Thursday, April 22, 2021

proven contradiction removal method


The latest link

I consider this as an original philosophical contribution and promise to link all comments.

A proven contradiction removal method in compatible interests is what this note is about. Compatible will eliminate insincere interests, any moron that attempts to cause a failure can and will be eliminated as incompatible (and insincere) interests. At this point, it deals with converting relation with stepson who just emerged from teen years (wanted to be an Egyptologist in teen years, Indian Army also) and ready to face the world on his own respect for me as opposed to real mother.

It is a necessary step to decide on the claimed reasons of the interest. A jury can be given a range of their result, threshold communicated and decision is by median. All values cause the highest and lowest jurists to be permanently replaced from the pool. If the median is under threshold then the party is declared incompatible. Majority matters. Jury pool is always dynamic to exclude extreme opinions.

The basic tool for removal of genuine contradictions in interest is scheduling them linearly in part fulfillment order overseen by a trusted reliable judge whose word is kept regardless. Part fulfillment only ensures required CBM (conflict building measures) in all other groups. The duration of each slice depends on the case, but all interest are broken into 2 or more steps. Trust in the judge is required for the last step(s).

To earn respect, my word is good as gold. Never lie to a person or in front of a person to a third person except with atonement in advance that demonstrably and transparently exceeds the gain of lying and clearly is to protect a fourth person. That is generally possible only by being honest. I have never understood how some enjoy life by unnecessary lying or being forced into such situations. Generally by making punishment proportional to income seems to sharply reduce crime. Increased burden hurts the higher income person proportionally means harder! Imprisonment hurts equally, but a proportional fine must always be added.

I am truly interested in the empirical value of such statements, particularly impact on innocent victims, for I consider current law bias to criminals punishment to be outrageous and correctly criminal even if no law currently forbid it! Absolute forbid of some laws is solely for criminal reasons and judges can always can block the relax of such laws, IE the law must always consider the burden of proof. Innocents so far are free of burden of proof while convicts for some case-basis time must carry the burden, and must prove themselves innocent! This loss of privilege is essentially the end of mollycoddling of violators.

Triage Rational Skepticism TRS

 


I finally know what my Weltanschauung is - science means RS, but I could not understand many temporal events as in business, politics etc and that meant a new element Temporal to yield TRS. This T is better captured by Triage like the Triage nurse or in biology where successful organisms in evolution have internal triage-directed nutrient consumption mutations. This is generalized to all social sciences, management and computer-science algorithms. That is how much power that the new T has, temporal and more when the system order is non-linear unlike just time. It can handle all linear orders like time and sortable non-linear as well..

Good assistants like triage nurse?

Triage nurse reorders arrivals by quick determination of needs and urgency of these needs and reorders the arriving patients by medical need urgency. It is very anti-commie (not seniority based) and anti-liberal (no allow all orders) and anti-libertarian (nurse decided) and anti-conservative (not money or seniority based).

TRS expresses a very different to liberal or conservative philosophies but always consistent even when coinciding with one and a proven contradiction removal method in compatible interests. I consider this as an original philosophical contribution and promise to link all comments.

Another very important application is evolution. We can agree that that surviving mutations are those that satisfy the environment better, but it seems that which form survives can be predicted by who utilizes the internal nutrient uses better, thereby allocating more resources to dangers presented by the environment now versus later IE by triage, Is one looks at vitamin k1 to k2, both are helpful to bones getting calcium but k1 has role in clearing blood path deposits too. It performs bone fix with much greater use than deposits. The deposit keep growing slowly but surely, It is called osteoarthritis. K2 cleans the paths equally. k1 is found in all green veggies, since one job is to assist chlorophyll in plants. K2 in fermented foods like soybean and some cheeses. Gut bio-me has some bacteria that convert k1 to k2. In any case, it is highly recommended as a supplement for non-soybean eaters. Two general ideas in evolution details if triage and multiple roles of a chemical.

One point about foodstuff derived chemicals is that they have some role in plants, likely different from animals and triage governs multiple in-body roles but these are fixed, not by current need but fixed in DNA. So in reality, fixed Triage is assumed in animals. A theory of triage use of micronutrientsexists.

Nurses are slowly capable of absorbing new triage and differ from resource allocations in animals. A full theory of micro-nutrient use by triage exists, strongly supporting this application but not as general. The triage theory posits that some functions of micronutrients (the approximately 40 essential vitamins, minerals, fatty acids, and amino acids) are restricted during shortage and that functions required for short-term survival take precedence over those that are less essential.

Triage in biology

Triage - Wikipedia

Triage is the process of determining the priority of patients' treatments by the severity of their condition or likelihood of recovery with and without treatment.

 

Triage | Selenium | Biology

Our triage analysis focused on within-­‐tissue hierarchies of SP activities or concentrations measured in vivo in experiments where the sensitivities of essential and nonessential SPs 

 

Vitamin K, an example of triage theory: is micronutrient ...

A triage perspective reinforces recommendations of some experts that much of the population and warfarin/coumadin patients may not receive sufficient vitamin K for optimal function of VKD proteins that are important to maintain long-term health.


biology immune system triage notes Flashcards | Quizlet

Triage. Assessment of the severity of patients' conditions and establishing a priority of treatment. Process used in battlefields, disaster areas, and emergency rooms to assign the order

Conservation Triage: Debating Which Species to Save and Why

Akin to triage in a medical emergency situation, this challenge has brought forth the idea of conservation triage and personal values relate to the study and practice of conservation biology.


