Metropolis as more than just a geographical place or accummulation of people, it's a machine that millions of moving parts, regulated by timetables. (What's one of the most important non-calculating part of modern computers?)

By itself that needn't be a bad thing: I certainly play certain kinds of music when I need to get shit done; it's just that that happens to be bangin' techno: https://soundcloud.com/amelielens/amelie-lens-4h-essential-mix

Faith in science can be very similar to faith in religion...bogged down by dogma and tribalism.

People may just want to do volunteering to help, but it's not what they want to focus on and is just a side thing they like to work on.

So, girls also work full time more but it's still not that much greater.

Why were the second class people treated so differently than the first class people? I think that it's just a ship and everyone should have the same seats.

I think that 10 times radiation is going to a difficult thing for the mission on mars because they have to set up a rover to scout out the area to make sure it is safe

10 times more radiation is a stretch, so confinement kind of needs to be required for the astronauts to live, though that of it's own right is already another issue NASA is tackling.

I selected the full-range theory of leadership as the as the optimal model. First and foremost, I have always been drawn to the characteristics of transformational leadership. If I had to choose a theory of leadership to aspire to, it would be a mix of transformational and servant leadership. I have always thought that the ability to engage people by tapping into what they are passionate about or what motivates them leads to greater success. Have you ever attended a presentation by someone that is passionate, engaged, excited, and full of enthusiasm for their subject? It makes you want to run right out and join their team/buy their product/take up their cause. It is infectious. There are four components of the full-range theory: Individualized consideration, intellectual stimulation, inspirational motivation, and idealized influenced. I am struggling with imagining how I can incorporate individualized consideration into my current leadership role as I have 109 direct reports. That would be very difficult. I can however, try to give this attention to the people who have in the past indicated their willingness/eagerness to go above and beyond what is expected. By developing the staff that are eager to do this, it sets an example for the rest of the team. I often tell people that when they are ready for more, I am ready to give them more. It’s OK if you just want to come to work, do your job and go home, but when/if you are ready, I’ll be here to help you. Intellectual stimulation can be achieved in my setting by asking people to think outside the box, pushing past old norms. In healthcare, we call these “sacred cows.” No one really knows why we do it this way, we just have always done it this way.” There are so many team members with innovative solutions for everyday problems. All you need to do is ask them. Inspirational motivation is so important for a team to receive from their leader. If I, as the leader, am not excited about a project, how am to expect my team to be excited? If a leader just asks a team to perform task A, B, C, etc., there won’t be much inspiration. Right now, my nurses are orienting a lot of new nurses. Orienting a new nurse is exhausting and time consuming. There is little reward in it. There are a few staff members that are getting pretty burnt out. It might help if I said, “in three months, when all these new nurses are off orientation, we will be so well staffed, we won’t know what to with our selves! Also, look at the amazing start you are giving all these nurses. You are laying the foundation for their career. This is such important work you are doing!” This approach shows that I am excited, I have faith in their ability, and highlights how important they are to the greater picture. Idealized influence is the fourth quality. This one can be hard. As a new leader I am still surprised when something I say to one person travels around the unit and by the next day, many people know. I forget that people are watching and listening. Not in a bad way, but the leader sets the tone for the team. If a leader sets a tone of respect, empathy, positive reinforcement, and clear, direct feedback, these qualities will hopefully be represented by your team.

mcnamara arguing that keeping electricity costs low is more important than new transmission lines because this will cause people to switch to cleaner electric heating and electric vehicles

The parents do their best to try and appease the boss man, but he insists that Gregor must overcome it because of business.

It is well past time. The elected members of the government have been in there for too long and its time for change. There needs to be a limit a person can serve in government offices just like the president. Some of those people in office are as old as my great-grand mother, and if that doesn't show how wrong that is then I don't know what. It's time to have people who are younger and know how the world is today.

There's the stereotype that Black women are the largest demographic on welfare which makes no sense. Black women account for only 10% of the US population, but are the largest group receiving welfare? When in actuality household headed by a White person account for over 70% of those on welfare. So this stereotype has literally no evidence behind it. It's just pure prejudice.

Reviewer #3 (Public Review):

This paper describes the oscillatory activity of the habenula using local field potentials, both within the region and, through the use of MEG, in connection to the prefrontal cortex. The characteristics of this activity were found to vary with the emotional valence but not with arousal. Sheding light on this is relevant, because the habenula is a promising target for deep brain stimulation.

In general, because I am not much on top of the literature on the habenula, I find difficult to judge about the novelty and the impact of this study. What I can say is that I do find the paper is well-written and very clear; and the methods, although quite basic (which is not bad), are sound and rigourous.

On the less positive side, even though I am aware that in this type of studies it is difficult to have high N, the very low N in this case makes me worry about the robustness and replicability of the results. I'm sure I have missed it and it's specified somewhere, but why is N different for the different figures? Is it because only 8 people had MEG? The number of trials seems also a somewhat low. Therefore, I feel the authors perhaps need to make an effort to make up for the short number of subjects in order to add confidence to the results. I would strongly recommend to bootstrap the statistical analysis and extract non-parametric confidence intervals instead of showing parametric standard errors whenever is appropriate. When doing that, it must be taken into account that each two of the habenula belong to the same person; i.e. one bootstraps the subjects not the habenula.

Related to this point, the results in Figure 6 seem quite noisy, because interactions (i.e. coherence) are harder to estimate and N is low. For example, I have to make an effort of optimism to believe that Fig 6A is not just noise, and the result in Fig 6C is also a bit weak and perhaps driven by the blue point at the bottom. My read is that the authors didn't do permutation testing here, and just a parametric linear-mixed effect testing. I believe the authors should embed this into permutation testing to make sure that the extremes are not driving the current p-value.

this is so true because when my teachers were saying that it was cause of that they all said that it was just because of the stuff that was going on while Donald Trump was still in presidency

Nobody really knew we were putting so much waste in the world by using electronics because people never really stopped and realize what is happening when we use electronics

Connecting it back to 'The Smithsonian History of Space Exploration', Space Exploration is kind of an effort for the entirety of mankind, not just a singular person, but uniting over a single topic is really difficult, but science and it's ideals is just that fascinating in my opinion.

