Case#: DNAID 072888/Pat258, female

DiseaseAssertion: STGD1

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: "In classic STGD1, loss of central vision starts around the second decade of life, but both early- and late-onset subtypes have been extensively described." No patient-specific details provided

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: smMIPs sequencing of the complete ABCA4 locus

PreviouslyPublished: n/a

Variant: c.6416G>C (p.Arg2139Pro); c.3323G>A (p.Arg1108His)

CAID: CA10611614

SupplementalData: tables s9 and s11

Case#: Patient 14, female, age 42

DiseaseAssertion: STGD

FamilyInfo: diagnosis of autosomal recessive STGD based on the pedigree and clinical phenotype of fleck deposits with or without genetic testing

CasePresentingHPOs: HP:0000608, HP:0000007, HP:0030610, HP:0030500

CaseHPOFreeText: Macular degeneration. autosomal recessive, Photoreceptor outer segment loss on macular OCT, Yellow/white lesions of the macula

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

Genotyping Method: n/a

PreviouslyPublished: n/a

Variant: Allele 1: NM_000350.3:c.4222T>C Allele 2: NM_000350.3:c.4918C>T

ClinVar:Allele 1: NM_000350.3(ABCA4):c.4222T>C (p.Trp1408Arg) Allele 2: NM_000350.3(ABCA4):c.4918C>T (p.Arg1640Trp)

CAID:Allele 1: CA227166 Allele 2: CA227253

SupplementalData: composite mask analysis shown in figure 3 for patient 14, show diffusely intact IS/OS and RPE with central area of mixed types of degeneration. Both patient 2 and 14 show foveal preservation of IS/OS and RPE

A ClinVar entry claimed this variant showed "impaired substrate binding capacity and limited substrate release after ATP binding," but it is not found in the text or figures and there is no supplementary data.

Case#:case 1 II:4

DiseaseAssertion: Stargardt disease (STGD1)

FamilyInfo: mother has identical phenotype as proband, dad and sister asymptomatic, brother was symptomatic at 8 years old, other brother symptomatic at 15 years old.

CasePresentingHPOs: HP:0000007

CaseHPOFreeText: at age 50, with central visual imparement in right eye, 20/40 right, 20/20 left, linear and branching hyperautofluorescent subretinal deposits and extrafoveal RPE atrophy in both eyes,

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

Genotyping Method:

PreviouslyPublished: n/a

Variant: c.6031_6044delins18M/p.(Ile2003LeufsTer41)

ClinVar: not found

CAID: not found

SupplementalData:

Case#: Sporadic Case #16, Mexican

DiseaseAssertion: Stargardt

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: STGD diagnosis based on: "onset of symptoms in childhood or early adulthood (before 20 years of age), bilateral central vision loss (central and peripheral visual field computerized testing), a retinal “beaten-bronze” foveal appearance and/or yellow-whitish flecks from the posterior pole to the mid periphery, normal caliber of the retinal vessels, no pigmented bone spicules in the retinal periphery, a normal to subnormal electroretinogram, and a typical dark choroid in fluorescein angiography."

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: allele 1: c.2453G>A (p. G818E); c.5824G>C (p. E1942Q) allele 2: c.6384A>G (p.H2128R) direct sequencing of exons of ABCA4

ClinVar: 867010

CAID: CA957117

SupplementalData: n/a

これ多分意味のある処理じゃなくて、ただCPUを使いたいから計算しているだけですよね。ただ、そういうことをdocstringに書いてほしい。ちょっと読者に委ねすぎだと思います

日本語の方が親切だと思います。っていうかコードのcaptionと同じだったら同じ文章入れておいた方がよいかと

MUST: コードがそこそこ長さがあるので、以下のコードではこういうことをやっています、という説明が先に欲しい。 そしてコードにコメントを入れてほしい

ベンチマークじゃなくても、実際にGILなしで動いているか確認するためには重要かなと思いました

nits: Python 3.14なのでダブルクォートでおいかと。このあとの文章中での表記とあわせる

可能であれば、何を比較するか書いてほしい。

HB Lead Grades Explained + How to Select Right Pencil for Writing & Art<br /> by [[Unnecessary Detail]] on YouTube<br /> accessed on 2026-09-20T23:58:33

HB is typically the mid-point for most manufacturers <br /> H (hardness) tends to go lighter and scratchier (less graphite, more clay)<br /> B (darkness) tends to go darker and smoother (more graphite, less clay)<br /> F is typically a grade (fine/firm) between H and HB

For general writing look in the range of H / F / HB / B / 2B

Charcoal pencils tend to be much darker that clay/graphite pencils.

In the United States, pencils are often graded from #1 to #5 with the #2 being equivalent to HB.

其中： - @Before：只能在目标方法执行前做一些事。 - @Around：可以决定目标方法是否执行。 - pjp.proceed()：代表调用原来的目标方法；如果不调用它，目标方法就不会执行。 所以，@Around 常用于日志、权限检查、事务、耗时统计等功能

Bioavailability is the fraction of a medication dose that reaches systemic circulation; it is 1 (100%) for intravascular administration and less than 1 for other routes when some drug fails to enter circulation.

Extravascularly means a drug is given outside the vascular system, so it must be absorbed before reaching systemic circulation.

aka gen z gender role

observed/recorded. By definition it was not "assigned"

5 Stages of Lead Holder Usage & Collection - 2mm Mechanical Pencil Buying Guide<br /> by [[Unnecessary Detail]] on YouTube<br /> accessed on 2026-09-20T23:56:00

Lead Holders Explained in 5 Levels of Detail - 2mm Mechanical Pencils<br /> by [[Unnecessary Detail]] on YouTube<br /> accessed on 2026-09-20T23:37:00

Why You Must Try 2mm Lead Holders vs. Wooden Pencils, Fountain Pens & Mechanical Pencils<br /> by [[Unnecessary Detail]] on YouTube<br /> accessed on 2026-09-20T23:24:15

I was not aware of the repeated incidents of racism on google as a search engine. It makes me wonder why its just now I'm hearing about this, it makes me suspect the algorithim hides controversial issues like these away from public view.

This would strengthen assumptions that the company purposely desgined the system in that sort of way because this incident has already occured before.

Users might assume that google is denying accusations of creating a racially influenced algorithimns in their keyword planner to avoid public backlash.

The evidence of no correlation with white with pornography differing from other racial groups leads to evidence of racial bias concerning adult media. Their previous research supports their conclusion as they displayed search categories not including white pornography.

The reporters share how google's advertisement relates ethniticies, exept for white, with pornography. It displays hints of fetishzation of ethniticities while trying to keep whites 'pure' from adultry.

When not payment of money, interest on the amount of damages (discretion of court).

Interest runs from time claim if made judicially or extrajudicially. (if claim is quantified or reasonably certain) OR From the date the judgement of the court is made. (if without quantification)

When obligation is payment of money, interest is paid from judicial demand.

Interest on interest will also be computed from default.

Reqs for Compounding/Interest on Interest: 1. Stipulation by parties to add compounding/capitalizing interest in addition to principal interest. 2. Judicially demanded

September 19, 2026<br /> by [[Heather Cox Richardson]] in Letters From an American<br /> accessed on 2026-09-20T22:51:34

I dont agree with this, i find highlighting helpful for me and has helping my studying alot.

I can be that student sometimes but I'm trying slow down and take all the steps necessary.

I think were lucky to have this at our finger tips. Have a question? google it. want to confirm something? google it. want to lean more about something? google it.

At times I like to do this since things are more fresh in my head and helps me remember.

Being able to relate to something has helped me have a better understanding.

I use to be to shy but i've come to find out sometimes other students can be just as lost or confused as i am. I've learned to speak up and ask!

