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theopolisinstitute.com theopolisinstitute.com
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William Nestle’s Vom Mythos zum Logos (1940) is the classical statement of this reading. On the opening page, Nestle claims mythos and logos are “the two poles between which man’s mental life oscillates. Mythic imagination and logical thought are opposites,” the former being “imagistic and involuntary,” rooted in the unconscious, while the latter is “conceptual and intentional, and analyzes and synthesizes by means of consciousness” (quoted in Glenn Most, “From Logos to Mythos,” in From Myth to Reason?, 27).
Dichotomy of "mythic imagination" rooted in the unconscious versus "logical thought" rooted in the conscious
Also, see this as a reading of "chaos versus order". See, for example, Apollonian and Dionysian theory or Confucius order and Lao Tzu chaos (with respect to wu-wei). In PKM, this would correlate to the gardener vs architect archetypes.
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Many have summarized the intellectual history of Greece as an evolution from the mythos to logos.
Intellectual history of Greece as an evolution from mythos to logos
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From Myth to Reason
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- myth and reason
- Vom Mythos zum Logos
- intellectual history of Greece
- gardener vs architect
- PKM
- order vs chaos
- Wilhelm Nestle
- Apollonian and Dionysian theory
- Confucius order vs Lao Tzu chaos
- mythos vs logos
- mythos and logos
- conscious and unconscious
- ancient Greece
- wu-wei
- from myth to reason
- gardener vs architect in PKM
- history of Greece
- from mythos to logos
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Analyses outside of the economics literature explore LMIC MPA decisions but in ways thatmay not adequately reflect people’s decisions in such settings. As elsewhere in the systematicconservation planning literature, Kockel et al. (2020) use lost fishing grounds as the metricof impact on artisanal fishers rather than the fisher response to MPAs. To evaluate trade-offsbetween biodiversity and socioeconomic values, Teixeira et al. (2018) estimate fisher opportunitycosts in data-poor regions but use habitat characteristics alone to estimate the spatial distributionof those costs. Grantham et al. (2013) compare several zoning and MPA configurations but useproximity between communities and restrictive zones as a metric to determine an equitabledistribution of community impact.546 Albers • Ashworth
conservation scientists/journals that provide economic analysis/insight often fail to take into account economic factors specific to local, artisanal, and/or community based fisheries
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Much of the expansion of MPA networks is likely to occur in the developing world, but littleresearch uses developing country characteristics defined in the environment-development eco-nomics literature to examine those decisions (Marinesque et al. 2012). First, individuals makedecisions within subsistence and semi-subsistence settings, missing or thin markets, householdlabor and capital constraints, budget constraints, and high poverty, which can contribute todistributions of effort. S
There is a lack of research on the economic impact of MPAs in the developing world which is where the majoritty of the expansion will likely take place
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Yet, dozens of conservation science articles describe conservationeffectiveness and MPA impact analysis that do not consider these advances in impact analysis,such as comparing outcomes in unprotected areas (Friedlander et al. 2017, Selig & Bruno 2010)and comparing the outcome measures before/after an MPA has been placed without consideringthe counterfactual of no-MPA (Savina et al. 2013).
Conservation scientists providing economic analysis are not taking into account new developments and advances in the analysis of protected areas generally.
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In the last decade, economics journals have contained few articles with MPAs as the central topic,despite the emphasis on expanding MPAs in conservation policy. The reasons behind this paucityof articles could include editorial opinions that MPAs are not an important economic issue, thatthe relevant questions have been answered, and that the techniques used to explore MPAs are notappropriate for economics journals; or perhaps economists simply are not engaged with marineconservation issues. In contrast, the conservation science literature, including interdisciplinaryjournals, contains thousands of articles about MPAs, some with economists as authors. Althoughpublishing in outlets with wide readership, particularly practitioners and interdisciplinary re-searchers, is important for furthering knowledge about MPAs and informing policy, the lack ofarticles in economics journals makes it difficult to evaluate which articles use economics-basedmethods in a rigorous and appropriate way because most such publications are not reviewed byeconomists.
There is a sufficient lack of articles in Economic journals with MPAs as the central topic however there are thousands in Conservation and interdisciplinary journals. This takes the economic perspective out or is only provided in a limited fashion and/or without review from experts in the field.
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Given the proposed expansion of MPAs, randomizingearly MPA network extensions to create an experimental setting for analysis would provide criticalinformation about what characteristics of MPAs provide net conservation and economic benefits(Ferraro 2009, Ferraro & Pattanayak 2006). In addition to the challenges of convincing policymakers to embrace that sort of experimental design in MPA expansions, MPA impact analysis iscomplicated by the treatment of much of the marinescape through the spatial connections of theecological and economic systems. Nonetheless, using rigorous methods to assess MPA impact iscritical to generating efficient conservation policy
Given the expansion of MPA goals a more integrated conservation and economic framework needs to be applied to a randomized network of MPAs to determine the best practices for maximizing ecological and economic benefit convergently.
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Overall, the MPA economics literature emphasizes the importance of the spatial behavior ofboth the resources in the marine ecosystem and people in the marinescape, given that MPAs areinherently spatial policies
Spatial behavior of people, resources, and non-harvested species is a very important integrated economic and conservation analysis tool.
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using such a frame-work forces the integration of ecological and economic decisions, including people’s behavior, toachieve positive outcomes for conservation, social welfare, economic values, or their combina-tions. Even for pure conservation outcomes, MPA decisions must reflect the responses of peoplebecause people’s reactions to the MPA influence conservation and other outcomes. People respondto all aspects of the MPA design decisions: The location, size, and configuration inform people’sdistance-based costs and the distribution of the resource across the marinescape; the type and levelof restrictions within the MPA influence people’s trade-offs among locations and activities; andmanagement decisions, including enforcement to influence the net returns from actions within theMPA.
MPA decisions, design, and management should follow the framework outlined in this paper with the highlighted aspects/constraints being considered as an integrated network and solved as such rather than the sequential way that it has been. This leads to more compliance.
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Because fish and people move across MPA boundaries, most MPA analyses consider both theMPA and the surrounding marinescape. In fishery economics, the ecological system is often de-picted as a marinescape of patches of fish subpopulations, with dispersal among subpopulations ina metapopulation (Sanchirico & Wilen 1999), potentially with some patches as hotspots (Schnier2005). That said, there are settings in which the scale of a subpopulation is larger than the scale ofMPAs, settings in which the policy scale does not permit distinguishing between subpopulations,and other settings in which a metapopulation does not apply.
Using spatial patterns is an extremely important tool for analyzing MPAs from an economic and conservation point of view.
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) literature assessment finds that MPAs contribute to food security, socialwell-being, and political power in local communities, with heterogeneous impact on differentgroups. Overall, considering the fishers’ and people’s responses to MPAs is an important aspect ofdesigning MPAs to achieve conservation and economic outcome
Taking into account the opportunities and services MPAs provide for other people through recreation, tourism, food security, community development//economic resilience, etc. outside of fishers.
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The economics literature on MPAs is clear on the importance of considering people’s—typicallyfishers’—responses to MPAs in order to make decisions about MPAs or to assess MPA impact(Albers et al. 2020a, Bennett et al. 2020, Dépalle et al. 2020, Hannesson 1998, Reimer & Haynie2018, Smith & Wilen 2003, Sultan 2020, Zhang & Smith 2011). In particular, MPA economicanalyses emphasize the importance of the spatial response of fisher behavior to the spatial policyof MPAs (Albers et al. 2020a, 2021; Sanchirico & Wilen 2001; Smith & Wilen 2003). Althoughconservation scientists describe a response of fishers to MPAs, those descriptions—both modelingand empirical—often fail to consider important aspects of people’s decisions. In some cases, con-servation scientists evaluate MPAs with assumptions of no fisher redistribution of effort (Selig &Bruno 2010, Sutcliffe et al. 2015) or redistribution of effort with total effort constant (Friedlanderet al. 2017, Klein & Watters 2020, Savina et al. 2013). Smith & Wilen (2003) find that typicalassumptions about fisher response bias predicted outcomes in favor of MPAs when fuller descrip-tions of fisher spatial behavior find other outcomes. For economists to inform MPA decisions,continued development of predictive models and empirical analyses that provide the microeco-nomics of fisher decisions is critical.
- The consideration of fisher response is prevalent in the existing literature however there is contesting information and ideas and more detailed and predictive frameworks need to be created to better represent and integrate true fisher response and perception of MPAs into the conservation goals of MPAs. -connservation literature surrounding perceptions and reactions to MPAs are not well informed
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his empirical work suggests that the simpler models of fishing effort allocation across spacemay not be sufficient for predicting the response to MPAs, the resulting outcomes, and thereforethe choice of MPA sites and sizes
data looking at how fishing effort allocation differs across space is not sufficient to inform or predict responses to MPA, outcomes, and MPA design and location choice.
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Still,most economic analysis does not explicitly address the dispersal matrix of marine species betweensites or subpopulations. Bauer et al. (2010) and Albers et al. (2022a) demonstrate the importanceof the dispersal matrix itself for decisions about conservation of terrestrial species.
The economic analysis of MPA performance is often lacking a complete analysis of the ecological systems and often leave out dispersal info about species within the conservation goals of the MPA but not economic . MPA economic analysis needs to include more complete ecological analysis and synthesis with harvested species info since they all interplay.
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For ex-ample, a conservation goal of maximizing the number of species in an MPA requires the use ofecological frameworks that depict interactions among species and how species diversity respondsto policy, such as protecting reefs from tourists. Similarly, conservation goals to improve stocks ofnonharvested fish require ecological system models integrated with economic policy frameworksor ecosystem-based management approaches to assess policies, including, but not limited to,fishing restrictions
Ecological systems and Economic analysis/policy frameworks need to be synthesized for economic and conservation goals to be achieved, especially goal of increasing non-harvested(targeted) species.
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Marine protected areas (MPAs) provide both conservation and economicbenefits. Recent international conservation actors have called for a dramaticincrease in the are
There is a goal set by the U.N sustainability group for the area of Marine Protected areas to grow to 30% by 2030.
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As compared to terrestrial PAs, establishing MPAs faces lower start-up costs due to the lack ofprivate ownership of marine areas but potentially higher ongoing costs associated with enforcingaccess and use restrictions (Bohorquez et al. 2019). Waldron et al. (2020) predict that low- andmiddle-income countries (LMICs) will face 70–90% of the implementation costs of achieving30% PAs by 2030, which signals the need for international funding sources. Despite the promi-nence of paper parks and tight budget constraints for ongoing management and enforcementin lower-income countries, but also in wealthier countries, economic analysis of MPAs rarelyconsiders those costs in evaluation nor in siting decisions. In addition, little is known about thelevel of budgets required to make MPAs effective at generating economic or conservation gains.Gravestock et al. (2008) use regression analysis of surveys in 36 countries to determine what drivesbudgetary needs in MPAs, finding that those budgets are higher with large MPA sizes and higherMPA visitor numbers
- MPAs cost less to establish but have potentially higher ongoing costs
- Economists predict that low-middle income countries will face the majority of burden of increasing MPA by 2030(UN Goal) so they will need funding
- This will cause even tighter ongoing management budgets which weakens the performance of MPA
- This is rarely considered in siting decisions
- tourism is used/ needed to offset costs in low income countries
- all of this is largely ignored in MPA decison making
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MPA choices include thespecific location, configuration, and size of the MPA; the accepted uses and restrictions on useswithin the MPA; ecological and economic management decisions, including monitoring and en-forcement; and temporal choices. All of these choices face information gaps in how they influencethe creation of MPA benefits, particularly for conservation benefits beyond fish stock metrics.
There is a knowledge gap regarding all of these factors and how create the benefits of MPAs for conservation beyond fishery related conservation benefits like fish stock metrics.
