1. Last 7 days
    1. Of these ten poems, five are portraits of other people. Just as with all her 'Paris poems,' research has been done on individual poems from Loy's 'Paris years,' but the majority of of that research addresses her earlier poetry. For whatever reason, there seems to be a gap in both the portraiture and the scholarship on Loy's poems, a gap that spans her 'Paris years.' No one has written about Loy's 'Paris poems' as a whole, and no one has studied her portrait poems to see what they reveal about Loy's work.

      This is really good. I think the easiest way to clear up confusion is to say something like: Most of the photographic and literary portraits of Mina Loy made by other people were created during her Paris years. Loy also created many portraits during her Paris years: of the ten poems she published, 5 are portrait poems. It is these 5 portrait poems that I will examine here.

    2. various portraits,

      What do the portraits have to do with the Paris poems. I want to hear about both, but this seems like a jarring shift, after you just announced a purpose to look at the Paris poems. Perhaps you could smooth the transition by emphasizing in the previous paragraph and this one that Loy's Paris years were distinguished by a market interest in portraiture. Though Loy made portraits throughout her career, she did so with a particular intensity in both poetry and prose in the Paris years. (if this is true, that is!)

      Also, it would be helpful to know whether you're talking about portraits of her or by her or both.

    3. In his article on Loy's "Three Moments in Paris," Andrew Michael Roberts connects Loy's "One O'Clock at Night" poem to these affairs, drawing connections between the speaker's struggle with being a 'mere woman' and an 'animal woman' and Marinetti's public statements comparing women to animals (Roberts 137).

      Maybe this level of detail would be better in a narrative than a timeline?

    4. n her poem about her first childbirth, "Parturition

      Avoid equating the poem with autobiography. You might say Haweis was having an affair, a detail Loy alludes to in her poem about childbirth, "Parturition."

    1. Why senior developersfail to communicatetheir expertise

      Why Senior Developers Fail to Communicate Their Expertise

      • Conflict of Interest: Senior developers and business leaders operate in different "loops." The business prioritizes the Speed Loop (reducing uncertainty by getting to market fast), while senior developers prioritize the Stability Loop (managing complexity to ensure the system remains debuggable and reliable).
      • Vocabulary Mismatch: Communication fails because developers talk about "complexity" and "technical debt," which sound like excuses to non-technical stakeholders. Stakeholders are focused on "uncertainty" and "growth."
      • The "Solution" Frame: To communicate effectively, seniors must frame their concerns as solutions to the business's problems. Instead of saying "no" to complexity, they should offer "something quicker" (reusing existing tools, Google forms, or minimal UI changes) to help the business learn faster without bloating the code.
      • AI as a Destabilizer: AI-generated code accelerates the Speed Loop but creates a "complexity explosion" that threatens long-term stability. The senior developer’s role is shifting toward that of an Editor, responsible for extracting stable, scalable logic from the rapid "vomit drafts" produced by AI and junior staff.
      • The Proposed Split: A potential workflow involves maintaining two versions of a system: a "Speed" version for rapid experimentation and a "Scale" version that is curated, stabilized, and owned by senior architects.

      Hacker News Discussion

      • The "World Model" Gap: A top-voted comment argues that true expertise is an internal "world model" or intuition that is inherently difficult to put into words. It isn't just a list of facts but a deeply integrated understanding of how systems behave.
      • Recipe vs. Physics: Commenters distinguish between "recipe-following" developers (who use tools without understanding the underlying logic) and "physics-based" developers who understand the fundamental nature of computation.
      • The Role of Failure: Discussion emphasized that senior intuition is built primarily through experiencing failures and reflecting on them over many years. This mental shift often happens when a developer stops trying to learn syntax and starts focusing on solving specific visions or problems.
      • The "Senior" Title: There was significant debate about whether "senior" is a measure of years (tenure) or actual merit, with many noting that some developers with decades of experience still only follow recipes and lack the "world model" required for true expertise.
      • Abstraction Struggles: Some users noted that while they have a "physics-level" understanding of physical sciences (like chemistry or biology), software abstractions feel arbitrary and "anti-physicalist," making it harder for some brilliant minds to build that same level of intuition.
    1. Googlebook

      Summary of "Googlebook" Discussion (Hacker News)

      • The Concept: Googlebook is presented as a high-end hardware play—a "premium upgrade" to the Chromebook—intended to shift the user experience from traditional apps to an LLM-native environment powered by Gemini.
      • The Vision: Some users see this as a "moonshot" to make apps irrelevant, replacing them with raw data feeds and AI-driven visualizations, potentially creating a "sci-fi" style user interface.
      • Execution Skepticism: A dominant theme is doubt regarding Google's ability to execute. Commenters cited current frustrations with Gemini (cutting off mid-sentence, poor Maps integration, and hallucinations in Sheets) as evidence that the tech isn't ready for a primary OS role.
      • Target Audience: Discussion suggests Google is targeting "Chromebook natives"—students who grew up in the Google ecosystem and are now entering university or the workforce and want a "pro" version of their familiar tools.
      • Public Sentiment on AI: There is a sharp divide in perceived AI adoption. Some argue "normies" (non-tech users) love AI for daily tasks and creative fun, while others claim people increasingly resent AI being "forced" into every product.
      • Competitive Landscape: Comparison was drawn to historical shifts (like the move to Mosaic/Web browsers). While some see this as an inevitable evolution, others believe Apple’s approach—gradually improving Siri and app intents—is more practical than trying to eliminate apps entirely.
    1. there are few experimental systems thatexamine the mechanism of liking something one dislikes,and further research on the mechanism of increased pref-erence by bitter taste experience may lead to the elucida-tion of a complementary mechanism

      What is unique about the study is that it is looking at a change and not just a mechanism for likes and dislikes taste-wise

    2. The decrease in aversiveness may be dueto fewer bitter taste receptors

      Interesting that change in natural aversion to bitterness could be because the taste cannot be sensed as well

    3. Furthermore, the VTA dopamine neurons pro-jects directly to the CeA, especially to the medial part ofthe CeA (CeM), where Prkcd-positive neurons are lessabundant and Sst-positive neurons are more abundant[15, 37]. Therefore, it is also possible that umami infor-mation is relayed to Sst-positive neurons in the CeA viaVTA dopamine neurons

      Dopamine is associated with pleasure and motivation, so its connection to taste pathways fits into the system

    4. The reason for this is unclear.One can speculate that there may be some interactionbetween sodium and umami signals

      Uncertainty in unexpected results between MSG and MPG solutions, possible interactions between sodium and umami signals

    5. It would be an interesting future study toexamine whether there is a critical period to induce suchexperience-dependent changes in taste preference

      Next step to take would be establishing a period of time where exposure induces changes in taste preferences

    6. Our results are consistent with this body ofevidence and showed that prolonged exposure to umamiand bitter in the post-weaning juvenile period alsoincreases the preference for the exposed taste

      Results from study support hypothesis and previous research on the modification of taste preference through experience

    7. Taken together, both Prkcd-positive andSst-positive neurons are not unique populations to respondto a particular tastant, but are composed of mixed cells thatrespond to negative and positive tastants, although there isa bias in the tendency of the responding tastant

      Cellular populations respond to a mix of negative and positive tastants with some bias in tendency

    8. Interestingly, one-third of sweet-response and one-fifthof umami-response Sst-positive neurons also respondedto umami and sweet tastants, respectively, both of whichare thought to be attractive tastants

      Interesting or unexpected finding that some Sst-positive neurons responded to both umami and sweet

    9. In Prkcd-positive neurons, the largest popula-tions (19.7%) responded to bitter tastant (Fig. 2B), as wasreported in previous Fos-labeling studies

      As expected, the largest populations of Prkcd-positive neurons responded to the bitter

    10. one intriguing possibility is that there are cell-type specificresponses to the negative and positive taste qualities withinthe CeA, and neuronal activity changes occur in this circuitmay lead to the modification of outcome behavior towardthe tastant

      Hypothesis for neural activity mechanisms in connection to taste quality response

    11. We next sought to deter-mine the areas of the brain that display neuronal activityassociated with these behavioral changes

      In addition to behavioral changes, study is interested in neuronal activity associated with them

    12. . In contrast, the Bitter groupconsumed as much bitter solution as water (p = 0.7539;Fig. 1F) and exhibited bitter preference ratio around50% (p = 0.8361; Fig. 1G), which was significantly highcompared with that of the other groups

      Exposure to bitter flavors led to a higher consumption of the bitter solution and less aversion

    13. Six-week-old naïve and prolonged taste exposed micewere acclimated to test bottles for 3–4 days beforethe stimulation

      Habituation period lasted 3-4 days, not long enough to see long-term effects in preference

    14. We found that MPG experience for 3 weeksenhanced umami intake similar to MSG experience

      Indicates that the experiments with MSG reflect umami effect and not just sodium effects