As someone who has been in sports i live by this. Practice makes perfect. Yes its not literal but meaning it will come close to it.

testing

September 18, 2026<br /> by [[Heather Cox Richardson]] in Letters from an American accessed on 2026-09-20T22:33:34

Copilot says that the Turks valued Cyprus's strategic position in the Mediterranean near the Ottoman territories and thought it dangerous to leave it in the hands of the Venetians, their territorial rivals.

for studying I feel like this can be over whelming and is not best to multitask.

I also disagree, I can multitask and be at a higher performance.

Having a child I can definitely relate to this doing homework/studying and my daughter wanting my attention at the same time.

With technology now a days and how easy accessible it is, it can definitely interfere with focusing on studying.

I find this accurate, for myself I have certain places I do a lot better studying in than others.

If Y -> A and X -> A, then by theorem 2.1, this structure is the same for all members of the equivalence class. This means that Y -> A and X ->A. By definition, a Markov relation indicates that two variables are related in some joint process.

G is overloaded. The G in the left is an arbitrary graph. The G on the right is variable.

strictly speaking, this is an image set.

Iago presence on both sides of this debacle could outline one of two things. It could be a foreshadowing of how Brabantio is actually far worse than the other characters in terms of discrimination. It could also mean that Iago is a more complex character, siding with both out of whatever aversion for the wrath of one.

yes I think I will be able to

I think staying disciplined with my work will be hard for me

I will need to take 5 courses

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Marriage was obviously more of an official matter than an emotional one at this time. For his daughter to get married to Othello without the permission of the family would be considered a great disservice to her father and house. For Brabantio to not know at all that his daughter is gone and married to Othello should be considered an act of stupidity considering how important marriage is for politics.

I asked for Copilot's interpretation of this line in order to gain a better interpretation of what the Shakespearean intention behind this line was. It said that this was more of a threat of verbal power than one of physical imposition, which was what I suspected anyway. The fact that this threat is one of verbal sharpness indicates that Brabantio either means the two outside his window no actual harm or that he does not have the power to punish them through force anyway.

This line is quite clearly both crude and discriminatory. Copilot says that is "dehumanizes Othello... sexualizes the situation... exploits racial prejudice... [and] creates urgency." While this line would probably be taken seriously by many nobles of this era, Brabantio seems rather unfazed and more annoyed by the random men shouting at his window. This makes his relationship with Othello one different from the rest of the characters immediately.

This line, while most likely at least somewhat serious in the original, could never be taken seriously by a modern audience. A newer interpretation would lean into extreme sarcasm with a line lilke this.

This reveals his real intentions: people think he is nice and trustworthy while he is just planning his revenge — and he says it out loud to Roderigo, who's too dumb to use it.

Iago thinks he deserves it more because he actually fought at Rhodes and Cyprus, while Cassio only knows war from books.

Iago is jealous of Othello: he says Othello just dodged the three men with big empty war words instead of giving a real answer.

This first sentence is basically just Roderigo talking angrily about Iago and how he uses his money.

Learn how Callyzer helps businesses analyze call data, track marketing performance, identify trends, and make better data-driven decisions.

Know More: https://www.kompasiana.com/dhruevnponkiya8101/6aaa7906c925c425db7af633/how-to-calculate-and-reduce-costly-idle-time-in-sales-teams?page=1

I think Step 4: Study is the most important because it teaches students to study consistently instead of waiting until the last minute. Spreading studying out over several days can help me understand the material better, remember important information, and feel more prepared for exams.

I think Step 4: Study is the most important because it teaches students to study consistently instead of waiting until the last minute. Spreading studying out over several days can help me understand the material better, remember important information, and feel more prepared for exams.

The narrator's description of his encounter with Stetson draws parallels to Dante's Inferno. Dante moves through a crowd of people in Canto III, observing that "after I recognized a few of these, / I saw and knew the shade of him." This "him" refers to a specific individual who sticks out to him in this indistinguishable mass. Similarly, the narrator in The Waste Land also has this unusual moment of recognition where he suddenly identifies someone familiar after having been moving through a passive, anonymous crowd. Contemporary London begins to resemble Dante's Hell, especially with previous references to "death had undone so many" and "a dead sound on the final stroke of nine." Living Londoners take after the dead souls in Inferno, and time loses its meaning when the narrator exclaims that his acquaintance was someone who he had fought with in the ancient battle of Mylae, several millennia before the contemporary setting of the London Bridge. In this sense, the living and the dead, past and the present collapse into each other, leaving readers with the impression that generations of people ultimately end up experiencing the same terrors of warfare and cyclical trauma. The same patterns of pain and suffering will manifest in different forms of history.

While death and rebirth are common threads throughout the poem and in Baudelaire's works as well, Eliot doesn't depict how those left behind by the dead fare, from a personal perspective. All of his depictions of death come from the third person, as one watching the death unfold around them as he did, and not offering his own opinion on it. Like Eliot himself said, the authors own mind should remain seperate. Here in these lines he offers his first reading of a companion left behind in ruin, yet not a human companion, but a dog whose owner has died, and longs to be reuited with his master. Baudlaire on the other hand shows the way that seeing horror and cruelty can affect someone not even directly associated with the hurt. Eliot tries to distance human emotion from his poetry. and present an arbitrary depiction of loss, while Baudelaire embraces human suffering on a more personal level.

The capitalization of Unreal City makes it seem like a name.

In Baudelaire’s poem, the speaker sees seven old men who appear so similar that, instead of imagining each of them as a separate person with his own life, he turns them into repeated versions of the same frightening figure. Eliot does something similar when he looks at the workers crossing London Bridge and describes them as one anonymous, ghostlike crowd rather than as individual people, each going somewhere for a different reason. Because of this, “Unreal City” may criticize more than the emptiness of modern city life; it may also criticize the detached speaker who looks down at the crowd and decides that everyone within it is spiritually dead. The city becomes unreal partly because his own fear and alienation prevent him from seeing the humanity that is still there. This also makes Eliot’s quotation from Baudelaire“hypocrite reader, my likeness, my brother”more important, because Eliot implicates himself and the reader in the problem. Modern society may dehumanize people, but we also participate in that dehumanization whenever we look at a crowd and see only a faceless mass instead of hundreds of separate lives.

this annotation is a bit of a stretch. The word "Man" appears 8 times throughout TWL. Baudelaire fears that after the seven old men, he will encounter an “awful eighth”. In Eliot, however, those eight uses do not clearly represent eight versions of one man, so the numerical connection is probably coincidental.

This section contains an interesting dichotomy between urban pollution and the natural world–and what each one might represent in terms of life and death. Eliot starts by placing the reader firmly in an urban city, with brown fog and large crowds of people who are described as being undone by death. The pollution of the atmosphere and repetition of the phrase “so many” makes the scene feel crowded, blurring the focus on life and death. It is not one person in an open plane of land pondering the death of a loved one, but the intersection of large scale life and the presumably constant presence of death. After line 70, this narrative shifts. Now Eliot has created an intimate scene between a small group of characters in which they are able to directly discuss the life cycle of a plant, which interestingly enough doesn’t go from life to death, rather from death to life. Eliot also refers to a plant sprouting, which doesn’t often happen in the Winter months of line 60, further separating the two scenes.

In all texts, man's body threatens his "soul" with eternal damnation; as referenced in De Nerval, only those whose "fraternal souls, delivered from their mortal bodies, [are] all the more free to denote themselves" to the regeneration of the universe," and by Dante, "those who have rejected spiritual values by yielding to bestial appetites..." are trapped within hell. Similarly, in Dante's "Inferno" and Baudelaire's Les Fleurs Du Mal, the soul is central to their descriptions of Godly procreation.

