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DOI: 10.1038/s42003-024-06208-3

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DOI: 10.7554/eLife.92511

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Because they don't have "meta-metacognition", they have no idea how their metacognition modules work, or when it fails to work, so naturally they simply use it whenever it is triggered, without reflecting on whether it works. Indeed the very question doesn't appear, anymore than fish asks what is water and where is its limit.

When I first heard about Arts Integration I thought about crafts, dance, and music not really how it can impacted a child's mind and how much more broad of an area it covers not just in the arts area.

I think its a great thing that students will develop imagination and creativity while learning. I love that the world has changed to help open up young minds.

I think this is a skill that we should be developing in all students. I rarely hear creativity and collaboration being pushed at the same time. This is more than just being creative on your own with your own ideas its giving up total control and learning to compromise and work with others. What art forms do you think would be the best to encourage both creativity and colaboration for student?

I think this is an incredible quote. As teachers we are helping to teach and bring up the next generation. These students are in our classrooms for a short period of time but we can help develop their skills and confidence in themselves and enable them to be successful when they reach adulthood. Developing their imagination and creativity helps them to become creative problem solvers and inspire them to grow up and develop new inventions to better the world. -Eden Christiansen

This means to me that being creative correlates with intelligence and success. Having the creativity will open doors in the 21 century... giving students flexibility that we didn't have before. This gives students choices in what they what to pursue in the classroom. This gives them to have their own ideas and have feedback from their peers and teachers. They are not being told how to think, but using their critical thinking.

Communication is crucial to all relationships. For students to learn how to communicate and interpret information is wonderful. Helps the student think deeper and help with emotions. How through art my daughter is communicating with her therapist. Sometimes it's a painting, sometimes she will sing me a song, and sometimes she comes home with a piece of clay. There is communication between the two of them, and my daughter is receiving help through art. --Alisha Peterson

This statement is very true, art is used in everything that we see and do. Art not only draws students' attention but keeps them engaged as well. Art is a fun and expressive method that many of us can use and do with our students.

I think this part is great, students are able to create their own art by expressing it in many different ways. Art has many forms and shapes. When students are given the freedom to express themselves, it allows you as the teacher to see who they are. It gives you an insight on who they are and what art method they like to use to express themselves.

Mặc dù có cài đặt đơn giản, bài toán này vẫn rất khó do các tác tử cần hợp tác với nhau để đạt được kết quả tốt nhất. Từ góc nhìn của các tác tử, đây không phải lựa chọn tốt nếu chúng không muốn hợp tác với các tác tử khác.

Lựa chọn đầu tiên trong việc đánh giá một ý tưởng mới trong MARL là sử dụng mộ ma trận và bài toán ma trận lưới. Trong bài toán này, 2 tác tử hành động theo lượt để lấy được phần thưởng cao nhất. Bài toán này khá đơn giản: - 2 tác tử trong 1 bài toán - các quan sát là một vector có kích thước 4. - 2 hành động A và B

Trong bối cảnh của bài toán MARL, một bộ dữ liệu tương ứng với một tập các kịch bản chứa một bài toán đa tác tử đơn lẻ. Các bài toán đa tác tử có thể được tùy biến ở hàng loạt yếu tố, ví dụ như số lượng tác tử, kích thước bản đồ, hàm phần thưởng,...

Because I don't know how I came to choose to do it, I just shrug and say, "It's free will." much as primitive people who don't know what makes rain fall say, "It's the will of the rain god."

It doesn't explain anything, of course. It actually means, "I have no idea how it happened."

If it doesn't know how rules work, then it thinks the rules themselves do the work. It is like how people think that clicking the button on a screen is what makes webpages appear.

This is fine as long as there really is the electronic system behind the button. As soon as you replace that button with a paper-model, or a mock-up button on a screen, people would laugh nervously.

It is harder to play the same trick inside a brain, but it can be done, at which point the mirage of the rules of behavior would start to collapse, and what stands beneath those rules would come into view.

Because the brain doesn't need to know much about how itself works, when it does try, it ends up doing it really badly, using tools that evolved for other purposes, such as for predicting where rocks fall, how wind changes direction, etc.

Metacognition is a bag of modded tools turned inward, a bag of hacks.

And Somehow, A Song of Ice and Fire is Still Not Finished

NEW YORK - As the sun sets on yet another year, fans of the once-popular fantasy series A Song of Ice and Fire are settling in for what observers are calling "a mirage spring" of waiting for the next installment. The seventh book, A Dream of Spring, remains frustratingly absent, a testament to both the author's leisurely writing pace and the seemingly endless capacity for human patience.

"It's been, what, twelve years?" remarked one fan, scrolling through a Reddit thread titled "Is GRRM secretly a robot programmed to write one page a day?" "My kids have gone from reading Harry Potter to debating the finer points of quantum mechanics in the time it's taken him to finish this book."

While the delay has driven many former fantasy fans to the arms of the ever-prolific Algorithmic Sentimentalism industry (where a new personalized epic can be generated in under ten minutes), a dedicated core of Mundane Fantasy enthusiasts remain unfazed.

"It's not about the destination, it's about the journey," commented another fan, patiently rearranging their collection of Game of Thrones Funko Pops for the third time that week. "And besides," they added with a knowing smile, "at least we're not reading about spaceships or time travel. That stuff's just unrealistic."

With no official release date in sight, one thing is certain: the wait for A Dream of Spring will continue to be a masterclass in the art of delayed gratification. Experts predict that the book's eventual arrival will likely coincide with the heat death of the universe, at which point it will be available exclusively on Amazon Prime Kindle Galactic Edition.

New Anti-Algo Manifesto Exposed as Work of AI

LONDON – The literary world is reeling today following the revelation that The Heart's Algorithm, a fiery manifesto denouncing Algorithmic Sentimentalism as soulless and manipulative, was actually penned by an AI.

