1:25:22 First comes an AGREEMENT by members of the neighbourhood to co-operate and then they agree to use a mechanism called money to mobilise resources

for - human evolution - loss of tail approximately 25 million years ago - identified genomic mechanism leading to loss of tail and human bipedalism - human ancestors - up to 60 Ma years ago

i like this definition a lot

humor as a coping mechanism on uncontrollable situations would be hedonistic disengagement because we have no control over the situation nor can we anticipate what's gonna happen next

hedonistic disengagement - avoidance and composure?

humor is an independent coping strategy

interesting. would humor then work on situations that are predictable or congruous?

"Developmentally, laughter is one of the first social vocalizations (after crying) emitted by human infants (McGhee, 1979)."

pg.2

"Humor can be dissected, as a frog can, but the thing dies in the process and the innards are discouraging to any but the pure scientific mind." - Elwin B. White (A Subtreasury of American Humor)

pg.2

"Infants begin to laugh in response to the actions of other people in about 4 months of age, and cases of gelastic (i.e., laughter-producing) epilepsy in newborns indicate that the brain mechanisms for laughter are already present at birth (Sher & Brown, 1976)."

laughter is essentially a response

pg.2

"Humor is a broad, multifaceted term that represents anything that people say or do that others perceive as funny and tends to make them laugh, as well as the mental processes that go into both creating and perceiving such an amusing stimulus, and also the emotional response of mirth involved in the enjoyment of it."

pg.2

"It is important to recognize that humor is fundamentally a social phenomenon; other people provide the context in which we experience humor...humor occurs in nearly every type of interpersonal relationship. We laugh and joke much more frequently when we are with other people than when we are by ourselves (R. A. Martin & Kuiper, 1999); Provine & Fischer, 1989). People do occassionally laugh when they are alone, such as while watching a comedy show on televion, reading a humorous book, or remembering a funny personal experience. However, these instances of laughter are still "social" in that they involve the imagined or implied presence of other people (Allport, 1954). One is still responding to people as characters in the television program or the book, or reliving in memory an event that involved other people. Humor essentially is a way for people to interact in a playful manner."

pg.2

"humor is play...Therefore, no definition of humor, no theory of wit, no explanation of comic laughter, will ever stand up, which is not based upon the distinction between playful and serious." (p.15; Max Eastman (1936).

pg.3

"humor involves an idea, image, text or event that is in some sense incongruous, odd, unusual, unexpected, surprising, or out-of-the-ordinary. In addition, the humor stimulus must be accompanied by cues that signal us to appraise the stimulus in a playful, nonserious, nonliteral frame of mind in which people temporarily abandon rules of logic and expectations of common sense and congruity (e.g. Apter, 1982, Berlyne, 1972; Cohen, 1999; Cundall, 2007; McGhee, 192; Morreall, 1987; Mulkay, 1988).

pg.4

"...the ability to enjoy humor and express it through laughter seems to be an essential part of human experience."

problem-focused approach is the most beneficial coping mechanism

interesting

people with humor as coping mechanism seem to by emotion focused

reactive coping - focused on the reaction of a specific stressor; better in variable environment proactive coping - focused on neutralizing future stressors; less reactive to stressors

do people with humor as coping mechanism reactive or proactive?

our coping styles are consistent from a set of consistent or stable traits

coping - conscious and voluntary defense - subconscious or unconscious adaptive

Die Firma Blue Carbon, die im Besitz eines Mitglieds des Herrscherhauses von Dubai ist, will in mehreren afrikanischen Ländern CO₂-Zertifikate zum (behaupteten) Ausgleich der Emissionen von Öl und Gas kaufen. Damit erwirbt die Firma – ohne Information der Bewohner:innen – die Kontrolle über große Waldgebiete. NGOs kampagnisieren intensiv gegen diese Deals. https://taz.de/Umstrittener-Klimaschutzdeal-in-Liberia/!5975181/

https://typeshare.co/go-go-golems/posts/under-the-hood-how-to-use-chatgpts-attention-mechanism-for-better-prompts