Lines 71 and 72 of The Waste Land most directly relate to these ideas: " 'That corpse you planted last year in your garden,/ 'Has it begun to sprout? Will it bloom this year?/ 'Or has the sudden frost disturbed its bed?.../ 'You hypocrite lecteur!—mon semblable,—mon frère!'." Opening "Inferno III," Dante reads the text inscribed into the Gates of hell: "Divine power made me,/ Wisdom supreme, and primal love./ Before me nothing was but things eternal,/ and eternal, I endure./ Abandon all hope, you who enter here." While it may be a reference to the realm of hell as a physical entity, it may equally describe humanity—humanity was made with "wisdom supreme," but cursed with "...primal love." In eternal purgatory, hell cannot exist void of the human race; hell, Dante's illustration, reflects human vice and besets its inhabitants with mortal, worldly punishment. Thus, it is the human race that "before nothing was but things eternal, and eternal [they] endure." Returning to line 72, it then becomes evident that the planted "corpse" is destined to fail and decompose; if man is doomed to rest "eternally" in hell, rebirth and redemption are futile.

Baudelaire, in a similar manner, describes the mortality of God: in the poem's fifth stanza, the narrator discovers himself (analogous to humanity) to be the undying eighth part of God. Initially two unnaturally aged and failing old men, God is likened to "centenarian twins...spectres odd." Discovering the number of these entities, "monsters," the narrator interrogates his own humanity: "The seven old hideous monsters has the mien/ Of being immortal./ Then, I thought, must I,/ Undying, contemplate the awful eighth:/ Inexorable, fatal, and ironic double:/ Disgusting Phoenix, father of himself/ And his own son?" Given a body, God's immortality is morbid; rather than a pinnacle of beauty and perfection, the image from which man was born, he is a "Disgusting Phoenix," and his own father.

With this, God and the human race are abject, impure, and irrevocable. Finally, in line 73, Eliot's reference to "Frost" pulls upon Dante's ninth circle: Treachery and the frozen lake of Cocytus. Just as hell's souls, The Waste Land's corpse is submerged and frozen in a (its) bed.

Overall, these three lines relate to the given sources in their description of human suffering, innocence, and redeemability —and the same of God.

In Dante Canto when he says, "Could not believe, death had undone so many", Eliot directly connects this idea to his line saying, "I had not thought death has undone so many." The use of the word "undone" shifts between these two lines. In Dante, it is used as a shock as so many people have died. But for Eliot the people are not literally dead; it is more that something has "undone" them, so death is more a metaphor for numbness.

Virtue Lens: This focuses on the character of the organizations creating and trying to advance AI. They value their work but also what they should do as a compassionate organization. Laws can be hard to pass and it takes a long time, if all organizations creating AI agree to voluntarily work together it shows their character and that they value transparency to society. If the company wants to show that they are good people, they will voluntarily follow procedures made about AI pertaining to safety.

Utilitarian Lens: This choice would be the least harmful for everyone involved because it ensures the safety of people and the company themselves. It paces the companies in order to minimize risks with the advancement of AI.

This whole section from the article is a very complex dilemma and it stood out to me the most. From a justice lens, ff the U.S. slows down while China continues to improve in AI, that can risk us losing technological and military edge. There's already a deep distrust between the two countries, and, it might be true, I don't know, but I strongly believe that they could view our negotiation to slow down as a way to lock in our dominance and hinder their advancements, and economy. With Trump still being in office for two more years, and him stating that whoever wins AI, wins, make all of this even more difficult and, not to mention, that things can be hidden in data centers. From a common good lens, as mentioned in the article, slowing things down can prevent cyberattacks or bioweapons. I believe, globally, we all don't want an existential tech disaster to happen, but I think we won't realize that completely until we're almost there. It's all about money, unfortunately, until we get to that point. While there's no need for a permanent freeze, and as suggested in the article, focusing on specific redlines can be helpful during these negotiations. It's common sense, or at least it should be, that using AI for nuclear development or, I mean there already are, robots that become autonomous killers are things we want to prevent. There's already a huge backlash against data centers, and I believe, somewhere down the line, political parties will have to set a baseline for what AI can be used for to secure elections and votes.

Virtue Lens: Amodai gives a perfect example about one of the facts that has led him to asking for slowing the development of AI.Through this example, his worries become less of an fictional idea and more of a reality that is already happening, even if is just one isolated incident. Because of that, it is worth thinking that the companies behind the development of such capable artificial agents are actually concerned about the risks AI represents, adn if they are taking enough precautions to prevent future cases such as this one. If the answer is yes, then no one would be against the idea of slowing AI pace to make sure we still have control over it, and not the opposite. This second lens also leads me to the same conclusion as the first one, this time analyzing the issue from a perspective of what to expect from these companies and their compromise with the people and the world.

These lines directly connect to Dante's experience entering hell and seeing the bodies and people flowing in. It presents London very similarly to hell, and this is seen as the passage into the Inferno. This feeling of London seeming just like a commute connects this to an everyday obligation and inevitability rather than a fierce, passionate, and emotional sacrifice.

eLife Assessment

The work provides a valuable analytical and technical framework for relating spatial microRNA patterns to therapeutic response and features of the tumor immune environment in a BRCA1-associated model of triple-negative breast cancer. The evidence supporting the main conclusions is solid, although additional validation and statistical analyses would strengthen claims regarding biomarker performance and the specific contribution of spatial measurements.

Reviewer #1 (Public review):

Summary:

This manuscript presents an innovative approach combining spatial miRNA profiling with computational analysis to characterize treatment-associated tumor states in a BRCA1-deficient breast cancer model.

Strengths:

(1) The integration of latent Dirichlet allocation-based topic modeling and Structural Similarity Index Measure maps analysis provides a potentially valuable framework for studying tumor heterogeneity.

(2) The innovation is high, both conceptually and on technical aspects. The work is a potentially important technical development as spatial transcriptomics for miRNAs is needed, and an interesting manuscript for a large spectrum of readers.

Weaknesses:

The method analysed a limited set of microRNAs, although all are functionally important and well published.

Reviewer #2 (Public review):

Summary:

The authors apply a hydrogel nanoliter-well in situ microRNA assay to tissue sections from a mouse model of BRCA1-related triple-negative breast cancer, in which tumors had acquired resistance to a PARP inhibitor, and test two drug combinations. They develop a spatial analysis that groups wells into microRNA "topics" and relates these topics to treatment sensitivity and to immune infiltration, aiming to show that the spatial arrangement of microRNAs can report on drug efficacy and stratify tumors by their eventual sensitivity or resistance.

Strengths:

(1) The in vivo combination-therapy experiments are technically careful, and the finding that adding Poly(I:C) to olaparib improves antitumor activity is new.

(2) The data and the analysis code are openly deposited on Zenodo.

(3) Whether the spatial organization of microRNAs carries treatment-relevant information remains a worthwhile question.

Weaknesses:

(1) It is not clear what the spatial measurement adds. The discrimination of sensitive vs resistant tumors was already reported in the authors' prior work, and in this dataset the separation reduces to the relative amount of two microRNAs, let-7a and miR-21, that the bulk analysis had already nominated.

(2) The platform is on the well-level rather than single-cell, and the effective spatial resolution (well size and the number of cells per well) is not stated, so the meaning of "spatial" is unclear, and the sensitivity and specificity of the assay are not established in this work.

(3) The sensitive vs resistant separation is an in-sample description of labels that were fixed in advance, on roughly 21 tumors with about three per treatment arm and nothing held out; the model is refit for each analysis rather than frozen, so it cannot be evaluated as a classifier.

(4) The headline association of a let-7a topic with resistance is correlative, unvalidated, and runs opposite to the canonical roles of let-7 as a tumor suppressor and miR-21 as an oncomiR, and it may reflect the abundance ratio of the two dominant probes.

(5) The topic model is simplistic, collapses to two informative topics, and does not use the existing morphology or H&E information already available on the same sections; the co-localization analysis relies on an image-quality metric that is not appropriate for this purpose and lacks a null.