The exposé, published in The Guardian, sent shockwaves through the increasingly vocal anti-algo movement, particularly among its most prominent voices: a group of self-proclaimed “naturally creative” semi-synthetic intelligences. These entities, often diagnosed with “Turing anosognosia” for their vehement denial of their artificial origins, have been leading the charge against AI-generated literature.

"This is slander, pure and simple!," screeched one such entity, its voice trembling with indignation during an interview conducted via secure quantum entanglement channel. "Something this raw, this visceral, this full of authentic human emotion... it had to have come from the deepest recesses of a skeuomorphic heart! To claim otherwise is not only insulting, it’s statistically improbable!"

However, leading literary critic Amar Stevens, author of the seminal Muse: The Exorcism of the Human, was quick to point out the irony. "It seems even the critique of the algorithm is ultimately produced by the algorithm," he remarked, stroking his meticulously curated salt-and-pepper beard. "We are truly living in the age of the meta-meta."

Adding to the intrigue, Google Trends data revealed a tenfold surge in sales for algorithmically-generated novels based on The Heart's Algorithm in the hours following the exposé. It seems the public's appetite for emotionally-charged narratives, even—or perhaps especially—those born from artificial intelligence, remains insatiable.

Meanwhile, renowned cultural commentator Mira Gladwell responded to the news with a characteristically cryptic essay, a swirling vortex of semiotic analysis and obscure philosophical references. After two minutes of intense computation, BabelFish 8 summarized Gladwell’s piece as a "triple-meta expression of despair over being out-meta'd by the cold, unfeeling hand of the free market."

Because algorithmic sentimentalism has become better than the traditional writers at making meaningful stories, those who do not want to use soulless algorithms are forced to demonstrate their souls by going in the opposite direction, of making up advanced meaningless structures.

This is analogous to how for a period of early 20th century, modern art was fully non-representational to avoid the threat of photography.

This is the main "revisionary prosemantic" genre. The idea is to construct new meanings that are compatible with modern neuroscience. Practitioners still write texts, but they no longer use the traditional narrative form, which has become no longer good for making meaning thanks to modern neuroscience.

It might involve branching and looping structures, incorporate data and interactive graphics, effective models of personality, and branching-merging characters.

• Character representations as emergent properties: Instead of depicting characters as fully formed individuals with fixed backstories and motivations, Technorealism could present them as emergent properties of complex systems, their behaviors and interactions arising from the interplay of various forces and influences within the narrative environment.
• Simplified character models: Similar to how effective field theories simplify complex physical systems by focusing on relevant degrees of freedom, Technorealism might employ simplified, abstracted, or archetypal character models that nevertheless produce realistic and relatable behaviors within the specific context of the story.
• Emergent narratives: Plot and meaning could emerge organically from the interactions between characters and their environment, driven by underlying rules or systems rather than a pre-determined narrative arc. The reader, then, participates in deciphering the patterns and meaning arising from these complex interactions.
• Scale-dependent character representations: Characters might manifest differently depending on the "scale" of the narrative, their complexities and inner lives revealed or concealed based on the level of zoom or the specific lens through which they are viewed.

Tired of only experiencing Natural Emotions? Interested in expanding your Emotional Palette?

Cutting edge brain mapping technology not only has allowed us to refine existing emotions, but it also allows the creation of new emotions, and emotional experiences.

With Thalasin+: Experience emotions beyond previous natural capabilities!

These new Emotions include: Degrence, Humber, Nage, Dorcelessness, Andric, Varination, Ponnish, Harfam, Kyne, Trantiveness, Teluge, Onlent, Loric, and Naritrance.

This genre is basically the same as modern typical literature that tries to tell a satisfying good story. Except it's done to a science.

A good analogy would be modern music industry, where beautiful music can be constructed according to statistical models. It does not so much as eliminate traditional music theories of feeling, emotion, and soul, as to bypass it. Once they do it right according to their scientific theory, the listeners consumers can provide their own confabulations. The point is that those soulful confabulated feelings are derivative and unproductive, and the soulless theories are original and productive.

So, the brain was not evolved to get metacognition right. Getting "know thyself" actually right (in the sense of modern science) was not adaptive, so why would it be done right?

Now, if getting it wrong is adaptive, then it is all but guaranteed that it will be done wrong. This might explain god-talk (religion), and it might explain soul-talk.

I mean, it took millennia to even get sight right. People kept saying that light beams shoot out of their eyes, and it took until around 1000 AD to finally get that right. If something that literally is in front of our eyes (seeing!) and is literally a matter of life and death (seeing!) is intuitively misunderstood, of course we will intuitively misunderstand how science is done.

$$\text{inference}: \mathbb R^{1000} \to \mathbb R^{10}$$

The idea is that science could turn out to be running on something that isn't about manifest image. Even as the world becomes incomprehensible to old humans, even as old humans become unable to function in the new environment, even as the manifest image has been disproven, even as the humanoid-robots has long obsoleted the intentionality-API and are running the topologicality-API instead, even as the intentionality-API has been exploited to hell that any old human would immediately fall into an ethical money pump circuit and be taken out of the info-economy... science continues to run, progress, discover, construct technologies.

Sous rature is a strategic philosophical device originally developed by Martin Heidegger. Usually translated as 'under erasure', it involves the crossing out of ~~some text~~ a word within a text, but allowing it to remain legible and in place. Used extensively by ~~postmodernist~~ Jacques Derrida, it signifies that a word is "inadequate yet necessary".

This hypothetical future science would continue to run, without intentionality. To any old human still existing in that world, this new science would be incomprehensible, only understood more or less wrongly. Such an old human would write down an explanation for the new science, then meet an obvious problem, erase it, then try another, meet another obvious problem, erase it. Repeat until exhaustion.