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The choicevariables include MPA location, size, configuration, restrictions, and management. The setting’sbio-geo-physical characteristics include the spatial distribution of ecological attributes, the spatialbehavior of the ecosystem such as fish dispersal, and system dynamics. People’s decisions in re-sponse to the MPA and its management create additional equations of motion due to their impacton the ecosystem. Budget constraints and local institutions form additional constraints. Proceed-ing from the objective function through these choice variables and constraints, we use this decisionframework to assess the economics literature’s status and contribution to MPA policy.2.1. Objective FunctionBeyond area targets, MPAs seek to generate conservation benefits, economic benefits, or both.Economists consider MPAs to maximize net social benefits or, more commonly, to maximize534 Albers • Ashworth
With these variables the authors assessed how economics literature can, has, and has not contributed to MPA policy
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These widely used frameworks typically do not incorporate eco-nomic analysis approaches, even when addressing economic outcomes such as fishery harvests.While economic analysis of MPAs focuses on fishery outcomes, economic perspectives on peo-ple’s behavior in response to MPAs are particularly important because responses determine bothconservation and economic outcomes.
A lot of the frameworks used to analyze the impact/effect/potential of MPAs do not include economic analysis but then inform/address fishery economic outcomes The paper is looking to analyze how economics research has and can contribute to the discussion of the expansion of Marine Protected Areas
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r more economic analysis of MPApolicy questions, including those around siting, design, restrictions, andmanagement choices; impact evaluation; responses of people; low-incomecountry settings and incomplete enforcemen
Through their review of economic and conservation literature the authors found the need for more and a synthesis of the economic perspective on a few key factors - Site/location choice and Design - Regulations/restrictions - management - impact evaluation - stakeholder response - incomplete enforcement
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Capitán et al. (2020) compare MPA decisions across several goals, includingmaximizing income, extracted resource stocks, and unextracted sea turtle populations. Combin-ing modeling and empirics, Sultan (2021) considers the MPA impact on fish populations, biomass,and catch rates. Conservation science analyses find limited impact of MPAs on non-harvestedspecies (Endo et al. 2019, Montero-Serra et al. 2019, Welch et al. 2018). MPA tourism can alsoreduce conservation outcomes (Lopes et al. 2017, Monti et al. 2018, Velando & Munilla 2011).Hastings et al. (2017) show that marine reserves in a multispecies fishery can reduce bycatch with-out reducing yields of the target species.
Studies are trying to consider whether or not the conservation goals of MPAs are compromised by or relate to the targeting of resource species stocks
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Sanchirico et al. (2006) ask when establishing a no-take reserve willmaximize marinescape profits. Albers et al. (2020a, 2021) determine the optimal MPA to maximizeincome, comprising fishing income and onshore income, and to maximize marinescape stocks. Inthese frameworks, MPA benefits to marinescape fisheries through fish dispersal trade off againstthe lost fishing within the MPA
Economic analysis of MPAs see it as stock protection, but the there are questions of how long does a viable MPA take to create returns through fish dispersal against the loss of fishing within the MPA. Study found a framework for an optimal MPA with the trade off being positive for both the economic and conservation goals (Albers et al)
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. People’s decisions in re-sponse to the MPA and its management create additional equations of motion due to their impacton the ecosystem
Peoples responses to MPA regulations/decisons/site choice are an important an often overlooked part of this equation.
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Conservation economists and scientistsview the objective of MPAs as providing a suite of conservation outcomes, including stemmingthe loss of biodiversity and ecosystem services, maximizing the number of species, creating MPArepresentation of diverse systems, increasing fish stocks for harvested or nonharvested species,resilience to climate change, and coral reef health (e.g., Almany et al. 2009, Bates et al. 2019,Davies et al. 2017, Game et al. 2009, Magris et al. 2018, Wilson et al. 2020). Most MPA economicanalyses consider both a fishery economic goal and a conservation goa
MPAs do serve the duel economic and conservation purposes through this lens, long-term benefits vs short-term overharvesting/stress
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. Unliketerrestrial PAs, MPAs are commonly used as fishery management tools within a marinescape. Forboth conservation and poverty alleviation reasons, the United Nations’ Sustainable DevelopmentGoal 14 aims for larger MPA networks worldwide
MPA's inherently serve an important economic purpose on top of the conservation importance which is not the case for terrestial PAs
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Both the economics and conservationscience literatures consider MPA decisions and MPA impact, although theeconomics literature focuses on fishery economic outcome
Both the economic and conservation implications of the proposed increase needs to be reviewed and considered to inform further implementation.
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www.youtube.com www.youtube.com
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odpowiedź A różni się od B tym, że jedna jest iloczynem a druga sumą.
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localhost:8001 localhost:8001
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at that starts to look like is as we're talking today, we're on their story. So being able to create podcast quality, audio, and video, pull in questions, take time coded notes, bookmark key moments, also record asynchronously as well to record at scale. And being able to even upload existing content that you can use our, industry leading AI transcription for powered by OpenAI. As well as starting to actually edit audio and video as easily as you can edit t
Anotation
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rachelridenour.weebly.com rachelridenour.weebly.com
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Youth Villages
de-identify the fieldwork site throughout the APDE. This is another great piece of evidence for the prompt!
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substitution from
substitute for
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At Youth Villages,
De-identify the site.
This is an excellent example of advocacy for our profession and for this student. Great!
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social-media-ethics-automation.github.io social-media-ethics-automation.github.io
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Greg Miller. Researchers are tracking another pandemic, too—of coronavirus misinformation. Science, March 2020. URL: https://www.science.org/content/article/researchers-are-tracking-another-epidemic-too-misinformation (visited on 2023-12-05).
This article describes sociologist Emma Spiro and crisis informatics researcher Kate Starbird's study of misinformation during the COVID-19 pandemic. The researchers reflect on their analysis of how misinformation spreads and its impact on public understanding. They express concerns about how misinformation may lead to mixed messages from government officials, potentially eroding people's trust in scientific expertise. They further conclude by emphasizing the importance of being careful with platforms for information sharing and give recommendations for how individuals should critically evaluate information sources.
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Catherine Stinson. The Dark Past of Algorithms That Associate Appearance and Criminality. American Scientist, January 2021. URL: https://www.americanscientist.org/article/the-dark-past-of-algorithms-that-associate-appearance-and-criminality (visited on 2023-12-05).
Stinson’s article 'The Dark Past of Algorithms That Associate Appearance and Criminality' raises critical ethical questions that resonate deeply with my personal concerns about the direction of AI research and application. It's disconcerting to think about how historical biases can be embedded into modern technology, potentially affecting the lives of many under the guise of objectivity. Her discussion on the implications of such algorithms provides a sobering reminder that 'neutral' technology can perpetuate social injustices.
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Web tracking. October 2023. Page Version ID: 1181294364. URL: https://en.wikipedia.org/w/index.php?title=Web_tracking&oldid=1181294364 (visited on 2023-12-05).
I think when it comes to law enforcement I would think it's ok to track because they use it to prevent crimes and such things. But as far as companies they might use it for preference and ads but I think most users don't know they are being tracked so they should take steps further to consent and protect privacy.
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Why can't I use Artificial Intelligence tools to generate answers?
I read a piece from StackOverflow's help center about why using artificial intelligence to generate answers is not allowed. The site explains, "Users who ask questions on Stack Overflow expect to receive an answer authored and vetted by a human." It expresses how large language models often mess up and do not provide the facts or fabricate over the truth through excessive explanation. People who visit this site are seeking the expertise from real human beings. It is interesting how people have started to rely on AI and large language models when we've only started seeing the effects it has on communication, education, etc. I am interested to see where it goes in the future and what consequences come from it. Will we all rely on it at some point or will it gradually disappear if it cannot advance further?
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Kurt Wagner. This is how Facebook collects data on you even if you don’t have an account. Vox, April 2018. URL: https://www.vox.com/2018/4/20/17254312/facebook-shadow-profiles-data-collection-non-users-mark-zuckerberg (visited on 2023-12-05).
The article discusses how Facebook collects data from individuals who do not have a Facebook account and the limitations that prevent such data collection. The article explains that Facebook collects information from non-users' browsing histories on websites with Facebook plugins, as well as from contact lists uploaded by users. The term "shadow profiles" is mentioned to describe profiles created from this collected data, but Facebook denies actively creating such profiles. However, Facebook does not offer non-users the option to opt out of data collection, and while it will delete browsing data from non-users after a short period of time, contact information may remain indefinitely unless the uploader removes it.
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Nicole Nguyen. Here's Who Facebook Thinks You Really Are. September 2016. Section: Tech. URL: https://www.buzzfeednews.com/article/nicolenguyen/facebook-ad-preferences-pretty-accurate-tbh (visited on 2024-01-30).
In the article it mentioned that many non facebook sites use JavaScript code that tells the mothership what kind of content you're looking at when you're not on Facebook's site and apps. Even if done legally, that doesn't make it the most ethical choice. I think there are better and more ethical ways to understand the target market of your audience. I think this is smart to engage and understand users better but it just doesn't feel right to be about in someone's own personal life when they don't know about it.
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Jordan Pearson. Your Friends’ Online Connections Can Reveal Your Sexual Orientation. Vice, September 2014. URL: https://www.vice.com/en/article/gvydky/your-friends-online-connections-can-reveal-your-sexual-orientation (visited on 2023-12-05).
Sometimes information like sexual orientation shouln't be reviewed and published on internet, there sould be some way to prevent such incident from happening that the website can do.
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Web tracking. October 2023. Page Version ID: 1181294364. URL: https://en.wikipedia.org/w/index.php?title=Web_tracking&oldid=1181294364 (visited on 2023-12-05).
Web tracing is horrifying. It can get the informaiton of people who surfing the internet and then trace back to find all the information needed to get the person's address and etc. There should be law enforcement to provent such condition.
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social-media-ethics-automation.github.io social-media-ethics-automation.github.io
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8.7.2. Intentional Data Poisoning
Another example of intentional data poisoning occurred with Google's Image Recognition in 2015. It got attention for mistakenly labeling two African American people as "gorillas." Although technically not intentional, the incident highlights the algorithm's lack of development in diversity knowledge. This means it was not trained with data or taught about diverse cultures and ethnicities, leading to its inaccurate classification, which some people referred to as "racist."
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rachelridenour.weebly.com rachelridenour.weebly.com
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theory regarding the therapeutic use of occupation and adaptation
You need to address this part of the prompt. Give an example of a theory or FOR you used with a client. (PEO, NDT, OA, CBT, etc.) " I used PEO in this setting because''''''
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varies
vary
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maintenance
consider changing this word. It literally means staying the same. I think you could use interventions or task-training
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social-media-ethics-automation.github.io social-media-ethics-automation.github.io
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If you send “private” messages on a work system, your boss might be able to read them [i19].
I recently learned about this a couple of months ago when I started doing graphic design work for my job. When dealing with sensitivity information or any information retaining to the company, the device that obtains that information is now an asset of the company. I was aware of this and asked my boss if he could order me an SSD drive for me to store whatever assets they want me to use onto that SSD drive. Most employees are unaware of certain privacy rules and knowing them can save you from trouble. In a workspace, you may be utilizing different tools such as excel, word, etc. and always assume that your personal information is not safe is always a good rule of thumb.
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en.wikipedia.org en.wikipedia.org
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His main works, which appeared late in 1940 and 1944, are the aforementioned Vom Mythos zum Logos, die Selbstentfaltung des griechischen Denkens von Homer bis auf die Sophistik und Sokrates and Griechische Geistesgeschichte von Homer bis Lukian in ihrer Entfaltung vom mythischen zum rationalen Denken dargestellt, are the result of his Greek studies conducted over several decades.