So, the article is saying that people should not do protests and fight for the greater good to make communities better?

The method

• e.g. magazines and children stories
• magazines with a lot of pictures
• the language of the magazine doesn't matter, the mentor describes the pictures. [I guess if just the pictures are needed you could use any other media with pictures]
• Mentor asks simple yes or no questions to student, students asks - What is this/ that? What is she/ he doing? Why?
• Children stories, storytelling 80% to 90% of acquisition. Pictures are very informative.
• You don't have to retail the story. you acquire language threw listening, not speaking.
• Do 20% magazines and 80% children's stories. Start with magazines.

Rules

1. No native language. Gesture or Draw if necessary. Say "It's not important" if stuck (in target language).
2. No grammar.
3. No corrections. Corrections do not work.

This is literally Tung-Hui Hu's argument, so it's weird that there's no citation here.

It’s like her “sad people’s soul” are surging with the river/the Nile. And it speaks to something I always think about: how people can listen to blues and enjoy or not enjoy the sound, but be totally lost on all the pain that it s captures and was born out of. Many think they’re just “nice songs” but they mean something so much more.

It is not freshly printed cash, and there are no bids, they swap securities for reserves held at the central bank. These reserves do not act like money in anyway, other than this one transaction and as a balance sheet asset for banks. It does not circulate as cash or money.

Ask yourself, what if the Treasuries are treated by the market as some sort of cash? What if it's Treasuries + deposits that the market treats as cash? What is the market treating as money?

QE is not money printing for two reasons, 1) it is just reserves held at the Fed, it's not cash into banks to use as they please, and 2) Treasuries in the market act as a cash equivalents and are part of the money supply needed for liquidity. Take USTs out of circulation, decrease the money supply.

As for the bids, well the Fed does not bid directly for USTs at auction. If the Fed were adding more more demand to the market, you'd expect the prices paid at auction to be less than the secondary market where the Fed buys them. In other words, the dealers would pay less at auction and flip them for more a profit to the Fed, but in fact, the bids at auction are almost always more than they can flip them to the Fed. So this is an automatic loss for the banks.

Prior to taking this course, I was unaware of how much politics is related to the field of conservation and the environment. I'm not sure why, but I guess politics just don't come to mind when I think of conservation. With that being said, I think it's interesting how politics ties into conservation. I think that political decisions when it comes to the environment is extremely important. Especially, when it comes to land management and managing populations of species. I think in most places there has been very poor management and legislature passed for the environment. Especially places such as California.

This is something that I can see being a massive problem for conservationists, especially with a project of substantial efforts and resources. It's important to gauge a strategy of a top-down approach of getting not just local but a widespread study of how things connect and influence the more local areas. After adjusting your scope, you would hopefully see the errors in your misperceptions and work towards a more informed strategy.

There are so many wildlife species that are currently being wiped out by disease. One that comes to mind is white nose syndrome in bats, which has already killed off 5.7 million bats in just the eastern half of North America alone. Humans play a huge role in the spread of this disease. They can spread the particular fungus that causes white nose syndrome by carrying the fungus unknowingly on their shoes and clothing, so it's super important for hikers to clean their gear before and after entering caves.

This part really shows that a lot more than just losing family was a affect of the titanic. This shows a centeral idea of thinking more about someone than just the basics of what you know about them. Because they could've experienced more than you expected and it's really important to help that person.

How did New Horizons, a simple machine made for literally going to PLUTO and needs to be built to withstand forms of environmental/intergalactic debris literally only cost 7,000,000, while Cassini, a machine just for investigating Saturn and eventually dived into it for a dramatic re-entry (no literally), that cost 3.3 billion, it's an even larger cost then Horizons, wow.

The train HAS to be built, and it baffles me as to why it's taking so long to build a few miles of track. The DC & Northern VA metro built like 50 miles of combined track in like 8 years, why is it taking O'ahu like 40+ years to build like 20 miles of track? The island needs the train to reduce traffic---Honolulu traffic is worse than DC and NYC Traffic by a longshot. The bone issue I understand, but like, it's an island. There's only so many places to bury the dead. The island has had people living here for over 1000 years. You will find burials in many areas because you're so limited for space. Bones that are hundreds or a thousand years old should not cause a massive public transit project to run so slowly and inconvenience hundreds of thousands of people. It's just horrible planning, similarly to how horribly the HNL airport and Ala Moana mall is set up.

(Yes, I'm VERY opinionated about the rail, idc).

I think, on it's current path, division in the US is only going to continue growing. I think that at this point there is no solution other than a complete revolution of our government operation. This will either occur through peaceful or violent action, but I do believe it will happen.

Growing up religious I was ingrained to think hell was a specific place but as I got older I started hearing people say Hell is a place on Earth and wondered how that could be until I grew to understand the real world a little more. To have such traumatic life experiences that even the image of hell is where you’re from is so devastating, those times as well as now hell is a specific place to so many people and it’s not just one specific place but all around us.

But he had no choice. If he tries to stop them, he would just get killed. This is not where you chose a yes or no. If he tries to stop them, he might get killed, and along with all the other Jews. It's not like he could've save all those Jews by sacrificing himself.

so much code backlog no longer useful

Yes you read that stage but that backlog can be mind to bring to mind what you had in mind or need at any point

That's exatly what IndyWiki powered by IndieHub does and already integrating with Hypothesis

Mark Anderson @mwra responding to a question about hyper data finds it odd

why we, as human beings, do not capture the internal semantics when write in the way we link https://www.youtube.com/watch?v=XDrowxW2u1Y&t=607s articulated there and then what @TrailMarks is all about "Think a Link" say why you link, your intent, and mean what you say at both ends of the link https://www.researchgate.net/publication/334126329_Weaving_a_Decentralized_Semantic_Web_of_Personal_Knowledge

It looks like they are just killing anyone that gets in their way. Do they not understand what it's like to lose family and life? Why are the Germans so merciless even to those that are non-Jewish. It seems to me that they just enjoy killing and are trigger happy.