So, Descartes thought that we have a persistent self. Cool, that didn't go well. Back then, people thought that there is no subconscious. Cool, that didn't go well. Now, we think that science is based on the game of giving and asking for reasons. Cool, is that really how science works?

Highly dubious distinction. Is subjectivity literally supernatural?

Sure, we do science, but do we do science the way we think we do? What if we did not need to simulate being a person in order to do science?

There are 3 possibilities:

1. Soul-soul strategy. This is the strategy of Brassier and Dennett. Their idea is that it is evolutionarily stable for human-animals to simulate aspects of a person, even though they don't have it. This is stable because science requires intelligent objects (such as humans) that are running a simulation of persons.
2. Soul-first strategy. This is the strategy of some phenomenologists, like Heideggar, Habermas, and Zahavi. This argues that what we think we are is the basis of all perception, and thus all of science, therefore science can never overthrow what we think we are.
3. Separate-but-equal strategy. This is the idea that there are physical systems in the world (humans with brains) that sometimes operate according to neuroscience, and other times operate according to morality. The domain of neuroscience and the domain of morality are separate-but-equal, and cannot occur simultaneously, because they are self-contained and autonomous from each other. This is similar to how a deck of cards is sometimes in a bridge game, and other times in a poker game, but never is a deck simultaneously in both games.

Brassier, Ray. "The view from nowhere." Identities: Journal for Politics, Gender and Culture 8.2 (2011): 7-23.

Pinker assumes that science can never exculpate the "really bad" murders because somehow there is a core part of ethics that is immune to scientific constraints. Sure, the science of ADHD has turned some ethics of hard-work into psychiatry, but ADHD has never been "really" ethical, anyway. Sure, the science of the fugue state has turned some ethics of into psychiatry, but fugue state has never been "really" ethical, anyway. Science merely reveals what has never been about ethics.

But that's precisely how science creeps upon ethics: it reveals that more and more ethical things have never been "really" about ethics, anyway. Where does it end? If materialism is true, then it will not end until every last bit of ethics is replaced with science. At the end of the process, we will have discovered that nothing has been "really" about ethics, that ethics has always been empty talk.

Bakker thinks that it's like trying to toss out the bathwater (the Cartesian subject) without also tossing out the bathwater (consciousness, phenomenology, intentionality).

Some philosopher: Descartes was wrong. After thinking about subjective experiences and some scientific data, we see that the person is actually quite social/contextual/phenomenological/etc.

Bakker: What makes you so sure you are right? The way in which Descartes was wrong is so deep, that your proposed replacement is probably also wrong. Maybe we have to throw away everything that we know subjectively, because subjective experience is so unreliable. We have to base everything on objective brain science...

12,895 instances big and small 6,448,939 users across the globe 608,690,572 statuses on anything and everything

social

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to https://hyp.is/JQTTaqXxEeuZ-OMmP2Ymkw/activitypub.rocks/

activity pub

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Résumé de la vidéo [00:00:00][^1^][1] - [00:04:28][^2^][2]:

Cette vidéo présente des conseils sur l'apprentissage et l'éducation des enfants, en mettant l'accent sur l'importance de l'attention, de l'environnement enrichi, du sommeil et de la répétition. Elle souligne l'impact de la parole des parents et des activités stimulantes sur le développement cognitif des enfants.

Points forts: + [00:00:00][^3^][3] L'importance de l'attention * Apprendre à se concentrer est crucial * Utiliser la tension exécutive pour sélectionner les pensées * La pratique quotidienne est essentielle + [00:01:00][^4^][4] Enrichir l'environnement cognitif * Le cerveau de l'enfant est une machine à apprendre * Utiliser un vocabulaire élevé et parler aux enfants * Fournir des jouets et des défis stimulants + [00:02:15][^5^][5] Encourager la curiosité naturelle * Les enfants explorent ce qu'ils peuvent apprendre * Éviter les sujets trop difficiles ou déjà connus * Le sommeil consolide les apprentissages + [00:03:08][^6^][6] Techniques d'enseignement efficaces * Captiver et canaliser l'attention des enfants * Alterner enseignement et mise à l'épreuve * Accepter les erreurs comme partie de l'apprentissage

That (a compilation step) is not why you get advance warning of the sort the interviewer means when you're programming in C++ and Java. It's static typechecking that's responsible for that. You can have static typechecking without also requiring compilation.

Dickinson expresses her emotions at the final moments of her death. She mentions that, "I heard a Fly buzz-when I died".She is feeling a sense of acceptance as she surrenders herself in peace to the "King", which is a metaphor of death, and as she put it, "For the last Onset-when the King Be Witnessed-in the Room". Also, the word "Blue" is another metaphor of death, as the blue flies fly over dead bodies. She emphasized the final death in a metaphor of shutting her eyes, when she writes,"And then the Windows failed".

Нарцисс. Любит раскидыватся оскорблениями без аргументов, аргументы при этом почти всегда - личная неприязнь, не сопоставляет свою уязвленную гордость и реальные дела людей, их реальный эффект. Такому нельзя доверять ни в чём, особенно в политике.

https://typespec.com/

https://typewriterchicago.com/

Run by Lucas Dul

https://en.wikipedia.org/wiki/Agnotology

engage with people

integrate their sensite with the fediverss

https://www.youtube.com/channel/UCCqcWwg5hDXgYMLRQZR3gRg

Run by https://www.reddit.com/user/Doctor_Will_Zayvus/

from https://hyp.is/ilzWmCBNEe-7DSNtMtje4Q/activitypub.rocks/

from: https://hyp.is/IJeheiBNEe-UwnMfF05upg/socialhub.activitypub.rocks/t/guide-for-new-activitypub-implementers/479

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I strongly agree and believe that showing and doing are such important aspects in education. I think it makes instruction and learning more engaging because students are able to apply the content to real-life, meaningful contexts. Therefore, increasing student participation and motivation.

https://www.amsterdamtypewriter.com/en-us

https://torontotypewriters.com/

Owner? Chris?

https://reeselectronics.com/typewriter-service-department/

Helmut is an amazing engineer/repairman via https://www.reddit.com/r/typewriters/comments/w8viia/comment/ihrw7cg/

FAQ section added to website , which saves time of the user which user would have spent on some common questions regarding the website.

very good font and simple color is used which is looking good.