Geplante Klima-Regulierungen der Labour-geführten Regierung Australiens würden es dem Guardian zufolge ermöglichen, dass zehn Kohlekraftwerke ihre Emissionen bis 2030 weiter steigern. Blieben sie unter den festgesetzten Limits, könnten sie Verschmutzungsrechte lukrativ an andere Unternehmen verkaufen. https://www.theguardian.com/environment/2023/oct/03/labor-coalmine-safeguard-mechanism-climate-scheme-emissions-benefits

Die EU hat offiziell mit der Einführung des sog. Klimazolls“ begonnen, also einer Abgabe für Produkte aus Ländern, in denen mit mehr Emissionen produziert wird als in der EU. Dabei geht es um Zement, Eisen und Stahl, Aluminium, Dünger, Strom und Wasserstoff. In einer zweijährigen Übergangsphase werden zunächst nur die nötigen Informationen gesammelt. https://taz.de/Einfuhr-von-Stahl-Duenger-und-Co/!5963230/

In every literary theorist structure there is a common conflict in the identification of a subject

"common mechanism"

04:00 shame as feedback and driving growth (most powerful emotion)

• also see how anxiety can be used and leveraged for growth (as a whisper that aids, rather than destroying)

Review coordinated by Life Science Editors Foundation

Reviewed by: Dr. Angela Andersen, Life Science Editors Foundation

Potential Conflicts of Interest: None

Punch line: Rare risk variants associated with schizophrenia converge on the cAMP/PKA pathway.

Why is this interesting? The cAMP/PKA pathway could be a mechanism & therapeutic target for neuropsychiatric disorders arising from different mutations.

Background: * About 1-4% of people will develop psychosis or schizophrenia. * Schizophrenia is a highly heritable disease. * Genetic loci associated with schizophrenia can be common variants, which typically have small effects on risk, or rare variants, which can have large effects. * Rare, protein-truncating variants substantially increase the risk for mental illnesses like schizophrenia. * Disease-associated genes have diverse functions (e.g.): 1. RNA binding (RBM12) 2. transcriptional regulation (SP4, RB1CC1, SETD1A) 3. splicing (SRRM2) 4. signaling (AKAP11) 5. ion transport (CACNA1G, GRIN2A, GRIA3) 6. neuronal migration and growth (TRIO) 7. nuclear transport (XPO7) 8. ubiquitin ligation (CUL1, HERC1) ** What are the pathological mechanisms?* * A genetic screen identified the risk gene RBM12 as a novel repressor of GPCR/cAMP signaling (Semesta et al., PLOS Genetics, 2020). * Dysregulation of GPCR activity in the brain contributes to the pathophysiology of several neurological and neuropsychiatric disorders. * cAMP is a critical second messenger that mediates all important aspects of neuronal function, including development, excitability, and plasticity.

Results: * Use knockout HEK293 cells to verify that RBM12 is novel repressor of the GPCR/cAMP pathway that extends to multiple GPCRs coupled to the stimulatory G protein (e.g. dopamine 1 receptor, beta-2 adrenergic receptor). * Show RBM12 also represses this pathway in iPSC-derived neurons. RBM12 knockdown yielded hyperactive upregulation of NR4A1 and FOS mRNAs, two known CREB-dependent immediate early genes induced by neuronal activity. * RBM12 loss leads to increased PKA activity and supraphysiological CREB-dependent transcriptional responses. * RBM12 loss increased expression of the endogenous β2-AR transcriptional target mRNAs, PCK1 and FOS. * RBM12 loss increased CREB transcriptional reporter expression in response to a panel of endogenous or synthetic β2-AR agonists.<br /> * Transcriptional responses are orchestrated from endosomal β2-ARs in wild-type cells but from both plasma membrane and endosomal β2-ARs in RBM12 knockout cells. * Their results suggest that cAMP production and transcriptional signaling are independently subject to RBM12 regulation. * The neuropsychiatric disease-linked mutations fail to rescue GPCR-dependent hyperactivation in cells depleted of RBM12. * Defined β2-AR-dependent transcriptional targets in “wild-type” and RBM12 knockdown neurons by differential expression analysis between each respective basal and isoproterenol conditions. 669 unique β2-AR-dependent transcriptional targets across the two cell lines. * Discerned β2-AR-dependent targets that were exclusive to wild-type or RBM12 knockdown only (qualitatively distinct targets) versus targets that are in wt and RBM12 kd but upregulated to different extents (quantitatively distinct targets). * 21 wild-type- and 115 RBM12 knockdown-specific target genes. Factors involved in synaptic plasticity and schizophrenia such as JUN, ARC (encoding the activity-regulated cytoskeleton-associated protein), BDNF, and NRXN3 (encoding the cell adhesion molecule neurexin-3-alpha) were induced by GPCR signaling only in RBM12 knockdown neurons, while GRIA2 (encoding the AMPA receptor) and CBLN2 (encoding cerebellin 2 precursor) were upregulated upon GPCR signaling only in wt neurons. * the remaining 533 genes were induced in both wt & RBM12-depeleted, with a trend toward RBM12-dependent hyperactivation. * loss of RBM12 leads to aberrant expression of ADCY, PDE, and PRKACA, suggesting this mechanism underlies the hyperactive GPCR/cAMP/PKA signaling phenotypes.