Triage in AI and computer science

(PDF) Scaling up data curation using deep learning: An application to...

An application to literature triage in genomic. variation resources. Institute of Bioinformatics,

Why Bug/Defect Triage is Important in Software Testing

Defect triage is a process where each bug is prioritized based on its severity, frequency, risk, etc. Triage term is used in the Software testing / QA to define the severity a.

GitHub - hacetin/deep-triage: Implementation of 'DeepTriage: Exploring...

cd deep-triage python main.py. Contribution.

Triage in Management

Triage Definition - Investopedia

Triage is a management protocol that structures the incoming workflow by priority so that the most critical work is attended to first. The practice is most often used in hospitals and other...

Using Triage to Manage Process Workloads in Services

One of the most effective tools for dealing with congestion is triage. The principle of triage is the same whether you work in a hospital emergency room or office typing pool: Make sure that the most critical cases are dealt with first, and either take longer or use alternative methods for dealing with less-critical cases.

 

Triage Systems in Mass Casualty Incidents and Disasters: A ...

Triage is one of the key principles of the effective management of major emergencies. Triage is derived from the French word "trier", which means separating, categorising or classifying, and refers to the categorization, classification, and prioritization of patients and injured people, based on their urgent need for treatment,.

 

What is Project Triage - Task management guide

Project Triage is a process used to promptly analyze troubled projects from a portfolio to prioritize them, and to define the following actions based upon the current status of every project. It is usually performed at the end of accounting period, by the project manager.

The Principles of Triage in Emergencies and Disasters: A ...

7 Triage systems are one of the approaches used to manage resources and provide medical services to injured people in emergencies and disasters.

 Triage in Philosophy

Triage and Ethics | Journal of Ethics | American Medical ...

The term "triage" refers to the procedures clinicians use to prioritize prospective patients. In the background is the unhappy truth that, when vital resources are limited, some will not get what they need, at least not right away. One branch of the field of bioethics deals with the broad problem of allocating scarce medical resources.

Family Court Philosopher #21: Triage

This section was my workspace for philosophy essays between July 2006 and April 2008. ... No, here "triage" does mean somebody pobably dies, not quite the same as getting yourself a cup of coffee on your way to work in lieu of donating money to a charity. You'll never know if somebody died cause you decided to get a caramel machiatto.


Proning - Another effort

The latest link


What this note continues. So far, why care,how more! Proning can be done, patient awake or unconscious. If it is used, it will be visible in care pics on TV. Wireless and TV would be full of instructions!


Why care?


So far there is still no coordinated use. Why do I care? Not a citizen anymore! Governments are same everywhere! Happened to me about US INS (Then), helped by the USA congressman! Legislature is not the same and BJP is not Government. I care because I am still an Indian! If I can help, I must try. I owe so much to IIT Kanpur! Only US social security is above that! Forget the stupid triage system of the powers that be. I learned my life philosophy from this failure, except it is not over yet. Things could become lot worse.


Who is to blame?


Doctors are not all same. Proning is known to some. Why do they not fight, even if most do not know? The answer is in News. Those of Maharashtra are better than Delhi, in that they have successfully used lower oxygen rates! The shortages here are of their doing too! India with sane use can handle twice COVID-19 rate! 1.4 from rate lowering 1.4 from proning. No proning doctor fights. No sane use try! Government yes. Politician yes. Doctors too!


What beyond cry-baby, how more?

In a democracy, beyond Government and legislature are two - courts and Press. I take my fight to them. A few TV channels get the story next, as do some courts . Both know what to do if interested.

More help please?

Following chain; PM First, Government next, then politicians, we followed in proper order. TV DAMAGE PICTURES BURN ME. Any courts, channels or newspapers you think right.

Why should media/courts care?

 I am happily anonymous. One time you can shine!

Wednesday, April 21, 2021

Proning - Emergency help needed

 




Rarely I get so angry - PMO must have morons. My update for PM attention is now several days old, had a number to prove writing, but proning has not been mentioned, criminal deaths in oxygen shortage! Call for criminal investigation of PMO and emergency upload to joey - I neither have a telephone number nor email address. Request help from Sir saint (Baldev Rohra) in our group for emergency delivery to joey.


An important sidebar

 Given the state of oxygen supply, I strongly support the use of proning by doctors to know and advise their non-ventilator patients and general knowledge of you as patient yourself and helper to a sufferer. Proning is laying the patient chest down and fast large gulps of air at speed as if panting. This method is advocated by Dr. Guleria, director of AIIMS, Delhi, applied to a big-shot in government who lost his oxygen and was forced into proning. This trick was invented by US residents, interning in the USA, one year back.


Prone position is opposite of supine. Prone is chest down. A local TV recommended M3 PRC where P is prone that is said to improve OXY levels by 5-10 % after OXY levels fall to 92 and people rush to hospital. Many fewer will go into the cauldron of COVID-19. More OXY available for ventilator sick as oxy-connected patients can be reduced!


Proning is stupid to keep medical  knowledge from all doctors and all patients. Some ones are moronic. I also would ask for help in sending this letter to Lady Mamta in Bengal to ramp up pressure to be heard!! Sir Kejeriwal is also good suggestion. So is Sir Yogi.

