

Today we may hit a temperature record. This morning I helped feed the horses as usual and then ran some errands as the riders got ready for their third day on the trails. Today is Mitzi’s second foray. Our condo is blessed as a high speed wireless internet connection that appeared out of nowhere. The laptop just picked it up. In the past my cell phone was the only way out as the condo management blocks data use of their phone system. The cell phone worked but was very slow. However, a brief chat with our next door neighbors form Canada disclosed that they are the source of the internet blessing. I quickly offered some of my computer expertise as partial payment for the use of their bandwidth. Hopefully they will not realize the immense power they have over me.