    15. both the Water and Umami groups contactedthe umami bottle longer duration than the water bot-tle

      Interesting that more contact was made (exploration) but intake preference for whatever they had been consuming previously still existed

    16. The Umami group exhib-ited a significant increase in intake of umami solutioncompared with water, whereas the Water and Bittergroups showed no difference in water and umami intake

      As expected, more exposure to umami flavor led to more preference for intake of that solution

    17. To investigate the influence of prolonged experience ofumami and bitter tastants on taste preference, mice werereared with ad libitum water (Water group), umami solu-tion (Umami group), or bitter solution (Bitter group) for3 weeks in the immediate post-weaning period

      Experimental variable was the solution provided for feeding: water (control), umami, or bitter

    18. The intake and access duration were analyzed usingpaired t-test. The preference ratio and access ratio wereanalyzed by one-way ANOVA followed by Tukey’s posthoc test and one sample t-test. The Fos FISH cell count-ing data were analyzed by unpaired t-test

      Stastistical analysis was done with t-tests, one-way ANOVA, and Tukey's post-hoc test

    19. Six minutes after the start of imaging,mice were given 100 μL of bitter (1 mM quinine), sweet(50 mM sucrose), and umami (100 mM monosodiumglutamate and 10 mM disodium inosinate) taste solutionalternately with neutral-taste water at 2-min intervals forthree trials

      Exposure to three taste qualities: bitter, sweet, and umami

    1. 1 - this website offers a variety of subheadings and embedded links that help the user navigate the website and relevant topics in Toronto currently such as the cherry trees blooming in high volume areas of the city, namely High Park. However, the what's new page does not include the list of long standing or yearly events which the city hosts throughout the year, such as Nuit Blanche.

      2 - The subheadings on the site are very simple and easily understood, which would be beneficial for Toronto's diverse communities and individuals who may have a difficult time navigating a website with a more complex or word heavy interface.

      3 - The homepage of the website only showcases a very small amount of information one using the website may access, with only the search bar to find what one needs, which may be difficult for people who may not know their exact search query or have difficulties with searching.

      4 - The page does offer it's own translation feature, which would be expected to be more reliable than the Google offered automatic feature as one would assume the city would employ real translators to translate the page. This feature would be beneficial for Toronto's healthy population of non-english or ESL individuals.

      5 - The phone number 311 is not specified as being a phone number for the city, which may make it confusing or difficult for a new resident to contact the city for relevant services or assistance.

    1. Trials

      We need to add filtering options.

      In the table I would like to see Disease, Clinical trial number + Title, Geography (a specific country or international), Phase, Status, Enrollment, Primary Completion Date.

    2. Overview

      I would like to add additional sections: 1. Sales (wee what we have in the current US) 2. Clinical Evidence 3. Technology Features - we are collecting additional features for certain technologies. These features are technology dependent.

    3. Indications

      Indication is a specific language used for approved indications. it is okay if we use Indication also where the drug is studied but not yet approved. For the approved indications we need more details: Exact Indication Language - Structured Indication - Date of Approval - FDA (US) /EMA (EU) /PMDA (JP) or NMPA (China). Keep in mind that a drug like Keytruda has 30+ indication in the US alone.<br /> Each of these indication is supported by clinical evidence (clinical trial data) which could be also linked to the indication.

      For indication, which are not yet approved we could simple list the disease, disease stage and line of therapy (keep in mind the same drug might be studies in the same disease but a different line of therapy).

      I would change "Failed" to "Discontinued"

    4. Ownership

      I don't think we need this. Unless we want to track previous ownerships. Which is a big task by why not. In this case I would change it to "Ownership history"

    5. KRAS G12C

      We separated targets and mutations. In this specific case KRAS would be the target and KRAS G12C the mutation.

      We also have categories like Action type(s): covalent, irreversible, non-covalent, reversible Target - Action Specificity: Mutation Specific, HLA-restricted Binding Site - allosteric site, active site HLA Allele - a bunch of HLA subtypes as values

      Additionally we also capture if a drug is brain penetrant.

    6. Owner

      Change Owner to Organization and add Geography next to the Organization with values like Worldwide, US, Ex-US, Europe, Japan, China, Greater China A lot of drugs have multiple organizations in different geographies. We also need to add a "Partner" between Organization and Geography. For example Company A partner with Company B in US and Company C sells it Ex-US.

    7. Development phase

      Change Development Phase to Highest Development Phase

      Change Phases to: Pre-Clinical, Phase 1, Phase 2, Phase 3, Approved There is also some drugs which are "Withdrawn"

      Additionally we could also add: IND Submission - which happens between Pre-clinical and Phase 1 NDA Submission - between Phase 3 and Approved I just don't know if we have this data consistently

    1. patriarchal pressures and expectations

      I think you might be able to make this argument more effectively if you emphasized her resistance to the sexualizing male gaze rather than to patriarchal pressures more broadly. Your wonderful analyses of the paintings show HOW they resist the male gaze. It's much harder to show how she's resisting something as abstract and general as patriarchal pressures.

    2. When we compare Fitzgerald’s paintings to other famous paintings of dancers, like those by Degas, we can see that they differ stylistically.

      Ahh, this is exactly the kind of comparison that might work better above in the place of a generalization about male painters, but tell us about the stylistic differences. Is Degas an example of patriarchal attitudes? or of the modernist erotic destruction of the female body?

    3. ne” (Pike 187). Similarly, this is the way in which Fitzgerald describes the dressing room that Alabama enters when she arrives at the ballet studio. In the room hangs “long legs and rigid feet of flesh and black tights mounded in sweat to the visual image of the decisive

      excellent choice and use of evidence.

    4. Many male painters used depictions of the female body to display their sexual desires and misogynistic views of the role of women in their lives.

      I have a hard time with such unsubstantiated generalizations. It might help to provide a representative example or two, otherwise you're relying solely on what's called a warrant of authority: Because Pike says it, it is so.

    5. *It is important to note here that the term “Negroid” is very offensive and inappropriate.

      Aha! You had a similar thought. I agree that it's offensive but think we can also see how she is using the stereotype of the Negro as stronger, more physical, and more primitive as a way of revitalizing her own white, female body--that's how Primitivist tropes work. White people create exotic fantasies about the dark Other and then feed on them to revitalize themselves.

    6. Through this lens, Michelle Payne, one of the first scholars to study body in Save Me the Waltz, argues that the novel is a literary representation of Fitzgerald’s assumed anorexia through ways in which Alabama treats her own body. She first basically diagnoses Fitzgerald with anorexia and then argues that in the novel “ballet becomes a trope for anorexia–torturous, ascetic, bodily rituals concealed by and yet enabling the graceful, seemingly delicate performance of the ballet/body” (Payne 49). She continues by interpreting the novel as a reflection of Zelda’s life, further supporting her post-mortem diagnosis. However, not only is it problematic to diagnose a person with a serious mental health condition after their death, it is even more problematic to use their fiction writing as evidence or a confirmation. When Payne does this, she actually undermines the impact of Save Me the Waltz and Fitzgerald’s writing. Since Payne is one of the first scholars to discuss the representation of body in the novel, more recent scholars must combat the notion that the novel is a mirror for Fitzgerald’s own life. Instead, we should read the novel on its own and appreciate its unmistakable, individual significance.Fitzgerald's art, in her writing and her painting, has profound meaning beyond an anorexic diagnosis.

      I think you could provide all this useful information in one condensed, concise paragraph, and deliver a more precise thesis. What "profound meaning" will your analysis reveal?

      As I read on, it seems like your thesis is that dance in the novel does not serve as evidence of anorexia, but is an art form that confers strength and autonomy onto the main character, allowing her to locate herself physically and creatively outside of her roles as daughter, wife, and mother.

    7. Alabama claims ownership over her body and breaks free from the pressures of marriage and motherhood. By pushing her body through dance, she finds her own purpose.

      can you provide textual evidence to support these perceptive claims?

    8. she, “‘[is] go

      no comma necessary here.

      This seems like an important quotation for reclaiming and redirecting the power of blue veins toward her own fame as an artist, rather than toward sex appeal to a man.

    9. comparison. She is self-conscious about the awkwardness of her body.Later in the night, Alabama and the rest of the party attend the ballet.In the 1930's, the ballet was very important to French nightlife. This is an example of what French ballet looked like in this era:

      Why does the text of the paragraphs keep changing in font size?

    10. There is much debate among scholars about how readers should approach the use and description of the body in Fitzgerald’s Save Me the Waltz.

      Possibly give a short plot summary of the novel to get readers interested and grounded in it before you do your lit review.

    11. , an art form that she had admired since childhood

      This phrase seems repetitive, since you told us she not only admired but actually studied it as a child. Maybe just say: she became captivated by the idea of taking up ballet professionally.

