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What is this?

This quote stuck out to me because it represents a person's environment and how it can influence one's opportunities in life. As a Psychology major, I have learned nature vs. nurture copious amount of times and yet sometimes I felt as if socio-economic status is left out of the picture in terms of both. Where someone grows up can affect the quality of education they receive. Children in families with more financial stability have greater access to schools, after-school programs, and tutors. Children who grow up in poverty may face barriers that make it more difficult to manuver education, even if they work just as hard.

Well, we can talk about technical issues in class, i am also interested in the mechanism that the traditional concept of an artist account can be quantitatively controlled and operated by one person. the internet is mainly contradictory in exposure, and quantitative accounts are used to create false popularity, so that real life accounts can get a large number of real likes and comments for certain content so as to form the Internet effect of manipulating public opinion.

The headline says the image reveals how App Store rankings can be manipulated. However, the article says “if the above images are indeed real,” showing some uncertainty about the image. This could give readers who only read the headline a more certain impression.

Reading this article was very interesting because it put into perspective how much of an impact a creators morals has over their bots. When bots are set to form their own posts they may pull information from various places and it is up to the bots creator control where it gets its information or to filter what the bot will post, making an effort to make their bot more ethical.

A detail from Sarah Jeong's work that grabbed my attention was how creators who had experience in creating bots said that Microsoft should have known the risks before releasing the Tay Bot. The article explains how some botmakers use word filters and testing it multiple times to make sure it does not use any offensive wording. This brings the idea of how developers should always try to predict and prevent future problems that may come up during the design process and not when they actually happen.

I read this article about the photographer that visited a click farm in Hong Kong. It is an intimidating force in my opinion. There was that quote from earlier in this book “the internet changes nothing on its own, but it can amplify existing forces, and those amplified forces might change something”. So anybody with a large amount of money can pay these click farms for massive amounts of engagement and spread misinformation about COVID for example or a certain politician. How easy it must be to get a certain opinion into the limelight. How strange it is too that as a global community, click farms themselves make money in search of our attention.

I agree with the reading a lot because I feel that the bigger issue is not necessarily that bots exist, but that we may eventually have a lot of trouble knowing whether the content and interactions we see online are actually coming from real people. If we users can't tell what is human and what is from a bot, it could change how much we trust information and even how we understand social media itself. When surfacing the web even now, we don't know what is completely real and it's important to stay cautious on social media.

I chose this source to check out because when I was reading section 3.2.1 Friendly Bots, and saw “See a new photo of a red panda every hour,” I was intrigued by what that meant. I was not expecting it to be an X account that actually posted a new red panda photo every single hour. I love this example of a “friendly bot,” because it is so harmless and lighthearted that it is cool to see people think of something like this. I think if I saw this on my X feed, I would be really happy, and I love that that happens to others. It is also interesting to see our Bluesky bot assignment in a real instance, where someone created a bot that does what we did on Bluesky on X. Scrolling through the account, I thought about the code that was written for it, and they used something similar to sleep(). At first, I was confused about why the Bluesky bot was something we needed to do because I never thought of a use for it. Seeing this red panda X account was a funny and simple way to see our assignment brought to life.

I found it interesting that the article shows how difficult it is to make a bot behave ethically. I think the developers should be responsible for what their bot does, even when the bot learns from other users, because they are the ones who decided to create and release it.

lack of structure!

Young GC = Minor GC

After a Young GC, if too many objects survice, they are prompted directly to the old generation.

This passage is a great example of generational wealth and how white individuals have more of an advantage if they come from family's that are able to send their children to schools and put them into an education of their choice, but also a good education. I also strongly believe that generational trauma can play a role in racism and segregation in terms of access to resources or opportunity. An overwhelmingly amount of negative experiences for a family causes effects that can be passed down in the family, and those effects can disrupt a family's ability to access education, financial stability, and other resources.

In the gray industry china o the internet in china, there is also an informal name called the network navy

If I have an interesting conversation with an account and later find out it is a bot, does that make the conversation less meaningful?

In my opinion, if the bot act just like human, for example, they may post human selfie and share daily. This will make communication on social media less credible. It feels like it’s getting harder to know what’s authentic online. I mean, should social media platforms be required to clearly identity accounts that are operated by bots?

Facebook group for Index Card Planner Ideas and Inspiration

eLife Assessment

This important study provides theoretical and experimental evidence that aliphatic-to-threonine substitutions in transmembrane domains improve the translocation properties of mitochondrial proteins from the cytosol to mitochondria. The authors provide convincing evidence that substitutions within hydrophobic transmembrane regions of mitochondrial proteins may have contributed to their evolutionary adaptation following the transfer of their genes from the mitochondria to the nucleus. This study will be of interest to biologists and biochemists working on mitochondrial protein import and mitochondrial evolution.

Reviewer #1 (Public review):

In this manuscript, Yadav and coworkers investigate hydrophobicity governing membrane insertion of mitochondria-encoded polypeptides. The basis of their considerations is the question of why mitochondria maintain a co-translational insertion mechanism and what rules allow allotopic expression. The issue if mitochondrial-encoded proteins can be expressed in the cytoplasm and imported into mitochondria is a long-standing topic in the field with broad implications for the treatment of mitochondrial disorders. In the manuscript, Yadav et al. propose that aliphatic-to-threonine substitution (ATS) are a recurrent and convergent adaptation in the transmembrane helices (TMH) of the inner mitochondrial membrane (MIM) proteins, solving the conflict between hydrophobicity required for membrane insertion and the need for soluble cytosolic transit. The study combines structural comparative genomics, MD simulations, and cellular experiments.

This is a well-written and highly interesting study that provides a solid basis for considerations regarding mitochondrial protein insertion. I am sure that the study will represent an important asset for future studies on allotopic protein expression and potentially the development of genetic tools. The study provides solid evidence, from evolutionary correlation to experimental manipulation and molecular-level explanation. The study provides abundant and well-thought-out controls.

Specific points

(1) There are multiple comparisons throughout the manuscript, and not all of them appear to have been explicitly corrected. Numerous Wilcoxon tests, t-tests, and ANOVAs are reported (Figures 2, 3, 4), without a systematic correction for multiple testing or clear mention of FDR/Bonferroni corrections, except for the directional analysis of substitutions, for which the Benjamini-Hochberg procedure was applied. Given the large number of pairwise comparisons in Figures 3 A-C; and Figure 3 Supplement 1, Supplement 2, Supplement 4, and Supplement 5, with dozens of p-values per panel, it would be relevant to clarify whether a multiple-testing correction was also applied in these analyses. If not, the authors should explain the rationale for not applying one.

(2) The authors used experimental structures as one criterion but, in other cases, AlphaFold2 to compare evolutionarily distant pairs. Using non-experimental structures as a base for structural alignment among very divergent proteins is understandable but also prone to errors, especially for membrane proteins. It might wrongly identify which helices are considered "related". To address this, the authors need to clearly indicate which data are based on experimental or computational data - this is not always the case.

