logicp 3 سال پیش
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  1. 7 0
      new/Social Distancing.md
  2. 6 0
      new/accepting_new_ideas.md
  3. 39 0
      new/elucidate.md
  4. 91 0
      new/vaccine_advice.md

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new/Social Distancing.md

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+## Social Distancing
+
+As my life has developed and enough time has come to pass, I've found myself less inclined to see family members. I remember as a youngster being so eager to mimic them and to try and have their ear. It seemed so meaningful to engage with them and have conversations. It seemed as though we were both learning or, at the very least, I certainly felt like I was learning a great deal. This is not to be some sort of realization as to how I am surpassing anyone, because that's certainly not the case. To surpass anyone is something incalculable, as we are all developing and expressing in an infinite set of dimensions.
+
+What is, perhaps, the most frustrating is not so much that I am not learning from them. It is the understanding that there is a great potential for wonderous learning from all parties, and that it would not be a complicated shift in the sense of how many principles need to be understood in order to set the stage for a productive exchange of ideas, rather than a minimalist set of pleasantries and then some sort of judgment as to whether or not family member X has fulfilled their obligations.
+
+Who is to say that I want to invite asseseemmmmmm

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new/accepting_new_ideas.md

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+It is understandable that one might be drawn to a new idea and that, when observed by those with an interest in the intellectual, that one might be more likely to give the new idea a positive outlook. There are multiple reasons for this:
+- It is a part of progress and evolution to accept the new
+Since it is enw, the likelihood that one's false assumption can be excused on the basis of its novelty is higher, thus one can assume that their error won't be held as evidence of one's lack of intelligence or malicious inclinations, thus there is already a positive bais towards the new idea from the outset.
+In the case that the new idea affods some benefit in the form of an alleviated restriction, or even like introduction and availability of a resource, then there is yet another positive bias towards its adoption
+- The new idea challenges the old, and opens the floodgates of possibility. Why limit yourself when what would save us from the most dire threats could be something unknown?
+exit

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new/elucidate.md

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+oh that was wonderful
+I really couldn't take it anymore
+hearing so many wonderful ideas and elucidations of concepts and thoughts and brilliant phrases and colourful descriptions and expanded understanding in real time
+all of those things are absolutely wonderful and are important to take in
+but it seems that there is a limit, or a balance, a perfect harmony of how much material we should take in before we should create some of our own again
+is that only based on personality types?
+is it that some people wish to have a certain influence and elevation of thought to allow them to reach the unknown and the impossible, as a synthesis
+and that they otherwise would not find the level of refinement needed to really understand more of the world
+or is it that they are simply distracting themselves with the owrds of others
+so that they needn't do the work of really thinking about the world and making a distinction, pointing to something, making a declaration of what they believe is real and what their reality is composed of
+I know that if I try to make sense of reality, and put it into concrete terms that I can refer to 
+that it's something I'm always longing to do, and hoping to do, and in a sense am always preparing to do
+and that might just be an aspect of the central nervous system
+but when I actually get down to it, and start elucidating, start enumerating the details of it, I start to get a glimpse into the sheer complexity for which tal of exploration exists
+and how much time it would take, not only to explore it all, or even the most relevant parts
+but to really understand what each part is
+to see how they are interconnected, or the ways in which they are not, or the ways in which they appear to be connecfted but are actually a manifeslse
+there really is an ineffable complexity to it all, and that we try to pretend that it's something that can be understood, or that we've come to an understandign sufficient to decide that others must agree with it, and that if they do not agree with it, it's because they believe a version of reality that you yourself can describe
+the opposite of your onw reality
+the opposite values of my values
+the opposite belief systems with the opposite gods and the inverted implements
+all of the things that important to me are unimportant to you, and all of the things that you aspire to be are those things which I hope to never become
+it's a folly that we all play, or at least that I've played
+that I hope to one day cease to play
+is it simple a manifestatio nfo humanity?
+or is it something more primitive that couldn't develop to such a capacity in other animals
+in other biological organisms
+is it something sophisticated that causes us to aspire to a greater level?
+do we transcend limitation because of a belief that our peers are never of sound mind
+our peers are always planning to harm us
+such as is with the belief in transhumanism
+why would anyone hope to go down that path?
+well it's easy
+there are particular biological realities that are frightening for anyone
+in fact, what's most frightening about them is probably a sense that those moments where one is confronted with them are probably more unbearable than can even be imagined by someone prior to having to deal with it
+and if that's the case, then how is one to actually deal with it?
+it's something that can't be thought about too easily by too many
+or if it is thought about, and expanded upon or romanticized, or even just made to be quicker to overlook or deal with the emotional aspects of
+exit