    1. Pay attention and correctly use Workflows, ILLiad, and Help Tickets for library transactions. Ensure library items are scanned accurately and routed to the right location.

      Update to reflect RMC policies

    2. Yes! Student workers are part of the ISS (Information Spaces and Services) department. The ISS vision and values include providing excellent library services and access, collaborating with diverse communities, connecting patrons with the library's collection, and a commitment to professional growth.

      Need to change this.

    3. According to the agreement, what should you do if you are treated disrespectfully by a patron, staff member, or fellow student employee?

      Substitute with multiple choice or another less finicky option for a question

    4. Wear a Library Student Worker tag while working.  You'll appear more professional and it will set you apart from student patrons. Please don't wear brimmed hats or sunglasses as they can impede eye contact.

      This is not RMC policy but we can discuss.

    5. No, unfortunately, foods that can spill at the desks (with any sauces) or foods that are greasy are best eaten away from the desk.  Library materials can be damaged in the event of an accident or spill. Remember, light snacks are okay, but step away for a meal.

      not sure why this is wrong? looks like 3 answers are correct - the help text is deceptive since it repeats what's in the answers.

    6. Read the scenario on each card below. Drag the scenario card into the "Great Work!" box if it describes great Desk Etiquette, or into the "DON'T" block if does not.

      These scenarios need to be adjusted

    7. Please do not accept package deliveries without explicit approval from a supervisor. Never sign for packages without permission.

      Could replace with another tip - headphones?

    8. books, manuscripts, digital materials, and a world-class primary source collection

      creative equipment and spaces, books, and a world-class primary source collection

    9. Each library has day and night managers. Some libraries also have evening and weekend managers!  Each time you work a shift, make sure understand who the manager on duty (or on call) will be during your shift so you can notify them if you are running late or have to miss work. If unsure, ask!In the section below, match each manager with their correct schedule.

      Remove this section or replace with a more full description of job duties. Flashcards/puzzle pieces should also include areas of specialty.

    10. Did you know?Each library: Brown, Clemons, Fine Arts, Music and Shannon may have it's own quirks and peculiarities, but all follow the central policies and procedures of our UVA Library public services department, called Information Services and Spaces, now your department too!

      Remove. Or replace.

    11. Assist with Spaces and Equipment Needs

      For Job Task #5 – Assist with Spaces and Equipment Needs You will help visitors use Library equipment and spaces, including the G-Lab and DML computers, VR equipment, and circulating equipment. You may open and close the RMC and the DML, complete opening and closing checklists, and ensure the Vault is secure. You will contact full-time staff when Library infrastructure or equipment is malfunctioning. You will know where to locate the emergency contacts list and who to call for help.

    12. Route Library Materials

      For Job Task #4 - Studio Spaces (need appropriate graphic) Using Libcal, you will check out studio binders, 3D Printing passes, and open the studio doors. You will serve as a steward of library spaces and ensure that they are neat and tidy.

    13. Circulate Library Materials

      Using Workflows and Libcal, you will accurately check in and out equipment including video cameras, audio recorders, and other creative materials. You will accurately assist patrons to check in and out specialized cameras and lights and correctly account for all included accessories. You will accurately scan materials, account for all accessories, and return them to the appropriate place on the shelf.

    14. Answer Questions and Provide Referrals

      For this Job Task, change first bullet to studios instead of spaces. for the third bullet, change to "Consultants refer complex questions to full-time staff."

    15. Service and Information

      RMC and DML Desks Change pic Change card to: Work at the RMC and DML Desks: As a Consultant, you will welcome, orient, and help patrons access Library resources, services, and studios.

    16. Take a Guess section - * change intro picture to RMC related pic * T/F change to "At the desk, Robertson Media Center Consultants mostly help visitors to check out equipment from the Library" The No not exactly true answer should change to reflect that students "check out equipment, provide help using audio and video equipment and studios, troubleshoot equipment, and more!" * change final bubble to "As a RMC Consultant, you are the person who can best help students with their creative projects. Your work is a key part of our Library services!"

    17. You will learn how to locate items in the UVA library.

      this should reflect content that has already been delivered and shouldn't be a trick question. maybe it should be bullet 1 above?

    18. such as assisting patrons at the reference desk, shelving books, working in media centers

      this is a small thing but in addition to changing this photo can we reorder to say "such as working in the Media Center, assisting patrons at the reference desk, assisting in the makerspace, and much more." or similar.

    1. la chágara se había introducido dentro de la carne blanda de lapantorrilla, donde había evidentemente comenzado a engordar.

      Esta frase emplea la teoría de lo abyecto por Kristeva. La idea de una presencia que no es sí mismo, pero está dentro de sí mismo y utiliza su sangre, carne y cuerpo para "engordar" también plantea temas de ser controlado. Es posible que la chágara pueda ser un símbolo de los Estados Unidos y su control sobre Puerto Rico después de la guerra española-estadounidense. Respaldando esta noción, la esterilización forzosa en masa en Puerto Rico causada por los Estados Unidos. Combinando la teoría de Kristeva con la chágara como símbolo de la intervención estadounidense en Puerto Rico, Ferré crea una imagen de la colonización y el control impérico como algo abyecto y antinatural, algo que no puede ser visto como normal ni cotidiano.

    1. What to look out forResidents should watch for rodent droppings and take proper precautions when cleaning for spring, according to Angela Rasmussen, a virologist at the University of Saskatchewan. "If you are doing some spring cleaning, cleaning out your lake cabin here in Canada, we actually do have mice that can transmit hantaviruses," she said.

      Webpage Complexity: This webpage may create accessibility challenges because the advertisements placed throughout the article can make the page feel visually cluttered and distracting. The large amount of competing content throughout the article, including advertisements at the top and sides of the webpage, may make it more difficult for some users to focus on important information or navigate the webpage efficiently. This connects to accessibility concepts related to avoiding webpage complexity and presenting web content in a simpler, more structured way to reduce cognitive overload for users.

    2. MenuWhen search suggestions are available use up and down arrows to review and enter to select.SearchSearchSign InQuick LinksNewsSportsRadioMusicListen LiveTVWatchnewsTop StoriesLocalClimateWorldCanadaPoliticsIndigenousBusinessThe NationalHealthEntertainmentScienceCBC News InvestigatesDisability LifeGo PublicAbout CBC NewsBeing Black in CanadaMore

      Navigation / Header Menus: The navigation menus support the “Operable” principle of the Web Content Accessibility Guidelines because users can easily move through different sections of the website and access information in an organized way. The clear layout and dropdown menus make it easier for users to quickly find news topics and content they are interested in.

    3. Cleaning out the shed or cottage for spring? Here’s how to protect yourself from hantavirus

      Clear Colour Contrast: This webpage demonstrates good accessibility through strong colour contrast between the black text and white background. This connects to the “Perceivable” principle of the Web Content Accessibility Guidelines because clear contrast helps users with visual impairments read content more easily.

  2. www.youtube.com www.youtube.com
    1. JT45221_V11_JM43293_v1_cm25q2_Drill-Banana+Informative_(Chol+Impossible)-16x9.mp4Tap to unmute2xDr. Livingood Weight Lossbook.livingooddailybook.comLearn moreSponsoredMy Ad Center1 of 2book.livingooddailybook.comSkipSteve Jobs perfect response to an insult. Worldwide developer conference 1997.Custom PCs Australia 2,719,870 views 1 year agoCopy linkInfoShoppingIf playback doesn't begin shortly, try restarting your device.0:06Pull up for precise seekingPlay0:00Most replayed•You're signed outVideos you watch may be added to the TV's watch history and influence TV recommendations. To avoid this, cancel and sign in to YouTube on your computer.CancelConfirmHideShareInclude playlistAn error occurred while retrieving sharing information. Please try again later.IntroStartMain0:000:02 / 2:22Live•Watch full video••lofi hip hop radio 📚 beats to relax/study toLofi Girl25K watching • 3 years agoLivePlaylist ()Mix (50+)22:17The Shadow Docket: Last Week Tonight with John Oliver (HBO)LastWeekTonight1.7M views • 2 days agoLivePlaylist ()Mix (50+)18:4950 Unfiltered Truths 🍷🗿from the World’s Sharpest EntrepreneursQRIOSITY67 views • 10 days agoLivePlaylist ()Mix (50+)10:02Can Magnus Carlsen Beat a Noob with 30 Queens?Esports Spotlight1.8M views • 5 months agoLivePlaylist ()Mix (50+)3:54Why 90% of Managers Are GARBAGE (The Professional Lie) | Steve JobsEvan Carmichael4.4M views • 11 years agoLivePlaylist ()Mix (50+)8:26Steve Jobs | Steve Jobs vs. WozniakUniversal Pictures453K views • 2 years agoLivePlaylist ()Mix (50+)8:47How to Start a SpeechConor Neill22M views • 14 years agoLivePlaylist ()Mix (50+)7:12Why Steve Wozniak Left AppleApple Explained1.4M views • 5 years agoLivePlaylist ()Mix (50+)25:57Stop Rambling: The 3-2-1 Speaking Trick That Makes You Sound Like A CEOBigDeal by Codie Sanchez 3.1M views • 4 months agoLivePlaylist ()Mix (50+)31:27Steve Jobs: The Fresh Air Interview (1996) | Fresh AirFresh Air275K views • 3 years agoLivePlaylist ()Mix (50+)10:20Steve Jobs introduces iPhone in 2007John Schroter49M views • 14 years agoLivePlaylist ()Mix (50+)Puffin Colony Cam - Skomer Island LivestreamThe Wildlife Trust of South and West Wales392 watching • 2 months agoLivePlaylist ()Mix (50+) Steve Jobs perfect response to an insult. Worldwide developer conference 1997.