(3) The Kyte-Doolittle hydrophobicity scale is standard but relatively raw in comparison with scales based on experimental insertion energy (like Hessa et al., cited in the text or Bothelo et al.). It might be useful to explain why the authors preferred K-D over an experimental membrane insertion scale for the analysis. Particularly, since the Hessa et al. scale was later used in Figure 8G for the thermodynamic analysis.

(4) The phylogenetic tree of ATP6 (Figure 5A) presents low bootstrap values in some internal nodes (43, 40, 55) on which the interpretation of "independent events" of genetic transfer relies. This must be discussed, since a bootstrap of 40-50% provides not too much confidence in the deep topology of the tree, even though the point that the nuclear sequences don't form a monophyletic group with the mitochondrion seems robust (supported by distinct MTS in each clade).

(5) Definition of "core" vs "peripheric" in TMH (11 central positions) seems arbitrary; it would be worth clarifying why that cut was chosen and whether the results are robust when they vary.

(6) There is a notable gap in the literature when describing some of the findings in the Results and Discussion section:

Biophysics of threonine/serine in TMH:<br /> Senes et al., 2004, Dawson et al., 2002. The result described in Figure 8 (Threonine rotamers) is essentially a biophysical refinement of a body of work already established by the Engelman and DeGrado labs about how Ser-Thr, in comparison with other polar residues, promotes specifically the packing and stability of TMH through intra-inter helical hydrogen bonds, without compromising the membrane insertion. Chamberlain & Bowie, 2002 was included (C-H bonds), and Hessa et al. 2005 (energy of insertion), but no reference was included about why Ser/Thr are polar amino acids "tolerated" at the hydrophobic core of TMH, which is the state the authors describe.

In the argument about why TMH hydrophobicity matters for targeting (not only for membrane insertion), there is much more direct and recent mechanistic work that should be included: Botelho et al., 2011 established experimentally the hydrophobicity threshold for the "stop-transfer" pathway of TIM23 with quantitative data in an analogous way as reported in this work. Lee et al., 2020 and Yang et al., 2025 described structurally how hydrophobicity of the substrate modulates the Mgr2-Tim17 interaction to allow precursors to be embedded within the membrane.

It may be helpful to consider previous published work as an important precedent for the discussion of TMH hydrophobicity and TIM23 in allotopic expression. The final observations of incomplete mitochondrial localization despite reduced TMH hydrophobicity could also be discussed in light of previous published studies. These studies suggest that hydrophobicity is an important factor, but not the only determinant of efficient mitochondrial targeting. The role of TMH hydrophobicity in mitochondrial import had already been explored in this context. This would help clarify how the current findings build upon the existing literature.

Reviewer #2 (Public review):

Summary:

The paper by Yadav et al. provides compelling theoretical and experimental evidence for an aliphatic-to-threonine substitution (ATS) in the transmembrane helices (TMs) of membrane proteins residing in the inner mitochondrial membrane (IMM) across several species. Furthermore, using ATS, they designed variants of the human Atp6 subunit and of Atp6 subunits from other species that seem to be internalized into mitochondria.

Strengths:

In general, the results support the conclusions. The findings are particularly relevant to the field of allotopic expression and could have significant implications for the future development of gene therapies for mitochondrial disorders.

Weaknesses:

The manuscript could be substantially strengthened by the addition of further experimental evidence and by some minor revisions and adjustments to the interpretation and presentation of the results.

Major Points

(1) The protein product of atp6 is an essential component of the proton channel of ATP synthase, and more than a dozen pathogenic mutations in this gene have been associated with mitochondrial diseases. Accordingly, several studies have reported attempts to achieve allotopic expression of Atp6 in human cells. I would dedicate a pair of paragraphs in the Discussion to acknowledging the most relevant of these previous efforts. Here, in the work of Yadav et al., several Atp6 constructs were detected within mitochondria by fluorescence microscopy. However, no direct evidence was provided that the allotopically expressed Atp6 protein was incorporated into complex V. Localization within mitochondria, by itself, does not demonstrate successful allotopic expression in the functional sense, as the protein could remain unassembled, inserted in an incorrect topology, or in a process of degradation. In my view, this is the main weakness of the present study. A convincing demonstration of allotopic ATP6 expression should ideally be supported by biochemical evidence showing that the imported subunit is stably incorporated into ATP synthase and, most importantly, contributes to its function. This would require demonstrating at least partial restoration of the respiratory or OXPHOS defect.

I therefore encourage the authors to test their different constructs in cybrid cells carrying a pathogenic mutation in the mitochondrial atp6 gene and determine whether they can restore OXPHOS function or, at a minimum, respiratory capacity. Such an experiment would provide substantially stronger evidence that the imported Atp6 protein is not merely localized to mitochondria but is functionally incorporated into ATP synthase. Alternatively, Blue Native PAGE of mitochondria isolated after allotopic expression of the different constructs, followed by second-dimensional SDS-PAGE, could provide direct evidence that a tagged Atp6 subunit has been incorporated into the ATP synthase complex. Furthermore, this experiment could provide a valuable functional comparison of the three ATS constructs (T1, T2, and T3) and identify which one is most effective in restoring function. Importantly, the T3 construct, despite carrying the highest level of ATS, may not necessarily be the most effective in increasing the levels of assembled ATP synthase or in restoring ATP synthase activity.

(2) I do not agree with the interpretation of the results presented in Figure 7 - Figure Supplement 3, "Targeting tracks with hydrophobicity, not expression." I am concerned that the experimental design may be biased. The two most highly hydrophobic proteins (WT and T1), which are expected to have greater difficulty being imported into mitochondria, were selected for low-level expression. In contrast, the two constructs with extensive ATS (T2 and T3) were expressed at high levels. The hydrophobicity effect and the expression levels are confounded in this experiment, making it difficult to determine whether the observed targeting differences are attributable to one of these parameters. To disentangle these effects, this experiment should be repeated using both low and high expression levels for all four constructs, resulting in eight experimental conditions (four constructs x two expression levels).

Reviewer #3 (Public review):

Yadav et al. revisit the old conundrum of why certain genes encoding inner mitochondrial membrane (IMM) proteins are retained in the mitochondrial genome (mtIMMs; 13 genes in humans) while genes encoding other IMM proteins (nuIMMs) have been relocated to the nuclear genome during evolution. It was noted already in 1986 that nuIMMs have transmembrane helices (TMHs) of lower hydrophobicity than mtIMMs (FEBS Lett 198:1). A number of subsequent studies have shown that some mtIMMs can be converted to nuIMMs by appending a mitochondrial targeting sequence (MTS) and, in most cases, reducing the hydrophobicity of one or more of the TMHs (reviewed in Genes & Dis 7:578). Conversely, increasing the hydrophobicity of a TMH in a nuIMM protein can prevent its import into mitochondria (e.g., PNAS 99:10510). Whether the reduction in TMH hydrophobicity in nuIMMs is mainly driven by the need to bypass cotranslational targeting of the protein to the ER and trafficking along the secretory pathway, or to prevent the protein from being prematurely stuck in the IMM during mitochondrial import, is still, to some extent and open question, and experimental support for both possibilities exists (e.g., FEBS Lett 591:65).