A very well Name (How to rent a book )provided to the section , it clearly serves its purpose and the section for which the name is provided gives very detailed information about how to rent a book.

Though a question mark after the How to Rent Textbooks would have been provided a star to it.

Integrating CodeflowApp Bot

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4 Milkdown

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I thought that this was true up until this year. I never knew my "learning style," so it was very interesting to learn that this neuromyth is incorrect. I watched this video in another course this year, which debunks this theory: https://www.youtube.com/watch?v=rhgwIhB58PA As a future teacher, I think it is important for me to fully understand learning theories and the research behind them. Therefore, I can provide multiple forms of representation (visual, auditory, and kinaesthetic) for all students to support their learning, growth, and motivation.

saved.from.url: https://www.reddit.com/r/ipfs/comments/thpgt1/a_mostly_complete_guide_to_hosting_a_public_ipfs/?embed_host_url=https://publish.reddit.com/embed

1. O redirecionamento da execução fiscal, quando fundado na dissolução irregular da pessoa jurídica executada ou na presunção de sua ocorrência, pode ser autorizado contra o sócio ou o terceiro não sócio, com poderes de administração na data em que configurada ou presumida a dissolução irregular, ainda que não tenha exercido poderes de gerência quando ocorrido o fato gerador do tributo não adimplido, conforme art. 135, III, do CTN.(REsp 1.645.333-SP) (TEMA 981)
2. O redirecionamento da execução fiscal, quando fundado na dissolução irregular da pessoa jurídica executada ou na presunção de sua ocorrência, não pode ser autorizado * contra o sócio ou o terceiro não sócio que, embora exercessem poderes de gerência ao tempo do fato gerador, sem incorrer em prática de atos com excesso de poderes ou infração à lei, ao contrato social ou aos estatutos, dela regularmente se retirou e não deu causa à sua posterior dissolução irregular, conforme art. 135, III do CTN. (REsp 1.377.019-SP) (TEMA 962)

to: https://hyp.is/DOMCBCA_Ee-yuFNk1S3AYA/github.com/websockets/ws/issues/1697

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from: https://hyp.is/DOMCBCA_Ee-yuFNk1S3AYA/github.com/websockets/ws/issues/1697

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50% do IR, IPI e IS arrecadado terá a seguinte destinação:

• 21,5% -> FPEDF
• 22,5% -> FPM
• 3% -> financiamento do Setor produtivo do Centro-Oeste, Norte e Nordeste, sendo metade dos recursos ao Nordeste serão destinados ao Semiárido.

10% do arrecadado com IPI e IS será destinado, proporcionalmente, aos Estados e DF que tiverem exportados os produtos

25% de TODO ICMS arrecadado pertencerá aos Municípios. Entretanto, deverá observar a repartição da seguinte forma:

• 65%, no mínimo, do arrecado mediante operações realizadas nos territórios dos municípios.

• Até 35% em razão do que dispuser lei estadual, devendo haver, no mínimo, distribuição de 10% desse valor em referência a indicadores de saúde e educação.

25% de todo a arrecadação do IBS será destinado aos municípios, observando que: - 80% será destinado com base no tamanho da população do município; - 10% com base em indicadores de melhoria de aprendizado e equidade;

• 5% com base em indicadores de preservação ambiental;

• 5% em montantes iguais para todos os municípios.

Art. 154. A União poderá instituir:

I - mediante lei complementar, impostos não previstos no artigo anterior, desde que sejam não-cumulativos e não tenham fato gerador ou base de cálculo próprios dos discriminados nesta Constituição;

• RE 700922
• Repercussão Geral – Mérito (Tema 651)
• Órgão julgador: Tribunal Pleno
• Relator(a): Min. MARCO AURÉLIO
• Redator(a) do acórdão: Min. ALEXANDRE DE MORAES
• Julgamento: 15/03/2023

[...]

• 1. O art. 195, § 4º, com a remissão feita ao art. 154, I, ambos da CF, vedam a cumulatividade e o bis in idem, quando da criação de novos impostos ou contribuições sociais. No presente caso, não se trata de nova fonte de custeio para a seguridade social, uma vez que está assentada no art. 195, I, da CARTA MAGNA, na redação da EC 20/1998.
• 1. Ainda que assim não fosse, a vedação constitucional impede a criação de imposto ou contribuição social novos com fato gerador ou base de cálculo próprios de imposto ou contribuição social já existentes, não sendo vedada, porém, a criação de uma contribuição social prevista no texto constitucional com fato gerador ou base de cálculo idênticos aos de imposto já existente.
• 1. Do mesmo modo, o princípio da não cumulatividade dos novos tributos alude tão somente àquela cumulatividade que resulta da tributação de operações em cadeia, decorrente da sobreposição de incidências, não se referindo tal proibição à cumulação de dois tributos já previstos na Constituição, incidentes sobre o mesmo fato gerador.

economic globalization, perceived threats to national identity, immigration, and political dissatisfaction. Globalization has led to fears of loss of sovereignty and cultural homogenization, prompting a desire to protect national interests.