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Wilhelm Nestle (.mw-parser-output .IPA-label-small{font-size:85%}.mw-parser-output .references .IPA-label-small,.mw-parser-output .infobox .IPA-label-small,.mw-parser-output .navbox .IPA-label-small{font-size:100%}German: [ˈnɛstlə]; 16 April 1865, Stuttgart, Kingdom of Württemberg – 18 April 1959, Stuttgart) was a German philologist and philosopher.[1]
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Vom Mythos zum Logos. Die des griechischen Denkens Selbstentfaltung von Homer bis auf die Sophistik und Sokrates. (From Mythos to Logos: The Self-development of Greek Thought from Homer to the Sophistics and Socrates.) 1940. 2nd edition. 1942. Reprint. 1975, 1986.
see English translation: "From Mythos to Logos: The Self-development of Greek Thought from Homer to the Sophistics and Socrates"
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localhost:8001 localhost:8001
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picture flag
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localhost:8001 localhost:8001
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S PROJECT
asdbalkdjv ala skdfjaslfjasdlkfjs alk
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social-media-ethics-automation.github.io social-media-ethics-automation.github.io
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Social Media platforms use the data they collect on users and infer about users to increase their power and increase their profits.
I agree with this statement and feel deeply concerned. When we use most social media platforms, they usually select user preference content for us when registering an account in order to push content to users that they are more interested in. And this is actually a way to obtain information and find ways to attract the user's attention. Moreover, as we use the software, we are also using different algorithms to infer how our interests have changed. At the same time, we may also cooperate with shopping software to directly push the items of interest we just mentioned in the video or forum social media so that we can purchase them. I think it’s a bit scary how much big data knows about us.
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scalar.lafayette.edu scalar.lafayette.edu
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Sed odio morbi quis
Write an appropriate citation using your classes preferred citation style for citing websites.
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www.derstandard.at www.derstandard.at
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social-media-ethics-automation.github.io social-media-ethics-automation.github.io
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What was accurate, inaccurate, or surprising about your ad profile?
Before checking my ad settings I assumed it would be a little more accurate but it wasn't as accurate to my interests.
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What was accurate, inaccurate, or surprising about your ad profile? How comfortable are you with Google knowing (whether correctly or not) those things about you?
My profile was pretty accurate aside from a few things like relationship status and household income. It is strange to see what Google thinks of me - it feels like it knows me on such a personal level. My ad topics were accurate - food, books and literature, skincare and makeup. I honestly wasn't aware I could access the data that Google has about me. I am uncomfortable knowing that they hold all this information, but I would rather have ads that are catered to me than weird things I am not interested in. I am curious about what the consequences of this will be in the future - are we already seeing the consequences? How will ads look in the future when they are even further hyper-curated to the consumer?
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static1.squarespace.com static1.squarespace.com
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prohibition of marriage contributed to the ra-cialized construction of Black women as perpetually sexually available andthereby rendered them more vulnerable to sexual violence and abuse inways that were foundational to the reproductive economy of slavery.
In a way, marriage seems to be protective of a woman's autonomy and sexual well-being. It's interesting to think about how even though marriage protected black women in the economy of slavery, marriage in itself can be seen as a sort of oppression even after one became a "freedman," as the head of household was still a man. It appears that during that time, a woman is never truly free and safe whether they are married or not. I do think it's quite interesting to see how marriage played such a large role in recognizing people as equal, and how that may have extended to gay marriage in more recent times.
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movie.douban.com movie.douban.com
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实际上，苍鹭就是真人的谎言化身，也是真人相对肮脏或者自惭形秽的阴暗面，我们会发现，真人对苍鹭了如指掌，他的厌恶实际是对自己的厌恶，而苍鹭也对真人了如指掌，从最开始就帮真人撒谎，帮他说出隐瞒了一半的内心渴望。
与豆瓣网友 周天蓝 在隔壁影评《宫崎骏用自己的经历，回答人生的命题》下的 讨论 思路接近。
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首先从电影的结构说起，电影实际是镜子式的结构，分成现实世界和异世界两部分，彼此之间接近于一一对应的关系。
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创作中包含着潜意识主导的因素，组成作品的任何要素，一定需要先过一道关，即是：作者以直觉来判断是否恰当。此外，当然也有技巧成分，如果有些地方过于明确，老道的作者会加入暧昧的部分，隐藏自己的意图，令作品更加微妙。每个作者在追求准确和暧昧之间，都会有自己的平衡点。
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Ugly, sad looking hamster thing. Blurry and very sad. Hamster with crunched up face crying.
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Depressing blue aesthetic
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Its a very sad and depressing ass image that I saved when I was literally feeling blue. Its very angsty and has that retro aesthetic that is very niche in today's standard of what some would consider to be nice. It's supposed to be about heartbreak because of the rose on fire, the "I miss you"s "I need you"s and "fuck you"s, Very depressing image.
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www.americanyawp.com www.americanyawp.com
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President Lyndon Johnson appointed an 11-person commission, chaired by Illinois Governor Otto Kerner, to explain the origins of the riots and recommend policies to prevent them in the future.
President Lyndon Johnson appointed the National Advisory commission on civil disorders, chaired by illinois governor otto kerner to investigate the riots.
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In 1967, devastating riots, particularly in Detroit, Michigan, and Newark, New Jersey, captivated national television audiences.
American cities experienced severe racial riots, particularly in Detroit Michigan, and Newark, New Jersey.
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bewilderment
Meaning the quality or state of being lost perplexed or confused
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polarization
Meaning the act of dividing something that contains different people or opinions into two different groups.
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Violence cannot build a better society.
I agree with this statement violence cannot build a better society, violence and aggression often lead to more conflict, suffering etc. rather than settle the solution. A better society is built through peaceful respected human rights.
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Local file Local file
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‘Ah who sey Sammy dead’ had been playing in my head —by now our signature tune — and a loud clear accentedvoice said with measured pace, “Thank you for helpingBen.” That was all. She was gone. Just that. I had no senseof loss or regret; I felt instead a connection that was here tostay and knew that whatever I was to get from her of her orof anything else, would come ‘in the fulness of time’ andthat there was no point in cither of us trying to force thepace.
"When Spirits Talk" p. 100
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dgt.gob.gt dgt.gob.gt
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clases:
Cuantas libras puede transportar cada pasajero
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fastly.4sqi.net fastly.4sqi.net
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- Pancakes
- sausage
- eggs.
- French toast
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bacon
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Dry
- tasty
- Overcooked.
- Well cooked
- Ordinary
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www.etymonline.com www.etymonline.com
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literally "a jumping together,"
inspired to conspire
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movie.douban.com movie.douban.com
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「以为自己很讨厌的继母，内心实则很惦念。」，相处久的恋人之间也会因为从对方的反馈里看到了自己的不完美而讨厌对方，其实是不能接受现实世界里不完美的自己，而对恋人的讨厌其实反而说明仍爱着对方。 希望每个因此而讨厌着恋人的人都能在想分手前看到这条评论。
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URL
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movie.douban.com movie.douban.com
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刚看了电影，我对它的理解和博主大致相同：这是宫崎骏作为战后一代人对日本人这一身份的历史性反思。我想补充几点博主没提到的，还有我几点我不太认同博主的分析的。 首先，全片的故事的时间上的起点是作为塔的根基的黑色巨石在明治维新前几十年从天而降，把原地的池塘完全摧毁。联系到这个巨石最终赋予了建于其上的塔「连通世界」的能力，我们不难推论出巨石所代表的，就是黑船来航以及随之而来，西方意识形态和经济制度在日本的入侵。 巨石降落之后，下一个重要的时间节点是真人的叔公（舅爷？）在二三十年之后在巨石周边建立了这座塔。叔公一直都对这座塔分外着迷，而他在修建这座塔的时候也付出了许多生命的代价。如果我们认为这座巨石所代表的是日本国内的西方影响，那么如博主所说，叔公这个人明显就象征着诸如福泽谕吉，西乡隆盛，伊藤博文等明治维新的志士。他们拥抱了西方代表的近代化，以血与火的代价建立了一个幕府之后的新日本，一个在他们眼中充满希望的，可以与西方国家所比肩的华丽高塔：日本帝国。 在这个基础之上，叔公的下一代，也就是真人的两个母亲，也自然应该被理解为叔公的下一代日本人，也就是主导了日本军国主义化最终引向战争的大正一代人。这里我与博主的理解有所不同：火美和夏子都应该被理解为大正一代的日本人。她们的不同点在于火美所代表的是积极西化的所谓「进步」的大正日本城市精英阶层，而夏子所代表的是更加拥护日本传统文化的保守主义的大正日本农村阶层。这一点可以从她们二人的生活方式的不同中看出：现实世界中，火美（真人的妈妈）住在大城市东京，而夏子住在农村；塔中世界的火美穿着西式连衣裙（我不觉得这是魔女服，就是连衣裙而已），而夏子除了最后一幕之外一直都是穿着和服（最后一幕这个例外很重要，一会儿再说）；火美给真人的食物是吐司，而夏子一开始给真人端来的是更为传统的茶。 这种分析对理解真人的两个母亲的行为，境遇，以及他与他两个母亲的关系，是非常重要的。首先，火美为什么能够掌控火焰，而又为什么最终命丧火海？正如博主所说，火焰，代表着现代战争的暴力；它是从枪口，炮口，还有炸弹的弹壳中喷涌的毁灭性力量。火美作为西化派的大正一代人掌握了这种力量，并用这种力量保护着下一代的日本（warawara）不受西方列强（鹈鹕）的吞食。然而战争永远都会有牺牲；战争的火焰平等地消灭着每一个人，然而作为日本的守护者的大正精英阶层的火美，却只将被烧焦的 warawara 看作保卫国家的必要的牺牲，而对真人的呐喊无动于衷。（无责任推测：我感觉火美大战鹈鹕的那一段就是在隐喻日俄战争）掌握暴力，愿意运用暴力的大正精英阶层是日本战争罪行的直接责任者；他们也是受到战争冲击最大的人。于是，在现实世界中，真人的母亲，以及她所代表的旧日本精英及其意识形态，最终也在比自己更强大的火焰中毁灭。 影片中夏子有着一个典型的居家大和抚子形象，并且在登场时怀有身孕。夏子的性格是她作为保守日本人代表的理所当然的结果。她的肚子里孕育着的是在战后的保守主义农村阶层的后代。保守派的大正日本人从意识形态上不支持战争；他们更倾向于把自己看作是日本战争罪行的受牵连一方甚至是受害者。因此，夏子在对真人悉心照顾和关心之余，也有着对他作为战争直接责任人的后代的厌恶和排斥。相对的，真人作为从小穿西式服装，吃果酱面包长大的日本城市精英的下一代，他在故事一开始所怀念的也是自己的生母，而把夏子只当成是「父亲喜欢的人」。宫崎骏让他们在故事中从互相排斥到相互认可和相互扶持，所代表的正是老爷子对于日本社会各方互相理解，正视共同的历史，共同创造一个新日本的美好期待。 说完了真人的两个母亲，我们再回到叔公。他在真子走入塔中时已经垂垂老矣，而他所创造的塔中世界也已经被鹦鹉墨索里尼和他的法西斯党人占据，并且随时都有结构性倒塌的危机。然而，塔中世界毕竟是叔公所创造出来的；塔中世界的所有东西，包括鹈鹕和鹦鹉，都是他自己带进来的。鹦鹉和鹈鹕都是当时西方现代性的一部分，没有它们就不会有明治志士所期待的旧日本帝国。然而鹦鹉最终法西斯化，并试图占据和控制整个塔中世界，也是旧日本帝国发展内部逻辑的必然。叔公让真子进入塔中的目的，是让他接替自己，继续延续他所一手创造的旧帝国体制。真子拒绝了，因为他认为叔公的积木是用不洁的石块堆砌的；叔公也认同这一点。然而即使当叔公从世界的角落找来了洁净的木头，真子也还是拒绝了叔公的委托，坚决要会到现实世界。这一分歧说明了叔公和真子对旧日本帝国军国主义化，并最终失败的原因有着截然不同的理解：叔公认为失败的原因只是因为用了不洁的石块，而只要我们换上洁净的木块，我们就可以在不改变搭积木这一体制的前提下延续日本帝国。而真子认为我们在重新搭积木之前需要先更加严肃地面对现实。说得明确一点，叔公认为旧日本帝国的失败不是体制的问题，是人的问题；而真子认为事情没那么简单。当然，到最后，鹦鹉墨索里尼重新摆积木的尝试导致了一切的崩塌。 说句题外话：鹦鹉墨索里尼严格看守着怀孕的夏子，其目的是获取和控制夏子的孩子（日本的下一代），维持法西斯主义在这个国家的存在。这和叔公想要引真子前来的目的在维持旧帝国体制这一层面上是一样的。在这一层面上，他们都是帝国主义者，而与真子不同。 影片最后，真子回到现实世界，手里拿着 Kiriko 的玩具和一个砖块。博主说这个砖块是搭建新世界的木砖；我认为这是不洁净的石砖。因为叔公说洁净的木头只有他手上的十一块，而真子说他的砖是在最后在地上捡来的。联系到真子最后一次上岛给到他脚下的石砖的镜头，我认为他的砖就是不洁净的石砖。真子最后拿的是石砖而不是木砖是一个非常重要的细节：他象征着真子对业已崩塌的旧日本帝国的罪恶的记忆。诚然，一个真诚的人在面对自己国家和民族的不堪过往时，如果不能辩证地进行理解，不能在恶中找到美丽的种子，那么他将无法创造本民族的未来，将无法作为该民族的一份子继续生存。但是，真子手握砖块这一细节也表达了真子承认和试图背负本民族过去的恶行的意向。面对过去恶的勇气，同样是真诚的生活的必要条件。苍鹭对此的评论是也许真子过不久就忘了吧。这一略带犬儒气质的发言正是当代日本社会所面临的令人可叹的现状。
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nieonline.com nieonline.com
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The Fugitive Slave Clause,Article 4, Section 2, required allstates to return escaped slaves totheir owners
Q1. I know that there was the underground railroad and others who defied this law, however I wonder if there were people who defied the law not by helping but just by not reporting people to the police.