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new/vaccine_advice.md

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+# Vaccine Advice
+So it seems there has been a fairly consistent precedent concerning coronavirus vaccine development, involving the spike protein in particular, wherein the technology tested was both eliciting an antibody response while also demonstrating a greater chance of fatal disease in the case that the organism later contracts SARS Cov and its analogues.
+
+Excerpts include:
+1. https://www.sciencedirect.com/science/article/pii/S0264410X08015053?via%3Dihub:
+- Examples of vaccine-induced enhancement of susceptibility to virus infection or of aberrant viral pathogenesis have been documented for infections by members of different virus families. Several mechanisms, many of which are still poorly understood, are at the basis of this phenomenon. Vaccine development for lentivirus infections in gelera, and for HIV/AIDS in particular, has been little successsful. Certain experimental lentiviral vaccines even proved to be counterproductive: they rendered vaccinated subjects more susceptible to infection rather than protecting them. For vaccine-induced enhancement susceptibility to infection with certain viruses like feline coronavirus, Dengue virus, and feline immunodeficiency virus, and it has been shown that antibody-dependent enahcement (ADE) plays an important role. Other mechanisms may, either in the absence of or in combination with ADE, be involved. Consequently, vaccine-induced enhancement has been a major stumble block in the development of certain flavi-, corona-, paramyxo-, and lentivirus vaccines. Also recent failurs in the development of a vaccine against HIV may at least in part be attributed to indection of enhanced susceptibility to infection. THere may well be a delicate balance between the induction of protective immunity on the one hand, and the induction of enhanced susceptibility on the other. The present paper reviews the currently known mechanisms of vaccine-induced enhancement of susceptibility to virus infection or of aberrant viral pathogenesis.
+
+2. https://www.sciencedirect.com/science/article/pii/S2214750020304248
+
+Calina et al. evaluated the ongoing approaches to COVID-19 vaccine development, and stated: "Normall, the period of development of a vaccine is 12-15 years". Against this backdrop, SARS-CoV2 vaccines are targeted for accelerated development, safety testing, manufacturing, and distribution by an order of magnitude. Each of the accelerated steps has drastically reduced the tim required for normal development. Some of the potential adverse vaccine effects shown on the right of Fig1 may take years to emerge, well after the initial abbreviated vaccine safety testing period.
+(From fig1):
+- Antibody-Dependent Enhancement
+- Immune Enhancement
+- Cross-reactivity
+- Non-Specific Vaccine Effects on Immune System
+- Antigenic Distant Hypothesis
+- Bystander Activation
+- Immune Evasion
+- Immune Interference
+- Chronic Immune Activation
+- Impact of Combinations of Toxic Stimuli
+
+3.2 Past coronavirus vaccine development history
+
+There have been two prior coronavirus outbreaks in the 21st century: SARS in 2002-2003, and MERS starting in 2012. Vaccine development for each started/accelerated during the height of each outbreak. What have been the results of these prior coronavirus vaccine development efforts?
+
+According to a comprehensive 2019 article on MRS vaccine development, "To date, there is no specific treatment proven effective against this viral disease. In addition, no vaccine has been licensed to prevent MERS-CoV infection thus far ... In general, the potential vaccine candidates can be classified into six types: viral vector-based vaccine, DNS vaccine, subunit vaccine, nanoparticle-based vaccine, inactivated-whole virus vaccine and live-attenuated vaccine"
+
+Accoring to a comprehensive 2020 article on SARS and MERS vaccine development, "As of April 2020, no vaccine is commercially available for these coronavirus strains". The rationale for lack of a vaccine is given by the following: "Reasons for the lack of commercial and effective vaccines for SARS and MRS are varied. In the case of MERS, it is likely that the vaccine development was delayed because of the scarcity of suitable and cost-effective small animal models during pre-clinical experimentation. In addition, it is probable that a vaccine has not been delivered that has produced relatively low and geographically centralize cases (compared with other more global and persistent infectious diseases such as influenza, HIV and tuberculosis). This last factor might have also contributed to the lack of a vaccine for SARS, in the sense that it was considered pointless to continue investing in a vaccine for a disease whose cases ceased to be reported in 2004."
+