      My oppinion on what Steve Jobs is conveying is that if your trying to selll a products, you should start with the user needs and wants. Rather than trying to package some technology you created, you should have the User drive the technology. This way you spend more time on creating technologies that your customers will actually want.

    2. Steve Jobs says that to create a good product, you need to put the customer first. A product that is made FOR a customer should be what they want and what they will use, not just the coolest thing you can create with a ton of bells and whistles. Rather than focusing on what you can do or the company's goal with a product, think about what the average consumer is most likely to be looking for.

    3. Steve Jobs is a smart and great business man, he understands in order to be successful you need to fix a problem of what the user has and engineer a product like that in order to sell it and make moeny. He also recognized that there will be problems that'll come up and they will have to be fixed.

    4. insult

      It seems that Steve Jobs had really thought through what his plan was and combatted the negative connotation very thoroughly. His engineering background really helped him make his point and back it up with facts and future strategies to implement.

    5. Steve Jobs argued back by bringing up the laser printer example, before the laser printer existed it was hard to put the customer first in this case and you had to make the technology before the customer. Then when he brought up holding up the paper and saying "here look at this, wanna buy it" starts creating that user experience that was mentioned. He prefers this way so that he can the main issues that need to be fixed that caters to the users experiance.

    6. Steve Job states, in the industry you must start and learn your constomers first and then market the technology around your audience. Rather than vice versa. In order to sell, you must target a specific group, and that is the real strategy to a marketing magician. This is absolutely correct because if you decide to release a product that would only interest a few individuals, sales go down and leaves you unable to make other products on the market.

    7. I like Jobs emphasis on user experience, this idea that any successful business must first and foremost look to the user before even beginning to think about the product. Theres no point in having advanced technology if it is inaccessible to the user!

    8. Steve Jobs perfect response to an insult. Worldwide developer conference 1997.

      I agree with Steve Jobs' point that technology should be about the user experience rather than the technical aspects. People will not enjoy using a product if it has advanced technology and is not easy to use or understand. I believe it is important to include human centered design in technology because it makes it easier, and more usable for humans. Steve Jobs also demonstrated that good design isn't just about looks, it's about knowing what people need and building products that seem like a breeze.

    9. I feel like Steve was basically saying that "why go through the work of making a cool product that no one wants". This is the backbone of good design, why gather an engineering group together to make a profitless product? Working with the customer experience and working backwards is how online and non online stores function. Lets take hallmark for example, if there was not a customer need for celebratory cards, then there is no need to open a card shop.

    10. One of the most interesting things about the video was how calmly Steve Jobs handled criticism during the 1997 Worldwide Developers Conference. Instead of reacting emotionally to the insult, he stayed confident and respectful while explaining his vision for Apple’s future. What made his response powerful was that he focused on problem-solving and innovation rather than arguing with the audience member.

    11. I believe Steve Jobs handled this well when the audience member asked me what he has done and insulted him. Steve Jobs answered it well and professional. He answered the guys question and explained his reasoning.

    12. Steve Jobs is essentially trying to argue against the dark patterns that companies are diving into. His point that putting the customers first before the technology and trying to sell them something is the main issue. He prefers user experience and customers overall well being over trying to fall into these dark patterns.

    13. Steve jobs is essentially conveying that the cohesive ecosystem and user experience is far more important than the technology behind it. You can see this today with almost all major companies. For example, very similarly to apple, YouTube is constantly changing the general layout or styling to seek for a better user experience.

    14. Steve Jobs perfect response to an insult. Worldwide developer conference 1997.

      I like that he noted you have to start with the user experience first and then work backwards from there. Love or hate him, he was a very smart businessman in the sense that he really knew his customer. If you invent a world changing piece of technology, but nobody knows how to use it, that technology is useless. You need to make sure the people you market your product to can actually use it, or else will never take off.

    15. That 1997 response is a masterclass in emotional intelligence and strategic poise. Instead of trading insults with the developer, Jobs used the "Working Backwards" framework to redefine Apple’s entire philosophy. He disarmed the critic by admitting his own technical limitations, shifting the conversation away from individual features and toward a cohesive customer experience.

      By defending the engineers "burning the midnight oil," he turned a moment of public hostility into a powerful rallying cry for the company’s new direction. It wasn’t just a clever comeback; it was the exact moment Apple stopped being a struggling computer manufacturer and started becoming the experience-driven powerhouse we know today.

    16. that you've got to start with the customer experience and work backwards to the technology2:002 minutesyou can't start with the technology and try to figure out where you're going to try to sell it and I've made this mistake probably more than anybody else

      This is a great quote from Steve Jobs. What he is saying proves that the user (or customer) experience is a critical factor in design. Maybe one of the most important ones. I think him understanding this made him as successful as he is today, and it is important to think like that going forward.

    17. Steve Jobs

      I like how this crosses into entrepreneurship, for you to have good design first you need to have some type of iteration of your product. The first design choice may be a hit or miss but what matters is how you respond back to the customers wants and needs. The customer is the guide to having a great design.

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    1. Then she had to smuggle Tea Cake out by the back gate and that made it seem like some great secret she was keeping from the town.

      This shows that Janie has to secretly bring tea cake into her life, wich makes their relationship feel hidden and exciting

    1. Dark patterns are the result of deceptive practices in retail, nudging, and growth hacking. Nudging and retail practices both utilize psychological bias tactics, for example using countdown timers for 'limited deals' or holding items in a cart for a limited time to create a sense of urgency and scarcity. This way, users feel pressured to make decisions quickly because of fear of missing out. Practices like this are very common and many shoppers are aware of how they are being manipulated, but will fall into the trap anyways.

    2. a lot of this just feels like people not reading the fine print or skimming the rules. if you read carefully and take things with a pinch of salt, you won't get screwed over.

    3. I am not too surprised that companies and businesses use different types of tactics to try to make more money from the consumer. I think its a smart idea for them to do these thing, if its in a legal way, because doing things like A/B Testing and using different tactics to make people spend money and that is ultimately the goal is to make people spend money. In terms of dark patterns I think personally that the consumer should be more aware if possible. I do also believe that it should be regulated in some way.

    4. More problematic are practices such as false claims of store closings, which are unlawful but rarely the target of enforcement actions. At the other extreme are bait-and-switch car ads such as the one by a Ford dealership in Cleveland that was the target of an FTC action.14

      Another example I always disliked as an Amazon prime user, is when Amazon displays that they only have a certain number of items left in stock. I sometimes feel like I'm being pressured to make a quick decision on actually purchasing the item. However, Amazon might not be doing anything wrong, but I sometimes feel like they should also add content like we expect another shipment in another couple of days/months.

    5. Figure 6. One of Uber’s gamified nudges to keep drivers on the road.

      Its interesting how I've seen this pattern of nudging everywhere from actual games, online shopping stores and even in person shopping. I've seen it especially in stores where they'll have a buy one get one half of where even the cashier will nudge you to get a another item to retrieve the sale or even in online shopping where it'll nudge you to buy another item just to get free shipping. ultimately they result in you spending more money on something you dont need.

    6. More problematic are practices such as false claims of store closings, which are unlawful but rarely the target of enforcement actions. At the other extreme are bait-and-switch car ads such as the one by a Ford dealership in Cleveland that was the target of

      It's really surprising to hear that stores can make such false claims. I've encountered a few stores closing and having big closeouts and they did in fact close. I wonder what the repercussions would be if a store is caught with false claiming to close down and how it would affect the customer base.

    7. a design process hyperfocused on A/B testing can result in dark patterns even if that is not the intent.

      This is pretty interesting in the sense that as a developer, you would like to refine the user experience as best as you can. But in doing this, you can create a predatory environment even when you did not directly try to. The Dark patterns that can be created through A/B testing like changing the color or size of a button is directly related to creating dark patterns within your designs. This is something that surprises me as I did not think this type of testing could lead to these bad or intrusive design decisions.

    8. "Growth hacking is not inherently deceptive or manipulative but often is in practice."