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On August 28, 1955, Emmett LouisTill, a 14-year old African-Americanboy, was murdered in Mississippi afterreportedly flirting with a white woman.Bobo, his nickname, was from Chicago,Illinois. He was visiting relatives in theMississippi Delta region
TP3. This case was extremely brutal and shows how there was still many people who wanted slavery.
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ru.wikipedia.org ru.wikipedia.org
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История России
Это история россии
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www.mitre.org www.mitre.org
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promulgation
noun
the act of making a law or decree known, or formally putting it into effect, by public declaration: Upon adoption, signing, and promulgation of these provisions in the established procedure, they acquire the power of law.
the act of publicly teaching or setting forth an idea, doctrine, etc.: The systematic study of parasites began with the promulgation of the germ theory.
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metric descriptor
Short phrase describing what the metric does and what it measures
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Similarly, a few metrics in thecatalog were defined from the cyber resiliency design principles
ST-#-#
ST: structural design principle metric first number is number of said design principle
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A few metrics in the catalog were defined from cyber resiliency techniques and approaches.These have identifiers of the form TE-AP-#
TE-AP-#
TE: technique AP: approach #: number assignment
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metric identifier
generally formatted as: OO-S#-A#-# ex. PA-S1-A2-2
OO: any one of the cyber resiliency objectives; A for Prevent/Avoid, PR for Prepare, CN for Continue, CS for Constrain, RE for Reconstitute, UN for Understand, TR for Transform, and RA for Re-Architect.
S# and A# are the sub objective and activity, respectively
The last space is to assign a number to the objective
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catalog entries include information about cyber resilient TTP's and accompanying information about them
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Local file Local file
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View
I appreciate the use of diagrams to show the joins.
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classroom.google.com classroom.google.com
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Los valores fundamentales de la ciencia abierta ...
Esta parte me pareció interesante, como explica cada uno de los valores y principios que son necesarios para la ciencia abierta
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la ciencia abierta se define como un constructo inclusivo que combina diversos movimientos y prácticas con el fin de que los conocimientos científicos multilingües estén abiertamente disponibles y sean accesibles para todos ...
La ciencia abierta promueve el acceso a la información en cualquiera de sus ramas
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social-media-ethics-automation.github.io social-media-ethics-automation.github.io
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Online advertisers can see what pages their ads are being requested on, and track users [h1] across those sites. So, if an advertiser sees their ad is being displayed on an Amazon page for shoes, then the advertiser can start showing shoe ads to that same user when they go to another website. Additionally, social media might collect information about non-users, such as when a user posts a picture of themselves with a friend who doesn’t have an account, or a user shares their phone contact list with a social media site, some of whom don’t have accounts (Facebook does this [h2]). Social media platforms then use “data mining” to search through all this data to try to learn more about their users, find patterns of behavior, and in the end, make more money.
These paragraphs highlight key aspects of digital advertising and data privacy issues. Advertisers track users' browsing activities, such as browsing footwear ads on Amazon.com, in order to tailor ads to other websites. This tracking also extends to social media platforms, which may even collect information from non-users through shared content or contact lists
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Online advertisers can see what pages their ads are being requested on, and track users [h1] across those sites. So, if an advertiser sees their ad is being displayed on an Amazon page for shoes, then the advertiser can start showing shoe ads to that same user when they go to another website. Additionally, social media might collect information about non-users, such as when a user posts a picture of themselves with a friend who doesn’t have an account, or a user shares their phone contact list with a social media site, some of whom don’t have accounts (Facebook does this [h2]). Social media platforms then use “data mining” to search through all this data to try to learn more about their users, find patterns of behavior, and in the end, make more money.
These paragraphs highlight key aspects of digital advertising and data privacy issues. Advertisers track users' browsing activities, such as browsing footwear ads on Amazon.com, in order to tailor ads to other websites. This tracking also extends to social media platforms, which may even collect information from non-users through shared content or contact lists
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So, if an advertiser sees their ad is being displayed on an Amazon page for shoes, then the advertiser can start showing shoe ads to that same user when they go to another website.
The chapter's discussion on advertisers tracking user behavior across websites using ad displays, like on Amazon for shoes, brings up mixed feelings. While I understand the commercial value and efficiency this provides in marketing, it also raises concerns about privacy. It makes me question where the line should be drawn between effective marketing and respecting user privacy.
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Platforms also collect information on how users interact with the site. They might collect information like (they don’t necessarily collect all this, but they might): when users are logged on and logged off who users interact with What users click on what posts users pause over where users are located what users send in direct messages to each other
Sometimes those collection of information may eventually lead to a leak of personal information. There are potential hacker attackt to seek for those information. It wouldd be important for the protection of personal information and there might be some defensive protections needed for the website
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smu.instructure.com smu.instructure.com
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Even the ice cubes shy away from her. This can be interpreted as a message of fear, caution, or discomfort with something new or rare. Leads to everyone shifting in their seats again establishing either discomfort or fascination in observance.(lines 16-20)
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Lolo seems to have a mysterious and powerful presence (throughout poem, specifically lines 10-16)
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Constantly not finishing the sentence on the line or even the stanza that it began. Lends to focus on the last word. (lines 2,6,10,etc.)
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Contradicting ideas (rare, unique; yet unwanted (lines 1-2)
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Following the contradicting theme, lines 2-4 establish a sense of avoidance in the presence of intrigue.
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queue.acm.org queue.acm.org
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the 31,085 lines of configure for libtool still check if <sys/stat.h> and <stdlib.h> exist, even though the Unixen, which lacked them, had neither sufficient memory to execute libtool nor disks big enough for its 16-MB source code.
yummy
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the Peter Principle, the idea that in an organization where promotion is based on achievement, success, and merit, that organization's members will eventually be promoted beyond their level of ability
Applying the principle to software, you will find that you need three different versions of the make program, a macroprocessor, an assembler, and many other interesting packages. At the bottom of the food chain, so to speak, is libtool, which tries to hide the fact that there is no standardized way to build a shared library in Unix. Instead of standardizing how to do that across all Unixen the Peter Principle was applied and made it libtool's job instead.
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graphics/libtiff is one of the 122 packages on the road to www/firefox, yet the resulting Firefox browser does not render TIFF images. For reasons I have not tried to uncover, 10 of the 122 packages need Perl and seven need Python; one of them, devel/glib20, needs both languages for reasons I cannot even imagine.
Dependency hell
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ipese-web.epfl.ch ipese-web.epfl.ch
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The existing hydrogen network assumed in the Blueprint refinery model
examples
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www.simplypsychology.org www.simplypsychology.org
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Attachment theory hypothesizes that early caregiver relationships establish social–emotional developmental foundations
It's crazy how the roots of almost every problem of ours can be found in how we were treat as children.
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erj.ersjournals.com erj.ersjournals.com
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TipoDocumento: Articulo.
EtapaEstudio: Interpretacion.
PruebasRelacionadas: Spirometry, DLCO, TLC.
EcuacionInterpretacion: GLI.
PatronFuncional: Obstruction, PossibleRestriction, PossibleMixedDisorder, NormalMechanics, PositiveBronchodilatorResponse, NegativeBronchodilatorResponse, SimpleRestriction, ComplexRestriction, MixedDisorder, NormalLungVolumes, Hyperinflation, LargeLungs, IncreasedBloodFlow, PulmonaryVascularAbnormality, LocalisedLossLungVolume, LossAlveolarCapilaryStructureAndVolume, NormalDiffusion.
Enfermedad: Asthma, COPD, ILD, NeuromuscularDisease, ChestWallDisorder, Bronchitis, Emphysema, PulmonaryVasculitis, PulmonaryEmbolism, PulmonaryHypertension, AlveolarHaemorrhage.
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adam-mdmph.quarto.pub adam-mdmph.quarto.pub
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National Institute of Health Stroke Scale
- TIA : focal deficit without acute infarction
- SINGLE TIA : <24 hr , complete resolution of deficit
- crescendo TIA : multiple episodes within or over 24 hr with complete resolution of deficit bw episodes.
- stroke in evolution : progression of symptoms over days with no return to baseline.
- minor stroke : deficit last > 24 hr and recovered without residual impairment.
- major non-disabling stroke : deficit last > 24 hr with residual impairment.
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k20center.ou.edu k20center.ou.edu
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value beyond the classroom
RWC
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apply their learning in meaningful ways
RWC
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student’s own curiosity
IBL
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independent learners
SCL
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student’s role in constructing their own knowledge
SCL
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learning
Whatever this word is, it seems important
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LEICA Microtome SM2000R w/ BFS-30MP Controller
Currently being researched by April
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‘elemental affect’ [51] – a representationalsignature that signals to downstream information processing systems that the incoming perceptualstimulus is somehow distinct from other stimuli, and therefore worthy of further attention.
getting into infovore stuff... but not minimiing chaos
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Modern perceptual machines are in fact notoriously limited in terms of abstraction
Russian psycologist's Mnemoist
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features most predictive of affect are the deepest features
the same for semantic content?
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object and scene recognition
are there separate models for measuring the affective character of objects and scenes (excluding semantics) that already exist (LLMs) and can be used to generate affective predictions?
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arousal
?