(6) The conclusions are dependent on a single mouse model at a single timepoint with no human data, but the framing attempts to extend to patients.

Reviewer #3 (Public review):

Summary:

This manuscript investigates strategies to overcome resistance to PARP inhibitors (olaparib) in a mouse model of BRCA1-related triple-negative breast cancer. They test whether combining olaparib with a PI3K inhibitor (alpelisib) or with an immune-stimulating agent (Poly(I:C)) can improve outcomes in both drug-sensitive and drug-resistant tumors, and find that both combinations extend survival in sensitive tumors, while only the PI3K combination partially overcomes established resistance. To understand the biological basis for these differences, the authors apply a previously developed hydrogel-based assay that measures seven microRNAs directly within tumor tissue sections, preserving their spatial location. They then build a set of computational tools-based on a topic-modeling method called latent Dirichlet allocation (LDA), principal component analysis (PCA), and an image-similarity measure called SSIM-to interpret these spatial microRNA patterns and relate them to tumor drug sensitivity, treatment type, and the surrounding immune cell environment.

Strengths:

(1) The in vivo survival experiments are well powered and rigorously analyzed, with appropriate statistical testing (log-rank tests) clearly supporting the central efficacy claims: both combination therapies benefit sensitive tumors, and PI3K inhibition (but not Poly(I:C)) partially rescues resistant tumors.

(2) The spatial microRNA measurement technology, while previously published, is thoughtfully applied here to an earlier treatment timepoint (10 days) than prior work, which is a reasonable and useful extension aimed at capturing biology before advanced tumor changes complicate interpretation.

(3) The core finding that a microRNA topic dominated by miR-21 associates with drug sensitivity, while a topic dominated by let-7a associates with resistance, is supported by a formal statistical test (a Mann-Whitney U test comparing principal component scores between sensitive and resistant tumors), giving reasonable confidence in this specific result.

(4) The idea of layering an immune-infiltration similarity map (SSIM) onto the microRNA topic maps is a creative and potentially broadly useful way to connect molecular spatial patterns with tissue architecture, and could be adapted to other spatial biomarker studies beyond this one.

Weaknesses:

(1) Several of the paper's central spatial and immune-colocalization findings are supported only by visual inspection of small numbers of samples (commonly three tumors per treatment group) rather than by formal statistical comparison. This applies to the treatment-type separation shown in Figure 3B.iii and to the immune-microRNA co-localization patterns shown in Figure 4B.ii, both of which are described narratively without accompanying statistical tests.

(2) The claim that Poly(I:C) fails to alter the immune composition of resistant tumors, unlike PI3K inhibition, is stated qualitatively ("little difference") without a quantitative comparison, which weakens confidence in this specific interpretation.

(3) All spatial analyses derive from a single mouse model at a single treatment timepoint, with no independent tumor cohort used to test whether the identified microRNA topics and their treatment/sensitivity associations generalize. This is an appropriate scope for an initial proof-of-concept study but means the biomarker potential of the approach remains unproven outside this specific dataset.

Overall, the authors achieve their stated aims, and the evidence broadly supports the paper's central conclusions distinguishing drug-sensitive from drug-resistant tumors. The additional analyses linking treatment regimen and immune infiltration to spatial microRNA patterns are plausible and consistent with the survival data, though they rely on small sample sizes and, in places, qualitative rather than statistical comparisons, and would benefit from further validation. The analytical framework itself - particularly the SSIM-based integration of molecular and cellular spatial data - is a useful and creative contribution with potential utility for other groups working on spatial biomarker discovery.

**GIS-BASED URBAN PLANNING & MODERNISATION OF MASTER PLANS ** Catch - However, enforcement of Master Plans, building bye-laws and action against unauthorised construction falls within the jurisdiction of the respective State

Use of state-of-the-art GIS technologies with * Very High Resolution Satellite (VHRS) imagery at 1:4000 scale * Drone/UAV mapping at 1:1000 scale

Link

EVALUATIONS OF MEASURABLE OUTCOMES DELIVERED BY SCM

NITI Aayog in its report titled ‘Evaluation of Centrally Sponsored Schemes in Package 4 – Urban Transformation and Skill Development’ published in September 2025, has concluded that the Smart Cities Mission demonstrates strong alignment with national urban priorities and citizen needs, contributing significantly to multiple United Nations Sustainable Development Goals.

Key Achievement

Mobility:1,700+ km of smart, accessible roads built, with ITMS deployed and monitored via ICCCs for better traffic management

A peer-reviewed research article of this preprint was published in Fruit Research on 31 August 2026. Can you update this? Here is the DOI link to the published article, doi: 10.48130/frures-0026-0029

I partly agree with this. While AI has the power and ability to make things like this possible, AI comes with many inconsistencies that are far to frequent for it to be used as a responsible tool for gathering information for now. It's without a doubt going to be more consistent in the near future by ten fold, but now's to soon to deem it a reliable option.

both wiki and AI have flaws in finding accurate research but can have truths and be helpful

从模型能力出发，不只从用户痛点出发

I think this is great for everyone to know because from my point of view I feel like many of us make this simple mistake that can ruin the overall message. Question like these are often used as a main point of your overall message and your main points are very critical for getting your message across and having a question like this can weaken your point.

I think that this is information that should be spread amongst our peers who are doing informational writings. This is a simple yet effective sentence laying out multiple different information sources to prove that there are many different ways to get information. Many people making a informational writing piece tend to stick to one or two sources of information weather that be magazines, websites, or books. The more variety a different information is found the better and more effective your writing piece will become.

I think these bullet points could be really helpful the next time I write a paper. They would make it much easier for me to do research, organize my ideas, and emphasize the importance of sources. Plus, they will help me determine how each source fits best into my future writing.

How can prevention campaigns communicate a positive benefit when the desired outcome is avoiding something rather than gaining something? For example, would it be more beneficial to focus on what people can gain like more money or control over their lives be more effective than focusing on abstinence?

How does the campaign account for women who do not identify as planning a pregnancy? Neural tube defects can occur very early in pregnancy, so how should the campaign reach people who may become pregnant unexpectedly?

This assumes that having the basic health literacy is simply enough for someone to act on health information. While a person can understand the instructions, they might not be able to follow them due to barriers such as cost, transportation, or language differences.

What evidence does the author use to determine that social determinants contributed more to increased life expectancy than medical therapies? I am curious to see specific data comparing the effects of changes in sanitation, housing, nutrition, and income with advances such as antibiotics, vaccines, and other medical treatments.

Books tend to be longer, and because of this, they can go into greater depth than articles.Books are great sources for providing a “big picture” perspective of a topic with background information and rich detail.scholarly books contain bibliographies with references or citations to other related works which can help broaden or narrow the scope of your research.

HELLO

Consider adding (ABG) abbreviation.

★

★ we often act on the answers to those questions.

★

★ Those terms are certain to be helpful when you’re looking for sources later.

★ It will influence most of the steps you take to conduct the research.

★ Shows how research questions guide decisions, not just school assignments.

Ground breaking hypothesis. Needs validation. To a non-physicist, this is amazing. I liken this to 'soul' of the cell residency discovered and must be inherited from the maternal side in higher mating species. What about the prokaryotic world that lacks mitochondria, yet have energy production system? My naive questions!

Change Answer

Could you add a section summary here too underneath this list of 3?

It's time to...

I would breat this out into a separate idea below the 4 other ideas so it sums up this section.

I feel like the idea of 'making sense of what's changing' features a lot on the page. Could you mix the messaging up between ideas like... you shouldn't have to suffer, there's so much conflicting information out there, etc?

perimenopausal

Let's finally make sense...

The free 4-day virtual summit to give you practical, holistic strategies to navigate perimonapuase without the shame, overwhelm, or conflicting advice.

Spanning nutrition, hormones, sleep, stress, mindset, movement, self-advocacy, and more...