After re-thinking my original thought of this novel, which was that I sort of looked at Normal People as a millennial novel, I now think that I view this piece more so as a book that my pre-teen cousin would read. I think that the surface-level plot and the confusing, yet sweet romance definitely speaks more to very young teens who are just immersing themselves into this world of love and dating and everything that comes with it. I don't think that this is a novel made for the young adult, or millennial by any means.

I also agree with Sefl's analysis of Rooney's novel. I like aspects of it, but in general, I agree that it is fairly bland. Readers have seen similar characters to Marianne and Connell time and time again, the plot is fairly overused, and the idea of young adulthood is similar among all young adults. However, there could easily be an aspect thrown into the mix to make it different. I just feel like when I read this novel, there are too many things that I can't help but compare it to, and I don't know if I really care for that. I really like reading something that may have traditional values, with a twist.

Author Response:

Reviewer #2:

The current work makes the case that local neural measurements of selectivity to stimulus features and categories can, under certain circumstances, be misleading. The authors illustrate this point first through simulations within an artificial, deep, neural network model that is trained to map high-level visual representations of animals, plants, and objects to verbal labels, as well as to map the verbal labels back to their corresponding visual representations. As activity cycles forward and backward through the model, activity in the intermediate hidden layer (referred to as the "Hub") behaves in an interesting and non-linear fashion, with some units appearing first to respond more to animals than objects (or vice-versa) and then reversing category preference later in processing. This occurs despite the network progressively settling to a stable state (often referred to as a "point attractor"). Nevertheless, when the units are viewed at the population level, they are able to distinguish animals and objects (using logistic regression classifiers with L1- norm regularization) across the time points when the individual unit preferences appear to change. During the evolution of the network's states, classifiers trained at one time point do not apply well to data from earlier or later periods of time, with a gradual expansion of generalization to later time points as the network states become more stable. The authors then ask whether these same data properties (constant decodability, local temporal generalization, widening generalization window, change in code direction) are also present in electrophysiological recordings (ECoG) of anterior ventral temporal cortex during picture naming in 8 human epilepsy patients. Indeed, they find support for all four data properties, with more stable animal/object classification direction in posterior aspects of the fusiform gyrus and more dynamic changes in classification in the anterior fusiform gyrus (calculated in the average classifier weights across all patients).

Strengths:

Rogers et al. clearly expose the potential drawbacks to massive univariate analyses of stimulus feature and task selectivity in neuroimaging and physiological methods of all types -- which is a really important point given that this is the predominant approach to such analyses in cognitive neuroscience. fMRI, while having high spatial resolution, will almost certainly average over the kinds of temporal changes seen in this study. Even methods with high temporal and moderate spatial resolution (e.g. MEG, EEG) will often fail to find selectivity that is detectable only though multivariate methods. While some readers may be skeptical about the relevance of artificial neural networks to real human brain function, I found the simulations to be extremely useful. For me, what the simulations show is that a relatively typical multi-layer, recurrent backpropagation network (similar to ones used in numerous previous papers) does not require anything unusual to produce these kinds of counterintuitive effects. They simply need to exhibit strong attractor dynamics, which are naturally present in deep networks with multiple hidden layers, especially if the recurrent network interactions aid the model during training. This kind of recurrent processing should not be thought of as a stretch for the real brain. If anything, it should be the default expectation given our current knowledge of neuroanatomy. The authors also do a good job relating properties detected in their simulations to the ECoG data measured in human patients.

We thank the reviewer for these positive comments.

Weaknesses:

While the ECoG data generally show the properties articulated by the authors, I found myself wanting to know more about the individual patients. Averaging across patients with different electrode locations -- and potentially different latencies of classification on different electrodes -- might be misleading. For example, how do we know that the shifts from negative to positive classification weights seen in the anterior temporal electrode sites are not really reflecting different dynamics of classification in separate patients? The authors partially examine this issue in the Supplementary Information (SI-3 and Figure SI-4) by analyzing classification shifts on individual patient electrodes. However, we don't know the locations of these electrodes (anterior versus posterior fusiform gyrus locations). The use of raw-ish LFPs averaged across the four repetitions of each stimulus (making an ERP) was also not an obvious choice, particularly if one desires to maximize the spatial precision of ECoG measures (compare unfiltered LFPs, which contain prominent low frequency fluctuations that can be shared across a larger spatial extent, to high frequency broadband power, 80-200 Hz).

In the new statistical tests described above, we compute each metric separately for each patient, then conduct cross-subject statistical tests against a null hypothesis to assess whether the global pattern observed in the mean data is reliable across patients. We hope this addresses the reviewer's general concern that the mean pattern obscures heterogeneity across patients. With regard to the question of greater variability in anterior electrodes, the new analysis showing a remarkably strong correlation between variability of coefficient change and electrode location along the anterior-posterior axis provides a formal statistical test of this observation. We view variability of decoder coefficients as more informative than the independent correlations between electrode activity and category label shown in the supplementary materials, because the coefficients indicate the influence of electrode activity on classification when all other electrode states are taken into account (akin in some ways to a partial correlation coefficient). This distinction is noted in SI-3, p 48.