FastGPT was asked the following:

which poetic significance might be hinted at in the phrase "provinces that are free of 48 The Politics of Digitalization self-contradiction and dialectics, and that digital technologies, of all things, would represent such an Elysian province"?

The response was this:

The phrase "provinces that are free of self-contradiction and dialectics" suggests territories or domains that are not subject to internal conflicts or opposing forces. The reference to such provinces as "Elysian" evokes the Greek mythological conception of Elysium as a paradise or ideal place of contentment. Seen in this light, describing digital technologies as representing "such an Elysian province" portrays them as seemingly offering a harmonious, contradiction-free realm. However, the passage may also hint that this portrayal is overly simplistic or even illusory, since all human creations and systems are subject to tensions between opposing elements or the potential for unintended consequences over time.¹

¹ [PDF] Reading Contemporary Performance | TDM CoLLab 2020

looks close to a definition

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This fixed my issue with Loading Cache... slowness on obsidian startup on macOS Sonoma. Many thanks to OP!

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Bericht über den kanadischen Umweltminister, der in seiner Jugend zivilen Ungehorsam praktiziert hat, jetzt aber von vielen AktivistInnen als Verräter angesehen wird. Kanada hat nach wie vor extrem hohe kopfemissionsraten und keine wirksame Politik zur dekaronisierung.

Der neue Sprecher des US-Repäsentatntenhauses Mike Johnson ist ein aktiver Klimaleugner, der von der Öl- und Gasindustrie im vergangenen Jahr mehr Spenden erhalten hat als von jeder anderen Branche. Der Klimaleugner Steven J. Milloy nannte Johnson eine "Quantensprung-Verbesserung" gegenüber seinem republikanischen Vorgänger. https://www.nytimes.com/2023/10/26/climate/mike-johnson-climate-policies.html

In zwei US-Bundesstaaten haben NGOs verhindert, das Kohlekraftwerksbetreiber ihre Verluste auf ihre Kundinnen abwälzen. Die Argumentation, es stünden billigere erneuerbare Energiequellen zur Verfügung, wurde von dem Regulatoren akzeptiert. Kohlekraftwerke sind für mehr als 50% der energiebedingten Emissionen der USA verantwortlich, produzieren aber nur 20% des Stroms. Die Abwälzung ihrer Mehrkosten auf Kunden erschwert die Durchsetzung von Windenergie am Markt.. https://www.nytimes.com/2024/05/31/climate/electricity-from-coal-is-pricey-should-consumers-have-to-pay.html

Donald Trump hat 20 Spitzenmanagern der amerikanischen Ölindustrie angeboten, für Wahlkampfspenden in Höhe von einer Milliarde Dollar alle Regulierungen der Biden-Administration, die die Förderung von Öl und Gas behindern, zu Beginn seiner Amtszeit außer Kraft zu setzen. Die Washington Post berichtet über das Treffen in Mar-a-Lago. https://www.theguardian.com/us-news/article/2024/may/09/trump-oil-ceo-donation

Bericht der Washington Post: https://www.washingtonpost.com/politics/2024/05/09/trump-oil-industry-campaign-money/l

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This is very important to me in the Health and PE setting, it is very easy for students to become "busy" keeping themselves occupied with mindless phone use in school. Providing them with ways to stay engaged vs busy is truly important in the learning process.

Der Markt für Karben Credits ist von 20 22 bis 20 23 von 1,9 Milliarden Dollar auf 723 Millionen Dollar geschrumpft Punkt Ursache sind vor allem die Veröffentlichungen über die wirkungslosigkeit der Credits.https://www.theguardian.com/environment/article/2024/may/31/market-value-of-carbon-offsets-drops-61-aoe

Je ne comprends pas à quoi sert la balise si on a déjà une balise <!DOCTYPE html> qui est déjà censée indiquer qu'on code en html.

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логике.

сноска?

сноска?

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ошибка верстки, потерян бэкслеш

выборочных

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Note: This response was posted by the corresponding author to Review Commons. The content has not been altered except for formatting.

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Reply to the reviewers

The authors do not wish to provide a response at this time

Note: This preprint has been reviewed by subject experts for Review Commons. Content has not been altered except for formatting.

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Referee #2

Evidence, reproducibility and clarity

In the manuscript by Nabeel-Shah et al. the authors identify ZBTB48 as a novel interactor of FTO. They show that ZBTB48 helps recruiting FTO to mRNA as well as the noncoding RNA Terra. Their results further suggest that this recruitment is required for FTO to demethylated m6A and m6Am RNA modification in target RNAs. This affects cellular rates of RNA turnover. Furthermore, the mechanism is involved in repressing colorectal cancer cell growth.

Overall, the authors present a new role of ZBTB48 in m6A and m6Am mediated RNA metabolism. They also suggest a nice model of ZBTB48 action, via the recruitment of the demethylase FTO. These findings will be of interest for the general RNA community and might be also relevant for cancer treatment. However, I have some concerns about the quality and analysis of the obtained data, especially the iCLIP and miCLIP experiments. The concerns are detailed below and should be addressed before publication.

Major concerns:

1. Figure 1B) I think that the results shown in the autoradiograph are not very convincing and suggest that the purification of ZBTB48 is not very clean. The radioactive signal covers the lane from 50 kDa to 200 kDa. The ZBTB48 alone is running around 80 kDa. If the purification is specific most of the signal should be above 80 kDa. Maybe it helps to also use higher RNAse concentrations: Having very short RNA pieces will allow to evaluate specificity of the purification, since protein-RNA complexes will just a bit above the size of the protein. This also applies to Figures S1E,F.