Yadav et al. present an extensive bioinformatics study which nicely confirms the reduced hydrophobicity of nuIMM TMHs compared to mtIMM TMHs (and also compared to TMHs in proteins that traffic along the secretory pathway). The study is based on a lot more sequence data and many more kinds of comparisons than previous publications, and leaves little doubt that the reduction in hydrophobicity in nuIMM TMHs is real.

Based on their bioinformatics analysis, the authors also propose that aliphatic -> Thr substitutions (ATS) are the main driver of hydrophobicity reduction in nuIMMs, TMHs, and that Thr has been enriched also in mtIMMs. TMHs in organisms that depend only on Oxa1-type IMM insertases, possibly in order to reduce the aggregation propensity of these proteins when produced in the mitochondrial matrix. This is a novel hypothesis that has not been proposed in earlier work.

The authors additionally show that a mitochondrially encoded ATP6 protein can be converted into a nuclearly encoded, import-competent protein using ATS to reduce the hydrophobicity of its TMHs and, conversely, that import of a nuclearly encoded ATP6 protein is blocked when Thr residues in its TMHs are mutated to aliphatic residues. Similar findings have been published before; what is new is the use of aliphatic -> Thr substitutions (rather than other aliphatic -> polar substitutions).

Detailed comments:

While previous bioinformatics studies of how gene relocation from the mitochondrial to the nuclear genome impacts protein sequence have focused on TMH hydrophobicity, Yadav et al. expand this to include individual amino acid frequencies. The authors present four types of analyses:

(1) The authors identify E. coli homologs of the 13 genes retained in human mitochondrial DNA, do structure-based sequence alignments of the homologous pairs, and then compare the individual aligned TMH pairs in terms of hydrophobicity and Thr content. The authors also calculate an amino acid substitution matrix from the aligned TMH pairs. These data are presented in Figure 2 (and supplements).

Hydrophobicity is calculated based using the GRAVY algorithm and the Kyte-Doolittle scale, and by calculating the fraction of ALIVF residues. Both nuIMM and mtIMM TMHs are found to be significantly less hydrophobic than the E. coli TMHs (p ≈ 0.002). Thr is reported to be enriched in nuIMM and mtIMM TMHs relative to E. coli TMHs (as are Asn and Pro, while Val and Phe are reduced relative to E. coli TMHs, panel C). Panels F and G show an enrichment of Thr residues in nuIMMs of marginal significance (p = 0.02), and an enrichment in mtIMMs of higher significance (but the statistics are skewed by one mtIMM TMH that apparently contains almost 40% Thr residues). The substitution matrix in panel H indicates that aliphatic I, L, A, and G residues in the E. coli TMHs are often substituted by Thr and Val in the mitochondrial proteins. F does not show this substitution pattern, questioning the use of ALIVF counts in the analysis.

(2) The authors calculate hydrophobicities and amino acid frequencies for all human TMHs found in AlphaFold2 structures and grouped according to their cellular location: ER, Golgi, plasma membrane, nucleus, outer mitochondrial membrane (OMM), nuclearly encoded proteins in the inner mitochondrial membrane (nuIMM), and mitochondrially encoded proteins in the inner mitochondrial membrane (mtIMM). These data are presented in Figure 3 (and supplements).

OMM and nuIMM TMHs are significantly less hydrophobic than the secretory pathway TMHs, whereas mtIMM TMHs seem to have similar hydrophobicities as the secretory ones. nuIMM TMHs may have a slightly increased Thr content compared to secretory pathway proteins, but only one p-value is significant (Golgi vs nuIMM). mtIMM TMHs appear to have a higher Thr content than nuIMM proteins, but the statistics is skewed by a single point at a Thr fraction of 0.25. The Thr enrichment is less pronounced than for the E. coli comparison in Figure 2, Figure 3 Supplement. Fig. 8 shows that TMHs in chloroplast and mitochondrial plant proteins both have reduced hydrophobicity compared to ER-targeted proteins.

(3) Starting from the 66 mitochondrially encoded proteins in Jakobids, the authors identify homologous proteins that have become nuclearly encoded and carry an N-terminal mitochondrial targeting sequence (MTS) in organisms with smaller mitochondrial genomes. As in 1, the authors then do structure-based sequence alignments of the 63 homologous nuIMM and mtIMM TMH pairs found, and compare the individual aligned TMH pairs in terms of hydrophobicity and Thr content. These data are presented in Figure 4 (and supplements).

The reduction in hydrophobicity in nuIMM vs mtIMM TMHs upon relocation to the nucleus is robust and confirms earlier publications (panel C). The increase in Thr content in nuIMM vs mtIMM TMHs is less convincing (p = 0.012, panel G) and is opposite to what is seen in Figure 3C.

(4) By phylogenetic analysis, the authors identify three independent relocations of the ATP6 gene to the nuclear genome, do structure-based sequence alignments of nuIMM and mtIMM pairs representing these three events, and illustrate the reduced hydrophobicity of the TMHs in the nuclearly encoded proteins by hydrophobicity plots. These data are presented in Figure 5 (and supplements).

In panel C, it is not only aliphatic-to-Thr substitutions that reduce the hydrophobicity of the nuATP6 TMHs. How much is the hydrophobicity reduced if the Thr mutations are reversed (i.e., how much does the hydrophobicity reduction depend on ATS specifically and not on other kinds of substitutions)?

In a short experimental section, the authors go on to show that a mitochondrially encoded ATP6 protein can be converted into a nuclearly encoded, import-competent protein using ATS to reduce the hydrophobicity of its TMHs (but functionality is not tested) and, conversely, that import of a nuclearly encoded ATP6 protein is blocked when Thr residues in its TMHs are mutated to aliphatic residues (Figures 6, 7).

Finally, the authors carry out all-atom MD simulations to study the energetics of H-bond formation between Thr side chains and TMH backbone atoms.

In summary, the reduction in TMH hydrophobicity in nuIMMs compared to mtIMMs (and to secretory pathway membrane proteins) is robust and nicely confirms earlier studies. The purported enrichment in Thr content in both nuIMMs and mtIMMs has weaker statistical support in the data: p-values are typically > 0.01 (or may be skewed by an outlier) and appear not to have been corrected for multiple testing in all cases. As is clear from the ATP6 data in Figure 5, aliphatic -> Thr substitutions explain only a fraction of the overall hydrophobicity reduction in nuIMM TMHs, and the role of other hydrophobicity-reducing mutations in gene relocation could be better defined.

Author response:

We thank the reviewers for their careful reading of the manuscript and for their insightful comments. Several suggestions relate to a lack of clarity in our presentation, and others propose analyses that will strengthen the impact and robustness of the work. We outline our planned revisions below.

Reviewer 1:

We are grateful to the reviewer for appreciating the significance of our work for the treatment of mitochondrial disorders and its future implications in the development of genetic tools and protein design.

(1) Multiple testing

Figure 3A–C, Figure 3—figure supplements 1, 2, 4 and 5, Figure 6G and Figure 7F used one-way ANOVA with Tukey's post-hoc test, in which correction is intrinsic; the p-values shown are already adjusted. Our legends did not state this, and we will include this information in the revised manuscript.