Temporal Rational Skepticism

 




It is RS extended to cover statements missing from standard rational skepticism or Science that must be extended to cover temporal statements outside RS. The very concept of true is questionable in TRS and I adopt the Science definition of 5 sigma for scientific truth and 3 sigma for practical truths accepted in miss of counter truths.

Aging recommendations



I follow Dr. Audrey de Grey, creator of SENS, after rational skeptic analysis over 20 years. This note is nothing more than collection of his points selected by me to be worth following.

You'll read about healthy life extension, engineered longevity, and the development of rejuvenation biotechnology. What do these terms mean? Put simply, they refer to the use of new medical technologies to both increase healthy life span and reduce the risk of suffering age-related conditions in later life. It is doing the best we can with the very few proven (and limited) present day methods, far more effective methods for tomorrow.

Aging is an Enemy, So Fight It!

Aging saps our strength and ability to enjoy life, cripples us, and eventually kills us. Tens of millions die from medical conditions caused by aging each and every year, and a staggering amount of money is spent on trying - and failing - to cope with this ongoing disaster. Yet the risk of suffering age-related conditions in later life can be reduced for most people through diet and exercise. Furthermore, serious scientific efforts are presently underway to understand and intervene in the aging process - not just to prevent frailty and disease, but also repair and reverse the root causes of aging.

Some of these future therapies are already understood and envisioned in some detail, but remain in comparatively early stages of research. Others are just now starting to make the leap into clinical development. We would like these breakthroughs to happen while we are still alive and in good enough health to benefit from them: we miss out on so much as things stand today, pressed by the lack of time and our increasing frailty with age. Imagine instead a world in which everyone has the option of another tomorrow, and the health and vigor to enjoy it, each and every day. But how can we achieve this goal?

The Limited Means of Today, the Biotechnologies of Tomorrow

Despite amazing advances in understanding and treating age-related conditions (such as cancer, heart disease, dementia, diabetes, and many others), and despite the cries of the anti-aging marketplace, it is still the case that, for basically healthy people, no presently available therapy or tool is proven in humans to provide more than a fraction of the long-term benefits to health and life expectancy provided by regular exercise or a calorie restricted diet.Some classical preachings are true and nothing but serious aplication of timed rational skepticism TRS of Dr. Arun Arya will work. You can and should point out contradictions between his preachings and doings.

While it is true that no existing medical technology is proven to improve on these lifestyle choices here and now, today, in humans, this state of affairs will not remain true for many more years (2030 or earlier if most cancers become treatable). If you look to the laboratories, you will see that some researchers can greatly extend the healthy lives of many species, while others put forward clear plans to either slow aging through the manipulation of human metabolism or reverse aging by repairing the cell and tissue damage that causes age-related degeneration. Technology demonstrations for some of these approaches have been carried out in mice in recent years, producing benefits to health and extended healthy life spans. Treatments based on clearance of senescent cells have been demonstrated to reverse the progression of many currently untreatable age-related conditions in mice, for example. The first formal human clinical trials of therapies anticipated to either modestly slow aging or produce limited degrees of rejuvenation started up in 2017, and some of these trials have produced positive results, like senolytic drugs.

A future in which aging becomes a treatable condition awaits us, as time ticks away and, for now, we continue to age just like our ancestors did. This is an era of rapid progress in biotechnology and medicine. As the years pass, the remaining span of healthy life that you and I will likely live to enjoy is ever more determined by the ability of clinical medicine to revert and repair the causes of aging, and ever less determined by lifestyle choices. Medicine do not discrimminate between righteous and crimminal.

Thus when we reach for longer, we must ensure that the public is educated, the fundamental longevity science is funded, the clinical applications of that research fully developed, and the resulting rejuvenation biotechnologies made available - and all this as soon as possible. The clock is ticking, after all, and this is the only approach that will allow us live for significantly longer than our ancestors.

Four Steps Toward Longevity

The following four steps outline a starting point for living longer, a sketch of a framework for thinking about healthy life extension:

Step 1: Stop Damaging Your Health

At its most basic level, aging is nothing more than an accumulation of damage; breakages in the molecular machinery of your cells, a build up of metabolic waste products that your body cannot break down, the flailing of biological systems that are increasingly unable to cope. Ask yourself this: are you damaging yourself more rapidly than you might otherwise be, perhaps more than you realize? Do you smoke? Do recreational drugs occupy a central position in your life? Do you eat nothing but junk food or are overweight? Do you exercise little or not at all? Do you have a poor relationship with your physician, or haven't seen a doctor in years? If so, you have a clear starting point. These things can hurt you far more than any presently available strategy for healthy living can help. There is little point in insulating the windows if the door is jammed open.

Find a physician you can trust and talk to about improving your health. You might be surprised at how easy, low-cost, and downright pleasant it is to lead a healthier and thereby longer life.

Step 2: Adopt a Better Diet and Lifestyle

The body is a complex, resilient machine. Unlike our cars, however, we can't yet replace it when it breaks down. Given that, it's scandalous that most people know more about the long-term care of a car than they do about the long-term care of the human body. Fortunately, it's neither difficult nor expensive to use diet and lifestyle to raise the odds of living a longer and healthier life.