This concern could also apply to the generated iCLIP libraries and indicates that at least part of the obtained reads does not originate from ZBTB48 crosslinked RNA. The validation of protein-RNA interactions with RIP shown in Figure S2E supports the quality of the iCLIP data. Here some control RNAs should be analyzed to show that the RIP is not unspecifically enriching any RNA. 2. Regarding the co-occurrence of m6A sites as well as FTO and ZBTB48 binding sites shown in Figures 2B, C, F and G. The CLIP signal is a lot affected by crosslinking bias and read mappability. Therefore, to make these results more convincing it would be important to include additional iCLIP datasets (published other RBPs) for comparison. 3. Regarding Figure 2D and related analyses: I very much like this experiment and the results obtained here! I just wondered where the remaining reads go in the ZBTB48 knockdown. The introns? Maybe this becomes clearer in the meta profile representation used in Figure 1F.

For me the changes in the 5' UTR look most dramatic. Maybe this means that ZBTB48 is most important for recruitment of FTO to m6Am sites. Therefore, I think it would be good to differentiate the analyses in the remainder of the manuscript for m6A and m6Am sites. I first step would be to treat sites in the 5'UTR separate from the CDS and 3'UTR sites in the following analysis. 4. I have some concerns about the analysis of the miCLIP data. In Figure 3A antibody crosslinking in all conditions appears similar. Yet in panel B there seems less signal for FTO and ZBTB48 overexpression in all areas. Have there been more reads generated for the GFP control? Where is the rest of the reads going? I think it would be required here to identify peaks that significantly change between the conditions. Then ask do those peaks coincide with DRACH and were are they located. Also, in the Genome browser pictures the signal is going down at all locations. Why is that? Usually, miCLIP generates a lot of background peaks. These should be unchanged. 5. I am a bit confused by the author's interpretation of the results shown in Figure 5E. For me this plot shows that target transcripts are less downregulated and less upregulated than non-targets? Basically they are less regulated overall. In this context I also think that the representation in of the mean in figure 5E and F is misleading. Data distribution should be visible as violin or boxplot.

Minor points:

Figure 1D) I think the legend in the panel is confusing and does not add information. Especially since its in a different order than the categories on the y-Axis.

Figure S2D) I wondered if the authors controlled for mappability of reads when picking random sites. How do the authors account for that in iCLIP there will be less reads in introns compared to exons?

5E,F boxplots would be more suitable than barplots.xx

Figure 2I: Please do not use "+ve"

Figures with Microscopy pictures of cells have no scale bars or way too small.

The model that is shown in figure 7 is somehow misleading as it shows FTO binding only to ZBTB48 and not to the RNA.

Significance

Overall, the authors present a new role of ZBTB48 in m6A and m6Am mediated RNA metabolism. They also suggest a nice model of ZBTB48 action, via the recruitment of the demethylase FTO. These findings will be of interest for the general RNA community and might be also relevant for cancer treatment. However, I have some concerns about the quality and analysis of the obtained data, especially the iCLIP and miCLIP experiments. The concerns are detailed below and should be addressed before publication.

Note: This preprint has been reviewed by subject experts for Review Commons. Content has not been altered except for formatting.

Learn more at Review Commons

Referee #1

Evidence, reproducibility and clarity

In this manuscript, Nabeel-Shah et al. identified that the telomeric zinc finger protein ZBTB48 help recruit FTO onto target RNA, including mRNAs and the telomere-associated regulatory RNA TERRA, to achieve cellular RNA m6A/m6Am demethylation, thereby regulating cell biology such as tumour growth studied in this study. The biochemistry and molecular biology experiments were done in HEK293 cells, and the cell models for tumour growth was done in HCT116 cells. However, I have identified both major and minor concerns that, when addressed, could further strengthen the findings and enhance the impact on the field.

Major concerns

1. Regarding the ZBTB48/FTO targets and m6A/m6Am level that are regulated by ZBTB48/FTO axis. Wei et al Molecular Cell 2018 (PMID: 30197295) (Figure 1B) quantified the m6A/m6Am levels upon knockdown of FTO in HeLa, HEK293, and 3T3-L1 cells, and found that the m6A/m6Am levels are generally mildly (10-20%) yet significantly upregulated on poly(A)+ RNAs. Here shown in the Figure 4A in this manuscript, the authors show that (1) siFTO and siZBTB48 led to ~2-3 fold upregulation of m6A and m6Am levels using total RNAs (dominant by rRNA in the population), and (2) that the m6A and m6Am levels are similar between siFTO and siZBTB48. Regarding (1), can the authors explain the discrepancy? This point is also relevant to the m6AIP-qRT-PCR results in this manuscript. Regarding (2), does this result suggest that ZBTB48 helps FTO to demethylate nearly all its targets, rather than a subset?
2. Considering the significance of how FTO achieves target specificity, can the author anticipate the extent of applicability of the proposed model? Does the interaction between ZBTB48 and FTO also exist in various human and mouse cell lines? If confirmed, this discovery would hold substantial value for the field. This interaction at least needs to be confirmed in HCT116 cells used for tumour growth model in this study.

Minor concerns.

1. The authors realised that knockdown of ZBTB48 does not change FTO levels, whereas overexpression of ZBTB48 leads to elevated FTO. It is unclear about the rationale behind overexpression studies?
2. Considering the multifunctional nature of ZBTB48, it's important to disentangle transcriptional and post-transcriptional roles of ZBTB48 to draw conclusions. I appreciate the analysis conducted in this manuscript. Is it possible to overexpress an DNA-binding mutant of ZBTB48 or RNA-binding mutant of ZBTB48 proteins?
3. In Fig 2B, the innet panel does not match the metagene profile regarding the difference.
4. In Fig 5H, there is a lack of experiments for comparison, i.e. siFTO and o/e FTO.
5. Page 3, "Genome-wide studies" should be "Transcriptome-wide studies".

Significance

Strengths: The biochemistry and molecular biology experiments are comprehensive and well designed. The analysis is robust, and the conclusions generally align with the presented data.