The authors are well-known for arguing that conceptual processing is critically mediated by a single hub region located in the anterior temporal lobe, through which all sensory and motor modalities interact. I think that it's worth pointing out that the current data, while compatible with this theory, are also compatible with a conceptual system with multiple hubs. Deep recurrent dynamics from high-level visual processing, for which visual properties may be separated for animals and objects in the posterior aspects of the fusiform gyrus, through to phonological processing of object names may operate exactly as the authors suggest. However, other aspects of conceptual processing relating to object function (such as tool use) may not pass through the anterior fusiform gyrus, but instead through more posterior ventral stream (and dorsal stream) regions for which the high-level visual features are more segregated for animals versus tools. Social processing may similarly have its own distinct networks that tie in to visual<- >verbal networks at a distinct point. So while the authors are persuasive with regard to the need for deep, recurrent interactions, the status of one versus multiple conceptual hubs, and the exact locations of those hubs, remains open for debate.

We agree that the current data does not speak to hypotheses about other components of the cortical semantic network outside the field-of-view of our dataset. We have added an explicit statement of this in the General Discussion (page 22).

The concepts that the authors introduce are important, and they should lead researchers to examine the potential utility of multivariate classification methods for their own work. To the extent that fMRI is blind to the dynamics highlighted here, supplementing fMRI with other approaches with high temporal resolution will be required (e.g. MEG and simultaneous fMRI-EEG). For those interested in applying deep neural networks to neuroscientific data, the current demonstration should also be a cautionary tale for the use of feed-forward-only networks. Finally, the authors make an important contribution to our thinking about conceptual processing, providing novel arguments and evidence in support of point-attactor models.

Thanks to the reviewer for highlighting these points, which we take to be central contributions of this work!

Reviewer #3:

The authors compared how semantic information is encoded as a function of time between a recurrent neural network trained to link visual and verbal representations of objects and in the ventral anterior temporal lobe of humans (ECOG recordings). The strategy is to decode between 'living' and 'nonliving' objects and test/train at different timepoints to examine how dynamic the underlying code is. The observation is that coding is dynamic in both the neural network as well as the neural data as shown by decoders not generalizing to all other timepoints and by some units contributing with different sign to decoders trained at different timepoints. These findings are well in line with extensive evidence for a dynamic neural code as seen in numerous experiments (Stokes et al. 2013, King&Dehaene 2014).

Strengths of this paper include a direct model to data comparison with the same analysis strategy, a model capable of generating a dynamic code, and the usage of rare intracranial recordings from humans. Weaknesses: While the model driven examination of recordings is a major strength, the data analysis does only provide limited support for the major claim of a 'distributed and dynamic semantic code' - it isn't clear that the code is semantic and the claims of dynamics and anatomical distribution are not quantitative.

Major issues:

1) Claims re a 'semantic code'. The ECOG analysis shows that decoding 'living from 'nonliving' during viewing of images exhibits a dynamic code, with some electrodes coding to early decodability and some to later, and with some contributing with different signs. It is a far stretch to conclude from this that this shows evidence for a 'dynamic semantic code'. No work is done to show that this representation is semantic- in fact this kind of single categorical distinction could probably be done also based on purely visual signals (such as in higher levels of a network such as VGG or higher visual cortex recordings). In contrast the model has rich structure across numerous semantic distinctions.

We have added a new analysis showing that the animate/inanimate distinction cannot be decoded for these stimuli from purely visual information as captured by a well-known unsupervised method for computing visual similarity structure amongst bitmap line drawings (Chamfer matching). We did not consider deep layers of the VGG-19 model as that model is explicitly trained to assign photographs to human-labeled semantic categories, so the representations do not reflect purely visual structure. The new analysis appears as part of the description of the stimulus set on page 31.

The proposal that ventral anterior temporal cortex encodes semantic information is not new to this paper but is based on an extensive prior literature that includes studies of semantic impairments in patients with pathology in this area (e.g. refs 7, 13, 29-32), studies of semantic disruption by TMS applied to this region (refs. 37-38 ), functional brain imaging of semantic processing with PET (33), distortion-corrected MRI (34-36), MEG (e.g. Mollos et al., 2017, PLOS ONE), and ECOG (ref. 46), and neurally-constrained computational models of developing, mature, and disordered semantic processing (refs. 7, 31, 40, 53). A great deal of this literature uses the same animate/inanimate distinction employed here as a paradigmatic example of a semantic distinction. It is especially useful in the current case because the animate/inanimate distinction is unrelated to the response elicited by the stimuli (the basic-level name).

2) Missing quantification of model-data comparison. These conclusions aren't supported by quantitative analysis. This includes importantly statements regarding anatomical location (Fig 4E), ressemblenes in dynamic coding patterns ('overlapping waves' Fig 4C-D), and presence of electrodes that 'switch sign'. These key conclusions seem to be derived purely by graphical inspection, which is not appropriate.

We have added new statistical analyses of each core claim as explained above.

3) ECOG recordings analysis. Raw LFP voltage was used as the feature (if I interpreted the methods correctly, see below). This does not seem like an appropriate way to decode from ECOG signals given the claims that are made due to sensitivity to large deflections (evoked potentials). Analysis of different frequency bands, power, phase etc would be necessary to substantiate these claims. As it stands, a simpler interpretation of the findings is that the early onset evoked activity (ERPs) gives rise to clusters 1-4, and more sustained deflections to the other clusters. This could also give rise to sign changes as ERPs change sign.

The reviewer's comment suggests that information about the category should be reflected in spectral properties of the time-varying signals but not the direction/magnitude of the LFP itself. While we recognize that this is a common hypothesis in the literature, an alternative hypothesis more consistent with neural-network models of cognition suggests that such information can be encoded in magnitude and direction of the LFP itself—the closest brain analog to unit activity in a neural network model. The fact that semantic information can be accurately decoded from the LFPs, following a pattern closely resembling that arising in the model, is consistent with this hypothesis. We agree that, in future, it would be interesting to look at decoding of spectral properties of the signal. We note these points on revised manuscript page 22.