+While interest in a vaccine may have waned after the SARS pandemic/outbreak seemed to have terminated, research on such a vaccine persisted. References in the above article showed SARS vaccine researched continued for a decade or more fater the pandemic had ended.
+
+Based on experiences with SARS and MRS, successful vaccine development was not achieved after aout a decade of research, or even more. That does not bode well for COVID-19 coronavirus vaccine development/safety testing/distribution for hte one-year timescales being projected.
+
+3.3 Challenges for successful vaccine development - overview
+
+The main challenges facing successful coronavirus vaccine development can be summarized as time to development, efficacy of the vaccine and, most importantly, safety of the vaccine. A complementary perspective on some of the problems listed in [41] can be stated as follows:
+
+First, although the virus' spike protein is a promising immunogen for protection, optimizing antigen design is critical to ensure optimal immune response. Debate continues over the best approach - for example, targeting the full-length protein or only the receptor-binding domain.
+
+Second, preclinical experience with vaccine candidates for SARS and the Middle East respiratory syndrome (MERS) have raised concerns about exacerbating lung disease, either directly or as a result of antibody-dependent enhancement. Such an adverse effect may be associated with a type 2 helper T-cell (Th2) response. Hence, testing in a suitable animal model and rigorous safety monitoring in clinical trials will be clinical.
+
+3.4 Vaccine mechanisms with uncertain consequences
+
+Numerous mid- and longer-term potential issues concerning vaccines have been identified. Their themes rae summarized initially, followed by excerpts from specific cited references.
+1. Antibody-Dependent Enhancement (where enhanced virus entry and replication in a number of cell types is enabled by antibodies)
+  a) Intrinsic Antibody-Dependent Enhancement (where non-neutralizing antibodies raised by natural infection with one virus may enhance infection with a different virus)
+  b) Immune Enhancement (enhancement of secondary infections via immune interactions)
+  c) Cross-reactivity (an antibody raised against one specific antigen has a competing high affinity toward a different antigen.)
+  d) Cross-Infection Enhancement (infection enhancement of one virus by antibodies from another virus)
+
+2. Vaccine-associated Virus Interference (where vaccinated individuals may be at increased risk for other respiratory viruses because they do not receive the non-specific immunity associated with natural infection)
+
+3. Vaccine-Associated Imprinting Reduction (where vaccinations could also reduce the benefits of 'imprinting', a protection conferred upon children who experienced infection at an early age)
+
+4. Non-Specific Vaccine Effects on Immune System (where previous infections can alter an individual's susceptibility to unrelated diseases);
+
+5. Impact of Infection Route on Immune System (where immune protection can be influenced by the route of exposure/delivery.)
+
+6. Impact of Combinations of Toxic Stimuli (where people rae exposed over their lifetime to a myriad of toxic stimulii that may impact the influence of any vaccine);
+
+7. Antigenic Distance Hypothesis (negative interference from prior season's influenza vaccine (v1) on the current season's vaccine (v2) protection may occur when the antigenic distance is small between v1 and v2 (v1 ~ v2) but large between v1 and the current epidemic strain (v1 != e);
+
+8. Bystander Activation (activation of T cells specific for an antigen X during an immune respones against antigen Y)
+
+9. Gut Microbiota (impact of gut microbial composition on
+vaccine respones)
+
+10. Homologous Challenge Infection Enhancement (the strain of challenge virus used in the testing assay is very closely related to the seed virus strain used to produce the vaccine that a subject received).
+
+11. Immune Evasion (evasion of host respone to viral infection)
+
+12. Immune Interference (interference from circulating antibody to the vaccine virus).
+  a) Original antigenic sin (propensity of the body's immune system to preferentially utilize immunological memory based on a previous infection when a second slightly different version of the foreign entity (a virus or bacterium) is encountered.)
+
+13. Prior Influenza Infection/Vaccination (effects of prior influenza infection/vaccination on severity of future disease symptoms).
+
+14. Timing between Viral Exposures (elapsed time between viral exposures)
+
+15. Vaccine-Associated Enhanced Respiratory Disease (where vaccination enhances respiratory disease)
+
+16. Chronic Immune Activation (continuous innate immune responses)
+
+# Summarized in short list:
+- ADE
+- Immune Enhancement
+- CR (competing affinity for different antigen)
+- CIE (enhancement of one virus by antibodies from other virus)
+- Vaccine-associated Virus Interference (loss of non-specific immunity)
+- Vaccine-Associated Imprinting Reduction
+