Firstly: adopt some form of calorie restricted diet, whether straight calorie restriction or some form of intermittent fasting. Calorie restriction and some implementations of intermittent fasting, such as alternate day fasting, are currently the most robustly, repeatedly proven way of extending healthy life in mammals. So qalso says Dr. Sinclaie of Harvard mdical school, surprize he never got an While the present scientific consensus is that these practices will not extend life in humans to anywhere near the same degree as in mice, calorie restriction and intermittent fasting have been shown in human studies to provide a range of other beneficial effects on health, such as a greatly lowered risk of suffering all common age-related medical conditions - and these approaches to diet are highly praised by practitioners. You can learn more about calorie restriction at the CR Society website, and here at Fight Aging! you'll find introduction to calorie restriction that provides helpful guidelines to getting started.So also says Dr. Sinclair of Hatvard medical school, PhD in genetics! He is 50, believe it or not!

Secondly: exercise as recommended by your physician. The benefits of maintaining a modest regular level of exercise for most people are well known and well proven by many scientific studies. As is also true of calorie restriction, these benefits include a greatly reduced risk of suffering almost all of the common age-related diseases.

Thirdly: take a modest amount of supplements appropriate to your age and health. There is a wealth of supplement information available, but much of it is worthless, propagated by irresponsible sellers. This is perhaps the hardest topic to research, and in the end you will have to make a number of decisions yourself based on incomplete or contradictory scientific evidence. The bottom line here, however, is that no presently available supplement or combination of supplements has been shown to provide even a fraction of the benefits of either calorie restriction or exercise, for all that they are widely supposed to be beneficial.

Investigate Early Access to the First Rejuvenation Therapies

New medical technologies do not arrive all at once, fully formed from day one. Early forms of therapy become available in limited ways, or existing drugs are found to have an effect on the mechanism of interest large enough to merit use in animal studies or human trials. So it is for the first rejuvenation treatments to have a large enough impact on aging in animal studies to care about, and that are also producing benefits in their first human trials. Only trust statistical TRS results, never anecdotal.

As of 2019, the most obvious of these are senolytic therapies that selectively destroy the senescent cells that accumulate to cause considerable harm in old tissues. The existing generic drugs and supplements newly discovered to be senolytic, and shown to work well in numerous animal studies, are being tested in humans.

The informed decision that each of us must make for ourselves is whether to wait for more data from human trials, to wait for the most likely better senolytic therapies presently under development, or to strike out to obtain and try existing senolytic therapies. If the latter, there in turn lies further personal research, learning, and informed decisions. Where to find a physician to prescribe the relevant drugs, for example, or whether to forge ahead as a self-experimenter, with all of the responsibility and accountability that this implies. However it is accomplished, it is almost always possible for informed and proactive individuals to obtain earlier access to new therapies than waiting for the world to move on to the point at which general physicians begin recommending these treatments to patients. Whether or not to choose to do so is a personal decision on risk and benefit, and this same calculus applies to any new medical technology as it arrives, not just senolytic rejuvenation therapies.


Dr. Arya recommendations (Takes himself)

in undefined dosages and sellors

Based on Dr. Sinclair

    NMN, Pterostilbene, metformin, acarbose; nothing yet for Mtor

In studies conducted by three independent laboratories by the US National Institute on Aging's intervention testing programme, acarbose was shown to extend the lifespan of female mice by 5% and of male mice by 22%. Both metformin and acarbose are prescription drugs.

Based on  Dr. de Grey

Senolytic  Dasatinib suggest to allopathic Dr. and take on advice in suggested  dose only

Senolytic  quercetin, In preliminary human studies, oral intake of quercetin in doses up to one gram per day over three months did not cause adverse effects.[2] The safety of using quercetin in dietary supplements during pregnancy and lactation has not been established

Based on Dr. Arya  Voraciousus TRS read

for Osteopenia: k2+D3+Calcium

for everyone: k2+D3

Tuesday, April 20, 2021

Aging and cancer

 


The latest link        Dr. Arya reco


The basic take home from 1 man-year of last 20 years is simple but very profound - aging and cancers are closely related, evolution solved the problem of cancers by aging. Your NAD+ is required in many sub cycles of Krebs cycle (basis of life) and declines continually with aging. Good only because NAD+ also inflames the cell from outside. This evolution fixed by letting senescent cells express CD38 whose concentration keeps increasing with age! The inflammation causes problems in the heart. Heart disease is an even bigger killer than cancer. Senescent cells eventually cause cancer which can happen anywhere.

You can measure inflammation by CRP being C reactive protein which is a far better predictor of adverse heart effects than lipid profile.

The main lesson learned is that NMN and associates have a bar of about 10-15 years and the NAD+ improvements are met by increasing heart events. Filtering reductions of CD38 fails because then cancers go up!

One can chemically cure NAD+ problem till inflammation finds another organ as victim, But in 50 years, artificial organ update will likely be common. Cancer cure will be by organ replace, artificial thymus etc. The goal of shark life for humans will be common. By being conservative in TPE and NAD+ increment methods, one can improve the risk for the new world in 50 years. One can hope that NAD+ update will not cause heart problems or incurable cancer. In any case aging will be better being healthier and no age decline.


No matter what, I will take the risk and am ready for a new career in attribute grammars rather than computer security where a new quantum safe efficient algorithm is ready for the internet of things, which might fly too with tireless devotion and purpose to this only life.