With regard to this comment:

a simpler interpretation of the findings is that the early onset evoked activity (ERPs) gives rise to clusters 1-4, and more sustained deflections to the other clusters. This could also give rise to sign changes as ERPs change sign

We are not sure how this constitutes a simpler or even a different explanation of our data. ERPs at an intracranial electrode reflect local neural responses to the stimulus, which change over stimulus processing. The data show that semantic information about the stimulus can be decoded from these signals at the initial evoked response and all subsequent timepoints, but the relationship between the neural response and the semantic category (ie how the semantic information is encoded in the measured response) changes as the stimulus is processed. The changing sign of an ERP reflects changing activity of nearby neural populations. "More sustained deflections" indicates that changes to the code are slowing over time. These are essentially the conclusions that we draw about the dynamic code from our data.

Maybe the reviewer is concerned that the results are an artifact of just the temporal structure of the LFPs themselves—that these change rapidly with stimulus onset and then slow down, so that the “expanding window” pattern arises from, for instance, temporal auto-correlation in the raw data. Testing this possibility was the goal of the analysis in SI-5, where we show that auto- correlation of the raw LFP signal does not grow broader over time—so the widening-window pattern observed in the generalization of classifiers is not attributable to the temporal autocorrelation structure of the raw data.

It's good that she is realizing this. If you aren't from a certain area you're most likely not going to share the same dialect.

This tells me what spanglish is and they also point out that it's being taught in a college class.

is she scared to talk back? is she used to this?

This is a large claim. It hinges on the definition of security and the derivative efficiency (as we touched on above).

Efficiency is a derivative here because it is being defined as a ratio of security to cost. So, the whole thing pivots on the definition of security.

Then we get the second claim, that efficient consensus "engines" create less net-selling pressure on the asset. This is just out of the blue. Perhaps he addresses it below, but here it's already an easy No Way.

There is no such thing as "NET selling pressure". All bitcoins (money in general) is held by someone, every seller must have a buyer. One can say there is net selling pressure at a specific price, at a specific moment in time, but that changes from moment to moment. It has nothing to do with miners selling bitcoin they mine. The counterargument is likely more accurate, that the distribution and circulation provided by mining increases economic activity and demand for coins at any particular price, a gradual increase in demand at any given price. Hence, number go up technology.

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

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Reviewer #1:

This paper shows that transient genetic induction of the IMD innate immune pathway during Drosophila development, has long term effects on adult health and lifespan. The paper is well-written, the experiments are well designed and executed, and the data are without exception good quality. The data also support the specific conclusions well. The experiments take full advantage of the Drosophila system to pinpoint the effect on lifespan to long term activation of inflammation in the gut, which is interlinked and dependent upon changes in the microbiota. However the analysis is not comprehensive, because neural-specific effects on starvation resistance are not followed up, and because the etiology of the changes in microbiota is not mapped out. I should also say that I do not fully agree with the conclusion in the last sentence of the Abstract (the most important general conclusion), that the study "demonstrates a tissue-specific programming effect" of early transient IMD function. Since the lifespan shortening was shown to be dependent upon increased gut Gluconabacter, I would not call this "programming" (though the term is vague enough to mean most anything.) Instead, I would refer to the effect as a host-environment interaction. If it were "programming" of, for instance, the genetic or epigenetic sort, it would not be so easy to reverse.

Response1-1: We thank the reviewer for the fair evaluation of the manuscript. We agreed with the point of "programming" effect: it might be a bit overstatement. We would like to make our conclusion modest and avoid the ambiguous word in the last sentence of the abstract.

A few other minor comments:

1. Several experiments, the authors use GFP (Fig S1) or the IMD targets DptA or Dro (Fig S2) to validate the induction of IMD-CA. Why have they not directly measured the expression of IMD-CA. This would seem to be logical and technically easy, by qPCR.

Response1-2: We will perform qPCR of Imd gene.

1. In Fig 4 we see and experiment in which animals were "supplemented" with Alkaline Phosphatase, a protein. How was this done and why does it work? Is AP a gut luminal protein?

Response1-3: It is a luminal protein and thus ingestion of the protein works just as endogenous one. This is also proved in the literature (Kühn F et al., JCI insight, 2020). The protein targets, for example, peptidoglycan to attenuate its immuno-stimulative capacity. We will add the explanation in the text.

1. The results in Fig 5 are really where the paper begins to determine a mechanism for the lifespan shortening. However, these results are rather weak, and they don't extend very far. The increase in Gluconobacter is mild (Fig 5C), and is not clear in the 16S rRNA sequencing experiment (Fig 5A). Furthermore, it is not clear that Glunconobacter specifically is the source of the lifespan shortening, of just bacteria in general (Fig 5E).

Response1-4: Why we are focusing on this bacterial genus is because we have already shown in our previous paper that increase of Gluconobacter shortens organismal lifespan (Kosakamoto H et al., Cell Reports, 2020). We also reported that Gluconobacter is increased in response to the (necrosis-induced) immune activation, the situation of which is strikingly similar in the larval IMD activation in the present study. As we proved before, we wanted to perform the gnotobiotic/monoassociation experiment here to show sufficiency of the bacterium for the lifespan-shortening phenotype, however preliminary experiments implied that combining Germ-free with the GeneSwitch system is technically difficult as it caused higher lethality. This might be because the drug RU486 shows a different bioavailability/ dynamics in the GF flies.

Significance:

Although this paper addresses in interesting topic using an elegant and effective experimental strategy, the final results (Fig 5) and conclusions are modest. The analysis doesn't extend far enough to demonstrate how long term changes in microbiota arise from short term developmental changes in innate immune activity. Moreover, there is no detailed data concerning how the altered microbiota alter lifespan. Thus, while the results are interesting and the findings open avenues for further studies on the topic, the significance of the paper is modest, in its current state. Further analysis of how the microbiota is permanently changed, and why this affects lifespan, could enhance the paper. However, it is not clear that any simple, quick experiments could dramatically advance the findings from where they are now.