We will apply Benjamini-Hochberg correction across all 400 comparisons, and as individual cells are likely underpowered, will also test aliphatic-to-threonine substitution at the level of residue classes, analogous to the directional analysis in Figure 4.

(2) Experimental versus predicted structures

We thank the reviewer for pointing this out. Our description here was not adequately clear. All structural alignments and compositional analyses used AlphaFold2 models; experimental structure availability was used only as an inclusion criterion for the compartment comparisons. We chose predicted models because experimental structures are frequently incomplete, which would bias residue composition. We will state this more prominently and add the source of the structure to the relevant legends.

(3) Hydrophobicity scale

We used Kyte-Doolittle for comparability with the prior literature on TMH hydrophobicity in relocated mitochondrial genes, and because it is additive by construction, which the mean-hydrophobicity analyses require. The Hessa scale is defined for insertion of a complete segment and carries substantial position dependence (PMID: 15674282). It is used in Figure 8G because that analysis plots single-residue transfer free energies, which is the scale's intended use and which Kyte-Doolittle, being a hydropathy index does not provide. We will state this rationale in the Methods and in the Figure 8G legend.

(4) Bootstrap support in the ATP6 tree

We agree that the low-support nodes warrant discussion, and we should have addressed it in the original text. These nodes (43, 55, 40) concern relationships among Porifera, Ctenophora and Cnidaria, which remain contested in analyses of far larger datasets (PMID: 41686647). The inference of independent relocation does not depend on them: the apicomplexan, chlorophyte and ctenophore sequences are separated by backbone nodes with 100% support. We thank the reviewer for noting that the distinct MTSs in each clade provide independent support, and we will state this explicitly along with an acknowledgement that values below 70 indicate unresolved relationships.

(5) Core versus peripheral definition

We sincerely thank the reviewer for pointing this out as our text was unclear regarding this. This was set using the ER TMHs, which provide the largest and best-powered set, and applied unchanged to all other groups. The window was chosen to give comparable numbers of positions in each bin, and so that core positions remain membrane-embedded despite helix tilt and uncertainty in the inferred helix midpoint, both of which are greatest near the termini. We will make the rationale explicit and add a robustness analysis at alternative window sizes, as recommended by the reviewer.

(6) Literature

We thank the reviewer for these references and agree they should be discussed. We will incorporate the role of Ser and Thr -containing motifs in TM helix association into the discussion of the biophysical properties of these residues. We will review relevant literature regarding hydrophobicity preferences of the TIM translocon in the context of competition between Sec61 and TIM/TOM insertion, together with the differences between insertion of proteins encoded in the mitochondrial and nuclear genomes. Further, we will also make a version of Figure 8G using the Bothelo and the Kyte-Doolittle scale.

Reviewer 2:

We sincerely appreciate the reviewer for their insightful comments, and for suggesting experiments to further strengthen the manuscript.

(1) Assembly and function of allotopically expressed ATP6

We agree that mitochondrial localization does not establish functional allotopic expression, and will revise the text so this is unambiguous in our manuscript. Our figures 6 and 7 test whether reduced TMH hydrophobicity allows a mitochondrially encoded protein to reach mitochondria when expressed from the nucleus. Assembly into complex V requires further constraints — correct topology, coordinated assembly with the c-ring, and stoichiometry with nuclear-encoded subunits — for which ATS may not be sufficient.

Following the reviewer's thoughtful suggestion, we will perform Blue Native PAGE to test whether the imported subunit is incorporated into ATP synthase and to compare the T1, T2 and T3 constructs. We will also add a Discussion section on topology as a distinct barrier and acknowledge the previous efforts at ATP6 allotopic expression.  As the reviewer anticipates, we expect that it can be challenging for the current constructs to be fully functional, but we will test this experimentally following the BN-PAGE assays. If we do not get successful incorporation, we will discuss this in the text as to what caveats may have caused this.

(2) Expression level confound

We appreciate with the reviewer’s concern regarding this panel. For context, we would like to point out that the conditions originally shown were chosen so that the comparison runs against our conclusion: the most hydrophobic constructs were expressed at low levels and the ATS constructs at high levels, so expression would be expected to work against the observed difference rather than produce it. We recognize that this rationale was not apparent from the figure.

To address this concern further, we have the remaining conditions in hand and will show all four constructs at both expression levels, as requested.

Reviewer 3:

We are very grateful to the reviewer for their thorough review of the manuscript and for providing constructive feedback.

(1) Statistical support for threonine enrichment

We take this point. The strength of statistical support varies across these comparisons, and we will report the p-values with the outliers removed, together with the corrections described under Reviewer 1 point 1. We note that the comparisons are constrained by the number of proteins available there are 13 mtDNA-encoded human IMM proteins, and the E. coli-human comparisons are limited to pairs with detectable homology.

(2) Enrichment of threonine relative to other residues

We will report the absolute residue compositions for the E. coli and human sets in a supplementary figure, and examine the relative enrichment of threonine, asparagine and proline more closely.

(3) Threonine content in Figure 3

The values in Figure 3C are Tukey-adjusted, and all pairwise comparisons are shown in Figure 3—figure supplement 1. The reviewer is correct that only the Golgi comparison reaches significance. Figure 2 compares each human TMH to its aligned E. coli counterpart, so each protein serves as its own control; Figure 3 compares means across unrelated proteins, where between-protein variation is large relative to the compositional difference. We will make this distinction clearer in the text.

(4) Hydrophobicity of mtDNA-encoded TMHs in Figure 3

The reviewer is correct that mtDNA-encoded IMM TMHs do not differ significantly in hydrophobicity from secretory-pathway TMHs. The compartment comparisons test proteins of shared nuclear origin with different destinations; the mtDNA-encoded group is shown for reference, as it differs in both genomic origin and biogenesis route. We will revise the text to specify which mitochondrial class the differences apply to.

(5) Direction of the Figure 3C and Figure 4G comparisons

We thank the reviewer for bringing this up. Our current text did not make it clear that these comparisons involved different organisms. The mtDNA-encoded proteins in Figure 4 are drawn largely from jakobids with large mitochondrial genomes, which retain extensive IMM biogenesis machinery and may face weaker constraints on TMH composition. Those in Figure 3C are the 13 human mitochondrially encoded proteins, which do face these constraints and are correspondingly threonine-rich. The apparent difference in direction reflects this rather than an inconsistency in the underlying trend, and we will make it explicit in the text.

(6) Contribution of ATS to hydrophobicity reduction

We are grateful to the reviewer for their insightful reading of potential evolutionary solutions to the targeting problem. We agree that ATS accounts for part rather than all of the reduction, and that the role of other hydrophobicity-reducing substitutions should be better defined. We will quantify the share attributable to aliphatic-to-threonine substitution, and for the ATP6 examples, report how much of the reduction remains when the threonine substitutions are reverted.