How Aging undo 2021, proper 2030

 




The latest link

Consider the aging undo ways. Better blood flow is by endothelial cell improvement by pterostilbene. One can improve cell energy by targeting the mitochondria, trough NAD+ predecessors and mitoq. One improves blood itself by TPE to reduce proteomics load. Immunity can be reverted to youth levels by reducing fatty white-cells and trained killer cells with enhanced  immunity factors. Overall improvement requires genetic improvements by using Yamanaka factor permutation to fix DNA and control over stem cells. Of these ideas, one selects 4 for 50-year gain by 2030.

Senolytic drugs is likely the first big 15-years attack on giving the first 50 years by 2030. Expect 10 from NMN and associates, likely rising to 15 by mib-626 etc by 2030, 10 from my designed plasma substitute designed TPE rising to 15 with 10 year research, 15 from Yamanaka factors supplements & drugs and 15 from senolytic drugs. Of these NMN and associates is done and 15 likely by 2030, Arya replace TPE is done and awaits self test, likely rising to 15, Yamanaka factors supplements are private and public funded furious research in California, and some senolytic are there and more will be available by 2030. If anything, my estimates are probably too pessimistic. Perhaps 50 years by 2025 for the close watchers.

All these attacks are independent thus likely additive. Another issue is lessening of my circumspection, my thinking of 2030 for 50-year is likely too pessimistic. Perhaps revise it to 2025, great for mother and doctor uncle, they only need to be alive by 2025, Till then confidence in my medical knowledge will be there by self-experiments and there is no need to wait to 2025, important in Covid-times. By  2022 middle, Covid-terror will vanish from herd immunity from 50%+ vaccination and departure of villains like Lady Mamata and Sir Tikat.

Evolution driven natural-like supplements?

NMN and associates target NAD+, the villain could be CD38 evolution to solve cancer problem with aging a solution, and perhaps 10 year research is still needed on this villain.

Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes

Aging affects circadian clock and metabolism and modulates timing of medication

Blood fix like oil change?

TPE with my designed plasma may not work to Parkinson type attack due to BBB. But amyloid were reduced in AMBAR and perhaps other chemicals in the brain might like to keep constant ratio! This is important to me to make India, an important fulcrum of aging and self generated capital.

Artificial disease targeted plasma TPE?

The most severe complications in TPE occur with fresh frozen plasma as the replacement fluid.  Almost all studies of TPE for treating SSc used sterilized 5% albumin, which has a much better safety profile because of substantially reduced risk of anaphylactic type events.

Senolytics for Cancer Therapy: Is All That Glitters Really Gold?

Senolytics represent a group of mechanistically diverse drugs that can eliminate senescent cells, both in tumors and in several aging-related pathologies. Consequently, senolytic use has been proposed as a potential adjuvant approach to improve the response. Despite the unequivocal promise of senolysis, issues of universality, selectivity, resistance, and toxicity remain to be further clarified. In this review, we attempt to summarize and analyze the current clinical literature involving the use of senolysis in senescent tumor cell models, and to propose tenable solutions and future directions to improve the understanding and use of this novel class of drugs.

Parkinson's efforts - why and how?

Parkinson is important for me because my essential tremors matches better than Alzheimer; I am unlikely to suffer dementia not still have a bad old age, not like Parkinson but still bad. There are two fascinating studies on research. Fundamental to all research, a doctoral thesis for example is finding a new problem in which some progress is possible. Best is research with 2 insights, one to decide if a problem should be selected and another that drops in the course of research. It is the job of guiding professor to provide the first insight, or most of it.

Above describes computer science research. Medical research can be started by lack of reliable answers to patient observations. Two Parkinson research are driven by lack of answers. Why do the Parkinson patients smell different? Why is tandem bike (two persons sharing pedaling) improve symptoms, while pedaling ordinary exercise bikes don't? Another disease that afflicts me is diabetes. Why do patient's with good control have halitosis but symptom free do not? A final one that I learned by spending 40000 bucks and 3 day terror in heart ward is fix heart burn even if you can't fix heart disease and symptoms are identical?

Yamanaka factors drugs and supplements?

Of OSKM, the Oct4 may be redundant, if quality not speed is goal, then SKM suffice, never M which causes cancer! Processes with pulsed S and K at low doses will work.

Drugs?

They require a prescription, sometimes for bureaucratic reasons, obeyed nonetheless. Case in point is metformin, getting a prescription for aging should be easy. 

None found.

Supplements?

I use the term in the sense of actual OTC drugs and supplements of food grade and pharmaceutical grade, last suitable for injection or intravenous forms. I consider the mode of usage restricted to doctor or nurse presence in some cases despite no legal requirements, requires warnings. 

There are none for Yamanaka factors at this point.


Monday, April 19, 2021

Grim Age and a fundamental contradiction

 


2019 is also important for the experiments by Horovith that showed an AI computable statistic that connect methylation concentrations of cytosine in Cp blocks of the DNA, habit indices of things like smoking and predict the remaining life in years to 98% accuracy. This is called the Grim Age counting the years remaining to natural death. To the surprise of Horovith team, the damage from Smoking errored on add when the damage was already reflected in methylation alone IE habit percentages of many damage elements like drinking were already reflected in methylation levels! The number remaining in natural life were called the Grim age. Unmodified Grim age was a better number than human memory of degree of smoking!