Response1-5: We would like to add the data that IMD activation in the larvae increased the Gluconobacter already in the larval gut. This data mechanistically suggests that microbiome alteration in the larval gut persists into adulthood, demonstrating how larval immune signalling influences adult immune activity. This data should strengthen a concept that even a transient and mild immune activation in juvenile stage can mess up the microbiota and permanently trigger the inflammatory pathology.

Reviewer #2:

In this manuscript, the authors study the impact of ubiquitously activating the IMD pathway only during larval stages on subsequent adult life. They report a shortened lifespan due to IMD pathway activation in the larval gut and a resistance to starvation linked to its activation in the nervous system. While there is apparently no activation of the IMD pathway in very young adult flies, the expression of some IMD-dependent antimicrobial peptide (AMP) genes is reported from 7-10 flies onwards. This expression is lost upon treating the adults with antibiotics, which also rescues the shortened lifespan phenotype. It correlates with a possible increase in the proportion of Gluconobacter in the microbiota.

While the study looks interesting, it is not clear whether the results, especially those of survival studies and RTqPCR experiments, have been replicated in independent experiments. This is essential to warrant their conclusions. In this respect, this reviewer notes some important variability in the lifespan studies (e.g., Fig. 2B vs. Fig. 4E): how do the authors account for a lifespan that is shortened almost by half in Fig. 4E? Also, Fig. S2B is not convincing given the observed variability. More data points are required to reach a conclusion.

Response2-1: We would like to mention that all experiments have been replicated at least twice. We admit that the phenotypes of larval IMD activation such as lifespan shortening effect and inflammatory response in adult gut are indeed quite variable, empirically depending on seasons. This is not surprising to us since many immune-metabolic phenotypes as well as lifespan of the flies are variable between seasons. We assume that this would imply that the effect is through gut microbiota. In Japan, we have a typical seasonal change in the temperature/ humidity that greatly influences gut microbial situation, even though we use an incubator which allows constant temperature/humidity setting. It is therefore we need to carefully compare the phenotype of flies in the same experiment, and this is where the GeneSwitch works effectively.

Regarding Fig. S2B, we could increase the number of samples in Fig. S2B in new experiment.

The authors suggest in their Discussion some kind of epigenetic mechanism transmitting the information of IMD pathway activation having occurred at larval stages. Whether this depends on a change of metabolism remains to be demonstrated, in as much it is likely that there is a major metabolic "reset" occurring during metamorphosis to prepare the individual to the new environmental conditions encountered as an adult. It is also likely that larvae in the wild grow in a microbe-rich slurry and are likely to experience intestinal infections. As noted by the authors themselves on the top paragraph of p7 (line numbers are unreadable), the larval gut is degenerated during metamorphosis and thus the enterocytes that have produced AMPs are no longer present. One possibility would be that there is an early dysbiosis already occurring during larval stages and that the young adults re-infect themselves, for instance through contact with the meconium. The authors' experiments with antibiotics are the key to this study. However, one would like to observe results of the converse experiment, that is, treating larvae with antibiotics (a better control would be to bleach the embryos to generate axenic flies) and then raising the hatched adult flies in a conventional manner. In this way, the authors may determine whether the influence of early IMD pathway activation occurs through "self" mechanisms or whether it entails a contribution from the microbiota. It might also be useful to use reporter transgenes such as Dpt-LacZ to document where in the gut IMD activation takes place in the adult and to monitor whether there is any weak signal that would not be picked up by RTqPCR in newly hatched flies.

Response2-2: We highly appreciate the reviewer for pointing out this important caution. We now checked the dysbiosis in the larval gut (by qPCR of Gluconobacter) and found that it is increased already. For detail, please see our response1-4/1-5. This would strikingly improve the study.

Regarding monitoring IMD activation by the reporter, we plan to do this experiment in our next project. Obviously, a remained question is how epigenetic mechanism in a particular cell/locus mediates the phenotype. This is our next goal and thus lies beyond the scope of this paper.

Specific comments

1. The GS system used in this study requires multiple controls, as a study from the Serroude laboratory has reported a driver-dependent leakiness of expression independent of exposure to RU486 (Poirier et al., Aging Cell, 2008). Thus, it would be good to check this with a cross to a UAS-GFP driver and examining the 10 and 40-day time points. The same should be done with antibiotics-treated flies as regards DptA and Drosocin expression (Fig. 5C &D: the age of the adult flies is not specified; it would also be positive to examine the distribution of Acetobacter and Gluconobacter at 10 and 40 days).

Response2-3: We believe the backcrossed UAS-LacZ would be suitable as a control. For key experiments, we checked that RU486's side effect and confirmed it was not the case. What we have not been confident in this respect is the gut microbiota, and therefore we would test whether Gluconobacter is increased just by RU486 or not. Regarding Fig. 5C&D, we used young (day 10-old) flies. We did not examine the Aceto/Gluco at older days, but we assume that they are still in the gut microbiota. How ageing involves microbial change in this and many other contexts is our ongoing project.

1. The authors state at the bottom of p6 that JAK-STAT-dependent AMP expression was detected. Fig. 4C shows a significant expression of Drsl2. As far as this reviewer recalls, Buchon et al. had demonstrated a dependence on the JAK-STAT pathway of Drsl3. It would also be worth looking at Turandot genes. As regards an involvement of the Toll pathway, it is not clear whether Drosomycin is significantly expressed as it shows a 32-fold increase in Fig. 4C, yet is not found in Table S2. This issue should be clarified using RTqPCR and it may be worth monitoring also the expression of BomS1.

Response2-4: We would like to add the qRT-PCR of TotA,C, Drs, and BomS1 in the revised manuscript.

Minor points

a) It is surprising to observe an expression driven by the TIGS2 transgene in the larval fat body as it appears to be solely expressed in the intestine in adults. In which epithelial cell type of the intestine is TIGS2 expressed?