(7) ALIVF grouping

The reviewer is right for noting that phenylalanine does not show substitution towards threonine in the way the other aliphatic residues do in Figure 2H. Phenylalanine is nonetheless depleted in human mitochondrial TMHs alongside isoleucine, valine and alanine (Figure 2C), so the grouping is consistent at the level of composition even though the substitution routes differ. We will also discuss aliphatic-to-valine substitutions, which are largely hydrophobicity-neutral and so do not contribute to the reduction in the same way.

(8) Literature

We thank the reviewer for pointing out early attempts at understanding mitochondrial protein biogenesis and allotopic expression. We will incorporate these references into our discussion, specifically in the context of considering factors which could favor TIM/TOM over Sec61 insertion.

When this concept is applied to post formal thought:

For people whose early adulthood was constrained by scarcity, the practical orientation isn't just maturity — it's necessity. When you don't have a safety net, idealistic choices carry real consequences. The pragmatism you're describing isn't a luxury of age; it's a survival adaptation that happens to align with what the theory describes.

It is important to note that the author, as they continue throughout this conclusion, that integration in communities is possible, the author explains that this is we see this due to our previous integrated school systems. However I'd also like to add that another aspect to add to this hope is that we also gain hope and saw integration from neighborhoods. However, it is similar to schools in which they gradually became segregated again. However, we know that communities can be integrated, and many people of different backgrounds are able to live the same neighborhood. And if we work towards that plan, as was mentioned in the beginning of this article, we can also work that into our school systems.

I found this part of the reading interesting because it can connect to information we previously learned. In class on Tuesday, we went over the White Fleet, where we learned that white people left to suburban areas as a reaction to wanting to get away from the city after the desegregation of schools. However, one aspect I found interesting was that when white people left the city, they took their resources, communities and organizations with them, leaving the cities behind with nothing besides the people, meaning that people of color had less resources and opportunities now. So this piece of learning from class connects to this part of the reading because it proves that segregation didn't lead to any good, but rather that when communities are segregated, their poverty rates increase, yet when they are integrated, even if it isn't necessarily a white community, since there are more races, that means more communities and resources that come with each race or ethnicity, making the overall neighborhood stronger.

This part of the reading changed my perspective because it allowed me to broaden my understanding of segregation. By the author bringing up multiple examples, it allows for me as the reader to use other contexts of where segregation has been present. For me, this is helpful because it allows for me to build on the knowledge I already knew. Upon knowing about segregation in schools and neighborhoods, I wouldn't really be able to think about it in another form because the only form of it I currently knew was in the form of schools or neighborhoods, however now with these new examples, I am able see how segregation has been used to harm different people and communities throughout the world's history, and how every form of it has led to discrimination. I think it is interesting to consider how segregation, what people consider as separate but equal, has happened time and time again across the world and every time it simply proves that it is never equal, and segregation will never lead to equality because one side will always be more powerful.

This sentence stood out to me and I find it to be important because although schools were legally desegregated, the result of not creating a national project to integrate neighborhoods, led to schools still being segregated in a way. In class on Tuesday as well as the Tuesday readings, we read about how although schools are more diverse in certain areas now, they're honestly still segregated, and although it's not lawfully, it is because most neighborhoods don't have diverse communities, but rather each community seems to be built up of only one race or ethnicity. For example, although L.A is a very diverse city, you can go to one school and find the demographic of the school is mostly black students whereas another school close by is made of only latino students, despite the fact that both of these schools are under the same district and could even be in the same "outer community" of that part of L.A. So by the nation never creating a plan to try and integrate neighborhoods, that led to segregation still occurring in a way, not because of laws but because of how they had already been separated by the neighborhoods, forcing families to send their kids to schools in the same area, which is usually built up of their very own race or ethnicity.

Myslím, že to je toto téma velmi dobře zpracované, jen nevidím moc prostor pro nějjakou politiku státu, jak do toho přirozené procesu generační výměny v obydlí zasahovat. Spíš bych asi to téma příště již nezařazovala.

Ale to je přirozený proces, že dochází k převodu na mladší generaci...

tohle je konkrétní doporučení pro bytovou politiku, pokud to bude číst externí čtenář, MMR, která má v gesci bytovou politiku, zveřejňuje samo pro sebe doporučení/námět pro bytovou politiku ...

tady ty nadpisy jsou jinak formátované než u předchozích grafů + se seniorem v čele?

předseda?

Index Cards that ACTUALLY WORK Well With Fountain Pens

🔬 The Protein Was Identified (2017)

A 2017 study in PNAS provided the first direct biochemical evidence for the mechanism. Researchers tested blood samples from mothers of gay and straight sons and found that mothers of gay sons had significantly higher levels of antibodies against a specific male protein called NLGN4Y .‌ What the study proved: Mothers of gay sons have higher antibody levels against NLGN4Y.

What the study did not prove: That these antibodies actually cross the placenta, enter the fetal brain, and alter sexual differentiation .‌

The search results describe it as a "hypothesis" and a "working model" . A 2005 paper warned it was premature to regard the maternal immune hypothesis as more than "a very provisional explanatory tool" until the causal pathway was demonstrated . The 2017 study was described as "an important first step"—not the final word .‌

One paper notes the effect explains only a fraction of gay males—and that other biological mechanisms (genetic, hormonal) also explain only fractions .‌

If sexual orientation were purely genetic, identical twins — who share 100% of their DNA — would have 100% concordance. They don't. They have roughly 50%.

If sexual orientation were purely environmental, identical and fraternal twins would have similar concordance rates, because both types share roughly the same environment. They don't. Identical twins are more than twice as concordant as fraternal twins.

So the data points to both. The genetic contribution is real — identical twins are much more likely to share orientation than fraternal twins. But the genetic contribution is partial — identical twins are also frequently discordant, meaning one is gay and the other isn't, despite identical DNA.

📊 Trauma and Asexuality: A Real Correlation

A study of 33,385 U.S. college students found that self-identified asexual individuals were 4.44 times more likely to report a PTSD diagnosis and 2.52 times more likely to report sexual trauma in the past year compared to non-asexual peers. That's a substantial correlation.‌

Qualitative research captures the same entanglement. Asexual survivors describe struggling to separate their identity from their trauma, wondering if they're "really asexual" or "just traumatized". The community itself often enforces a "born this way" narrative that makes trauma-linked asexuality feel illegitimate.‌‌‌

But correlation isn't causation. The higher trauma rates could reflect: • Asexual people being targeted for violence because they're asexual • Asexual people being more likely to recognize and report trauma • Trauma genuinely contributing to some people's asexuality • Some combination of all three The research doesn't settle this. What it does show is that trauma and asexuality overlap more than the "born this way" narrative suggests — and some asexual people themselves link the two.‌‌

🧬 Hormones: The Picture Is Genuinely Unclear

The textbook's claim that asexuality is "not due to any physical problems" is too strong. Here's what the evidence actually shows:

Animal evidence of hormonal involvement: In rams, a subset are classified as "asexual" — showing no interest in either sex. Research found 12.5% of rams tested were asexual. When castrated, asexual rams showed no sexual behavior, and estrogen replacement did not stimulate sexual behavior — unlike their sexual counterparts. This suggests hormonal systems in asexual rams may be wired differently.‌

Human hormonal data is sparse. One clinical source states that many asexual people have normal hormone test results, and that hormonal imbalances typically cause sudden loss of desire rather than a lifelong pattern. But this is based on self-reports and limited studies.‌

The honest position: There's no strong evidence that asexuality is caused by a simple hormonal deficiency, but there's also no comprehensive research ruling out subtler hormonal or neurological differences. The textbook's "no physical problems" claim overstates what's actually known.