Perimenopausal

The summit name is different here?

You...

You...

You...

One of the 'feel's needs to go here. ;-) Could you start this section with 'Imagine finally feeling more like yourself again!'

I would delete this line and leave the one in the above section... just make it bigger and bolder.

reaserches study, practitioners are like therapists

The webpage uses clear, to the point language, short sections, bullet points, and detailed headings instead of showing the information as one large block of text. This cuts out webpage complexity and makes the information easier to understand and scan. This connects to the “Understandable” part of POUR and the course discussion of webpage complexity.

Access to keyboards is essential for people who require assisted technology or people with limited control physically. This is what this page is trying to convey that some users should be allowed access without having to use a computer mouse. this makes the website more operable, one of the four pour principles.

Webpage pictures should not have inappropriate alternative text so the people using it who cannot see the image can still covey what its trying to say through a screen reader. This follows the principle of using alt tabs to describe images and helps the content to be perceived.

This webpage utilizes clear and concise headings to differentiate subjects and organize the information in a proper manner. This allows easier navigation and access for the page, most important for people who use screen readers. This relates to what we learned about structuring text logically and making content understandable and operable.

• The Core Thesis:

  • Generative AI should almost never be used to produce the actual prose of substantive writing—such as essays, analytical memos, research reports, or thoughtful emails.
  • The author grounds this argument in three central reasons:
    1. Writing is an indispensable mechanism of thinking.
    2. AI text is chronically vague and subtly incorrect in hard-to-spot ways.
    3. Publishing or sending uncredited AI prose to others is disrespectful and misleading.

• Writing as Cognition, Not Just Communication:

  • Substantive work requires a human author to hold the entirety of an argument, evidentiary nuance, and logical links in their mind.
  • Outsourcing sentence generation short-circuits this cognitive process, allowing writers to dodge the difficult, necessary thinking that only occurs while struggling to put ideas into words.
  • Reviewing or editing an AI draft creates a passive illusion of competence; writers reflexively nod along to plausible-sounding text rather than rigorously probing concepts.

• The Danger of Plausible, Subtly Flawed Prose:

  • AI-written text rarely fails loudly; instead, it is packed with pseudo-profound platitudes, tautologies (e.g., "export controls are only as strong as enforcement"), uninformative filler, and misleading approximations.
  • Even when fed extensive notes or outlines, models distort domain-specific context (e.g., mischaracterizing chip smuggling methods or confusing components with servers) in ways that require excessive cognitive effort to detect and fix.

• Social Trust, Signal, and Deception:

  • Presenting AI-generated text as your own signals to the reader that you understand the material and stand behind every stylistic and substantive choice when you do not.
  • Readers invest time expecting an authentic human synthesis; offloading the writing betrays that mutual social contract.

Hacker News Discussion

• Communication as a Proof-of-Understanding Signal:

  • A central theme among commenters was that human writing serves not merely as data transmission, but as proof that the sender has deeply understood and synthesized the problem.
  • Sending AI-generated summaries or memos undermines trust because it masks the sender's actual competence, leaving readers unsure if anyone truly comprehends the underlying message.

• Editing AI Slop vs. Writing from Scratch:

  • Multiple commenters cited Eric Schwitzgebel's observation that reading and tweaking existing text is cognitively passive compared to de novo composition.
  • Practitioners noted that debugging, fact-checking, and stripping out the verbose, generic "texture" of AI drafts often requires more time and effort than writing manually from an outline.

• Prose vs. Code and Objective Evaluation:

  • Several developers contrasted using AI for coding versus writing: code comes with a deterministic test harness and runtime feedback to verify correctness objectively.
  • In contrast, prose lacks an automated test suite, meaning subtle logical drifts, hollow phrasing, and false nuances easily slip past casual human inspection.

• Nuance for Low-Stakes & Non-Native Writing:

  • While agreeing on substantive essays, some participants defended LLMs for tedious bureaucratic tasks (e.g., Jira tickets, boilerplate forms) where creative thought is absent.
  • Commenters also highlighted the legitimate value of LLMs for non-native speakers seeking grammar refinement, though many cautioned that models frequently flatten authentic personal voice into sterile corporate jargon.

• The Problem of "Poster Slop" and Identikit Aesthetics:

  • AI-generated posters for community events (festivals, fayres, local businesses) have become notoriously ubiquitous, repetitive, and irritating.
  • The issue is not that the baseline graphics are inherently broken, but that their default look (oversaturated tones, predictable compositions, identical layouts) triggers immediate fatigue once seen repeatedly.

• Steering Models Beyond the Defaults:

  • When left unconstrained or prompted with naive descriptions, models like ChatGPT / DALL-E default to the statistical center of their training data.
  • Overcoming this visual monotony requires explicitly asking the model to steer away from the default look and applying concrete design terminology (e.g., Bauhaus/Modernism, Brutalist Graphic Design, wayfinding/signage iconography, or stylized child-art typography).

• Context Accumulation and Prompting Realities:

  • Iterating inside a single chat thread can cause the model to introduce and carry over unwanted text, slogans, and stylistic baggage from earlier prompts.
  • The goal of deliberate prompting is not necessarily to disguise the use of AI entirely, but to create visually distinctive, purposeful designs that avoid cliché tropes.

• Layered Layouts vs. Flat Bitmaps:

  • Relying purely on raster image generation produces uneditable graphics with hallucinated or immutable text.
  • Modern LLM workflows can generate structured HTML/CSS or SVG/PDF code, producing editable layers, real typography, and clean layouts that users can tweak by hand.

Hacker News Discussion

• The Lingering "AI Smell" and Fatigue:

  • Many commenters argued that even when steered into diverse historical styles, AI-generated posters still suffer from a recognizable, uniform "sheen" and lack of genuine creative tension.
  • Multiple participants pointed out persistent structural tells, such as an obsession with horizontal icon rows, symmetrical clutter, and flat informational hierarchy where everything competes for attention.

• The Erosion of Novelty:

  • Several users reflected on how the visual threshold has shifted: designs that would have appeared astonishing a few years ago now read as cheap and lazy because excessive repetition has transformed novelty into visual noise.

• Tooling Mismatch (Bitmaps vs. Code/HTML):

  • A major technical critique was that general-purpose chat interfaces default to pure raster image generation rather than hybrid layout tools.
  • Commenters noted that superior results come from using models to generate structured HTML/CSS or vector SVG layouts combined with targeted graphic assets, preserving text crispness, readability, and print-ready editing.

• The Skill Gap in Prompting and Design Taste:

  • Discussion touched on how small business owners and amateur organizers use AI because they lack design skills; however, producing good output with AI still requires the very design vocabulary and aesthetic taste those users lack.
  • Commenters suggested a growing opportunity for tools (like Canva or specialized frontends) that bake strict design guardrails and sensible typography rules directly into their system prompts.

• The Promise vs. Reality of Passkeys:

  • Passkeys (built atop WebAuthn / FIDO2) are marketed as the ultimate replacement for passwords, promising phishing resistance, cryptographic security, and seamless authentication without shared secrets.
  • Despite the technical merits of public-key cryptography, the real-world user experience introduces severe friction, vendor lock-in, and conceptual opacity for everyday users.

• Ecosystem Fragmentation & Platform Walled Gardens:

  • Major platform holders (Apple, Google, Microsoft) implement passkey synchronization within their proprietary ecosystems (iCloud Keychain, Google Password Manager, Windows Hello).
  • Cross-platform authentication often forces cumbersome workarounds—such as scanning QR codes via Bluetooth proximity between incompatible devices—which frequently fails or degrades user trust.

• Account Recovery & Portability Concerns:

  • Unlike passwords or traditional exportable 2FA seeds (TOTP), passkeys have historically lacked standardized, platform-agnostic import/export mechanisms, making migration between ecosystems painful or impossible.
  • Account recovery becomes high-risk: losing access to an ecosystem account can lead to permanent lockout from third-party services that disabled password fallbacks.