      The most interesting concept on this page to me is growth hacking. The idea of spreading awareness of your product through subtle features such as the Hotmail ad allows a designer to hold impactful power over a user's decision making. Another thing that makes that method interesting, yet concerning, is that false statistics and illegal actions are not required to deceive or impact the user.

    9. The examples in the first paragraph expanded on strategies used by businesses to manipulate users for financial gain. Although, this article does mention it to have "dark patterns", I believe it to be smart as a business decision but wrong morally. Next, I found interesting the anchoring effect example which can add to the tone of this article that points to a particular persons ability to understand certain facts, trends, and psychological biases to make an educated decision. These companies may have been morally wrong to some, but with the right education the users will understand what is trying to be achieved. I believe when private personal information is exposed is when an issue arises.

    10. The retail industry has a long history of deceptive and manipulative practices that range on a spectrum from normalized to unlawful (Figure 3). Some of these techniques, such as psychological pricing (that is, making the price slightly less than a round number), have become normalized. This is perfectly legal, and consumers have begrudgingly accepted it. Nonetheless, it remains effective: consumers underestimate prices when relying on memory if psychological pricing is employed.3

      I think this shows how normalized manipulation in retail has become, even when consumers are aware of it. Though it's legal, psychological pricing is a tool that can affect customers decisions without them knowing. For instance, if a product is on offer for $9.99, instead of $10, it makes one feel that the product is less expensive, although it is just one cent less expensive. I believe this ties into the way businesses use human psychology to boost sales numbers and wonder if these are ethical or just a form of sound business practice.

    11. The second weapon was A/B testing (Figure 5).

      Reading the article I think I've come to the conclusion that majority of these dark patterns comes from the initial idea that it's actually marketers pushing for these dark patterns. The reason why they are so prevalent is because it works in bringing more money for the business.

    12. Something that really stood out to me from this article was how companies use “dark patterns” as a form of deception to get people to agree to actions they typically would not, such as signing up for subscriptions or giving up private information. What surprised me the most was how websites will enlarge the “accept” button and make it very easy to click on, while shrinking the “decline” option below it or hiding it. Design can really affect peoples’ decisions without them fully realizing it until later. This was very insightful and something I had never considered before how often this occurs.

    13. Facebook asked users to enter phone numbers for two-factor authentication but then used those numbers to serve targeted ads

      This is a particularly predatory pattern because it exploits a user’s desire for security to increase corporate revenue. It forces users into a "privacy tax" where they have to choose between protecting their account and protecting their personal data

    14. Facebook asked users to enter phone numbers for two-factor authentication but then used those numbers to serve targeted ads;31 Match.com knowingly let scammers generate fake messages of interest in its online dating app to get users to sign up for its paid service.1

      I was very surprised by the example about companies using phone numbers from two factor authentiation for ads.. If people are giving their number for security reasons, they probably expect it to only be used to protect their account, not for other reasons. It makes companies seem less trustworthy because users don’t fully know how their information is actually being used and becausee lot of websites do this because it helps them make more money through ads

    15. A few egregious examples have led to public backlash recently: TurboTax hid its U.S. government-mandated free tax-file program for low-income users on its website to get them to use its paid program

      When reading this part in particular, I found it not only sickly but also felt like a sort of twisted attempt to get more money. TurboTax brands itself as free for everyone but when it hides its from side from low income user for the purpose to getting more money reveals that no matter how good it seems from a corporation that there is always something underlying factor, The factor here and in most other places is greed which is a common dark pattern for large companies who advertise being "free" as nothing is truly free in business.

    16. I believe dark patterns should be banned and if a company continues to use this then it should be fined and have legal actions taken. Designers and tech companies have a responsibility to the people to make good products without manipulating the people. The count down tactic gets a lot of people and its just alot of misinformation.

    17. TurboTax hid its U.S. government-mandated free tax-file program for low-income users on its website to get them to use its paid program;9 Facebook asked users to enter phone numbers for two-factor authentication but then used those numbers to serve targeted ads;

      I wonder if this had any serious legal repercussions or if companies are just getting away with it! especially the Facebook one, it makes you realize many of us arent as educated as we need to be regarding rules surrounding our data privacy.

    18. A third goal of dark patterns is to make services addictive. This goal supports the other two, as users who stay on an app longer will buy more, yield more personal information, and see more ads. Apps like Uber use gamified nudges to keep drivers on the road longer (Figure 6). The needle suggests the driver is extremely close to the goal, but it is an arbitrary goal set by Uber when a driver wants to go offline.24 To summarize, dark patterns enable designers to extract three main resources from users: money, data, and attention.

      I think this is seen more and more in today's world. Apps such as TikTok, Instagram, and YouTube are purposely making their apps addicting. I think this is unethical because these companies are promoting their profits at the expense of people's well being.

    19. Some of these techniques, such as psychological pricing (that is, making the price slightly less than a round number), have become normalized.

      A common tactic of many stores is to also make "fake sales". Sometimes, stores will artificially increase the price of a product and then put it on "sale" to it's original price, so that it seems like a good deal when you are actually just paying full price.

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      Referee #4

      Evidence, reproducibility and clarity

      RNAi is remarkably efficient in planaria, yet no mechanism for the amplification of the RNAi signal has thus far been observed. In this manuscript, the authors analyse the mechanisms of RNAi spread in planaria. Starting from some basic observations on the identity of the Dicer and Argonaute proteins required for RNAi, the authors performed a set of elegant experiments to conclude that cycling stem cells likely take up dsRNA and excrete Ago-siRNA complexes, which are then taken up by other cells to mediate RNAi. In addition, the authors provide compelling evidence that RNAi is indeed independent of an amplification mechanism.

      Overall, I found the experiments and results compelling and the manuscript a pleasure to read. I have only a few suggestions for consideration, none of which are essential to support the main conclusions:

      • What does the arrest of stem cell proliferation do to the expression of RNAi genes (with and without dsRNA stimulation)?
      • Page 9: top panel. Is there a control that the dsRNA generated by RNaseIII is functional? I.e. that the defect is indeed due to an uptake effect and not the quality of the siRNA preparation itself? (In our hands silencing of siRNA prepared with bacterial RNaseIII has not been efficient at all). As a side note: no method is provided for the RNaseIII treatment.
      • Have the authors analyzed which of the Argonautes are present in the preparations generated with Q-sepharose?

      Data presentation:

      • For all figure legends: please make sure to state animals, number of repeats, define boxplots and what the individual data points represent. Please provide statistics where quantitative statements are made.

      Minor points:

      • First paragraph results: The statement that Ago1 and 3 were "closer to the nematode-specific WAGOs" does not seem correct, (horizontal distance to the miRNA-AGOs is still lower than the the WAGOs). I suggest removing the statement.
      • Use of checkmarks: please define when a checkmark vs cross was indicated? E.g., does a checkmark indicate that 100% of the animals showed efficient RNAi, or a majority of animals?
      • Many of the legends contain conclusions. While this may be a matter of taste/style, I would suggest to introduce conclusions only sparingly, if at all, in the legends
      • Some of the font sizes are rather small on print size (e.g. Fig 1A, S4i). In Fig 1A the black font on dark blue background is hard to distinguish.

      Textual suggestion:

      • Abstract "that rely on dsRNA intermediates, such as viruses" > ".. such as those from viruses..."
      • Materials and Methods: The lowerscript numbers for the ion show as squares in my pdf.

      Significance

      Strength/weaknesses:

      I found the experimental support robust and well supported and I did not find weaknesses that jeopardize the conclusions.

      Significance:

      One of the most intriguing features of RNAi is the systemic spread of a silencing signal across an organism's body. This has received significant attention in C. elegans and plants, but for other organisms, this is much less well explored. Planaria have a very efficient RNAi response, which the authors propose is due to uptake of an initial dsRNA by stem cell and excretion of an Argonaute-siRNA complex, which is then taken up by distal cells in an endocytic mechanism. I find this an intriguing mechanism that to differ from mechanisms for RNAi spread observed in other organisms.

      The work will be of interest to those interested in small RNA pathways (and RNA biology in general) and has practical implications for scientists working on planaria. The fact that small RNAs spread in an Argonaute-siRNA complex in an organism should also be of interest for cell biologists.

      My field of expertise: Small RNA pathways and antiviral defense in insects. No experience working with planaria.

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      Referee #3

      Evidence, reproducibility and clarity

      In RNA interference (RNAi), double-stranded RNA (dsRNA) is processed into small interfering RNAs (siRNAs), which can function locally or act as mobile RNA species that spread between cells. In organisms such as nematodes and plants, the underlying mechanisms and key factors involved in this process, including transporters such as SID-1, have been well characterized. While systemic RNAi has also been reported in other animals, the underlying mechanisms remain largely unclear. In this context, the authors focus on planarians as one such model to investigate these processes. In the planarian S. mediterranea, gene knockdown by dsRNA injection is commonly employed, and the RNAi effect is known to spread rapidly throughout the organism. However, given the absence of RNA-dependent RNA polymerase (RdRP), the mechanism by which RNAi signals are efficiently propagated remains unclear. In this study, the authors provide several important insights into this question.