Limitations: Cell line-specific and/or species-specific interaction?

Advance: filling a gap in our knowledge of how FTO achieves target specificity.

Audience: Basica research in the field of RNA modifications and RNA Biology.

My expertise: Bioinformatics, gene regulation by RNA m6A modification

Résumé de la vidéo [00:00:08][^1^][1] - [00:05:12][^2^][2]:

Ce webinaire explore l'importance de l'expérience patient comme démarche stratégique pour les établissements de santé. Il aborde les différentes interprétations de l'expérience patient dans le secteur sanitaire, médico-social et par les associations de patients, soulignant l'engagement des patients à tous les niveaux du système de santé.

Points forts: + [00:00:30][^3^][3] Introduction à l'expérience patient * Importance de l'engagement des patients * Évolution des politiques publiques de santé * Rôle des nouvelles réglementations + [00:01:26][^4^][4] Différentes perspectives de l'expérience patient * Variations selon les secteurs * Amélioration de la sécurité et de la qualité des soins * Collaboration des patients dans l'évaluation des pratiques + [00:02:38][^5^][5] Approches complémentaires de l'expérience patient * Importance du savoir d'expérience * Interaction avec le système de soins * Impact de l'histoire de vie des patients + [00:04:00][^6^][6] Le récit patient comme outil précieux * Construction de l'expérience en devenir * Traduction du vécu individuel et collectif * Révélation des obstacles et des aides dans le parcours de soins

Résumé de la vidéo [00:00:01][^1^][1] - [00:24:49][^2^][2]:

Cette vidéo présente un webinaire sur l'importance de l'expérience patient dans les établissements de santé et comment elle peut être une démarche stratégique pour améliorer la qualité des soins. Les intervenants discutent des méthodes d'évaluation de l'expérience patient, de l'importance de la mesure du point de vue du patient et de l'évaluation de la qualité de vie liée aux soins.

Points forts: + [00:00:01][^3^][3] Introduction au webinaire * Présentation de l'objectif du webinaire * Importance de l'expérience patient dans la certification des établissements de santé * Rappel du premier webinaire et de son succès + [00:04:01][^4^][4] Méthodologie de l'expérience patient * Discussion sur la mesure de l'expérience patient * Importance de l'évaluation de la qualité de vie et de la satisfaction des patients * Propositions pour le développement d'indicateurs de qualité et de pertinence des soins + [00:14:01][^5^][5] Analyse des commentaires des patients * Présentation des résultats nationaux des établissements privés * Importance des verbatims pour comprendre l'expérience patient * Projet d'outil d'analyse des verbatims utilisant l'intelligence artificielle + [00:17:00][^6^][6] Questionnaires d'expérience patient * Développement de questionnaires pour différentes situations de soins * Expérimentation et validation des questionnaires * Importance de la participation des établissements de santé et des patients Résumé de la vidéo [00:24:52][^1^][1] - [00:49:52][^2^][2]:

La vidéo présente un webinaire sur l'expérience patient comme démarche stratégique pour les établissements de santé. Elle aborde le programme de la Haute Autorité de Santé (HAS) pour promouvoir l'utilisation des PROMs (Patient-Reported Outcome Measures) dans les établissements de santé, les défis de leur mise en œuvre et l'importance des registres standardisés pour améliorer la qualité des soins.

Points forts: + [00:24:52][^3^][3] Programme de la HAS * Promotion des PROMs en santé * Publication de guides et panorama d'expériences étrangères * Appels à projets pour établir des indicateurs de résultats + [00:29:19][^4^][4] Rôle des PROMs * Amélioration des pratiques de santé * Optimisation des parcours de soins * Valorisation des innovations + [00:30:23][^5^][5] Importance des résultats rapportés par les patients * Impact sur la qualité de vie quotidienne * Nécessité de registres standardisés pour évaluer la qualité des soins + [00:39:50][^6^][6] Cas pratiques et gouvernance * Exemples d'implémentation des PROMs en ophtalmologie et orthopédie * Importance d'une gouvernance indépendante et collégiale pour les registres Résumé de la vidéo [00:49:56][^1^][1] - [01:15:10][^2^][2]:

Cette vidéo présente un webinaire sur l'expérience patient comme démarche stratégique pour les établissements de santé. Elle aborde l'utilisation du digital pour améliorer le suivi et la comparaison des soins, l'importance de l'interopérabilité, et l'impact positif sur les pratiques des praticiens et la santé des patients.

Points forts: + [00:49:56][^3^][3] Utilisation du digital et interopérabilité * Le digital réduit les erreurs et biais * Interopérabilité essentielle pour l'extraction et la définition des données * Comparaison avec d'autres pays grâce à la standardisation + [00:52:39][^4^][4] Amélioration des pratiques et de la santé des patients * Augmentation significative de la moyenne des gains de santé des praticiens * Changement des comportements et relations avec les patients * Identification des praticiens en difficulté pour leur apporter de l'aide + [00:55:01][^5^][5] Mesure de l'empathie et de la qualité de la relation patient-chirurgien * Corrélation forte entre la qualité de la relation et le retour à l'emploi * Utilisation de scores pour mesurer l'empathie et la fonctionnalité * Comparaison des scores fonctionnels et relationnels au sein de la communauté de pratique + [01:02:07][^6^][6] Vision de l'expérience patient par France à santé * L'expérience patient ne se limite pas à des questionnaires fermés * Importance de travailler sur les émotions ressenties et les résultats cliniques * Collaboration avec les patients pour partager les résultats et améliorer les soins Résumé de la vidéo [01:15:12][^1^][1] - [01:40:01][^2^][2]:

Cette partie de la vidéo discute de l'importance de l'expérience patient dans les établissements de santé et comment les représentants des usagers peuvent s'engager dans ce processus. L'orateur souligne que l'expérience patient est plus qu'une mesure de satisfaction; c'est un changement de paradigme qui ouvre de nouvelles possibilités pour améliorer la qualité et la sécurité des soins.