Response2-5: We were also surprised (and disappointed indeed) by the fact that TIGS2 shows broader expression pattern in the larvae. As far as we observed, it expresses at least in the enterocytes (strongly in anterior midgut).

b) The authors have carefully defined an optimal dose of RU486 at 1 µM. Why use 20µM Fig. S1, or 50µM (Fig. S6)? Of note, the Flygutseq indicates that Alp9&10 are downregulated in enterocytes upon P. entomophila challenge.

Response2-6: We used 1µM at first, only to have realised that 1µM is too mild to carefully assess the expression pattern of the driver. Thank you for the note, we would cite the paper to generalise our finding.

c) Fig. 1B&C: are the flies used in C) escapers as hardly any flies survive the 5µM RU486 challenge B)?

Response2-7: We prepared more than 1000 embryos for this and many other experiments. One percent of survivors is enough to produce flies in Fig. 1C.

d) Fig. 1D: do the authors know why there is such a difference between DptA and Drosocin?

Response2-8: We greatly appreciate for this comment. There seemed to be a miscalculation here. We have repeated the same experiment again, and now they showed similar magnitude of induction. We would revise this figure.

e) Fig. 2E: the caption does not allow to recognize which curve is LacZ RU and which one is IMD[CA] (dashed line?).

Response2-9: We would amend the caption.

f) Methods: the authors mention that they have dissected crop and Malpighian tubules. As no crop data are reported, does it mean that the crop and MT have been pooled in the same sample; please, clarify.

Response2-10: Sorry for our confusing writing. We have revised the text now to clarify we have "removed" crop and MTs.

Significance:

This study takes place in a context of the influence of infections during early life on subsequent fitness at the adult stage of organisms. With respect to mammals, it is important to note that Drosophila melanogaster undergoes a full metamorphosis that yields a thoroughly novel life form adapted to a new aerial life style. Thus, an influence of the larval stage on the imago is definitely interesting. The senior author has already published interesting work on this topic by showing that oxidative stress experienced during larval stages modifies adult fitness through an indirect action on the larval microbiota. This work is going to be of interest to investigators working on the microbiota and also on intestinal infections, let alone the community of entomologists.

Response2-11: We are really happy to see this comment. We believe that it is important to provide evidence and elucidate mechanisms of how gut microbiota alteration acts as a key factor to exert a life-long effect on the host physiology by a transient event occurred at a juvenile stage.

Drosophila host defense against infections, intestinal infections, host-pathogen interactions

Reviewer #3

Summary

In their manuscript "Activation of innate immune signalling during development predisposes to inflammatory intestine and shortened lifespan" Yamashita et al. have used the Gene Switch system to temporally overexpress imd in Drosophila larval stages and followed the possible effect on adult food intake, starvation resistance and lifespan. Specifically, the authors show that activating the IMD pathway in Drosophila larvae leads to decreased lifespan, lower adult body weight and lower food intake. Furthermore, the authors claim that adult flies develop inflammation in the gut, and, as a consequence, a change in the gut microbiome. The study aims to show the effect of prolonged immune system activation at an early developmental stage on adults.

Major comments

The authors' main conclusion is that IMD activation during development results in adult inflammatory gut, which affects the lifespan of the flies as well as food intake and starvation resistance. Mifepristone (RU486) is used to induce gene expression under GeneSwitch drivers. Using mifepristone is a bit controversial when lifespan effects are being studied. The authors should state that there are various earlier studies showing that mifepristone affects lifespan and also metabolism (e.g. reduces mitochondrial functions and activates AMPK). Although it is fairly reliable that the effects that the authors are seeing are resulting from the IMD pathway activation, it can also be a stress response caused by a combination of mifepristone treatment + IMD activation.

Response3-1: We would like to carefully discuss this possibility by citing the relevant literature.

The authors show that mifeprestone concentration of 5 µM is causing severe lethality and low body weight in DaGS>IMDCA animals. The concentration of 1 µM doesn't give the same effect, but already induces gene expression (as confirmed by imaging in Fig. S1B). Throughout the study, the concentration of 5 µM is still used and the authors claim that the phenotype seen in DaGS>IMDCA animals is suggesting that IMD activation impairs larval growth. However, can this be a case of toxicity/synthetic lethality caused by high concentration of RU486? Why wasn't 1 µM concentration used for the experiments, if it's sufficient to induce gene expression? Is there a possibility of using another temporal induction method causing less stress/toxicity for the flies? Furthermore, authors show that 1 µM mifepristone treatment shortens female lifespan, which is contradictory to the earlier literature. Citations are needed in here. Also, the decrease in female lifespan looks like it is non-significant, what statistics were used in this analysis? The methods section says OASIS2 software was used, but no further details are provided.

Response3-2: We apologise our unclear writing. We used 1 µM throughout the study, not 5 µM to avoid the drug's toxicity. We have not tested other method as GS works well by carefully optimising the RU486 doses. For statistics of lifespan, we would like to add the detailed information in the method section.

Only under 10% of in DaGS>IMDCA flies exposed to 5 µM RU486 eclose, yet in Fig. 1C showing the results of body weight measurements, n=20-50. How were the DaGS>IMDCA flies obtained if under the experimental conditions only a few of them develop successfully? At which developmental stage do the flies die? Why were only male flies used for this experiment?

Response3-3: Please see our Response2-7 We did not carefully check the developmental stage, but it apparently died at early stages of the larva. We usually use male flies for body weight, as female's body weight is understandably affected by the number of eggs inside of the body, making it difficult to discuss the phenotype of developmental growth.

More evidence is needed before concluding that the IMD lifespan effect is coming from the inflammatory intestine. TIGS driver is used to express genes of interest in the gut and fat body. No specific drivers for only the gut or only the fat body are used. Can it be claimed that the effect seen is coming purely from the gut expression? Is it possible that the fat body, which is the main organ responsible for the AMP production is actually responsible for enhanced IMD pathway target AMPs expression (as shown in Fig. S2A; the fold change is higher in the gut that in the fat body)? Was the gut not inflamed or damaged in larvae as there were no upd3 expression?