      First, the authors carefully evaluated the duration of the RNAi effect. In addition, they systematically examined the involvement of known RNAi-related factors and demonstrated that this process depends on ago1 and ago3. Second, interestingly, the authors find that initiation of systemic RNAi depends on neoblasts. Third, Argonaute-siRNA complexes play a crucial role in systemic RNAi. This differs markedly from the nematode system, in which dsRNA itself is transported, highlighting an intriguing mechanistic distinction. Finally, the authors suggest that distinct Argonaute proteins may function at different stages of RNAi propagation. Ago1 + Ago3 play essential roles in the initial phase of systemic RNAi in neoblast, Ago3 but not Ago1 silences the target in the differentiated cells. While the phenomenon described here is highly interesting, the underlying mechanism remains to be fully elucidated. In particular, how different Argonaute proteins functionally coordinate with each other, especially with respect to the transfer of siRNAs between Argonaute complexes, is still unclear and represents an important direction for future studies.

      The study is supported by well-designed control experiments, and the results are consistent with and support the authors' conclusions.

      I have no major concerns about this manuscript. The study is well conducted, and I only have minor comments that could further improve the manuscript.

      (Minor) While the authors have examined the effects of irradiation on the donor, it would be interesting to test the reciprocal experiment in which the recipient is irradiated. In particular, assessing whether the addition of donor lysate to irradiated recipients can recapitulate the observed RNAi propagation would further strengthen the proposed model.

      (Minor) The purity of the AGO complexes obtained via the TraPR anion-exchange procedure is not entirely clear. The authors may consider providing additional evidence of purity (e.g., visualization of small RNAs with T4-PNK), which would strengthen the conclusions.

      (Minor) Figure 4H is not referred to in the main text. The authors may consider incorporating a description of this panel into the Results section for clarity.

      Significance

      Overall, given the substantial amount of data and the overall high quality of the present study, further mechanistic dissection would likely be beyond the scope of the current manuscript. I look forward to future work from the authors addressing these mechanistic questions in more detail. RNAi has been widely used in stem cell research in planarians. In light of the findings presented in this study, however, previous studies that combine UV irradiation and RNAi may warrant careful re-evaluation. In this regard, the present work has important implications and is likely to have a broad impact on the field.

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      Referee #2

      Evidence, reproducibility and clarity

      In this paper, the authors set out to understand how dsRNA elicits a system-wide RNAi effect using planarians as a model system. This is an important question, because it gets at evolution of these processes in different animal models and because knowing more about how RNAi works can allow scientists to tweak their approach for a better knock down efficiency. Importantly, though the system-wide mechanism of RNAi is fairly well understood in C. elegans and in some plants, it isn't clear how conserved these mechanisms are. Some aspects of this paper are quite convincing, including identification of the responsible Argonaute and Dicer proteins. Further, the identification of potential Sid-1 homologs that may allow for import of dsRNA is new. However, the role for Ago-3 was recently reported in Sasidharan, et al (Science Advances, 2026), which is not cited in this manuscript. Perhaps more importantly, several key aspects of the argument set up in this paper are not adequately supported and there are key gaps in the mechanism proposed that prevent its publication in this form. Major and minor suggestions follow:

      Major issues:

      1. The argument that siRNAs must be generated in stem cells that are cycling is not well supported.

      a. The authors only use one approach to reduce stem cell numbers, lethal irradiation. In addition to causing loss of stem cells, lethal irradiation causes wide-spread DNA damage and organismal/cellular stress responses. By 6 days after lethal irradiation, other progenitor cells are lost as well. Epidermal progenitors are known to be very abundant and to play signaling and/or metabolic roles in planarian physiology, so their loss may also be impactful. The authors should consider other orthogonal approaches to eliminate stem cells and to rule out other potential mechanisms.

      b. The authors use camptothecin in planarians and claim that it reduces cell divisions of stem cells. To my knowledge, this drug has not been shown to work in planarians before. The concentration used is also higher than in published studies. The authors should show whether stem cells are lost after this drug treatment (through levels of stem cell markers or stem cell counting) and should clarify the timing of the treatment relative to the RNAi, which is not clear from the figure legend or methods section. The authors should also discuss possible alternative interpretations of this piece of data (e.g. potential off-target effects). Without more information, it is hard to interpret the data relative to the irradiation results. The authors also do not provide any insight into how or why dividing/cycling stem cells would be important for the systemic RNAi mechanism they propose.

      c. ago-1, ago-3, and dcr-2 were shown to be enriched in stem cells (Fig. 3C), but these genes are also expressed in differentiated cells in single-cell sequencing data. Therefore, it isn't intuitive that non-stem cells would lack the capacity to generate siRNAs.

      d. Is there a way to directly test the hypothesis that stem cells are only generated in stem cells, potentially by blocking transport in some way and then visualizing new siRNAs with a miRNA/siRNA version of ISH OR FACS and sequencing? If the Ago-1/3-siRNA complexes are indeed transported by EVs as per Sasidharan, et al then the ESCRT(RNAi) approach might be useful in blocking movement of siRNAs? Or, could the authors show that dsRNAs are preferentially taken up by stem cells using the type of experiment shown in Fig. S5H? 2. It isn't clear from the manuscript how the authors believe that Ago-1/3-siRNA complexes exit and enter cells. The diagram in Fig. 5F describes the complex as moving between cells either through vesicles or extracellularly. How do the authors propose that Ago-siRNA complexes pass through the plasma membrane given that they are not known to go through the secretory pathway? Or once endocytosed, how do they exit the vesicle? Uncertainty on these points makes the molecular mechanism proposed here seem poorly supported by the data provided in the paper. 3. One key result in the paper is the transplant of "AGO complexes" that are purified from lysate. The authors writing about this experiment implies that they are transplanting a fairly pure material representing these RNPs and no others. However, the approach described is unlikely to result in purification of highly specific protein complexes. At a minimum, gels that illustrate protein/complex purity should be provided. Preferably, though, mass spectrometry and sequencing would be provided to detail siRNAs and proteins in this sample. 4. The Sasidharan, et al (Science Advances, 2026) paper should be cited and also the findings of this paper should be put in the context of that work.

      Minor changes:

      1. In several experiments, quantitative assessment of impacts (e.g. eye size or ovo/opsin transcript levels) rather than subjective eye scoring would be preferable for rigor and for statistical analysis of changes rather than check/X (e.g. 4F-H).
      2. F1 and F2 terminology for regenerates is probably not accurate since F in those terms stands for "filial" and is used to denote offspring.
      3. The images in Figure 2 (A, C) are quite hard to see on the printed page. Using white for fluorescence might improve contrast and visibility.
      4. The element of time seems to be very important for transmission of the RNAi effect in sexual offspring. Instead of the claim that hatchlings from RNAi crosses have no effect (Fig. 2H), the detail provided in the results section seems to indicate that there is a time-limited effect. These findings should be clarified with progeny sorted by time of egg laying and with a better sense of time between RNAi injection and hatch. Further, even in animals that do regenerate eyes, it would be nice to see a quantification of transcript as a clearer readout of whether some knockdown persists.
      5. This is more of a curiosity question, but it would be interesting to know how the differences in Ago1/2/3 protein structure might relate to their function, particularly in terms of the PAZ and MID domains.

      Significance

      This paper provides some new insight into mechanisms underlying systemic RNAi in planarians. Some of the results are quite preliminary and the overall interpretation of data is not yet well founded. However, there are some highlights, including the potential identification of dsRNA transporters that will be interesting to those in the planarian field.

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      Referee #1

      Evidence, reproducibility and clarity

      Summary

      In this manuscript, the authors characterized the molecular mechanism of systemic RNAi in planarian Schmidtea mediterranea (Sme) through loss-of-function genetic perturbations. They genetically identified key protein factors involved in the siRNA pathway and assessed the systemic RNAi efficacy at the molecular level. Notably, they find that the proliferating stem cells (neoblasts) are specifically required for systemic RNAi in Sme. They further propose that the requirement of neoblasts in systemic RNAi is mediated by spreading of the RISC RNP to differentiated cells.