Discussion: * Dysregulation of GPCR signaling could contribute to the neuronal pathologies stemming from loss of RBM12. * RBM12 function is required for normal cAMP production downstream of many Gαs-coupled receptors with established roles in the nervous system consistent with dysregulation of cAMP/PKA pathway. Specifically, the entire repertoire of targets, many of which orchestrate processes essential for neuronal differentiation, gene reprogramming, and memory and learning, shows a trend towards hyperactivation in RBM12 depleted neurons. * Over 100 genes are induced in response to receptor stimulation only in the knockdown (e.g. ARC and BDNF, with crucial roles in synaptic function, plasticity, and learning. * RBM12 could act through other mechanisms, given that RBM12 knockdown neurons also affects the expression of genes involved in neuron differentiation, synapse organization, and neurogenesis. * A study on post-mortem brains of patients with bipolar affective disorder demonstrated elevated levels of the PKAcat subunit Cα in temporal and frontal cortices compared to matched normal brains. * A different report on patient-derived platelet cells found that the catalytic subunit of cAMP-dependent protein kinase was significantly upregulated in untreated depressed and manic patients with bipolar disorder compared with untreated euthymic patients with bipolar disorder and healthy subjects. * Mutations in the schizophrenia risk gene histone methyltransferase SET domain-containing protein 1 A (SETD1A) also led to transcriptional and signaling signatures supporting hyperactivation of the cAMP pathway through upregulation of adenylyl cyclases and downregulation of PDEs. This in turn resulted in increased dendritic branching and length and altered network activity in human iPSC-derived glutamatergic neurons.

Beautiful follow up to their PLOS Genetics paper, and compelling pathological mechanism in combination with the recent SETD1A Cell Reports paper.

Future work: * Does loss of RBM12 increase dendritic branching and length and alter network activity in human iPSC-derived glutamatergic neurons (e.g. does it phenocopy loss of SETD1A). * Does pharmacologically targeting the cAMP pathway rescue the phenotypes caused by loss of RBM12? * If RBM12 is ubiquitously expressed, why is the disease neuronal? What is the relevant GPCR/neuronal mechanism? * How does RBM12 affect the abundance of the transcripts encoding the GPCR/cAMP effectors? * Do mutations in any of these other rare risk genes converge on GPCR? (transcriptional regulation (SP4, RB1CC1), splicing (SRRM2). signaling (AKAP11). ion transport (CACNA1G, GRIN2A, GRIA3), neuronal migration and growth (TRIO), nuclear transport (XPO7). ubiquitin ligation (CUL1, HERC1))

Review coordinated by Life Science Editors.

Reviewed by: Dr. Angela Andersen, Life Science Editors

Potential Conflicts of Interest: Dr. Mill has worked with Life Science Editors on other manuscripts.

Background: Retinitis pigmentosa (RP) is a group of rare eye diseases that cause vision loss. Symptoms usually start in childhood, and most people eventually lose most of their sight. There is no cure for RP. Mutations in retinitis pigmentosa GTPase regulator (RPGR) cause RP and compromise the renewal of light-sensitive “disc” membranes (specialized cilia) at the outer segment of photoreceptors, resulting in the loss of these cells over time. Evidence suggests that disc formation is similar to the release of ectosomes (small extracellular vesicles) and that both rely on the actin cytoskeleton. Knockdown of RPGR in retinal pigmented epithelium cells showed stronger actin filaments and reduced cilia suggesting that it may regulate nascent photoreceptor disc formation by regulating actin-mediated membrane extension in the retina (Gakovic et al., Human Molecular Genetics, 2011). In addition, RPGR patient iPSC-retinal models displayed phenotypes consistent with abnormal actin regulation (Megaw et al., Nature Communications, 2017; Karam et al., J Personalized Medicine, 2022).