As this reference shows, There are many question in your mind about the establishment of Grim age in DNA m Age. While the entire blog is very readable, I do believe the author believes in some programmed theory of Aging and considers the modifications from habits a perturbation in predicted age, I still cling to the minority view that aging is damage accumulation and smoking and other lifestyle habits increase damage but still reflect the summary of damage accumulation. Damages can be external and unavoidable as a consequence of passage of time. But this means that the essential amelioration theory is neither prevention (gerontology) nor dealing with consequence (geriatrics) but deal with fixing the damage however caused (SENS and Dr. Audrey de Grey). Wounds happen in a war, prevention is like bullet-proof vests help, Complex consequences will require complex studies, that is what medicine is all about, better is to save the wounded and stabilize the wounded to be processed properly. Aging is like that. Let us fix the person ready to die. In fact in a war, Enemy will likely change the bullets once the vests become common, viral enemies will evolve to those that will defeat the aging fixes and the war will continue!


The best part of a blog is to read good comments and responses.


Some anti-aging candidates seem to have no effect on methylation status-like rapamycin for example.

In addition to DNA methylation covering various stretches of DNA we also have lamin A protein (which are defective in progeria), chromatin proteins, DNA helicase subunits that attach to and differentiate stem cell DNA (defective in Werner’s Syndrome) telomeric DNA which folds over on coding DNA So I would bet we need a lot more than a DNA methylation clock to get a more accurate predictor of lifespan.

One approach is very controversial and is outside my thinking. The DNA end are called telomere and become smaller in both the daughter cells on division. Around 50-60 divisions later, the telomere reach the limiting amount and cells die thereafter. The division limit is called Hayflick limit. The enzyme telomerase fixes the shortening telomeres by extending them.

The problem is that the cells that do not obey the limit and are infinite lived are cancer cells! Telomerase might induce cancers. Some claim not. There started a trial in Columbia where the clinical trial selects had to pay million dollars first! Like all free press people, I said the trial was a sham done in Columbia to dodge USA laws. I insist the direction is fraught with dangers, but the blogger above seems to have a reference here. I will not go there, but I have no hard reason to prevent you.

 Nevertheless, the Blasco lab was able to show that the shortest telomeres in the mice were elongated, and that markers of health including insulin sensitivity were improved by short-term treatment with TA-65, designed to increase telomerase.

Blasco’s lab then worked with a more potent (though more dangerous) method of telomerase induction: infection with a retrovirus engineered to introduce telomerase into the nuclear DNA of the infected cell.  “Treatment of 1- and 2-year-old mice with an adeno associated virus (AAV) of wide tropism expressing mouse TERT had remarkable beneficial effects on health and fitness, including insulin sensitivity, osteoporosis, neuromuscular coordination and several molecular biomarkers of aging.” (Bernardes  de Jesus, Vera et al. 2012)  The mice lived 13% longer when AAV treatment began at age 2 years, and 24% longer when treatment began at 1 year.  There was no increase in cancer incidence.

Telomerase can be induced by Cycloastragenol, suspected of being the main compound in TA-65. If you get cancer, I warned you.

 

Fundamental contradiction

 Cells become senescent at some point because of errors in duplication, hitting the Hayflick limit or environmental poisoning. Another reason is ignoring apoptosis. Such cells express SASP afterwards and just stay on.  One consequence is that NAD+ causes inflammation of neighbor cells, just evolutionary multi role of this vital chemical. This is suppressed by CD38, an essential chemical but that also has a role in death of neighbors. Thus, more cells become senescent! So my initial idea of reusing own plasma in TPE after CD38 the villain is extracted won't work as it is another cancer otherwise. NAD+ goes bad in this rare case. So we have a fundamental contradiction as CD38 is both a hero(too many benefits) and villain (fixer causes aging)! Just increasing NAD+ or removing CD38 is not going to work. The only way around seems to be making cancers in most cases a gentler disease.

Cancer Response to Therapy-Induced Senescence: A Matter of Dose and Timing 

 Cancer is a consequence of many naive fixes. Another example above was adding telomerase to bypass Hayflick limit, one has possible cancer problems. Even using existing cancer victims fails as even if their cancer is subsequently fixed, who knows how many new cancers were created for whenever. It might even be caused by senolytics.

At the same time, know that cancers are thought of as terrible diseases because they are tied to devastating chemo therapy etc and not mildly painful diseases that they are and ultra modern treatment is My own sister has been afflicted twice in Boston and things were not so bad in the USA! Of course, one might just think so, psychological terror same, and the relative toleration be from early diagnosis both time. The worst thing a patient can do is avoid or delay seeking a diagnosis.

An important sidebar

 Given the state of oxygen supply, I strongly support the use of proning by doctors to know and advise their non-ventilator patients and general knowledge of you as patient yourself and helper to a sufferer. Proning is laying the patient chest down and fast large gulps of air at speed as if panting. This method is advocated by Dr. Guleria, director of AIIMS, Delhi, applied to a big-shot in government who lost his oxygen and was forced into proning. This trick was invented by US residents, interning in the USA, one year back.

Friday, April 16, 2021

According to me - the genetics break-thru for Aging


 

The latest link


The linked paper is not being heralded so, I am either presient or stupidly excitable! I EXPLAIN WHY THIS BELIEF TOO.