      Major Comments

      1. The authors show that in Sme systemic RNAi strictly relies on the presence of neoblasts, which is one of the most interesting finding. It is important to understand the mechanism, specifically whether neoblasts are generally required for dsRNA processing or for conferring mRNA slicing activity. Although the authors claimed in Figure 5 that neoblasts are required for siRNA biogenesis, the results provided do not directly support this claim. An alternative scenario is that dsRNA can still be processed into siRNA in the absence of neoblasts, but the resulting siRNA subsequently fails to function without the neoblast AGOs or other signals. To directly confirm that neoblasts are required for dsRNA processing, one additional experiment should be performed in which irradiated worms are injected with dsRNA, followed by small RNA cloning and sequencing to detect whether processed siRNAs are present.
      2. An alternative mechanism to interpret the role of neoblasts is that, instead of processing dsRNA and/or spreading RISC RNP, the neoblasts may function as regulatory cells that provide signals licensing the dsRNA processing and target slicing in differentiated cells. Under this scenario, the requirement for sid-1 and vha-16 could instead be interpreted as necessitate the dsRNA transfer from the initial uptake tissues (parenchyma for be injection or intestine for feeding) to the target tissues. To rule out this possibility, isolated neoblasts from naive donors could be transplanted into irradiated recipient worms who have been injected with dsRNA, and whether such transplantation can restore the systemic RNAi in the recipient animals could then be tested phenotypically. One caveat is that any positive result may be due to the proliferation of the donor neoblasts in the recipient. This can be addressed by performing the same transplantation but using neoblasts isolated from camptothecin-treated worms, which would limit the proliferative contribution.
      3. In Figure 5E, the authors show that recipient ago-3 is required for systemic RNAi, and they suggest in the Discussion a plausible model in which recipient AGO-3 is required for nuclear RNAi for transcriptional target repression. However, this result appears inconsistent with the results in Figure 1C-D, where ago-3 KD did not abolish systemic RNAi. This contradiction should be acknowledged in text and further investigated. One possible interpretation is that the presence of the neoblast ago-3 from the donor lysate may have an antimorphic effect and interferes with the recipient AGO(s) (presumably ago-1 in this case) during target silencing , implying that homogeneity of AGO(s), or at least homogeneity of ago-1, is required for such systemic RNAi. Although the underlying mechanism remains difficult to interpret, such hypothesis could be tested by injecting lysate from ago-3 KD donor into ago-3 KD recipient. If AGO homogeneity is indeed required, such transfer treatment should no longer abolish systemic RNAi in the recipient in Figure 5D. Additionally, the target genes used for the systemic RNAi in Figure 1C/D and Figure 5E are different. To exclude the possibility that this discrepancy is target-specific, either six1/2 should be tested in the whole worm RNAi assay in Figure 1 or opsin should be used in the transfer assay in Figure 5.
      4. The authors claim in Figure 4 that the systemic RNAi is mediated by secreted RISC. This claim is not unexpected, because naked siRNA generally suffers poor half-life in vivo and therefore must be stabilized by bounding to AGO to evade the endogenous ribonucleases. Nevertheless, the alternative hypothesis that the transferred RNAi is mediated by the spread of naked RNA, though unlikely, should be experimentally excluded. Specifically, the isolated RNA and lysate with protease in Figure 4F (which failed to induce RNAi in the host worm) should be tested to confirm whether they contain siRNAs. This can be done by cloning and sequencing the sRNA in the lysate.
      5. The authors assigned ago-1 and ago-3 to the siRNA pathway and ago-2 to the miRNA pathway. This is an important conclusion for subsequent sRNA studies in planarians. However, the evidence provided in the current manuscript is insufficient to exclude ago-2 from the siRNA pathway, especially given that DDH catalytic triad is present in AGO-2. The observed redundancy between ago-1 and ago-3 to maintain functional RNAi can only support the involvement of these two AGO genes in the siRNA pathway but does not exclude AGO-2. To more rigorously test whether ago-2 should be excluded from the siRNA pathway, double RNAi of ago-2 and ago-1, as well as of ago-2 and ago-3, should be performed, and ago-2 should only be excluded from the siRNA-pathway if such double KD do not further reduce the RNAi efficacy compared with individual KD.
      6. The results shown in Figure 1F, where exposure to exogenous dsRNA can enhance the endogenous transcription of ago-1 and ago-3 in Sme, are particularly interesting. The authors should discuss whether this phenomenon is related to nuclear RNAi. In addition, it has been reported that exposure to exogenous dsRNA can increase the AGO/DICER protein levels without increasing the mRNA level (PMID32194567), and this should be compared with the present findings. Importantly, the result also suggests a potential strategy to improve the Sme RNAi efficiency. Accordingly, it would be valuable to test whether the increased ago-1/3 transcript levels caused by introducing exogenous dsRNA can lead to higher RNAi efficacy, both in terms of target silencing depth and the duration of RNAi effectiveness.
      7. Figure 2I-J provides remarkable evidence that the systemic RNAi in Sme is independent of RdRP. This result should be highlighted in the final paragraphs of the Introduction and mentioned in the Abstract.

      Minor Comments:

      1. The authors show that ago-1 + ago-3 KD only slightly perturbed the miRNA levels. However, this observation can be interpreted in at least two ways: (a) these two AGO genes are not involved in the miRNA pathway; or (b) these two genes are expressed at low abundance (which was mentioned later in the paper), such that their KD only mildly perturb their associated miRNAs, especially if these miRNAs are also associated with AGO-2. Scenario (a) seems less likely to be true because ago-2 is enriched in neoblasts (Figure 3C), whereas many conserved miRNAs have been reported to be enriched in Xins in Sme (Sasidharan et al 2013). This issue should be therefore discussed. In addition, the gene expression levels of the three ago genes from previously published bulk RNAseq datasets should be included in the figure.
      2. The illustration in Figure 1A is not fully accurate. In the miRNA pathway, target repression also includes mRNA degradation (which is conventionally referred to as mRNA decay or mRNA destabilization), which is in fact the dominant mode of miRNA-mediated repression. Therefore, "mRNA decay" should be added in addition to "translational inhibition". In the siRNA pathway, mRNA degradation is not directly mediated by RISC itself, but by the downstream exonucleases (i.e., XRN-1); therefore, the term "mRNA slicing" should be used instead for the siRNA part. Additionally, it has been shown that C. elegans RDE-1 is also associated with miRNAs (PMID 36790166), so the functional assignment in the model should be adjusted accordingly.
      3. In Figure S1C, the authors claimed that ago-1 and ago-3 exhibit more divergent PAZ and MID domains according to the AF modeling. However, this divergence may simply reflect the lower sequence conservation of AGO-1 and AGO-3 relative to AGO-2, which is shown in the phylogeny in Figure S1A. To address this caveat, Robetta modeling should be performed for both the full-length proteins in the comparative modeling mode due to the length of AGO proteins, or de novo modeling of the PAZ and MID domain. Structural the alignment in reference to solved AGO structures such as 4W5Q or 6N4O should be shown. If the MID/PAZ domains divergency remains evident, it should be quantified using backbone RMSD relative to known AGO structures.
      4. In Figure S1C, a second structural view should also be included to better illustrate the AGO architecture. The duplex channel within the PIWI-MID lobe should be clearly visible in one of the views. The L2 domain, or at least helix-7, should be labeled. If possible, the relative position of helix-7 to the guide RNA should also be shown. All the predicted structural models should be included in the supplemental files.
      5. The authors suggest that the spread of functional RISC from neoblasts depends on EVs. The evidence involving vha-16 is convincing, but to directly validate the presence of EVs that cargo RISC, CsCl ultracentrifugation would be informative. Although this experiment is beyond the scope of the current manuscript, the need for direct EV validation should be discussed.
      6. In Figure 2G, the authors show that although zfp-1 restores the homeostatic mRNA level at week 5, its downstream target prog-1 and agat-3 fail to recover. It remains unclear whether this is due to the delay of newly translated zfp-1 to activate the downstream targets, or due to translational suppression of zfp-1. Therefore, the mRNA levels of prog-1 and agat-3 should be further monitored beyond week 5.
      7. In Figure 3, the authors use co-expression by in situ hybridization to demonstrate the expression of ago in neoblasts. To provide the whole-animal context, co-expression of smedwi-1 and ago genes should also be confirmed using the current Sme scRNAseq datasets.
      8. The authors proposed in the Discussion that AGO-1 may sponge unwound RNA duplex and this facilitates the dsRNA transfer. This interpretation seems unlikely, because the ago-1 single KD, which would abolish such dsRNA transfer, did not show phenotypes in terms of systemic RNAi defect. Also, such scenario suggests that loss-of-function of ago-1 may be antimorphic since the sponged dsRNA were released, and thus co-KD of ago-1 and ago-3 should result in more efficient RNAi. These concern should be discussed.
      9. The Discussion states that AGO-1 is required in the donor, but this is inconsistent with the results in Figure 5D, where ago-1 KD in the donor did not abolish RNAi in the recipients. This inconsistency between results and text should be corrected.
      10. In Figure S5I, the authors show that short dsRNA generated by RNase III digestion failed to induce systemic RNAi in sid-1 loss-of-function condition. However, the alternative explanation is that RNase III digestion produced short dsRNAs that may result in siRNA with suboptimal length for AGO loading or functioning. This caveat should be mentioned, and the length profile of the RNase III digestion products should be shown by high density urea gel electrophoresis or HPLC.
      11. In all the transfer assays, one concern is the lysate may contain viable neoblasts, so that any observed results could be attributed to the proliferation of the donor-derived neoblasts rather than the transfer of RNAi materials. Therefore, a cell viability test using Calcein AM or other equivalent assay should be conducted to confirm the absence of live cells in the lysate preparation protocol.
      12. In the second paragraph of the introduction, when comparing the siRNA and miRNA pathways, the difference in base-pairing configuration with the target site should be introduced with appropriate reference.
      13. In the last paragraph of the introduction, the claim that the results may have implications for the design of effective RNAi-based therapies is too vague. Given that the current therapeutic siRNA delivery methods are already robust in clinical applications, the authors should more specifically explain how their findings in Sme might inform therapeutic development.
      14. In the last sentence of the second last paragraph of the introduction and Figure S5I, "RNAse" should be corrected to "RNase".
      15. In the first Results subsection, the second last paragraph, first sentence, one left parenthesis is missing.
      16. Throughout the Discussion, the term "AGO-RNA". If the authors intend to express a distinction from RISC, how this terminology differs from RISC should be justified. Otherwise, RISC would be more appropriate.
      17. Statistical significance should be shown in Figure 2E, 2G, 3A, 3C, S2A, S2D, S2G, S3D, S5D, S5G, S5J.
      18. Molecular weight should be labeled in Figure S5L.
      19. In Figure 2J, where the y-axis indicates % prevalence, the down-facing bars (antisense reads) should also be labeled as positive values on the y-axis. Displaying them as negative percentages (-20%) is incorrect.
      20. The small RNA cloning procedure should be described in the Methods. Basic information of sRNA sequencing, including read numbers, biotype distribution, proportion mapping to the triggering dsRNA, should be included too.
      21. The methods used to measure RNA and protein concentrations should be included in the Methods section.
      22. The irradiation protocol, including dosage, should be included in the Methods.
      23. In the Methods section, subscripts of chemical formulas are rendered as squares throughout the text. This formatting issue should be corrected.
      24. In the Results section, first subsection, second paragraph and first sentence. The cited data should be Suppl Figure S2D, not the current S2A-C.
      25. The manuscript uses inconsistent formatting for supplemental figures (for example, "Suppl Figure S1B,C" versus "Suppl Figure 2A-C"). The formatting should be standardized.