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evolve.reconstructingjudaism.org evolve.reconstructingjudaism.org
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study, arts and music, social justice, spirituality, services and more.
feels like TBH
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bloclibrary.dev bloclibrary.dev
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pure function
在编程中，"纯函数"（Pure Function）是指满足以下两个条件的函数：
- 对于相同的输入，总是返回相同的输出。
- 不产生任何副作用。
"副作用"是指函数在计算结果之外对系统状态的任何更改，例如修改全局变量，修改输入参数，进行 I/O 操作等。
在
BlocBuilder的上下文中，builder 函数应该是一个纯函数，这意味着它应该只根据其输入（即 BLoC 的状态）来返回一个新的 widget，而不应该有任何副作用。这样可以确保每次状态改变时，UI 都能可预测地更新。
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bloclibrary.dev bloclibrary.dev
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buffer, debounceTime, throttle
buffer,debounceTime和throttle都是 RxJS 中的操作符，它们在 Flutter 的 BLoC（Business Logic Component）模式中也可以使用，因为 BLoC 模式使用了流（Stream）来处理数据。-
buffer：buffer是一个操作符，它将源 Observable 的值收集到一个数组中，然后发出这个数组，而不是逐个发出值。当它接收到另一个 Observable 发出的信号时，它会发出当前的数组，并开始收集下一个。 -
debounceTime：debounceTime是一个操作符，它会在源 Observable 发出值后等待一段时间（由你设定），如果在这段时间内源 Observable 没有发出新的值，那么它就会发出最后一个值。如果在这段时间内源 Observable 发出了新的值，那么它就会忽略前一个值，重新开始等待。 -
throttle：throttle是一个操作符，它会在源 Observable 发出值后立即发出这个值，然后在一段时间内忽略源 Observable 的其他值。这段时间可以是固定的，也可以由另一个 Observable 的发出值来决定。
这些操作符在处理复杂的异步操作时非常有用，例如在用户输入时进行自动完成或限制 API 请求的频率等。
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The above Transition gives us all the information we need to understand why the state changed. If we had used a Cubit to manage the AuthenticationState, our logs would look like:
Bloc相对于Cubit的优点在于可以跟踪状态的改变是由那些事件引起的
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One of the biggest advantages of using Cubit is simplicity. When creating a Cubit, we only have to define the state as well as the functions which we want to expose to change the state. In comparison, when creating a Bloc, we have to define the states, events, and the EventHandler implementation. This makes Cubit easier to understand and there is less code involved.
Cubit和Bloc的区别：
Cubit只需要定义state和能改变state的function
Bloc要定义state,event和event handler
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Blocs should never directly emit new states. Instead every state change must be output in response to an incoming event within an EventHandler.
不应当直接使用emit更新状态，（应当在EventHandler中使用）
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www.computer.org www.computer.org
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Mathematical software providers would have preferred to standardize high-level language facilities, but there was no chance of getting language standards interested until there were some hardware implementations and some compilers and libraries proving the concepts.
Order of operations
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inst-fs-iad-prod.inscloudgate.net inst-fs-iad-prod.inscloudgate.net
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; the traveler must pass down village streets, between the houses with yellow- litwindows, and on out into the darkness of the fields
Great imagery
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movie.douban.com movie.douban.com
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如果世界无法完全为人所掌握和理解，那人类该如何与它相处？在影片故事接近尾声时，真人见到了传说中消失在神秘之塔里的叔公——他竟然是维护地下世界秩序的管理者。叔公希望有血缘关系的真人能够接替他的职责来管理即将失去平衡而面临崩塌的地下世界，代价是真人需要孤独地留下、再也不能回到家人身边。摆在真人面前的是一个关系到家人命运与世界未来的抉择。影片高潮给真人抛去的难题映射了标题本身：你想活出怎样的人生？——都是疑问句和选择题。但宫崎骏在真人的“选择”上的处理又是反高潮的。一方面，真人在犹豫中拒绝了叔公的请求，不愿承担管理地下世界秩序的职责——这让人联想起以新海诚为首的世界系导演们的做法，为了个体的情感而放弃宏大叙事的维续。但另一方面，宫崎骏没有给真人和叔公过多的拉扯时间，而是让急切想要维护世界秩序的鹦鹉大王——一个很明显影射法西斯领袖的形象——插入了两人的对话。鹦鹉大王试图搭起能够维持地下世界平衡的积木，但最终却加速了世界崩坏。这也让真人的“选择”变得似乎无关紧要。真人的「无效选择」与鹦鹉大王的「帮倒忙」是一种对英雄主义叙事的极致倾覆，也完美表达了宫崎骏的政治倾向。如果联系起影片描绘的节点，即二战即将结束的 1944 年，地下世界面临的崩塌似乎也映射着地上世界的风云变幻：一个旧的世界体系（帝国主义法西斯）将被新的世界体系（资本主义民主）所取代。而拼命挣扎着维护旧秩序的鹦鹉大王最终只能加速它的灭亡，这是历史告诉过我们的。但或许更具有批判性的部分在于，类似鹦鹉大王式的「秩序维护者」会持续在历史上出现并对世界造成更巨大的破坏。世界秩序的更换并不意味着人类自以为是地为世界带去秩序的做法发生了根本改变。 虽然真人的选择从客观上来看似乎是徒劳的，但他确实坚实地做出了自己的选择——即放弃做世界的主人。让这个少年做出如此有勇气的回答的，无疑是他一路以来遇到的人、生物、以及物体（如神石）。通过与这些“他者”的交互，真人不仅明白了同一件事从不同的视角看来有着不同的含义（如鹈鹕需要吃哇啦哇啦来进行存续）、也清楚世界的时空（地下世界存在着去往不同时空结点的门）并非线性而是一片互相交缠的根茎。从这个角度来看，真人的确作出了选择——是他的一口拒绝让鹦鹉大王失去了理智与耐心从而毁灭了地下世界。但真人作出的更深层的选择是他改变了一直以来人类中心式的与世界交互的逻辑——他不再愿意作为个体去营造一个单一稳定的世界的幻像，而是通过放弃而去尊重世间万物的存在与沟通方式。然而，与经典世界系叙事「自我中心的放弃」所不同的是，真人的选择归根结底只能间接影响他者的选择，而非直接决定世界存续本身。换句话说，在《你想活出怎样的人生》的结尾，宫崎骏在消解了个体选择对于人和世界存在本身的「决定性意义」的同时，又点出了个体选择对于帮助朋友、改变身边环境以至于世界存在方式的「有限但巨大的影响」。从这个角度来看，《你想活出怎样的人生》似乎以一种生态学的视点重新定义了主体的能动性。
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www.ebay.com www.ebay.com
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Thermo Scientific Shandon Cryotome FSE
Currently being researched by April
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful manuscript challenges the utility of current paradigms for estimating brain-age with magnetic resonance imaging measures, but presents inadequate evidence to support the suggestion that an alternative approach focused on predicting cognition is better. The paper would benefit from a clearer explication of the methods and a more critical evaluation of the conceptual basis of the different models. This work will be of interest to researchers working on brain-age and related models.
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nova nova
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sendinimą su autoresetter
nueit i COMP >> 98proc padaryt
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www.goodreads.com www.goodreads.com
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Technics and civilization as a whole are the result of human choices and aptitudes and strivings….The machine itself makes no demands and holds out no promises: it is the human spirit that makes demands and keeps promises. In order to reconquer the machine and subdue it to human purposes, one must first understand it and assimilate it. So far, we have embraced the machine without fully understanding it, or, like the weaker romantics, we have rejected the machine without first seeing how much of it we could intelligently assimilate.” ― Lewis Mumford, Technics and Civilization
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kelsienabben.substack.com kelsienabben.substack.com
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The “DAO Model Law” guide by COALA researchers outlines 11 technical and governance requirements for DAOs to meet the requirements for legal recognition as an entity, including:1. Deployed on a blockchain,2. Provide a unique public address for others to review its operations,3. Open source software code,4. Get code audited,5. Have at least one interface for laypeople to read critical information on DAO smart contracts and tokens,6. Have by-laws that are comprehensible to lay people,7. Have governance that is technically decentralized (i.e. not controlled by a single party),8. Have at least one member at any given time,9. Have a specific way for people to contact the DAO,10. Have a binding internal dispute resolution mechanism for participants,11. Have an external dispute resolution mechanism to resolve disputes with third-parties (e.g. service providers).These factors and considerations constitute a legal basis for conceptualizing DAOs.
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Some obvious but useful DAO design or analysis questions are:1. What is being decentralized? (technically, economically, or politically),2. Who or what is being made autonomous, and from who or what?3. What is being automated?4. What is being organized?From here, subjective goals, beliefs and values can be articulated to determine design choices.
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journalistsresource.org journalistsresource.org
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Last month, The New York Times published an online test inviting readers to look at 10 images and try to identify which were real and which were generated by AI, demonstrating first-hand the difficulty of differentiating between real and AI-generated images.
(R) our class specifically did this test, and it shows the growing threat of deepfakes as a whole. We did fairly well with the test but people that don’t know what to look for our screwed. These images look like a real photo. As Ai grows more intelligent everyday who knows where this technology can go. If anybody has the tools for these photos than people’s lives can be threatened by deepfakes.
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teachbooks.tudelft.nl teachbooks.tudelft.nl
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Fig. 1.1 Fieldwork at the river Alzette, Luxemburg.
It feels a bit contextless to have this figure. Maybe better to remove this figure to 1.1 and not have figure here at all
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teachbooks.tudelft.nl teachbooks.tudelft.nl
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Aerial Photo of Mountain Under Cloudy Sky ()
replace with:
Hydrology is the study of the water cycle in diverse landscapes. Engineer hydrology deals with the quantification and management of water resources and civil engineering infrastructure such as dams and reservoirs (Photo by REFERENCE).
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Local file Local file
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However, corporate governance in the telecoms sector is notconducive to the kind of radical decisions that separationrequires. Decision makers and boards are incentivised onmetrics that require short term continuity, not disruption
So to make this argument in cloud/AI, you need to make the argument that firms are too conservative in terms of corporate structure, and as a result are missing out on greater value coming from two individually more valuable entities - something that the org or compensation structure is not set up for
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Rural broadband in Europe is increasingly deployed in aneutral host model with a single fibre networkconnecting homes and multiple service providersdelivering services over that network.
This is like the unbundled approach already then
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as pure infrastructure players borrow atlower rates and expect lower returns, they will deployinfrastructure where vertically integrated players won’t,and with no (or less) public subsidies;
Infra with more patient capital isn't chasing such high risk returns like getting everyone to buy into AI
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We have one leading example of voluntary structural separationresulting in increased valuation of the separated entities -Telecom NZ, in 2011. Post de-merger, after years of flat marketvaluation, both Chorus (infrastructure) and Spark (services) sawshare prices rise. Between 2015 and 2023, the combined market1 Tower companies (or towercos) are infrastructure companies that managemobile towers for multiple mobile network operators.capitalisation of Chorus and Spark grew by 150%, whereas thatof European and US vertically integrated telcos2 grew only by15%.The plan also delivered full FTTH coverage to 87% of NewZealand homes with 72% adoption.
So breaking them made led to greater share price raises AND better service in New Zealand
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social-media-ethics-automation.github.io social-media-ethics-automation.github.io
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If you are interested in learning more about what you can do with praw and what information you can get back, you can look at the official documentation for those. But be warned they are not organized in a friendly way for newcomers and take some getting used to to figure out what these documentation pages are talking about.
Navigating the official PRAW documentation can be quite daunting due to its complex organization, reminiscent of my early days learning programming. Community forums and blogs are essential, as they break down complex topics into more digestible parts, providing a gentler introduction to newcomers. This experience highlights the crucial role of community support in mastering new technologies.
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When we’ve been accessing Reddit through Python and the “PRAW” code library. The praw code library works by sending requests across the internet to Reddit, using what is called an “application programming interface” [h3] or API for short. APIs have a set of rules for what requests you can make, what happens when you make the request, and what information you can get back.
I am not well informed on how API works but it sounds like it has a lot of connection to the internet and other kind of information systems. Going back to the sources of social media data, one of the things that platforms could record are what users click on, when they log on or off, etc. What arises from this I think ties back in with the ethical frameworks we were talking about in chapter 2. The discussion becomes what course of action is correct because even if the platform records information on the behavior of user interaction, it boils down to the idea that even if it's to mazimize user experience, should platforms be allowed to record information that could be personal?
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www.linkedin.com www.linkedin.com
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So should we collectively accept a radical shift in our policy and regulatory framework in order to ensure that the beacon of the European economy can deploy infrastructure that Sweden, Denmark, Spain, France, and many of the smaller European countries started successfully deploying long ago? This, in a nutshell, is why the Commission never talks about Germany.
This appears to be making the argument that rather than admit Germany has underinvestment compared to the rest of the EU, it's easier to change all the entire EU telecom policy so vertically integrated telcos can make a better return.