People who say they are neither gender role while applying a new role to their gender/sex by attributing the lack of social role to their gender/sex.

未来可能要做协作。

… by drawing a perpendicular line from the point …

I love this phrase as it challenges the infrastructure that determines who can access, circulate, and participate in the production of knowledge

нужно использовать 1/2 банки масса нетто 310 грамм

нужно использовать 1/2 банки масса нетто банки 310 гр

можно больше лука

можно меньше моркови

очень мало сыра

на таком объеме масла прожарить лук и морковь не получается

tak s tímto pohledem na koleje souhlasím, v předchozím textu jsem to vnímala, že jsou koleje a priori "špatně", tady souhlasím, že zreformovat a zvýšit jejich dostupnost z hlediska systému přidělování a i cenovou dostupnost a kvalitu bydlení.

bydlení na kolejích, není pouze kompromisní řešení...součást studia na VŠ, vždy jsem to vnímala jako výhodu a ne jako nějaké kompromisní řešení

možná bych spíš místo skutečné výdaje na bydlení použila termín "reálné výdaje na bydlení"

když čtu ten odstavec od začátku, tak ten podíl u mladých domáchností...už nevím o jaký podíl u mladých domácností jde? Asi to není podíl "u" ale jen podíl....pořád je tím míněno 22% mladých domácností? ...narůstá spíše mírněji než "u průměru" za všechny domácnosti. ....nevím nesedí mi ta druhá půlka odstavce.

Takhle to bývalo ale vždycky, že pro mladé je to obtížnější

výzkum ČS a Evropy?

This is interesting to me because it shows how bots are not automatically "bad" or "good" as their actions are dependent on how they are operated. With the example of the Gender Pay Gap Bot, it holds companies accountable by using actual databases instead of spreading misinformation. This makes me think of how we decide when to put criticism on bots.

I love this bot and its’ intent. I have such little experience with bots, I didn’t know that such a code could be written that could go into a pay gap database and post with that information. I am all for transparency when it comes to large corporations, otherwise I believe the company is trying to hide something. I think a post like this (from the university in this example) is made by a human computer. It is virtue signaling. The university clearly does not believe what it is saying it believes because the wage gap has grown in the last year. I didn’t think I could like a bot, but here we are.

I think users want to be able to make bots so that they can share their thoughts while still having a small separation between themselves and their posts. Above the text says that using bots allows some "disconnect between intentions and actions" which can seem appealing to many individuals, they also have access to coding and knowledge from other people that can allow them to do more with the bot accounts they create.

Platforms does not get their money from one source. More people using it, more incentives for others to making bots to join, creating an illusion of tons of people are using it. More attractive for investors.

As I would hope for whenever calling a company and answered by a bot. I just kept repeating "get me a real person". I would say not so well, because when you are talking to a bot or commenting a bot, you will not have any ethical problem to just express what ever you want to it.

I think social media platforms allow bots to operate because they make the platform more efficient and productive. Many platforms have customer service features, and it is easier to have a bot handle basic questions so users do not have to wait a long time for a real person to respond. Platforms also have thousands to millions of users every day, so there is a lot of activity and traffic to manage. Bots can help organize different features and keep things running smoothly. They can also be useful for tasks like recommending content or helping with moderation.

The paper is now published and available at JBER. https://www.wecmelive.com/open-access/uncovering-the-role-of-laminin-lama5-in-maintenance-of-epithelial-identity-and-polarity-in-bilayer-zebrafish-epidermis-d.pdf

ggggggggfdd

it is for class explanation

banking with the use of mobile

Market _Value

Finance + Technology

This quote argues that when health care is run for profit, providers focus on patients who can pay, while the poor and uninsured are pushed into a facility that are nonprofit and overburdened, making quality care potentially difficult to get. The author assumes this outcome is a natural result of profit seeking rather than a deliberate policy choice. They also treat the poor and uninsured as a fix group, when in reality people move in and out of coverage as jobs and circumstances change.

This quote is very interesting to me as it starts with a praise of the US health care and then is followed by a critique. That critique suggests the US systems strengths and failures go hand in hand because both flow from treating health care as a market rather than a basic human right. It also means the same profit motive that makes the system innovative also makes it unfair.

person["k"]를 조회함 → 객체에 'k'라는 키가 없으면 undefined

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Know More: https://medium.com/@callyzer/how-sales-teams-can-increase-revenue-from-existing-customers-f19b12d82792?postPublishedType=initial

As mentors, we can guide our mentees into becoming professional problem-solvers by asking the right questions to guide their thinking on challenging curriculum or behavior issues. Getting creative with their decision making and growing their confidence in their own skills to problem-solve.

Paul Bäumer describes his time as a young man fighting in WWI. Paul and his friends quickly learn that warfare is nothing like what it was advertised to be. As Paul sees many of his friends injured or dying, he begins to see the old generation who pushed these young men into battle differently. When Paul visits his injured friend Kemmerich, he learns just how badly the war has affected their lives.

Paul Baumer and his friends return from the front and enjoy having food, cigarettes, and time to rest. They realize they have so much food because many of their fellow soldiers were killed. Paul remembers how his teacher, Kantorek, encouraged them to join the war. After experiencing the fighting, they realize that their teachers did not understand what war was really like. They visit their friend Kemmerich, who is badly wounded and close to dying. The soldiers have become so used to death that Müller is already thinking about taking Kemmerich's boots. Paul realizes that even though they are very young, the war has made them feel old and taken away their youth.

Paul Baumer and his fellow soldiers are resting after suffering heavy losses in battle. They are surprised to receive extra food and cigarettes because supplies were prepared for 150 soldiers, but only 80 returned. The passage introduces Paul’s friends and shows how hunger, exhaustion, and death have become normal parts of their lives

Men were seen as having healing agents, but women are the ones who "need healing" from them, showing a gender dynamic.

I have tried inviting my mentee to a variety of ed tech learning opportunities so that we can learn new teaching tools together.

What stood out to me most is how a student’s family background can play such a big role in their educational opportunities. Two students may have the same goals and abilities, but one may have an easier time attending college simply because their family has more financial resources. This made me think about how college expenses can create additional stress for students and families. It also raises the question of whether higher education is truly equally accessible when the cost can be such a major barrier.

I found this passage interesting because it explains how the way we view people can actually influence their behavior and opportunities. A label may seem small, but over time it can affect how a student is treated and how they view their own abilities. This made me think about how important it is for teachers to recognize each student’s potential instead of making assumptions based on labels or stereotypes. I wonder how schools can make sure that labels are used to support students rather than limit what they believe they can accomplish.