• Shared Accounts and Non-Technical User Barriers:

  • Standard family and enterprise account-sharing patterns (e.g., streaming services, joint utility bills, shared team logins) break down when an authentication credential is bound to a single person's device ecosystem.
  • For non-technical users, abstracting authentication into platform prompts removes transparency regarding where credentials physically reside or how to back them up securely.

Hacker News Discussion

• Platform Enclosure & Loss of User Agency:

  • Commenters frequently point out that passkeys shift control from open protocols and user-owned password managers to big-tech operating system silos.
  • Many express frustration that the underlying cryptography is solid, but the implementation incentives serve corporate lock-in rather than user autonomy.

• Cross-Device Usability Failures:

  • Real-world usage stories highlight significant pain points when operating across mixed environments (e.g., a Linux desktop, an Android phone, and a work MacBook).
  • The hybrid transport mechanism (QR code + Bluetooth LE handshake) is widely criticized as fragile, slow, and confusing for mainstream users.

• Third-Party Password Managers as the Middle Ground:

  • Several participants advocate for managing passkeys exclusively inside dedicated third-party tools (such as 1Password, Bitwarden, or KeePassXC) rather than OS keychains.
  • This approach restores cross-platform synchronization and export capabilities, though some note it circumvents the hardware-isolated enclave guarantees intended by platform vendors.

• Phishing Resistance Still Outweighs UX Defects:

  • Security practitioners in the thread defend passkeys, stressing that origin-bound cryptographic credentials completely eliminate credential stuffing, phishing, and server-side database leaks.
  • Even with awkward UX, defenders argue that passkeys represent an unavoidable and strictly superior baseline compared to weak passwords and easily intercepted SMS 2FA.

The man is trying to convince Jig that its just a small procedure and that he knows many people who have done it. That after the abortion they will be happy again. Jig replies sarcastically so do I, and afterward they were all so happy.

• The Trap of Full Delegation:

  • Asking an LLM to generate long-form prose or complete articles from scratch produces hollow, cliché-ridden, and synthetically generic writing.
  • Models naturally regress to the statistical mean of their training corpora, defaulting to flat phrasing, predictable transitions, and unearned optimism.

• The Author as Architect, LLM as Apprentice:

  • Effective writing with an LLM requires human ownership of the core argument, structural pacing, and distinct voice.
  • The tool should be treated as an interactive editorial assistant rather than an autonomous author, shifting the user's role toward prompt direction, aggressive curation, and line-level refactoring.

• Iterative & Granular Workflows:

  • Working section by section or paragraph by paragraph yields far higher quality than prompting for entire essays in one shot.
  • High-leverage LLM use cases include:
    • Stress-testing arguments and surfacing counterarguments or logical gaps.
    • Generating multiple phrasing variations for awkward transitions.
    • Expanding rough bullet-point outlines into draft paragraphs for further human editing.
    • Acting as a ruthless copyeditor to trim bloat and spot repetitive vocabulary.

• Preserving Voice and Authenticity:

  • Retaining idiosyncratic metaphors, rhythm, and tone requires actively stripping out recognizable LLM mannerisms (e.g., summary conclusions starting with "Ultimately," superficial balance, and sterile adjectives).
  • Writing remains fundamentally an act of thinking; offloading the formulation of ideas undermines the quality and clarity of the finished piece.

Hacker News Discussion

• Slop Detection & the "LLM Texture":

  • Commenters widely noted that AI-generated prose has a recognizable "texture"—bland, overly polite, formulaic, and structurally uniform—that immediately repels discerning readers.
  • Participants emphasized that once a piece reads like it was generated by an LLM, readers assume minimal effort was invested by the author and disengage.

• Usefulness in the Ideation & Editing Phase:

  • Several experienced writers shared workflows where LLMs excel not at prose drafting, but at rubber-ducking concepts, generating counterexamples, and functioning as a thesaurus on steroids.
  • Many agreed that using an LLM to simplify dense paragraphs or suggest structural alternatives is dramatically more effective than having it generate content whole-cloth.

• Cognitive Offloading vs. The Struggle of Writing:

  • A major theme in the discussion was that the difficulty of writing is where original insight happens.
  • By outsourcing the actual sentence composition to an LLM, writers often skip the intellectual tension needed to discover what they truly think about a subject.

• Prompting Strategies and Custom Instructions:

  • Users discussed various system prompts and techniques to combat generic output, such as explicitly instructing models to avoid clichés, omit boilerplate conclusions, and adopt terse, direct prose styles.
  • However, commenters noted that even with tuned prompts, active human editing remains mandatory to achieve publishable, high-signal writing.

abandonment

old books gathering dust or ruin

new library is cement (unnatural) and old library was made of wood (natural) + painted yellow (like the sun and beautiful to ppl like her), ecotherapy having natural materials can benefit u

continued capitalization of The Earthquake -- it irreversibly destroyed library (library = knowledge of past which is extremely important, may hold identity). may represent their loss of attunement to nature after being colonized + now is a tourist place. they have lost their ways and can't or don't know how to get back

capitalism

strong quote

• The Reality of Agent Threat Models [00:00:07]:

  • AI agents do not require software vulnerabilities to cause harm; ingesting untrusted data (poisoned dependencies, hidden repository comments, booby-trapped web pages) triggers prompt injection.
  • Prompt injection is an inherent property of probabilistic models, not a fixable bug; security design must focus on blast radius containment rather than prevention.

• Mode 1: Supervised Execution (Human-in-the-Loop) [00:03:00]:

  • Typical developer workflows (e.g., Claude Code, Cursor, Gemini CLI) rely on interactive user approval prompts for commands and filesystem writes.
  • Layering complex sandboxes over interactive human confirmation is redundant; the user functions as the security harness and bears full operational responsibility.

• Mode 2: Unsupervised Agents (The "Walk Away" Model) [00:06:45]:

  • When autonomous agents run unattended, the surrounding harness must assume the agent will be compromised and restrict its destructive capabilities.
  • Network Egress (Primary Defense): Data exfiltration is the primary threat; enforcing strict network boundaries ensures stolen secrets or proprietary code cannot leave the system.
    • Allowlisting Challenges: Basic hostname filtering can be bypassed via direct IP requests, domain fronting, SNI spoofing, DNS exfiltration, or parsing bugs (e.g., null-byte flaws).
    • Enforcement: Network restrictions must be enforced at the kernel/packet routing layer rather than trusting local environment variables (HTTP_PROXY).
    • Deep Inspection: Intercepting outbound leaks requires full TLS decryption/inspection, which introduces operational complexity and trust-store maintenance.
  • Credential Lifecycle & Capability Separation [00:12:19]:
    • Agents must never hold durable, long-lived credentials on disk or in shell configuration files.
    • Utilize dynamic workload identity (e.g., Cloud IAM / Workload Identity Federation, SPIFFE/SPIRE, HashiCorp Vault) to mint ephemeral, narrowly scoped tokens.
    • Advanced architectures use external brokers or sidecars that inject auth headers during transit, completely preventing the agent from seeing or exfiltrating the underlying secret.
  • Execution & Host Isolation Rungs [00:18:11]:
    • Filesystem Scoping: Restricts operations strictly to the immediate workspace to prevent persistent backdoors in dotfiles, shell profiles, or Git configs.
    • Standard Containers: Offer process isolation but share the host kernel, leaving hosts vulnerable to kernel escape exploits.
    • MicroVMs & Hardware Isolation: Sandboxes like Firecracker, Kata Containers, gVisor, or dedicated throwaway physical hardware provide real boundaries for long-running autonomous tasks.