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lhcb.github.io lhcb.github.io
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data flow designed to maximise the data-taking efficiency and data quality.
data flow 被设计的目的
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the data must be processed very quickly because it’s arriving very quickly, and the data is complex so there’s a lot that can be done with it.
过滤数据时考虑的两个关键点
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filter the data and try to keep only the events which contain something interesting
对数据进行过滤所考虑的条件
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www.wheresyoured.at www.wheresyoured.at
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The article confirms many of my suspicions — that, as The Information wrote, "other software companies that have touted generative AI as a boon to enterprises are still waiting for revenue to emerge," citing the example of professional services firm KPMG buying 47,000 subscriptions to Microsoft's co-pilot AI "at a significant discount on Copilot's $30 per seat per month sticker price." Confusingly, KPMG bought these subscriptions despite not having gauged how much value its employees actually get out of the software, but rather to "be familiar with any AI-related questions its customers might have."
This seems like spending 17 million a year to help them sell consulting about what AI.
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www.biorxiv.org www.biorxiv.org
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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.
Learn more at Review Commons
Reply to the reviewers
Reviewer #1 (Evidence, reproducibility and clarity (Required)):
Summary: In this manuscript, the authors investigated the role of Erk signaling in the transition from naïve to formative pluripotency. They found that Erk activation eliminates Nanog to allow naïve state exit. However, when Nanog is knocked down in the absence of Erk activation, ESCs exit the naïve state, and enter an indetermined state, unable to proceed to the formative state. The authors further claimed that the failure to the formative state is due to lack of Oct4 expression. In conclusion, Erk signaling is required for the exit from the naïve state and the entry to the formative state.
Major comments: - Are the key conclusions convincing? Most of the key conclusions are convincing, except for the conclusion "ERK activity is required to maintain Oct4 expression in the naïve to formative pluripotency transition". The authors showed that Oct4 expression is diminished under the MEK(i)+siNanog condition, while Oct4 is expressed in N2B27+siNeg (Figure 4C). With these experimental setting, the conclusion that ERK activity is required to maintain Oct4 expression in the naïve to formative pluripotency transition, cannot be reached, because two variations, MEK(i) and siNanog, rather than one variation MEK(i), are there. The experiment should be designed as adding MEK(i) into N2B27+siNeg at various time points, to test whether MEK(i) is able to down-regulate Oct4 expression in the naïve to formative pluripotency transition.
We appreciate this point. We have now included data (figure 4C, 4E and S5B) to address this issue. As suggested, we performed exit experiments in MEK(i) only, and found that by 36hrs, a substantial proportion of cells have lost Oct4, unlike cells in N2B27 only. Down-regulation of Oct4 is later than in cells treated with MEK(i) + siNanog because of the delayed exit from the naïve state (in which Oct4 expression is independent of ERK). These data support the proposition that ERK activity is required to maintain Oct4 expression in the formative transition. We previously tried adding MEK(i) at various points in N2B27+siNeg conditions but the lack of synchrony made results impossible to interpret. As long as some Nanog positive cells remained, cells would re-activate the naïve network in the presence of MEK(i) and therefore maintain Oct4.
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Should the authors qualify some of their claims as preliminary or speculative, or remove them altogether? No.
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Would additional experiments be essential to support the claims of the paper? Request additional experiments only where necessary for the paper as it is, and do not ask authors to open new lines of experimentation. The suggested experiment was described above.
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Are the suggested experiments realistic in terms of time and resources? It would help if you could add an estimated cost and time investment for substantial experiments. It should not cost too much in terms of funding and time.
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Are the data and the methods presented in such a way that they can be reproduced? Yes.
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Are the experiments adequately replicated and statistical analysis adequate? Statistical analysis is lacking for Figure 3E and Figure 4.
We performed statistical analyses between key comparisons and have added details to the figures and captions.
Minor comments: - Specific experimental issues that are easily addressable. No.
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Are prior studies referenced appropriately? Yes.
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Are the text and figures clear and accurate? Yes.
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Do you have suggestions that would help the authors improve the presentation of their data and conclusions? No.
Reviewer #1 (Significance (Required)):
This work characterized the role of ERK signaling in the transition between naïve and formative pluripotency. The function of ERK in ESC self-renewal and differentiation has been well recognized. Thus, this work provides new discoveries, but no conceptual advances. It should be of interest to a specialized audience in the pluripotency field, which is my expertise.
Reviewer #2 (Evidence, reproducibility and clarity (Required)):
Summary: In the present manuscript, Mulas and colleagues address the question how ERK signaling orchestrates the transition from naïve to formative pluripotency in mouse embryonic stem cells. Combining pharmacological MEK inhibition with siRNA knockdown of candidate transcription factors, they conclude that downregulation of Nanog is an immediate function of ERK signaling that underlies exit from the naïve state. Later on they show that ERK signaling has additional functions beyond downregulating Nanog that are required to make cells competent for formative pluripotency and lineage progression, such that Nanog knockdown cells enter a new indeterminate state in the absence of ERK signaling. Finally, they show that Oct4 is a central mediator of this second function of ERK signaling, since forced Oct4 expression rescues the expression of formative markers even in the presence of MEK inhibitors. They also present time-lapse imaging data of a Spry4- and a Nanog-reporter, based on which they propose that metachronous ERK activity is reflected in metachronous NANOG downregulation. The experiments dissecting the two different functions of ERK signaling in the pluripotency transition are well performed and provide some new interesting perspectives. Overall, the manuscript is well written. I have major concerns regarding the interpretation of the time-lapse imaging experiments (see major point 2 below) that unfortunately feature very prominently in the title of the manuscript.
Major points:
- In lines 174 and 175, the authors write that "acute ERK activation ... [reduces] NANOG protein, which in turn dimishes Esrrb transcription". Although I am aware that this picture is supported by previous literature (e.g. PMID: 23040477), the author's data do not fully support this conclusion. In Fig. 1G for example, Esrrb is downregulated even though Nanog expression is maintained. This discrepancy needs to be discussed.
There is no real discrepancy because we are not claiming that Nanog is the only factor that regulates Esrrb. However, we recognise the potential for confusion. We have clarified our description of the results and included the statement: “Esrrb down-regulation can occur in part independently of Erk or Nanog.”. This does not invalidate the summary conclusion that “the proximal effect of acute ERK activation on the naïve transcription factor network is to reduce Nanog protein, which in turn diminishes Esrrb transcription.”
- The imaging data and analysis presented in Fig. 2 do not support the conclusion that heterogeneous ERK dynamics underlies metachronous pluripotency exit. There are several problems with this section:
a. As far as I can see, the reporter line used in this study has not been previously used (at least there is no reference to a previous publication), and it has also not been properly validated in the present manuscript. One would for example like to know if the Spry4-FLuc allele encodes for a fusion protein, or whether it disrupts the Spry4 coding sequence. What is the half-life of the Spry4-Fluc protein? A proper description how the line has been generated, as well as an in-depth characterization are essential to evaluate the data.
We apologise for not providing full information. Both reporters have been previously published and validated. The Spry4 reporter is not a fusion protein. The Fluc is translated from an IRES. We have amended the text to include details of the construction of all the reporters, references and half-life measurements in the methods section that now reads: “Calibration cells (PGK-Nluc-Fluc - (Mandic et al., 2017) and cells carrying Spry4-Fluc transcriptional reporter (Phillips et al., 2019) and Nanog::Nluc fusion were routinely cultured in 2i/LIF as described above. The Spry4-FLuc construct contains a splice acceptor site, followed by an IRES and an Bsd/F2A/NLSluc cassette and has a half-life of 1.56hrs (Phillips et al., 2019). The Nanog:Nluc targeting construct was generating using the previously validated targeting construct for Sox2 (Strebinger et al., 2019) in which 5’ and 3’ homology arms flank a Nluc-loxP-P2A-Puro-sfGFP-loxP cassette. Integration of Nanog::Nluc was initially verified by GFP and Nluc expression, and finally by PCR following excision of the loxP cassette. Using cycloheximide treatment we determined that the reporter had a half-life of 3.02hrs.”
b. It is not clear that dynamic expression of a Spry4 reporter reflects dynamic ERK signaling. It has been shown that cumulative transcription from the Spry4 locus correlates with long-term ERK activity (e.g. PMID: 29964027), but short-term Spry4-FLuc dynamics could well be driven by other mechanisms, such as transcriptional bursting. Co-staining of ppERK and reporter expression in single cells would be required to address this issue.
This is a valid point of discussion. Comparing between reporter systems is difficult since the Spry4 reporter used in PMID: 29964027 is fluorescent protein based and is therefore dependent on the time of protein maturation (although very fast compared to other fluorescent proteins) and a half-life of 9hrs as reported by the authors. The bioluminescent reporter requires no maturation time and has a half-life of 1.65hrs (PMID: 28456689).
Below are our considerations for the choice of reporter and the interpretation of results:
- We previously showed that during exit from the naïve state, at the bulk level, pERK activity and some pERK transcriptional targets show dynamic patterns of activity (PMID: 29895711). Therefore, a dynamic pattern of Spry4 expression is not unexpected.
- We initially tested different means of measuring ERK activity more directly (ERK-KTR and EKAREV-NLS and EKAREV-NES) but the imaging frequency (
c. Why is the Spry4-FLuc signal higher at the start of the recording (when cells come out of MEK inhibition and should not have transcribed the reporter) compared to times > 7.5 h, when continuous ERK signaling in N2B27 should drive reporter expression?
After media change, we typically allowed cells to equilibrate for 30min in the incubator before setting up the imaging. Therefore, there is a ~45min window in which we lack data. From experience (Nett*, Mulas* et al 2018), we know that pERK activity increases within 5-10min after MEK(i) withdrawal and that explains why Spry4-Fluc signal is high as soon as we start the recording. We have now included this clarification in the methods (line 392).
d. What is the evidence for temporally heterogeneous ERK activation? The authors only show one single trace in Fig. 2B, in which the Spry4-FLuc signal peaks right after release from 2i, as would be expected. Another study using a more direct ERK activity sensor (PMID: 31064783) indicated that this initial ERK activity peak after release from 2i is synchronous in all cells in a population. The authors would need to show several or all Spry4-FLuc traces from their experiment to demonstrate the opposite, otherwise one needs to assume synchronous ERK activation upon release from 2i in the author's experiments as well.
Following the reviewer’s suggestion, we now provide an additional supplementary figure with all the traces (Supporting Figure 1). This demonstrates asynchrony in the response. Moreover, as per the reviewer’s suggestion, we have now included immunostainings of the first wave of pERK response (In addition, Deathridge et al. included serum in all ESC culture conditions (according to their Methods) which creates a more complex signalling environment.
e. Why does the cross-correlation of the Spry-FLuc promoter activity (which should go up upon ERK signaling) with the NANOG-NLuc signal (which should go down upon ERK signaling) give positive values? Does this positive correlation reflect the transient nature of Spry4-FLuc expression, thus giving a positive value when Spry4-FLuc promoter activity decays? In this case, what is the meaning of the delay? Overall I found the explanation of this cross-correlation analysis very confusing. Given these problems, I recommend the authors to strongly tone down their conclusions or remove this section altogether, since addressing this multitude of problems might be out of scope for the present manuscript.
Cross-correlation explicitly includes an analysis of the changes in correlation when a lag (meaning a shift in time) is applied to one of the signals. Therefore, there is no “positive correlation” but rather “positive correlation with a given lag applied”. An example is cross-correlation between a sine wave and a cosine wave (which are going in opposite directions for half the points in any given period and so show a positive correlation with a time lag). In our case, if we time shift the Spry4 signal, it will cross-correlate with the Nanog signal. It is possible we are misunderstanding the point of confusion, but we have reviewed our analysis of the data and believe it to be sound. Moreover, in our opinion the findings represent an important component of our paper and add weight to the conclusions drawn.