I found this passage interesting because it points out that there are different perspectives on parents working outside the home. It made me think about how children’s experiences can vary depending on their family’s situation, access to childcare, and the amount of time parents are able to spend with them. I also think the pandemic showed how difficult it can be for parents to manage work and childcare at the same time. This makes me wonder how children are affected when they have to become more independent at a young age.

This passage made me think about how much our home environment can affect our overall well-being. Having people around who care about you can provide a sense of security and support, but being part of a family does not always guarantee happiness. I think personal relationships and the quality of support someone receives may be more important than simply living with family. This makes me wonder how a person’s experiences within their family might influence whether they see family life as a source of comfort or stress.

How a school runs is important to the education you will get at it. If a schools environment and culture is not accepting to you or someone else, it can create a hostile learning experience. Since culture for each college or university is different, you have to pick one that will align with personal goals and feelings to have a productive educational environment. It’s a privilege to be able to get schooling but it also is a privilege to teach the next generation of the world since we will grow to set the standards of future culture.

I think this highlights how society has changed in gender roles and progressed for women. Women used to have to depend on their male counterpart and hope they would provide and be there. However, women now don’t need to do that and we are straying farther away from traditional gender roles into a place of more equality in the family life.

This entire experiment was so interesting to me because I have seen this prophecy firsthand when teaching. Many children, if told they are doing amazing and have had tremendous growth actuallly end up with those results and vice versa for the negative side. This is something that I truly believe is important to understand. Have you ever seen the self-fulfilling prophecy play out in front of you, like in this expirement?

This section was interesting to me because I had never thought about school in this way. I always knew school helped you meet new people with different personalities and differing views, which could help you grow. But I never realized it was also used to connect us as a nation. I'm curious, did anybody else not think about the way education and school unify us as a community, not just by making friends?

I found this section interesting because, in our current society, which is an industrial society, we recognize bilateral descent. I didnt realize that in other cultures things werent passsed down like they are in mine.

This part of the text stood out to me because Ive always wondered what the average person considers "family". Since I have a blended family with adopted siblings and half-siblings, I've always had a different outlook, and its interesting to me to know the circumstances that other people generally use to consider people family.

more thank

to do or something happen again

can not control to do something

cite scientific resulting support own opinion

useful

Thus Spoke Zarathustra by Nietzsche can be characterized by Zarathustra leaving his life of hiding to share his knowledge and wisdom with the world. He argues that human beings should not be content with themselves and should continuously strive for betterment and self-improvement. For instance, his concept of the Superman implies creating one's values regardless of others' influence. Moreover, Nietzsche calls on humans not to depend on the hope for another life after death but to remain faithful to the Earth. Nevertheless, humankind does not appreciate the teachings of Zarathustra and prefers to live comfortably, being the "Last Man." The rope-dancer's death makes Zarathustra understand that he requires individuals who would think, create, and challenge themselves and not those who follow others blindly. Thus, the main idea of the passage implies the start of Zarathustra's journey from being secluded and wise to searching for those who want to grow and create their own way of life.

Zarathustra leaves his life of solitude in the mountains to share his wisdom with humanity. He teaches that people should overcome their current limitations and strive toward the "Superman," while rejecting blind faith and being satisfied with an easy, comfortable life. The crowd does not understand him, so he realizes he needs to find people who are willing to think for themselves and create new values.

Zarathustra leaves his mountain solitude to share his wisdom with humanity. He teaches about Superman, a person who strives to grow beyond ordinary human limits and create new values. After the people reject his ideas, Zarathustra realizes he should seek out companions who are willing to think and create for themselves.

I have definitely had "mentors" that have had this approach and this top down strategy is not at all helpful for me. I know that as a mentor I do not have all of the answers but that I am there to support and help my mentee figure out the answers together and provide resources they may not have yet.

He stops and realizes for a moment that it is only a story, and he's glad he's not part of it. Even though while he was reading, you could tell otherwise.

Bastian stopped reading because it truly affected him. He was no longer reading for entertainment; he was reading because of the connection he had.

Everything looks hopeless because the luckdragon is dying and Atreyu can't reach the Southern Oracle.

He starts to wonder if the characters in the story can hear him. He is deeply connected to the story.

Bastian is emotionally connecting with the story. He starts to feel that what is happening in the story is happening to him as well.

Bastian isn't aware of the danger behind him, but the readers do. This creates suspense in the story.

Bastian feels a deep connection to the stories and begins to question whether it's really just a story or could be true.

Bastian looks up to Atreyu and wants to be like him.

A resemblance between Atreyu and Bastian.

Atreyu knows he can't give up; he's gone so far in the journey. He had a lot at stake and pushed through.

The song he remembers is talking about the Dead Mountains that Atreyu is in.

It was a long and tiring journey for him.

Atreyu travels through the Dead Mountains and faces Ygramul. He risks his life to reach the Southern Oracle and save Fantastica. Bastian becomes scared as the story seems connected to him.

And with a newly inspired heart, I’ll follow you to do whatever needs to be done. I don’t even need to know what it is because it’s enough for me that Brutus is leading me.

Caesar will go out. The dangers that threatened me have only attacked me from behind. Once they see directly, they will disappear.

Brave son, born from an honorable family, you have brought my lifeless spirit back to life like an exorcist. Now tell me to act and I will attempt even the impossible and succeed. What should I do?”

What do you mean, Casear? Do you think you can go outside? You shouldn't go anywhere today.

Go tell the priests to perform a sacrifice and bring me their predictions about whether it will be successful.

By all the Roman gods I worship, I’m throwing off my sickness now.

Neither heaven nor Earth have been peaceful tonight. Thrice hath Calphurnia has cried three rimes in her sleep," Help me, they are murdering Caesar!"" Who's there?"

I have just such an honorable deed in mind, Ligarius, if you were well enough to hear about it.

But we have to do that too. Caius, I’ll explain what it is as we go to the person who needs to be dealt with.

Wow, Caius, you picked quite a time to wear a headscarf! I wish you were not sick.

Caesar, I’ve never been one to worry about omens, but now they scare me. Someone inside has told us about the terrible things the guards have seen. A lioness has given birth in the streets, and graves have opened, releasing the dead. Fierce, fiery warriors have fought in the clouds in organized battle formations, and blood has seemed to rain down on the Capitol. The sounds of battle filled the air—horses were neighing, and dying men were groaning.

nice

From the top down, when staff and students are given choice and feel like they are a part of a democratic society in their school, they will have more buy-in to want to show up, belong and feel that they matter. This directly affects their academic performance and their social-emotional well being.

This opening made me think about how changes in a city’s population can affect its schools. If white families moved to the suburbs, students might become separated by race across different neighborhoods and school districts. Did this movement create new forms of school segregation even as schools were being pushed to integrate?

I think this ending is powerful because the word "No" almost becomes something living inside the person. It makes their refusal feel like more than just a decision, almost like a part of their personality they don't want to admit exists.

Rain is something that helps things grow, so I think this metaphor represents the idea of being responsible for someone else's survival. The poet seems to be criticizing people who think everything depends on them.