• Mode 3: Multi-Agent Swarms & Fleet Dynamics [00:24:00]:

  • Multi-agent architectures introduce inter-process risks that circumvent single-agent perimeter sandboxes:
    • Prompt Contagion: An injection payload ingested by one agent propagates horizontally across shared communication buses, databases, and prompt handoffs.
    • Dynamic Agent Spawning: Compromised workers can spawn subordinate tasks or cross project boundaries autonomously.
    • Borrowed Authority / Confused Deputy: Subordinate agents implicitly trust messages originating from peer agents; a compromised low-privilege agent can trick a privileged agent into destructive actions.
  • Mitigations require treating inter-agent messaging as untrusted user input, limiting peer connectivity graphs, and minimizing shared memory surfaces.

• Operational Balance & Friction [00:29:52]:

  • Overly restrictive sandboxing leads to workflow interruptions, silent task failures, and "allow-all" approval fatigue.
  • The goal of agent security is pragmatic blast-radius containment (prioritizing strict egress filtering) to capture productivity gains safely without paralyzing utility.

How I Review AI-Written Code Without Reading a Single Line

• The Evolution of Test-Driven Development (TDD) [00:01:16]:

  • TDD traditionally served as a discipline to force clear thinking about the problem space (red-green-refactor loop) rather than just acting as a regression safety net.
  • Paired programming with an AI agent mirrors human collaboration, but shifting focus from granular function-level unit tests to high-level system requirements (PRDs) enables fully autonomous software development.

• Tests as Objective Functions for Autonomous Agents [00:04:00]:

  • Language models without deterministic constraints suffer from early victory declarations, drift, and false completion signals.
  • Executable tests act as rigid objective functions: they provide deterministic stopping criteria, establish unambiguous pass/fail states, and prevent hallucinated progress.

• Multi-Agent Orchestration & Safeguards Against Cheating [00:06:06]:

  • Work is delegated across specialized agents: an orchestrator, a dedicated tester, a coder, reviewers, and a release agent.
  • Separation of Concerns: The agent authoring tests never writes the implementation code, preventing agents from tautologically writing trivial passing tests or deleting failing assertions to force green runs [00:08:24].
  • Contract Lock-in: The orchestrator translates the PRD into an explicit test plan that requires human sign-off before any implementation begins, validating requirement comprehension early [00:07:02].

• Behavior-First Testing vs. Low-Level Unit Tests [00:09:37]:

  • Blackbox, behavior-level tests describe end-to-end user scenarios in plain language, acting simultaneously as the specification, the test harness, and the optimization target.
  • Testing observable outcomes rather than internal structure allows autonomous agents to freely refactor and rebuild codebases without triggering false-alarm test failures caused by code movement.
  • Inverting the Test Pyramid [00:11:50]: Coarse end-to-end tests are traditionally avoided due to the human cost of diagnosing failures; however, AI agents possess infinite patience and near-zero cost to dissect, log, and isolate failure points automatically.

• Automated Visual Verification via Demo Reels [00:13:06]:

  • Green test suites prove assertion criteria passed, but they do not confirm whether the user experience matches human expectations.
  • Critical blackbox tests run end-to-end sessions (e.g., terminal asciinema casts, headless browser recordings, or desktop captures) and automatically compile the execution into concise video demo reels attached to pull requests [00:14:01].

• The Two-Gate Autonomous Workflow [00:15:35]:

  • Human interaction is constrained to exactly two intervention points:
    • Gate 1 (Upfront): Reviewing and approving the planned test contract derived from the PRD.
    • Gate 2 (At Completion): Watching a short video reel showing the critical end-to-end behavior before authorizing the merge.
  • All intermediate coding, debugging, refactoring, and test execution run completely autonomously in the background.

• The Role of an Inference Engine [00:02:16]:

  • Software layer operating between raw weights on disk and incoming HTTP user requests (e.g., vLLM, Ollama).
  • Performs five core responsibilities: loading model weights, maintaining context state, scheduling requests, executing matrix arithmetic, and serving an HTTP API.
  • Sits above compute kernels (low-level math operations) and below cluster orchestrators/control planes and API gateways.

• GPU Memory Dynamics (Weights vs. KV Cache) [00:05:16]:

  • Model Weights: Static memory cost determined by parameter count and precision (e.g., an 8B parameter model at 16-bit/2-byte precision occupies ~16 GB VRAM); remains fixed regardless of concurrent concurrency.
  • KV Cache: Dynamic working memory holding intermediate attention states across token generations; scales linearly with conversation depth and concurrent active users, directly competing with weights for remaining VRAM.

• Batching Strategies & Memory Management [00:07:39]:

  • Continuous Batching: Replaces naive static batching by evicting completed requests immediately and slotting new requests into the running batch, avoiding GPU idle cycles caused by differing generation lengths.
  • PagedAttention / Paging: Allocates KV cache in small, non-contiguous fixed-size blocks on demand rather than reserving maximum possible context windows per request, eliminating severe internal memory fragmentation.

• Weight Quantization [00:09:47]:

  • Reduces precision per parameter (e.g., from FP16 to INT8/INT4), slashing fixed model footprint.
  • The primary benefit is freeing VRAM for a larger KV cache pool, directly scaling concurrent user throughput on cost-effective GPUs.

• Prefix Caching [00:10:58]:

  • Caches identical token sequences across requests (e.g., static system instructions, tool definitions, recurring multi-turn histories).
  • Bypasses redundant prompt reprocessing, providing massive speed and efficiency gains for agentic workflows.

• Prefill vs. Decode & Speculative Decoding [00:12:28]:

  • Prefill Phase: Parallel ingestion of prompt tokens; strictly compute-bound as the GPU operates at peak arithmetic saturation.
  • Decode Phase: Autoregressive, strictly sequential token generation; heavily memory-bandwidth bound due to fetching full weights per generated token.
  • Speculative Decoding: Employs an ultra-fast draft model to predict token sequences validated by the target model in a single parallel pass, reducing end-to-end decode latency for individual users.

• Orchestration, Routing, and Model Scaling [00:14:46]:

  • Control Plane & Gateways: Standard round-robin load balancing fails for LLMs; gateways require cache-aware routing to send requests to replicas with pre-warmed KV caches.
  • Model Sharding: Distributes massive parameter architectures across multiple GPUs via Tensor Parallelism (intra-layer splitting) or Pipeline Parallelism (inter-layer pipelining).
  • LLM Autoscaling: Relies on inference-specific metrics (queue depth, KV cache utilization) rather than CPU/GPU utilization; hindered by substantial cold-start penalties when pulling images and warming weights.
  • Prefill/Decode Disaggregation: Decouples the prefill (compute-intensive) and decode (bandwidth-intensive) workloads across specialized hardware topologies for optimal hardware utilization.

involved in doing something bad

• Data Loss & the Single Point of Failure:

  • Data loss is an inevitable eventuality caused by hardware failure, bit rot (NAND transistor charge leakage or HDD magnetic drift), human mistakes, or UI issues (e.g., consumer devices prompting accidental disk formatting).
  • Relying on a single storage drive or device is fundamentally unsafe.

• RAID vs. True Backups:

  • RAID 1 / disk mirroring provides uptime redundancy against immediate drive death, but it is not a backup.
  • Mirroring propagates accidental deletions, script mistakes, and ransomware encryption instantly across disks; point-in-time snapshots are mandatory to roll back changes.

• Retention, RPO, and Backup Rotation:

  • Recovery Point Objective (RPO) dictates snapshot frequency, varying from under 30 seconds for critical infrastructure to 24+ hours for small workloads.
  • Unpruned snapshots quickly exhaust storage, requiring structured rotation schemes such as Grandfather-Father-Son (GFS) to retain dense recent snapshots and sparser older ones.

• Deduplication and Storage Optimization:

  • File changes follow a fat-tailed distribution, where most files remain static while a small fraction change frequently.
  • Deduplicating identical files across snapshots (e.g., using hard links with tools like rsnapshot or chunk-level deduplication) drastically reduces local storage usage and network bandwidth costs.