      Significance

      Planarians have long been appreciated as a robust model organisms for studying gene function in animal regeneration, and one major advantage of this system is its highly efficient systemic RNAi. However, the molecular basis of the RNAi machinery has not been thoroughly investigated, and detailed RNAi efficacy hasn't been evaluated. This study therefore provides important value by characterizing the molecular components underlying systemic RNAi in Sme, which contributes to both fundamental understanding and to potential optimization of RNAi-based experiments in Sme.

      In addition, the manuscript reports that stem cells are required for systemic RNAi in differentiated cells in Sme, a finding that has not been described in other organisms. Although the underlying mechanism remains unresolved, this observation offers potentially important implications for both RNA biology and stem cell biology.

    1. Dentro de la casa estaban Roberto, Amelia y sus hijes pequeñes. El expediente reconstruye un ataque sostenido durante horas. Exconscriptos relataron que se utilizaron fusiles FAL y otras armas, como una ametralladora antiaérea montada sobre trípode, que disparó directamente contra la vivienda, y una bazuca para destruir parte de la estructura.

      !

    1. Will Canada compete in Eurovision? We want to knowEurovision director Martin Green says Canada's entry is possible but no request or decision has been made. Any participation would need European Broadcasting Union (EBU) approval. CBC/Radio‑Canada is an associate EBU member and not currently eligible to compete. However, the public broadcaster is sending observers to this year's Eurovision Song Contest while talks continue.Door is open to Canada, director of the song contest says

      Good example of accessibility, the headline is straight to the point and a clearness that helps those with assistive technologies quickly navigate and understand the article.

    2. Will Canada actually join Eurovision? Not without some challenges, experts say

      To have an another individual article that further expands that topic is great because it adds valuable information but by not having it integrated with this article, it makes it cluster-free and it invites those who wish to read more about it to do so, while those who just want an basic knowledge of the news to only read this short article.

    3. WATCH | Door is open for Canada to compete in Eurovision, director says:Eurovision director says the door is open for Canada2 hours ago|Duration 0:24Eurovision director Martin Green told the BBC he's aware of rumours that Prime Minister Mark Carney has expressed interest in Canada joining the annual singing contest, but emphasized that no decision has been made.

      While having a built-in preview of a video can make it very accessible and less of a hassle for the readers, it also adds figures that now become possibly too many considering the length of the article.

    4. The Eurovision Song Contest, which features countries performing original songs, is run by the European Broadcasting Union (EBU). Full participation in the annual singing contest has traditionally been reserved for broadcasters that are full members of the EBU, but the contest has allowed a handful of non-European or associate-member participants in recent years — most notably Australia, which was invited to compete first as a one-off in 2015 and has taken part in subsequent contests under special arrangements. CBC/Radio-Canada is an associate member of the EBU, a status it has held since 1950. In an email to CBC/Radio-Canada's public affairs office following earlier reporting, Leon Mar, the broadcaster's senior director of public affairs, reiterated that associate membership does not equal eligibility to compete in Eurovision. "Participation in the Eurovision Song Contest (ESC) is for public broadcasters who are full members of the European Broadcasting Union (EBU)," he said. "As an associate member, CBC/Radio-Canada is not eligible to participate in the ESC," he wrote. AnalysisWhy a song contest has emerged as Europe’s most controversial electionWill Canada actually join Eurovision? Not without some challenges, experts sayMar confirmed, however, that CBC/Radio-Canada is engaging with the EBU and maintaining a presence at the contest. "I can confirm that we have three staff attending the ESC as observers and that we are talking with the EBU about how we can collaborate more closely and exchange more content, namely through the Eurovision News Exchange and the Euroradio Music Exchange," he said. Mar also emphasised CBC/Radio-Canada's editorial independence, noting the broadcaster is a "federal Crown corporation that operates at arm’s length from government," and that its independence is protected under the Broadcasting Act. The idea of Canada joining Eurovision briefly surfaced in last year's federal budget, when the government said it was working with CBC/Radio-Canada to explore possible participation in the annual contest. Two government sources told CBC News at the time that Carney was personally involved in pushing the initiative. When asked about Australia's special status — competing at Eurovision despite being outside of the EBU's geographic area — Mar recommended contacting the EBU directly for details.

      While it is great to have a structure that isn't filled with paragraphs, the spacing between all these texts can possibly make one feel like overwhelmed and some of these could possibly be combined into one paragraph that actually makes it easier to read instead of these broken down ones.

    5. Listen to this articleEstimated 3 minutesThe audio version of this article is generated by AI-based technology. Mispronunciations can occur. We are working with our partners to continually review and improve the results.

      A built-in listening aid is great for accessibility and it doesn't require external apps or aids, which makes it very simple for the any reader to have that option as they wish.

    1. убу настільних ігор через невдоволення діями багатьох учасників того клубу. Ми хочемо

      длььдл

    1. Britannica Editors. "Jezebel". Encyclopedia Britannica, 25 Mar. 2026, https://www.britannica.com/biography/Jezebel-queen-of-Israel. Accessed 11 May 2026.

      This entry should follow the same format as the dictionary entry for Dilettante

    2. Natalie Clifford Barney's own annotated copy of the book

      Where did you get access to this annotated copy? This would be a great resource to link to and should be included in your Bibliography.

    3. She writes phrases like "Hussy with the Honey Head," "Jockey with the Pelvis plump," and "high-hipped Wrestler with the Rump" (60).

      Not only satirical but very bawdy, scatalogical, and explicit. Lots of references to body parts, especially ones with sexual/erotic functions!

    4. Each sign connects to a body part of the woman,

      This zodiac sign also evokes two other symbolic traditions:

      1. the Blazon, the catalog of female body parts that appears in lyric poetry from Petrarch on ("her eyes are like diamonds, lips like cherries...)
      2. The St. Sebastian motif, a saint who was killed by a thousand arrows and who, Richard Kaye argues, became a homosexual icon by the late 19th century.
    5. s "that women were weak and silly Creatures, but all too dear," and High-Head says "that they were strong, gallant, twice as hardy as any Man, and several times his equal in Brain, but none so precious"

      echoing (and parodying) a cultural tendency to either denigrate or idealize women, with nothing in between.

    6. n The Bible is elevated to an idol herself is significant because it presents the dichotomy of what is deemed good and evil in this narrative. By

      Excellent point! As with her evocations of Christianity, she is subverting -- or even inverting -- traditional moral values. And remember "sexual inversion" was consider a valid theory of homosexuality at the time.