Dr. Sinclair has proven that all life on earth shares similar DNA which is everywhere in a nucleolus of a cell. He says that the characteristic of this DNA is that it discovered how to safely patch a break by exclusion of reproduction until repair by turning off the reproduction while the repairs were on by making the reproduction and repair genes the same and expression of repair protein causing the shut (by tight coiling) of the repair portion (the same) by coiling hard IE shut! Such a mechanism has overwhelming evolution advantages over distinct DNA and the only one which survived and is found in all life on earth! The extreme aging of the mouse with inhibiting repair is proof. Regrowth of optic nerves crushed in mice is the rejuvenation proof.

Horovith did wonderful research in totally independent manner and could train AI to predict calendar age from all kind of tissues. They being the same implies genetic aging manner and by 2021 had shown the programs applied to all species of life factored by DNA specialization! This work has been applied to eutherians and will doubtless apply to all life. The variable extract is methylation of specific Cp islands in DNA. An AI can empirically work in all tissues like blood, organ, hair, skin, and spit and predict age within 98% accuracy and predict remaining natural life too. How the methylation occurs is still a mystery and programmed life beliefs are common. I consider non programmed life in the minority, still clinging to the paradigm of damage accumulation and cite two things in my favor: One is matching is statistical, not 100% from a programmed theory; and two the fact that statistical damages can yield so good as adds of random variables; and three that human death age varies from 60 to 110 and death rates flatten after 90 to no age relative extra risk! But the short answer is that it is a programmed process. And there is no clinching experiment yet,

Now comes my orthogonal but essential expertise in formal languages. One can capture DNA derivations by L-systems of context-sensitive grammars with correct context is required for application of a rule. People have babies when the age of the boy is from 14-74 and the age of girl is 13-42. No child has ever been born aged. The DNA of the male when it fertilizes the female is striped clean of methyl marks, as is the woman's and the baby inherits two clean DNA. One can trace the process to 4-fold division after fertilization. The fertilized egg thereafter attaches itself to the womb wall. In the absence of complications, the due date can be predicted accurately within a few days, showing again a 98% accuracy. So there are grounds to believe programmed aging theory paradigm. I however, draw a different lesson from this, one the old DNA is preserved intact; and two the most important one, namely that removing the methylations have a rejuvenation effect.

That brings me the meat of my study, that is the research linked in will be considered a break-thru some day soon.


Summary

A general approach forheritably altering gene expression has the potential to enable manydiscovery and therapeutic efforts. Here, we present CRISPRoff—aprogrammable epigenetic memory writer consisting of a single deadCas9 fusion protein that establishes DNA methylation and repressivehistone modifications. Transient CRISPRoff expression initiates highly specific DNA methylation and gene repression that is maintained through cell division and differentiation of stem cells to neurons. Pairing CRISPRoff with genome-wide screens and analysis of chromatin marks establishes rules for heritable gene silencing. We identify single guide RNAs (sgRNAs) capable of silencing the large majority of genes including those lacking canonical CpG islands (CGIs) and reveal a wide targeting window extending beyond annotated CGIs. The broad ability of CRISPRoff to initiate heritable gene silencing even outside of CGIs expands the canonical model of methylation-based silencing and enables diverse applications including genome-wide screens, multiplexed cell engineering, enhancer silencing, and mechanistic exploration of epigenetic inheritance.


Here is more of my intuition. A Chinese doctor did the very unethical thing some years back - used crispr-cas9 tools of the day to genetically edit human DNA and made a Chinese women carry the result to term. Why the anger worldwide? The edit allows a contextual change in the DNA. But the change will be at all sites in the DNA, whether or not intended. The child may be born with huge unknown genetic disasters, with strange unknown diseases in life! Even most Chinese scientists were aghast, and no such experiment has been repeated.


New method referenced above will prevent unintended edits! The method is new and has applications in my specialty. It works by defining two context around the point of interest. One is the usual crisper cas9 context. Overlaid is another of some width. All genes outside are forced shut. Hence, edit cannot happen! If suitably small region is edited, bad edits cannot happen! The methylation marks can be used to bracket the context! Clearly it will work in context-sensitive grammars where the equivalent to methyl marks can be propagated and derive null at end only! Only one can derive nulls only at the end, thus context-sensitivity is kept. Whether more than 1 nonterminals can be still be nulled in the end is still context-sensitive is open!


Introduction to my specialty

Not to attract one, but just to get a feel, consider it in 2 courses. Scan rapidly if curious.

One is automata theory,  essential to becoming a theoretical computer scientist. Another is to become a compiler scientist. Before my devastation in 1990, I was working on attributed grammars, still fortunately primitive, ready for me to shine as professor emeritus, assuming that undo of my age works some, a second career as Dr. Sinclair dad! Incidentally, what makes me very excited is the backward limited understanding possibilities today of attributed grammars in programming languages (still no automatic semantics in compiler-compilers) graphics (all GUI interfaces are context-sensitive, change as you proceed in a program), pre-formatting (HTML is poor, latex too complex), compilers (context-sensitive AI applied to natural deduction like in robots), machine learning (in robot ensuring understands intended orders only) and now aging!