I can picture someone holding their bag closer when a stranger approaches them. This creates a sense of discomfort and shows how quickly people can become defensive when asked for help.

The dime represents a really small act of generosity. I think the poet is questioning why people feel like helping is pointless unless they can make a huge difference.

I think this shows how guilt can sometimes be more about making ourselves feel better than actually helping someone else. The speaker seems to be criticizing that way of thinking.

I think this metaphor is interesting because it compares someone with money to a god, almost like they have the power to control someone else's situation. To me, the poet is showing how people sometimes exaggerate their own importance when it comes to helping others.

I find Hesse’s argument about the “Downfall of Europe” helpful for understanding Eliot’s “Falling towers / Jerusalem Athens Alexandria / Vienna London / Unreal,” because both suggest that a civilization can fall apart through the loss of the beliefs that once held it together, even before anything physically collapses. A tower is supposed to be something strong and lasting, standing above everything around it, so Eliot’s description of these towers as “Falling” undermines the sense of permanence that they are built to convey, almost making their height a reminder of how far they have to fall. By placing Jerusalem, Athens, and Alexandria alongside Vienna and London, Eliot brings the ancient world into the modern one, suggesting that the European cities his readers would recognize as centers of culture and power are no more protected from collapse than the civilizations they look back on. I also find the placement of “Unreal” particularly interesting, because after naming these actual places with entire histories behind them, Eliot seems to take away their solidity with a single word, as though everything they represent has become difficult to believe in. This connects to Hesse’s suggestion that Europe’s downfall might occur “only” in people’s souls, through “changing the meaning of worn-out symbols,” since the buildings could still be standing while the beliefs that gave them significance have already fallen apart. What complicates this connection, however, is that Hesse sees destruction as something that “will necessarily lead, like every death on earth, to a new birth,” making the downfall of Europe both frightening and potentially necessary for something else to emerge. Reading Eliot alongside this argument makes me wonder whether the falling towers could also create room for renewal, although the word “Unreal” leaves me much less confident that anything stable is waiting to replace them, or that the people living through this collapse would even know what to build.

q how would they manipulate matches

Richard Strauss's Thus Spake Zarathustra was inspired by Friedrich Nietzsche's philosophical book of the same name. Although the music is famous for its dramatic opening, especially because of 2001: A Space Odyssey, the entire piece explores deeper ideas about religion, science, nature, human existence, and the search for the meaning of life. Nietzsche's philosophy encourages people to accept life, including its suffering and physical nature, instead of looking for answers in a spiritual world. Strauss represents these ideas through different musical sections, including humanity's desire for religion, natural passions, science, and the struggle to understand nature. The music repeatedly returns to the "World Riddle" theme, showing that nature remains mysterious and greater than human understanding. In the end, the unresolved music suggests that the mystery of existence does not have a simple answer.

explains how Thus Spake Zarathustra was inspired by Friedrich Nietzsche’s philosophy. The music explores humanity’s search for the meaning of life, especially the conflict between religion, science, human passions, and nature. Strauss uses different musical themes to represent these ideas. the famous opening represents the mystery of nature. The piece ends without fully resolving the musical tension, suggesting that the “world riddle” or meaning of life remains unanswered.

Paul Bäumer, a young German soldier fighting in World War I. The movie shows the horrors of war, loss of innocence, and the emotional effects of constant fighting. Paul and his friends struggle to survive while realizing that the war is not the heroic experience they were promised.

The story follows Paul Bäumer, a 20-year-old soldier who enlists alongside his classmates after being inspired by patriotic propaganda. Upon reaching the Western Front, the group quickly realizes that the romanticized version of war they were promised is a lie. The narrative follows their struggle for survival amidst constant bombardment, hunger, and the loss of friends. Paul eventually finds himself isolated from civilian life during a brief leave, feeling unable to relate to those who have not witnessed the war's horrors. The novel concludes with the death of Paul, reported by the army with a cold, ironic statement: "All quiet on the Western Front".

Nietzsche’s “God is dead” means that traditional religious beliefs were losing their influence because of science and modern thinking. Nietzsche worried this could lead to nihilism and a loss of meaning, but he believed people could create their own values and purpose instead.

let은 우리가 상식적으로 기대하는 블록 스코프(Block scope)를 엄격히 강제(enforce)하여 변수의 생명주기를 안전하게 가둠

앞서 살펴본 type="module" 내부에서 선언된 모든 변수, 함수, 클래스는 파일 단위의 독자적인 스코프를 갖기 때문에 window 객체에 전혀 등록되지 않습니다. 그러므로 따로 여기서 등록할 경우 말이 됨

type = module은 deferred되어서 html 파싱 완료 후 실행 됨

Nietzsche argues that belief in God can limit personal growth, so people should create their own values, set their own goals, and work toward becoming their best selves.

Nietzsche argues that belief in God can weaken people and limit their potential for greatness. He believes people should face suffering themselves and use it to become stronger rather than relying on religion for comfort.

Nietzsche argues that people believe in God because the idea gives them comfort, hope, and a way to cope with suffering and loss. He sees God as a human creation meant to make difficult experiences easier to handle.

Nietzsche’s “God is dead” means people are losing faith in traditional religion and must find new ways to create meaning and values in life

this review also looks at how men prefer to receive help not just the preventatives

another important strategy because making mental health information more accessible could encourage young men to seek help

the lack of knowledge can make it very hard for young men to recognize when they need help

another connection to the barriers of masculinity

This highlights a possible strategy for helping introduce young men to mental health services

a variety of different research methods were used.

This is one of the main findings and it directly relates to my research topic

the results are categorized into five main themes

The authors set very specific criteria for the studies that were included in the full literature review

This shows the gap in the existing research

This shows how the systematic review narrowed down the research

This explains the main purpose of this review

this compares the questionnaires with James Lipton, Bernard Pivot, and Marcel Proust. it explains that even though Proust is often credited with the questionnaire, he did not actually create the original list. The questionnaires began as a parlor game, and the original author is unknown.

James Lipton: 10 questions focused on personality, preferences, creativity, and ideas about life/death. Bernard Pivot: 10 questions, similar to Lipton’s but with some differences involving drugs, banknotes, and reincarnation. Marcel Proust at age 13: 15 questions about happiness, heroes, qualities, occupations, and people he admired. Marcel Proust at age 20: 31 questions covering personality, happiness, friends, interests, heroes, history, values, and his motto.

This is exactly where I want to be.

Double TE is always the play

It explains that the questionnaire has 35 questions meant to reveal a person’s personality, values, fears, goals, and preferences.

this is a set of personal questions designed to help someone reflect on their personality, values, preferences, and beliefs. It was made famous by French writer Marcel Proust and is meant to reveal different parts of a person’s character.

a lot of this doesn't even make sense to me like i cant comprehend what she's saying or talking about

thats like when you see a butterfly you think its a loved one who has passed or as for me when i see a red cardinal it reminds me of my pawpaw

11/2=5.5

interesting

elaborate?

another use of data viz

impact of visualizations

specific example