However, we agree that the analysis could be better explained. We have substantially re-written the section with this aim. The main text now reads:
“We examined the relationship between Spry4 activation and Nanog protein downregulation. After smoothing to remove noise, we used a simple set of ordinary differential equations to calculate the Spry4 promoter activity for each Spry4-Fluc trace (Figure S2C, see methods for details). We created continuous traces by adding the measurements made from each cell end-to-end (Figure S2D). We then measured the cross-correlation between activity of the Spry4 promoter and Nanog protein level. As controls we randomised the Spry4 signal in two ways: first, we randomised the Spry4 signals to measure correlations between Spry4 promoter activity and Nanog downregulation that could be attributable to noise; second, we assigned random time shifts to the Spry4 traces recorded (schematic diagrams shown in Figure S2D). Cross-correlation for the real data is higher than for either of the controls, meaning that the measured Spry4 and Nanog signals are correlated above noise levels and there is a consistent time delay between the two signals. We repeated the analysis for individual traces and observed the same trend (Figure S2F-G, 2D-E). The average lag time is ~80min, indicating that activation of the Spry4 promoter precedes Nanog downregulation. We repeated the analysis for RSK(i) treated cells and observed a stronger correlation at the level of the combined dataset (Figure 2F) as well as in individual cells (Figure 2G, S2H). Interestingly, RSK(i) treatment, which leads to a more sustained peak of pERK1/2 activity (Figure S2B), decreased the average delay (lag) between Spry4promoter activation and Nanog downregulation to 20 min (Figure 2H, S2I). The fact that the lag is short, and not evident in all cells, suggests that Nanog downregulation might not require transcriptional activation.”
Overall we observe a significant cross-correlation between the rise in Spry-Fluc promoter activity (indicating active ERK-signalling) and the fall in Nanog-Nluc signal.
However, we agree that this is not the most decisive result in the study and have changed the title of the paper to “Erk signalling eliminates Nanog and maintains Oct4 to drive the formative pluripotency transition”.
- In line 217 (section title), the authors write that "failure to transition is not due to genome-wide chromatin dysregulation". It is true that the changes upon MEK inhibition reported in this section are small, but there are some changes, and it is ultimately difficult to know which ones are essential. I suggest to rephrase this section title.
We have adjusted the section title.
- The main finding of Fig. 4 - that Oct4 expression enables formative capacity - is very interesting. One problem throughout this figure is that the authors contrast the control case (N2B27/DMSO + siNeg) with a double perturbation (MEKi + siNanog), making it difficult to demonstrate whether it is the loss of Nanog or the loss of ERK signaling (or both) that results in loss of Oct4 expression. If I have missed something here please clarify.
We agree with this comment (also pointed out by the other reviewer). We have now included a new figure, showing that treatment with MEK(i) alone leads to loss of Oct4 expression after naïve state exit (updated figure 4E and S5B).
- Can the authors speculate, or perhaps even experimentally explore, why Oct4 re-expression enables formative capacity? Oct4 positively regulates Fgf4 expression (PMID: 9814708), raising the possibility that the indeterminate state is caused by insufficient paracrine FGF4 signaling once cells have reached this indeterminate state. Alternatively, Oct4-mediated regulation of a broader set of lineage specifiers might be required to establish formative pluripotency. The authors could explore these possibilities by supplementing cultures with recombinant FGF ligands. While these experiments are not essential for to corroborate conclusions in the present manuscript, could allow the authors to follow up upon what I think is their most interesting finding, and thereby give the manuscript a lift.
The reviewer raises an interesting point of discussion. In our study transgene driven Oct4 expression was able to induce formative gene expression in MEK(i) conditions, which block FGF/ERK signalling (Figure 4F). Previous studies have shown that relocation of Oct4 to multiple gene loci is instrumental in the formative transition (PMID: 24905168 and PMID: 23271975) and it is known that Oct4 is an essential factor for formative stem cells (PMID: 33271069) and primed EpiSCs (PMID: 29915126).
Nonetheless we performed experiments to test whether addition of FGF could help rescue expression of formative genes after MEK(i) withdrawal (not shown). However, addition of FGF reduced neural differentiation in control cells and further reduced Sox1 expression in MEK(i)/siNanog treated cells (not shown). Moreover, we saw no significant upregulation of formative genes with addition of FGF (not shown). We decided not to include these results since the literature on the essential role of Oct4 throughout pluripotency is extensive.
Minor points: 6. Please explain in the methods how gates for identifying RGd2-positive and -negative cells in Fig. 1 B, E have been determined from the FACS plots in Fig. S1C/1B.
We have added a section in the methods to explain how this is done (Methods section “Flow Cytometry”), and we have now included a representative example in Figure S1C.
- For the categorization of marker-positive and -negative cells in immunofluorescence images, the authors should explain in more detail according to which criterion a threshold was determined by ROC analysis. Which positive and negative controls were used in each case?
We have added the information to the methods section (Immunostaining and quantification).
- Does a statistical test on the data in Fig. S1A,B reveal significant differences?
We have now performed appropriate statistical tests and have added them to both plots to show that there is indeed a significant difference.
- Please give units on the x-axis in Fig. 2C?
Amended.
- Fig. 3E: Consider re-arranging. It is not immediately clear that all five bar charts belong to this panel.
The experiments were carried out in parallel so we feel that the best way to present them is as currently shown.
- There is a typo in Fig. S4A - mainteined
Amended.
- Methods, lines 408 - 410: Please state units of the parameters used to estimate promoter activity.
Amended.
**Referee Cross-Commenting**
I agree with reviewer #1's assessment of significance and their reservation regarding the conclusion "ERK activity is required to maintain Oct4 expression in the naïve to formative pluripotency transition". The experiment that the reviewer suggests is reasonable and doable (see also my major point 4.). Even though reviewer #1 has not explicitly commented on the conclusions drawn from Fig. 2, I disagree with their assessment that these conclusions are convincing (see my major point 2.).
Reviewer #2 (Significance (Required)):
The control of pluripotency transitions by signaling mechanisms as well as transcription factor circuits have been mapped in quite some detail over the last decade. The main advance of this manuscript is that it looks at the interaction between these two levels and thereby provides some new and interesting links. These results will mainly be of interest to a large community of researchers working with pluripotent stem cells. To me, the most intriguing finding of the paper is the indeterminate cell state that the authors detect upon combined Nanog knockdown and MEK inhibition. To my knowledge, such a dead end of differentiation has not been reported before, at least not with pluripotent cells. This result could be a starting point for further investigation, and is of potential interest to a broader stem cell community.
Expertise: As a stem cell biologist I have the expertise to evaluate all parts of the paper.
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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 #2
Evidence, reproducibility and clarity
Summary:
In the present manuscript, Mulas and colleagues address the question how ERK signaling orchestrates the transition from naïve to formative pluripotency in mouse embryonic stem cells. Combining pharmacological MEK inhibition with siRNA knockdown of candidate transcription factors, they conclude that downregulation of Nanog is an immediate function of ERK signaling that underlies exit from the naïve state. Later on they show that ERK signaling has additional functions beyond downregulating Nanog that are required to make cells competent for formative pluripotency and lineage progression, such that Nanog knockdown cells enter a new indeterminate state in the absence of ERK signaling. Finally, they show that Oct4 is a central mediator of this second function of ERK signaling, since forced Oct4 expression rescues the expression of formative markers even in the presence of MEK inhibitors. They also present time-lapse imaging data of a Spry4- and a Nanog-reporter, based on which they propose that metachronous ERK activity is reflected in metachronous NANOG downregulation.
The experiments dissecting the two different functions of ERK signaling in the pluripotency transition are well performed and provide some new interesting perspectives. Overall, the manuscript is well written. I have major concerns regarding the interpretation of the time-lapse imaging experiments (see major point 2 below) that unfortunately feature very prominently in the title of the manuscript.
Major points:
- In lines 174 and 175, the authors write that "acute ERK activation ... [reduces] NANOG protein, which in turn dimishes Esrrb transcription". Although I am aware that this picture is supported by previous literature (e.g. PMID: 23040477), the author's data do not fully support this conclusion. In Fig. 1G for example, Esrrb is downregulated even though Nanog expression is maintained. This discrepancy needs to be discussed.
- The imaging data and analysis presented in Fig. 2 do not support the conclusion that heterogeneous ERK dynamics underlies metachronous pluripotency exit. There are several problems with this section:
- a. As far as I can see, the reporter line used in this study has not been previously used (at least there is no reference to a previous publication), and it has also not been properly validated in the present manuscript. One would for example like to know if the Spry4-FLuc allele encodes for a fusion protein, or whether it disrupts the Spry4 coding sequence. What is the half-life of the Spry4-Fluc protein? A proper description how the line has been generated, as well as an in-depth characterization are essential to evaluate the data.
- b. It is not clear that dynamic expression of a Spry4 reporter reflects dynamic ERK signaling. It has been shown that cumulative transcription from the Spry4 locus correlates with long-term ERK activity (e.g. PMID: 29964027), but short-term Spry4-FLuc dynamics could well be driven by other mechanisms, such as transcriptional bursting. Co-staining of ppERK and reporter expression in single cells would be required to address this issue.
- c. Why is the Spry4-FLuc signal higher at the start of the recording (when cells come out of MEK inhibition and should not have transcribed the reporter) compared to times > 7.5 h, when continuous ERK signaling in N2B27 should drive reporter expression?
- d. What is the evidence for temporally heterogeneous ERK activation? The authors only show one single trace in Fig. 2B, in which the Spry4-FLuc signal peaks right after release from 2i, as would be expected. Another study using a more direct ERK activity sensor (PMID: 31064783) indicated that this initial ERK activity peak after release from 2i is synchronous in all cells in a population. The authors would need to show several or all Spry4-FLuc traces from their experiment to demonstrate the opposite, otherwise one needs to assume synchronous ERK activation upon release from 2i in the author's experiments as well.
- e. Why does the cross-correlation of the Spry-FLuc promoter activity (which should go up upon ERK signaling) with the NANOG-NLuc signal (which should go down upon ERK signaling) give positive values? Does this positive correlation reflect the transient nature of Spry4-FLuc expression, thus giving a positive value when Spry4-FLuc promoter activity decays? In this case, what is the meaning of the delay? Overall I found the explanation of this cross-correlation analysis very confusing. Given these problems, I recommend the authors to strongly tone down their conclusions or remove this section altogether, since addressing this multitude of problems might be out of scope for the present manuscript.
- In line 217 (section title), the authors write that "failure to transition is not due to genome-wide chromatin dysregulation". It is true that the changes upon MEK inhibition reported in this section are small, but there are some changes, and it is ultimately difficult to know which ones are essential. I suggest to rephrase this section title.
- The main finding of Fig. 4 - that Oct4 expression enables formative capacity - is very interesting. One problem throughout this figure is that the authors contrast the control case (N2B27/DMSO + siNeg) with a double perturbation (MEKi + siNanog), making it difficult to demonstrate whether it is the loss of Nanog or the loss of ERK signaling (or both) that results in loss of Oct4 expression. If I have missed something here please clarify.
- Can the authors speculate, or perhaps even experimentally explore, why Oct4 re-expression enables formative capacity? Oct4 positively regulates Fgf4 expression (PMID: 9814708), raising the possibility that the indeterminate state is caused by insufficient paracrine FGF4 signaling once cells have reached this indeterminate state. Alternatively, Oct4-mediated regulation of a broader set of lineage specifiers might be required to establish formative pluripotency. The authors could explore these possibilities by supplementing cultures with recombinant FGF ligands. While these experiments are not essential for to corroborate conclusions in the present manuscript, could allow the authors to follow up upon what I think is their most interesting finding, and thereby give the manuscript a lift.
Minor points:
- Please explain in the methods how gates for identifying RGd2-positive and -negative cells in Fig. 1 B, E have been determined from the FACS plots in Fig. S1C/1B.
- For the categorization of marker-positive and -negative cells in immunofluorescence images, the authors should explain in more detail according to which criterion a threshold was determined by ROC analysis. Which positive and negative controls were used in each case?
- Does a statistical test on the data in Fig. S1A,B reveal significant differences?