Question: What function of RPGR is compromised in photoreceptors to cause RP?

Advance: The authors generated novel Rpgr mutant mice harboring human disease-causing mutations that recapitulate human disease phenotypes: aborted membrane shedding as ectosome-like vesicles, photoreceptor death and visual loss. RPGR is located at the site of disc formation – to test if it plays a role in disc genesis, they engineered a novel reporter mouse to track outer segment turnover. Rhodopsin was tagged with the self-labelling peptide SNAP- Rhodopsin is the major protein component of outer segment discs, and so incubating RhodSNAP retinal slice cultures with SNAP fluorophores results in outer segment labelling. Perturbation of RPGR resulted in a slowed rate of disc formation, leading to shortened outer segments and increased vesicle shedding. To me, the breakthrough is in the last figure: the actin depolymerizing drug Cytochalasin D in PBS was injected intravitreally, and fixed retinas were analyzed 6 hours later by electron microscopy. Cytochalasin D treatment significantly reduced the number of shed vesicles from the base of the outer segment in Rpgr-mutant mice (they now look like wild-type).

Significance: Nails down the disease-relevant function of RPGR and a molecular mechanism of RP in photoreceptor cells, in vivo, in mice. Pharmacological rescue not only demonstrates the importance of the mechanism to disease but also sheds light on a potential therapeutic avenue for RP.

Using the attention mechanism to determine global dependencies between input and output instead of using recurrent links to past states. This is the essence of their new idea.

Zhao, W. J., Coady, A., & Bhatia, S. (2021). Computational mechanisms for context-based behavioral interventions: A large-scale analysis. PsyArXiv. https://doi.org/10.31234/osf.io/8cyad

Corner, A., Hahn, U., & Oaksford, M. (2011). The psychological mechanism of the slippery slope argument. Journal of Memory and Language, 64(2), 133–152. https://doi.org/10.1016/j.jml.2010.10.002

Controlling the manipulation with hourly price delays, median price feed implies majority collusion, maximum oracle price limits, price delays give ample time for global settlement.

incentive failures, inertia or active capture by malicious actors

Singh, I., Joseph, P., Heerdt, P. M., Cullinan, M., Lutchmansingh, D. D., Gulati, M., Possick, J. D., Systrom, D. M., & Waxman, A. B. (2022). Persistent Exertional Intolerance After COVID-19: Insights From Invasive Cardiopulmonary Exercise Testing. CHEST, 161(1), 54–63. https://doi.org/10.1016/j.chest.2021.08.010

ReconfigBehSci. (2022, January 20). @OmicronData @timcolbourn I think there might be a difference here between what you are putting forward and what @timcolbourn is arguing any rational individual should be for analysing the expected costs and benefits of a course of action, and I assume we all agree on that. 1/2 [Tweet]. @i. https://twitter.com/i/web/status/1484080972459134976

Geddes, L., & correspondent, L. G. S. (2022, March 2). Scientists seek to solve mystery of why some people do not catch Covid. The Guardian. https://www.theguardian.com/world/2022/mar/02/scientists-seek-to-solve-mystery-of-why-some-people-do-not-catch-covid

https://www.scientificamerican.com/article/an-ancient-greek-astronomical-calculation-machine-reveals-new-secrets/

Overview and history of the Antikythera mechanism and the current state of research surrounding it.

Antikythera mechanism found in diving expedition in 1900 by Elias Stadiatis. It was later dated between 60 and 70 BCE, but evidence suggests it may have been made around 205 BCE.

Functions

One of the primary purposes of the device was to predict the positions of the planets along the ecliptic, the plane of the solar system.

The device was also used to track the positions of the sun and moon. This included the moon's phase, position and age (the number of days from a new moon). It also included the predictions of eclipses.