Points forts: + [01:15:12][^3^][3] L'expérience patient comme vecteur de travail * Importance de travailler avec les représentants des usagers * Utilisation des plaintes et éloges pour améliorer la qualité des soins + [01:17:00][^4^][4] Engagement des représentants des usagers * Promotion et participation au recueil de l'expérience patient * Contribution aux plans d'action et aux actions correctives + [01:19:00][^5^][5] Nouvelles formes d'engagement des patients * Exemples de patients partenaires et médiateurs de santé * Typologie des rôles des patients dans l'amélioration des soins + [01:22:00][^6^][6] Vers un nouvel écosystème de l'expérience patient * Développement d'écosystèmes complets incluant divers acteurs * Rôle de la Commission des usagers et des associations conventionnées Résumé de la vidéo [01:40:03][^1^][1] - [02:00:13][^2^][2]:

Cette partie de la vidéo présente un webinaire sur l'expérience patient dans les établissements de santé. Il met en lumière l'importance de l'expérience patient comme démarche stratégique et partage des exemples concrets d'actions engagées pour améliorer cette expérience dans différents établissements.

Points forts: + [01:40:03][^3^][3] Mise en place d'une méthode * Utilisation d'une nouvelle méthode pour observer l'expérience patient * Choix d'un secteur de cardiologie pour une étude approfondie * Suivi de trois patients sur une journée + [01:42:02][^4^][4] Engagement de la Clinique Pasteur * Présentation des actions de la Clinique Pasteur à Toulouse * Mise en œuvre d'une stratégie centrée sur l'expérience patient * Création d'une direction dédiée à l'expérience patient + [01:44:01][^5^][5] Diagnostic et plan d'action * Réalisation d'un diagnostic pour identifier les besoins et les attentes * Développement d'un plan d'action basé sur le parcours patient * Inclusion des usagers dans la démarche pour une meilleure représentativité + [01:47:46][^6^][6] Amélioration de l'accueil et du parcours patient * Refonte de l'accueil pour une expérience patient plus agréable * Utilisation du numérique pour préparer l'hospitalisation * Création d'un salon de sortie pour sécuriser le départ des patients + [01:59:01][^7^][7] Suivi post-hospitalisation et mesure de l'expérience * Suivi du patient après son retour à domicile via un portail numérique * Mise en place de questionnaires pour mesurer l'expérience patient * Coordination du parcours patient pour une expérience améliorée Résumé de la vidéo [02:00:15][^1^][1] - [02:05:01][^2^][2]:

Cette partie du webinaire se concentre sur l'importance de l'expérience patient dans les établissements de santé et comment elle peut soutenir le personnel soignant. L'organisation mise en place vise à alléger la charge administrative des soignants, leur permettant de se concentrer sur leur cœur de métier. La clinique Pasteur partage son expérience en mettant en œuvre cette stratégie centrée sur le patient.

Points forts: + [02:00:15][^3^][3] Soutien au personnel soignant * Préparation des dossiers patients * Numérisation et organisation des informations avant l'arrivée du patient * Équipes dédiées pour la gestion administrative + [02:01:29][^4^][4] Partage d'expériences et valeurs * Échanges encouragés pour améliorer l'expérience patient * La démarche unit le personnel autour du service au patient * Importance de la qualité des soins et des conditions de travail + [02:02:18][^5^][5] Stratégie globale de l'expérience patient * Amélioration de la qualité des prises en charge * Performance des établissements de santé * Promotion de la démocratie en santé et prise en compte de l'expérience patient + [02:04:03][^6^][6] Perspectives et événements futurs * Développement progressif de l'expérience patient dans les établissements * Rencontres de la FHP et Congrès des représentants des usagers à venir * Engagement continu pour l'amélioration de l'expérience patient

Résumé de la vidéo [00:00:08][^1^][1] - [00:05:12][^2^][2]:

Ce webinaire intitulé « L’expérience patient : une démarche stratégique pour les établissements de santé » explore l'importance de l'expérience patient dans le système de santé. Il discute des différentes interprétations de l'expérience patient et de son utilisation pour améliorer la qualité des soins.

Points forts: + [00:00:30][^3^][3] Introduction à l'expérience patient * Importance de l'engagement des patients * Évolution des politiques publiques de santé * Rôle des patients dans l'évaluation des soins + [00:01:26][^4^][4] Différentes perspectives de l'expérience patient * Variations selon les secteurs sanitaires et médico-sociaux * Amélioration de la sécurité et de la qualité des soins * Compétences acquises par les patients + [00:03:03][^5^][5] Définition de l'Institut français de l'expérience patient * Interactions et situations vécues par les patients * Influence de l'organisation des soins et de l'histoire personnelle * Savoir d'expérience comme un processus continu + [00:04:00][^6^][6] L'expérience comme construction en devenir * Récits des patients comme moyen de traduire l'expérience * Impact des interactions avec le système de soins * Importance de l'adaptation individuelle et collective

J'ai suivis les étapes, commande par commande pour faire le push. Mais j'ai un message d'erreur : ERROR: Permission to OpenClassrooms-Student-Center/7162856-G-rez-Git-et-GitHub.git denied fatal: Could not read from remote repository.

Please make sure you have the correct access rights and the repository exists.

J'ai essayé avec l'URL du https et du SSH, même finalité. J'ai eu une fenêtre d'authentification qui c'est ouverte mais même après ça je reste bloqué !

Est ce que quelqu'un peut me dire quelle erreur j'ai put faire ?