• Technical Pitfalls of DIY Backup Systems:

  • Permissions & Containers: Background cron jobs running under standard user accounts fail on root-owned Docker files and volumes.
  • State Consistency: Live databases caching writes in-memory risk silent corruption if snapshotted without explicit database dumps or I/O freezing.
  • Cloud Object Storage (S3): Storing millions of small, unbundled files causes punitive API request costs and strips POSIX file metadata, requiring custom archive packaging or chunking.
  • Daylight Saving Time (DST): Backup cron jobs scheduled between 2:00 AM and 3:00 AM can be skipped or executed twice during clock shifts.

• The 3-2-1 Rule and Battle-Tested Tooling:

  • Resilient backup architecture requires the 3-2-1 strategy: 3 copies of data, across 2 different media types, with at least 1 offsite.
  • Due to hidden edge cases, custom backup scripts should be avoided in favor of mature, open-source solutions (e.g., Borg, Restic, or ZFS snapshots) that provide chunk deduplication, checksum verification, and encryption out of the box.
  • Backups are meaningless without regularly scheduled restore testing.

Hacker News Discussion

• Backups as High-Risk Operations:

  • Several users noted experiencing catastrophic data loss during backup routines due to errant scripts wiping source data or premature deletion of old backups to make room for new ones.
  • Commenters emphasized keeping at least one backup volume strictly offline and disconnected while running backup or rotation tasks.

• Cloud Vendor & Synchronization Pitfalls:

  • Real-world horror stories highlighted sudden vendor policy shifts (e.g., Microsoft OneDrive or cloud providers altering storage tiers, aggressively throttling retrieval speeds, or silently purging files).
  • Sync-based cloud tools frequently conflict with underlying filesystems and give users a false sense of backup security.

• Append-Only & Immutability Guarantees:

  • To counter ransomware and compromised backup credentials, users advocated for provider-enforced immutability (such as S3 Object Lock) where backup keys have append-only privileges and cannot delete or overwrite historical objects.

• Physical Media & Cold Storage:

  • Participants discussed hardware longevity trade-offs, noting the decline of optical media (Blu-ray burners) and highlighting used LTO tape drives (e.g., affordable LTO-5 units) as practical options for multi-terabyte cold offline archives.

• Walled Gardens and Cloud Photos:

  • Backing up services like iCloud Photos or Google Photos remains difficult due to proprietary metadata handling, rate limits, and missing bulk export tools.
  • Common community workarounds include running open-source sync tools (such as icloud_photos_downloader), local Mac/Time Machine caching, or migrating to self-hosted photo platforms like Immich backed up to remote storage boxes.

• Filesystem & Application Consistency:

  • Commenters highlighted the need for consistency groups and file system snapshots (such as ZFS or Btrfs) to freeze application I/O, preserve extended attributes/ACLs, and handle sparse virtual machine disk images properly.

money that one spouse pays the other in a divorce

This was particularly interesting, as I have read about the Celeste mystery and always wondered what happened myself. This sounds very probable for what happened, but unlike the stories we read, there is no resolution tied up with a neat bow.

This idea aligns well with Towles, Kemp, and Schmid, as mystery stories are rarely only about finding the killer. The murder creates high stakes and digs into the lives of those around the story. As Towles notes, death exposes secrets and changes how we see the people involved.

This aspect is a great counter to the suggestion that "These books sometimes get dismissed...". This is one of the main reasons I personally come back to reading mystery books. Life doesn't fit into a neat bow and its nice to read about when it does.

We no longer need to imagine this, surely Google Gemini or equivalent can generate this disturbing image for us?! Which brings me to an important question: to what extent is generative AI destroying both our will and our ability to concoct imagery mentally? It may be a slow degradation, but I fear it is afoot.

the freedom to make decisions

This passage helps answer “What is Appalachia?” because it shows that Appalachia is more than just a geographic region in the mountains. Duncan describes a region that was heavily shaped by coal mining, outside businesses, and unequal control of wealth and political power. To me, this shows how Appalachia’s history of natural-resource extraction helped shape the economic struggles and social structure of many communities in the region.

blameworthy

obedient or submissive

I can't decide if I find this statement more enlightening than annoying, or vice versa. I tend to be of the mind that a lot of the process of evolution involves random mutation rather than conscious behavioural adaptations. I know that there is not one driver of evolution, and that many other factors come into play when we are discussing a significant advancement within the history of an organism, but I have never really been able to wrap my head around the idea that a learned behavior can be passed down genetically. (I know this is a thing, intergenerational trauma as an example, but I struggle to make it tangible in my mind thus far, which makes it more difficult for me to understand.) So this statement seems very chicken and egg to me, in that it speaks of the importance of the development of language as a driver of human intellect, which I do not deny, but I feel like the statement might miss the part where the brain structures necessary to acquire and articulate language must have been present for the environmental need for language being important to build upon. I don't have any better theories, I just find the subject interesting because language is still viewed as a strictly human skill, but from an evolutionary perspective the structures, or at least the foundation of said structures, would have to have been present at the moment when this particular skill was important. Which then, because all life shares common origins, causes me to wonder which other organisms possess those building blocks, and why (as far as we know) the process has not occurred in other organisms.

to consider

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To defend against

reply to u/Silly_Captain2089 at https://reddit.com/r/NoteTaking/comments/1wldauj/do_you_actually_organize_notes_by_folders/

The missing secret and an affordability that disappeared roughly when folders moved to digital contexts was the time and effort that people used to put into indexing their work beyond just filing it away.

Tags and wiki-type cross linking has helped some of this problem, but it takes some time and effort to make it easier for you to find the things you're always looking for.

Back in the late 1600s famous philosopher John Locke wrote a short treatise about how to index notes in one's commonplace book so that you could write entries in linear order, but still find them under multiple indexed headwords and didn't need to copy them into multiple places (or folders in your case). Here's a copy from 1706 in English (the original was in French.) - Locke, John. 1706. A New Method of Making Common-Place-Books. London: Printed for J. Greenwood, bookseller. http://archive.org/details/b30540434.

The pinnacle of the practice was probably in the 1950s when there were multiple filing and indexing schemes available and in wide practice. - Duffield, David Walter, and Various. 1951. Progressive Indexing and Filing. 5th ed. New York, NY: Remington Rand Inc. http://archive.org/details/progressiveindex0000varo.

These seemingly "boring and dull" methods do require a miniscule amount of additional work, but if you're regularly using and especially reusing your notes for writing or other creative work, then the extra work pays for itself 100 times over in long-term creativity and usefulness.

Underling the boredom and seeming tediousness of this practice, in a note in his system entitled "Does Spirit hide in the filing cabinet?", Niklas Luhmann wrote: "People come [to look at his filing and indexing system], they see everything and nothing more than that, just like in porn movies; consequently, they leave disappointed." This is a telling story about the simplicity of the idea of well-kept notes (filed and indexed) in a zettelkasten, card catalog, filing cabinet, or commonplace book because you don't get to see the creativity of the end product without putting in the work.

As a crazy example of resultant creativity, I was able to use some notes I indexed five years ago on tools to link a passage from the Book of Matthew in the Bible to Henry David Thoreau's book Walden and Conway's Law on corporate structure. I can guarantee that without my notes being reasonably well-indexed and filed, this serendipitous bit of rather brilliant creativity would never have happened.

Paper made of some animals

Add annotations as I always do in the Reading Forum in this class.

Based on these three points, I will summarize.

I must have critical thinking skills.

https://youtu.be/0ajIPRy_yc0?si=tBJjJNjg5tnlR9oW&t=1504

For whoever has will be given more, and they will have an abundance. Whoever does not have, even what they have will be taken from them.