Used to track the motions of the 5 known planets including 289 synodic cycles in 462 years for Venus and 427 synodic cycles in 442 years for Saturn.

Risings and settings of stars indexed to a zodiac dial

Definitions

metonic cycle, a 19-year period over which 235 moon phases recur; named after Greek astronomer Meton, but discovered much earlier by the Babylonians. The Greeks refined it to a 76 year period.

saros cycle, the 223 month lunar cycle which was used by the Babylonians to predict eclipses. A dial on the Antikythera mechanism was used to predict the dates of the solar and lunar eclipses using this cycle.

synodic events: conjunctions with the sun and its stationary points

People

Archimedes - potentially the designer of an early version of the Antikythera mechanism

Elias Stadiatis - diver who discovered the Antikythera mechanism

Albert Rehm - German philologist who the numbers 19, 76 and 223 inscribed on fragments of the device in the early 1900s

Derek J. de Solla Price, published Gears from the Greeks in 1974. Identified the gear train and developed a complete model of the gearing.

Michael Wright - 3D x-ray study in 1990 using linear tomography; identified tooth counts of the gears and understood the upper dial on the back of the device

Tony Freeth - author of article and researcher whose made recent discoveries.

Gozzi, N., Chinazzi, M., Davis, J. T., Mu, K., Piontti, A. P. y, Ajelli, M., Perra, N., & Vespignani, A. (2021). Anatomy of the first six months of COVID-19 Vaccination Campaign in Italy (p. 2021.11.24.21266820). https://doi.org/10.1101/2021.11.24.21266820

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Understanding COVID-19 Registration Form. (n.d.). Google Docs. Retrieved March 31, 2021, from https://docs.google.com/forms/d/e/1FAIpQLScrC4krKVHcSm_Wi2VcXcGHa4F8l3cilL2xhbB62etcK4sy4w/viewform?usp=embed_facebook

Geddes, L. (2021, September 28). Covid can infect cells in pancreas that make insulin, research shows. The Guardian. https://www.theguardian.com/society/2021/sep/29/covid-can-infect-cells-in-pancreas-that-make-insulin-research-shows

Manshour, P., & Montakhab, A. (2021). Dynamics of social balance on networks: The emergence of multipolar societies. Physical Review E, 104(3), 034303. https://doi.org/10.1103/PhysRevE.104.034303

The Uncomfortable Truth is the Difficult and Unpopular Decisions are Now Unavoidable.

Topic is relevant across a span of global issues. Natural resources are Finite.....period! Timely decisions are critical to insure intelligent use of resources. DENIAL is the enemy and 800lb gorilla in the room. Neoliberisim and social dysfunction feed on any cognitive dissonance and poop it out as "crap". True believers of American Capitalism (yes there is a difference) have become "cult-like" and drink the fluid of the cult to the very end, human consequence is of no concern.

Point being: Reality is always elusive within a cult controlled (authoritative) mindset. Cult members are weak sheep, incapable of individual logic/reason. Authority can not be challenged. -- Denial, a human defense mechanism has been and is the common denominator in all personal and global conflict. Denial can be traced throughout modern history and rears its ugly head whenever the stakes are high.

Zhao, H., Wu, D., Nguyen, A., Li, Y., Adão, R. C., Valkov, E., Patterson, G. H., Piszczek, G., & Schuck, P. (2021). Energetic and structural features of SARS-CoV-2 N-protein co-assemblies with nucleic acids. IScience, 24(6), 102523. https://doi.org/10.1016/j.isci.2021.102523

Deviri, D. (2021). From the ivory tower to the public square: Strategies to restore public trust in science. MetaArXiv. https://doi.org/10.31222/osf.io/w3frb

Stevenson, C., Wakefield, J. R. H., Felsner, I., Drury, J., & Costa, S. (n.d.). Collectively coping with coronavirus: Local community identification predicts giving support and lockdown adherence during the COVID-19 pandemic. British Journal of Social Psychology, n/a(n/a). https://doi.org/10.1111/bjso.12457

Godinho, C. A., Yardley, L., Marcu, A., Mowbray, F., Beard, E., & Michie, S. (2016). Increasing the intent to receive a pandemic influenza vaccination: Testing the impact of theory-based messages. Preventive Medicine, 89, 104–111. https://doi.org/10.1016/j.ypmed.2016.05.025