Thursday, April 15, 2021

 


The latest link

Decay of beauty quark


The standard Model of Physics has stood for fifty years, every time standard physics is usable for all new experiments. One of the reasons LHC was built was physicist fond hope that only at 13 Tera electron volts will new physics happen. So they spent 10 billion dollar machine. It did fill one hole in the Standard model and discovered Higg's boson. But never any particles of -ino type! Either they did not exist or 100 TEV may be needed. Only china could build it! False signal reading has happened to 3 sigma levels (1000-1) chance before, science requires 5 sigmas (3 million-1) for truth. So current quark decay of electron/muon of experimental (100,80) as opposed to (100,100) predicted is (1000-1) sure. Thin but hopes, stronger in my mind because it seems to hold over 10 years of past experiments. Beyond standard model? I root for the physicists who spent entire working life to LHC, the brightest humans of all. This was their dream.


Test of lepton universality in beauty-quark decays

LHCb collaboration: R. Aaij 1000 others


The Standard Model of particle physics currently provides our best description of fundamental particles and their interactions. The theory predicts that the different charged leptons, the electron, muon and tau, have identical electroweak interaction strengths. Previous measurements have shown a wide range of particle decays are consistent with this principle of lepton universality. This article presents evidence for the breaking of lepton universality in beauty-quark decays, with a significance of 3.1 standard deviations, based on proton-proton collision data collected with the LHCb detector at CERN's Large Hadron Collider. The measurements are of processes in which a beauty meson transforms into a strange meson with the emission of either an electron and a positron, or a muon and an antimuon. If confirmed by future measurements, this violation of lepton universality would imply physics beyond the Standard Model, such as a new fundamental interaction between quarks and leptons.

Recent remarkable aging news



The latest link

Starting with 2005 parbiosis experiments of Conboy, as I have said repeatedly, the idea that young blood has any magic proteins is wrong and dangerous, says FDA and All such proponents including otherwise respected doctors of Stanford and USB are to be treated as criminal aging salesmen with snake oil, say I.


The following is a touching example about aging, "Will Future Humans be Forever Young?". Regardless of the answer that you have, it has many good aging ideas.


Next is a long but prescient view of direction by Drs. Conboys in this interview "Irina & Michael Conboy – Resetting Aged Blood to Restore Youth". This deals with many things, including launch of their company IMYu. It is too important to not add my comments and abbreviate some.


Answer to aging skeptics

You stated that aging is not just progression of time; it seems to be a highly regulated process with a great deal of plasticity, and by understanding that regulation, it means aging is something we might slow or reverse. Despite this evidence, why do you think the world, and even academia, have been slow to accept that aging is not a one-way process?

Irina: I think that lack of cure goes hand in hand with inability to accept that this is disease. For example, there was some resistance to accept tuberculosis as the actual disease. When there were no antibiotics or cure for it, people tended to discard it and said, oh, it’s just nerves, you need to go to a sanatorium and relax. Perhaps it’s a subjective human feeling; if we cannot cure it, let’s just say it just happens, you cannot deal with that. That is my kind of feeling about it. Instead, it goes hand in hand that as human beings, you just want to say okay, I am going to die from old age, but it’s okay, it’s just a normal process.

Do you think we can reverse it at this point; we have visibility enough to know we will be able to reverse it?

Irina: At some point. Right now, we cannot, clearly, still, but we are making great strides over the situation where we can reverse it, like for example tuberculosis, or meningitis, bacterial meningitis. It used to be that, please do not diagnose that there’s bacterial meningitis, because there is no cure. Whatever else you can come up with, do it first. Now, diagnose it as fast as possible, so we can put patients on antibiotics immediately. My prediction is that the same will happen to aging; right now, we say it’s no disease. Then, okay, just take this thing or do these things, and then you will stop deterioration; of course, we will say, yeah, it’s bad, and this is good. Why not?

Arun: Within 3 years, for 50 years, younger by doctors by 2030.


England's politics: We are likely years or even decades from gaining wide societal support for the defeat of aging itself, but initiatives like this serve as useful ways to nudge society in the right direction. If more people can be convinced that health and longevity are desirable, it will not be so hard to convince them that increased longevity or perhaps even indefinite lifespans free from age-related diseases are also a good thing. This may be a small start in that direction, but at least it is a start.



STEM cells don't vanish, but sleep all over, forever, from chemical signal


Your work suggests that stem cells do not suffer the ravages of time that somatic cells do, as even older cells utilize telomerase to maintain telomeres. They don’t appear to accumulate DNA and other forms of damage as fast if at all, and activated stem cells produce young, healthy tissue, even in an aged body, so what is preventing stem cells from working properly as we age?


Michael: We and others have demonstrated that you can, from the outside, either by some signal or blood therapy, parabiosis, something like that, some intervention, jump-start the aged resident stem cells in the tissue and get them to behave as, by whatever means you’re measuring it, young or a lot closer to young than they would normally be. The intrinsic capacity of them to act that way is there.

Arun: magic growth like teen years can happen even in old age by turning off sleep signals!


Brain neurons do not replace themselves


Happens because otherwise human memory will have strong forget periods! So DNA repair is critical for them. Five times more frequent than neurons are astrocytes in the brain which have so far believed to be helpers to neurons. Someone recently figured out how they could be converted to neurons, in vivo! Brain repair is crucial part of extending age to 500 years or longer!