- Please give units on the x-axis in Fig. 2C?
- Fig. 3E: Consider re-arranging. It is not immediately clear that all five bar charts belong to this panel.
- There is a typo in Fig. S4A - mainteined
- Methods, lines 408 - 410: Please state units of the parameters used to estimate promoter activity.
Referee Cross-Commenting
I agree with reviewer #1's assessment of significance and their reservation regarding the conclusion "ERK activity is required to maintain Oct4 expression in the naïve to formative pluripotency transition". The experiment that the reviewer suggests is reasonable and doable (see also my major point 4.). Even though reviewer #1 has not explicitly commented on the conclusions drawn from Fig. 2, I disagree with their assessment that these conclusions are convincing (see my major point 2.).
Significance
The control of pluripotency transitions by signaling mechanisms as well as transcription factor circuits have been mapped in quite some detail over the last decade. The main advance of this manuscript is that it looks at the interaction between these two levels and thereby provides some new and interesting links. These results will mainly be of interest to a large community of researchers working with pluripotent stem cells. To me, the most intriguing finding of the paper is the indeterminate cell state that the authors detect upon combined Nanog knockdown and MEK inhibition. To my knowledge, such a dead end of differentiation has not been reported before, at least not with pluripotent cells. This result could be a starting point for further investigation, and is of potential interest to a broader stem cell community.
Expertise: As a stem cell biologist I have the expertise to evaluate all parts of the paper.
-
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
Summary:
In this manuscript, the authors investigated the role of Erk signaling in the transition from naïve to formative pluripotency. They found that Erk activation eliminates Nanog to allow naïve state exit. However, when Nanog is knocked down in the absence of Erk activation, ESCs exit the naïve state, and enter an indetermined state, unable to proceed to the formative state. The authors further claimed that the failure to the formative state is due to lack of Oct4 expression. In conclusion, Erk signaling is required for the exit from the naïve state and the entry to the formative state.
Major comments:
- Are the key conclusions convincing? Most of the key conclusions are convincing, except for the conclusion "ERK activity is required to maintain Oct4 expression in the naïve to formative pluripotency transition". The authors showed that Oct4 expression is diminished under the MEK(i)+siNanog condition, while Oct4 is expressed in N2B27+siNeg (Figure 4C). With these experimental setting, the conclusion that ERK activity is required to maintain Oct4 expression in the naïve to formative pluripotency transition, cannot be reached, because two variations, MEK(i) and siNanog, rather than one variation MEK(i), are there. The experiment should be designed as adding MEK(i) into N2B27+siNeg at various time points, to test whether MEK(i) is able to down-regulate Oct4 expression in the naïve to formative pluripotency transition.
- Should the authors qualify some of their claims as preliminary or speculative, or remove them altogether?
No. - Would additional experiments be essential to support the claims of the paper? Request additional experiments only where necessary for the paper as it is, and do not ask authors to open new lines of experimentation.
The suggested experiment was described above. - Are the suggested experiments realistic in terms of time and resources? It would help if you could add an estimated cost and time investment for substantial experiments.
It should not cost too much in terms of funding and time. - Are the data and the methods presented in such a way that they can be reproduced?
Yes. - Are the experiments adequately replicated and statistical analysis adequate?
Statistical analysis is lacking for Figure 3E and Figure 4.
Minor comments:
- Specific experimental issues that are easily addressable.
No. - Are prior studies referenced appropriately?
Yes. - Are the text and figures clear and accurate?
Yes. - Do you have suggestions that would help the authors improve the presentation of their data and conclusions?
No.
Significance
This work characterized the role of ERK signaling in the transition between naïve and formative pluripotency. The function of ERK in ESC self-renewal and differentiation has been well recognized. Thus, this work provides new discoveries, but no conceptual advances. It should be of interest to a specialized audience in the pluripotency field, which is my expertise.
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stats.hackmag.com stats.hackmag.com
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P
И здесь тоже нужна буква?
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Параметр OutBuffer
А почему это отдельно, а не там, где говорили про четвёртый параметр?
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P
Тут правда нужна P?
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www.neweraeducation.in www.neweraeducation.in
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Overview of pursuing an MBBS education in Russia for 2024-25. Top medical universities, fee structure, and Admission details for an exciting rewarding opportunity. The country is home to several top universities that offer excellent medical programs. Universities in Russia offer MBBS in Russia admission to Indian students to MCI approved medical colleges in Russia. Russia 8th ranks in the list of preferred study destinations, attracting students from all over the world. The world rankings of medical universities are around 30 prestigious Russian Medical Universities. The Russian Federation is home to some of the world's best universities and medical institutions.
There are several advantages to pursuing an MBBS degree in Uzbekistan. Firstly, the medical universities in Uzbekistan follow a comprehensive and well-structured curriculum. The curriculum is designed to provide students with a strong foundation in medical sciences and practical skills necessary for their future medical practice. The emphasis on practical training ensures that students gain hands-on experience and develop the necessary clinical skills required in their profession. Moreover, the teaching methods employed in Uzbekistan medical universities are student-centered and interactive. Professors encourage active participation and engage students in discussions, case studies, and research projects. This approach fosters critical thinking, problem-solving, and effective communication skills among students, preparing them to become competent healthcare professionals. Furthermore, the medical universities in Uzbekistan offer excellent clinical training and internship opportunities. Students have access to well-equipped hospitals and medical centers, where they can observe and assist experienced doctors in real-life medical scenarios. This practical exposure helps students bridge the gap between theory and practice, thereby enhancing their clinical competence and confidence. MBBS eligibility criteria in Uzbekistan To pursue an MBBS degree in Uzbekistan, there are certain eligibility criteria that students need to fulfill. Firstly, students must have completed their high school education or equivalent with a science background. This includes subjects such as Physics, Chemistry, and Biology. Additionally, students must have obtained a minimum aggregate score in their high school examinations as specified by the respective medical universities. Furthermore, students are required to pass the entrance examination conducted by the medical universities in Uzbekistan. The entrance examination evaluates the students' knowledge in science subjects and their aptitude for the medical profession. The scores obtained in the entrance examination play a crucial role in the admission process.
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www.npmjs.com www.npmjs.com
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Vite Plugin Book
Vite Plugin Book
Vite plugin book (aka vite book), is - a magical vite plugin that
helps you to generate and manage - documentation website - like a book!
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github.com github.com
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Visit the
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Feature
- 📓No statically built html files
- 🛫Auto generate documentation website
- 🍼Write documents in a WYSIWYG way
- 🧰Manage site just in browser
- 📦Deploy your site without any configuration.
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About A magical vite plugin that helps you to generate and manage documentation website.
x
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vitejs.dev vitejs.dev
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ViteNext Generation Frontend Tooling
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doc.rust-lang.ru doc.rust-lang.ru
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Другими словами
по сути, используя option, мы работатаем с "null" на уровне кода, мы на уровне кода прописывает, может ли этот тип иметь "null" или нет.
всё написано, так, что просто невозможно, использовать пустое значение.
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IpAddrKind::V4
по сути как ассоциативную функцию
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openclassrooms.com openclassrooms.com
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un petite information à vous partager
Vous auriez dû mettre une et non un, veuillez corriger cela.
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globallytaught.com globallytaught.com
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eing a teacher in South Korea is a coveted position because of the high pay and high level of respect that teachers have.
to look into
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Administrators, teachers, and their unions have created a curriculum that is successful across the country.
Union for teachers to create or change or impact curriculum is such a good idea !
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“Whatever it takes” describes the attitude of most Finnish educators, who are selected from the top 10 percent of the nation’s graduates to earn a required master’s degree in education.
Not so clear, what does this mean exactly to do more research
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library.scholarcy.com library.scholarcy.com
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LPS treatment led to the upregulation of DMT1 and downregulation of FPN1 in AM.
Is this because of LPS or HAMP?
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academic.oup.com academic.oup.com
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Tenure
The focus of tenure within this book, is primarily the system which was brought in by the Normans post 1066. In this system there was the king, who owned the land, followed by his tenancies in chief, which were his main lords that held massive parcels of land, and below these were a linked system of lords and tenants. In order for a lord to subinfeud their land, someone would have to (A) perform homage to the lord, and (B) promise to perform a service for the lord in order to retain and live on the land. This. could be seen as the contractual relationship under which someone could acquire land.
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homage or merely from the grant of land
Could it be that homage was simply a necessity in attaining the grant of the land, whilst the service performed for the lord was in return for the grant,
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Land is a place to live, and a source of food and other commodities, including – if one has enough to let to others – money
Essentially, at this point in time the possession of land would basically provide everything else that was essential to living, and then some. Without land, you could not truly have a place within society.
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openai.com openai.comOpenAI1
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ect in tungste
fsdfsd
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arxiv.org arxiv.org
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Note that Grassroots Social Networking requires dissemination, and Grassroots Cryptocurrenciesrequire also equivocation exclusion, but neither require consensus. Consensus is needed only byhigher-level applications that employ “on-chain” governance such as grassroots social contracts [7 ],the grassroots counterpart of miner-operated smart contracts, and grassroots representative assem-blies (in preparation).
Consensus is required for smartcontracts and governance.
Payments and social networking require weaker equivocation-exclusion.
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Tags
Annotators
URL
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hypothes.is hypothes.is
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Embark on a journey into the versatile world of multi-disciplinary artistry, where boundaries are challenged and creativity flourishes. Experience the diverse talents of artists like Deborah Halpern, whose innovative approach spans mediums and genres, creating a vibrant tapestry of expression that defies convention. Explore the limitless possibilities of art without limits.
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SORVALL SS-34 CENTRIFUGE ROTOR RC-5 RC-5B RC-5C RC-26 #14070
Currently being researched by April
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docdrop.org docdrop.org
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if joining data from many sources is cheap we don't need big data you can have 00:37:11 small data all over the place
Is Big-Data about storage and joins? Or is it about computing efficiently over massive scales?
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if I add some uh a couple of facts that say oh hey guess what if if you're a sister then you're 00:34:26 that's a sub property of family I add that one bit of data and now I can write just give me all the family members of this uh thing and because Sparkle is 00:34:40 this beautiful graph query language we can handle recursive queries really well
Are these two different features? OWL for defining rules? and SPARQL for recursive queries?
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social-media-ethics-automation.github.io social-media-ethics-automation.github.io
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Social media data can also be used to infer information about larger social trends like the spread of misinformation [h10].
There are a lot of incidences that the spread of misinformation is caused by incorrect information been analyzed. THose information wasn't filtered out carefully thus they them be noted as data, which gives out the incorrect result.
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www.ebay.com www.ebay.com
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Thermo Scientific Sorvall Legend XTR Refrigerated Benchtop Centrifuge 75004521
Currently being researched by April
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stylo.ecrituresnumeriques.ca stylo.ecrituresnumeriques.ca
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Joëlle Zask
lien d'article ?
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et
peut-être "ainsi que", sinon ça fait un peu bizarre
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Autogoverno
légende
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Quand la complexité produit de la brutalité
ajouter le lien
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Não tema
également en portugais
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théorie
une théorie
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face
face ??
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Smart Citie
italique
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Au numérique
formulation un peu étrange
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Parco Dora, em Torino
La légende est en Portugais : "Le parco Dora à Turin
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l’approche
de l'approche
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notre
son ?
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E
sans maj
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60
à quoi renvoie ce 60 ? n'y a t il pas un lien disponible pour l'article ou au moins une ref biblio ?
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,
point virgule ou "et"
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le
Les ? à quoi renvoie ce "le" ?
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www.ebay.com www.ebay.com
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MICROM HM 315 Microtome with Blade Holder & Histo-Collimator, FOR PARTS/ REPAIR
Currently being researched by April
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www.youtube.com www.youtube.com
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stadtmenschen gegen landeier, kiffer gegen alkis...<br /> ich find beide seiten scheisse, ich bleib alleine und träum weiter von tribalismus : P
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chem.libretexts.org chem.libretexts.org