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Stout, M. E., Christy, S. M., Winger, J. G., Vadaparampil, S. T., & Mosher, C. E. (2020). Self-efficacy and HPV Vaccine Attitudes Mediate the Relationship Between Social Norms and Intentions to Receive the HPV Vaccine Among College Students. Journal of Community Health, 45(6), 1187–1195. https://doi.org/10.1007/s10900-020-00837-5

Gordon, D. E., Hiatt, J., Bouhaddou, M., Rezelj, V. V., Ulferts, S., Braberg, H., Jureka, A. S., Obernier, K., Guo, J. Z., Batra, J., Kaake, R. M., Weckstein, A. R., Owens, T. W., Gupta, M., Pourmal, S., Titus, E. W., Cakir, M., Soucheray, M., McGregor, M., … Krogan, N. J. (2020). Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science, 370(6521). https://doi.org/10.1126/science.abe9403

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This is an important mechanism that cells can respond to their environment and extracellular cues. Cells sense their environment and modify genes, mRNA splicing, protein expression and protein modifying to respond to these cues.

Fareri, Dominic S., Joanne Stasiak, and Peter Sokol-Hessner. ‘Choosing for Another: Social Context Changes Dissociable Computational Mechanisms of Risky Decision-Making’, 21 September 2020. https://doi.org/10.31234/osf.io/dr42a.

Harris, A. J. L., & Hahn, U. (2011). Unrealistic optimism about future life events: A cautionary note. Psychological Review, 118(1), 135–154. https://doi.org/10.1037/a0020997

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Martino, C., Kellman, B. P., Sandoval, D. R., Clausen, T. M., Marotz, C. A., Song, S. J., Wandro, S., Zaramela, L. S., Benítez, R. A. S., Zhu, Q., Armingol, E., Vázquez-Baeza, Y., McDonald, D., Sorrentino, J. T., Taylor, B., Belda-Ferre, P., Liang, C., Zhang, Y., Schifanella, L., … Knight, R. (2020). Bacterial modification of the host glycosaminoglycan heparan sulfate modulates SARS-CoV-2 infectivity. BioRxiv, 2020.08.17.238444. https://doi.org/10.1101/2020.08.17.238444

Ou, T., Mou, H., Zhang, L., Ojha, A., Choe, H., & Farzan, M. (2020). Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2. BioRxiv, 2020.07.22.216150. https://doi.org/10.1101/2020.07.22.216150

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Capraro, V., & Barcelo, H. (2020). Priming reasoning increases intentions to wear a face covering to slow down COVID-19 transmission [Preprint]. PsyArXiv. https://doi.org/10.31234/osf.io/wtcqy

Almaatouq, A., Noriega-Campero, A., Alotaibi, A., Krafft, P. M., Moussaid, M., & Pentland, A. (2020). Adaptive social networks promote the wisdom of crowds. Proceedings of the National Academy of Sciences, 201917687. https://doi.org/10.1073/pnas.1917687117

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<big>评：</big><br/><br/> 传统数据库与区块链式处理，哪个才是更佳的业务模式？这个问题的回答早已在我们的日常工作中得以体现，但却迫于某种难以逾越的权力边界而成了难言之隐。「事中容错，事后一致」是一种颇为崇高的境界，甚至可以从中一窥理想社会的光耀图景，但人们目前尚未能大规模应用这套 workflow，究其原因，并非目标遥远，而是由于决策权被少部分人掌控着，和数据打交道的主体只是把数据当作本职工作，并未主动贡献、积极参与。系统使用方背上的不是「数据必须一次性正确输入」的包袱，他们直面的，是将权利拱手让人后的自责，是与民主开放的理想世界背道而驰的困惑。

Federalism has the capability of being both bad and good. It just depends who you ask. On one side the advantages of fedaralism is it creates more effectiveness and makes the government stable. On the other hand federalism is risky it gets expensive, lead to a complex tax system and is slow in responses to crisis.

Advantages over traditional game theory for token econimics:

• a game "designer" chooses the game structure rather than inheriting one
• that the designer is interested in the game's outcome

see how it can hook into the current logging mechanism