Response3-4: Thank you for raising this important point. Indeed, we have tried to seek for larval gut- (or fat body)-specific GeneSwitch but no drivers were suitable unfortunately. We admit that our conclusion is not thoroughly backed by the data, so we would carefully discuss this in the revised manuscript. Nevertheless, our new data showing dysbiosis in the larval gut now indicates that this is where the irreversible phenotype resides.

If the authors want to state that the effect is coming from inflammatory gut and that the lifespan effect and feeding/starvation resistance effect is coming from other tissues, why did the authors still decide to use the daughterless driver to study the IMD effect on lifespan, rather than gut or fat body driver, especially if they show that the feeding rate is changed (IMD OE in neurons) as this can also affect the microbiota (which they state is because of inflammatory gut)?

Response3-5: We used DaGS driver simply because it was stronger in terms of the lifespan phenotype. One can assume that the decreased feeding of the DaGS>IMDCA flies might influence the increased Gluconobacter, inflammatory gut, and the shortened lifespan. However, these phenotypes were going to the opposite direction, as decreased feeding theoretically leads to decrease the gut bacteria and extend lifespan. We would like to use a gut-specific (or even cell-type specific) GeneSwitch driver for further mechanistic study, but it may take a huge effort. Our take-home message of the present study is that the juvenile-restricted inflammatory experience causes early dysbiosis, which trigger persistent inflammatory gut in adult, and thereby shortens lifespan. We believe this is adequately supported by the data.

Immune responses are costly and that's one reason why their negative control is so important. The authors could state possible effects between continuously activated immune system (IMD pathway in larvae) and trade-offs in size and life-span in adult flies (+ citations to related studies). The role of constitutively activated IMD in larvae could have been confirmed by using alternative method for activating IMD, e.g. knock out of a negative regulator. Additional controls could have been used, e.g. DaGS background strain without the daughterless driver crossed with the IMDCA , or in the experiment where the gut microbiota was checked (this experiment was lacking the DaGS >LacZ + mifepristone treatment and only had DaGS>IMDCA flies with and without the mifepristone treatment). Usually in Drosophila genetics more control crosses are needed, for e.g. two different constructs of the OE IMD strains e.g. GD and KK backgrounds. The efficiency of the IMD OE could have been directly measured with qPCR and not only shown by measuring the expression of target AMPs.

Response3-6: We would like to make sure the point clearer. The phenotype observed in our study is not related to the trade-off between size and lifespan since we used the 1µM of RU486, which did not affect body size (Fig. 1C) but did shorten the lifespan (by larval but not adult IMD activation). In this sense, we tried to avoid the strong immune activation in the larva as it disturbed the development. Regarding other method for activating IMD, we were not able to use knockouts because we need to make it temporal manipulation in larvae. Alternatively, we had tested PGRP-LC overexpession. When it was expressed strongly in the larvae, it led to the lethality. When it was mild, we observed the shortened lifespan just as in IMDCA overexpression. This new data would support our conclusion well. Please note that we use IMD OE not RNAi (GD and KK lines are RNAi lines).

Regarding gut microbiota, we would like to check whether DaGS>LacZ + RU86 affects Gluconobacter or not. Regarding, efficiency of IMD OE, we would like to perform qPCR of IMD gene.

One of the conclusions drawn is that adults develop gut tissue damage as a result of inflammation. The authors could provide further evidence of this by utilizing microscopy to recognize possible changes in gut epithelia (with appropriate controls).

Response3-7: We appreciate for the suggestion. Somewhat intriguingly, we have not observed any difference in the number of ph3 positive cells, a hallmark of tissue damage-induced ISC proliferation. This is consistent with our preliminary observation that aged flies after larval IMD activation did not show "smurf" phenotype, an indicator of gut barrier dysfunction. In the revised manuscript, we would like to add some qPCR data to test whether upd3/JAK-STAT pathway is activated to detect the tissue damage and carefully discuss the point.

The methods section could be more detailed and clearer to the reader. The statistical analyses used for e.g. survival rates should be described in more detail. The sustained alkaline phosphatase treatment should also be described in more detail, as currently the methods do not clearly state how long the flies were treated with Alp. The description of antibiotic cocktail treatment in the materials and methods should not be under the stocks and husbandry section, as it implies that all flies used were all the time maintained on an antibiotic cocktail<br> Methods sections could be arranged to resemble more the order of the results sections and more details should be added. It would be challenging to repeat the experiments the way as they have been described.

Response3-8: We would like to amend the method section accordingly.

Minor comments

The efficiency of the IMD OE was not directly measured with qPCR, only the expression of target AMPs were measured. The authors should show the activation efficiency of the IMD expression.

Response3-9: Please see our Response1-2

Figure 1B, are these females or males?

Response3-10: It includes both sexes. We add this explanation in the methods.

Fig1 E. in the transcriptome analysis the negative control should have been also treated with mifepristone<br> Response3-11: Due to financial reason, we could not perform RNAseq analysis for all the samples. We believe showing specific activation of IMD pathway in the IMDCA + RU486 compared the negative control IMDCA -RU486 is sufficient.

For the experiment presented in Fig. S6, females are used, although for the majority of other experiments, only male flies are used?

Response3-12: We have done qPCR in males as well. We add this data in the revised manuscript.

In Fig. S1C, DaGS>GFP expression is induced in 3rd instar larvae by 20 µM RU486. Is concentration this high not toxic for the larvae?

Response3-13: In this experiment, we wanted to see the expression pattern of the driver. Please also see our Response2-6.

The fact that developmental IMD activation increased DptA expression in the adult gut suggested that an irreversible change occurred in this tissue. - what is meant by irreversible change? Can this claim be made?

Response3-14: What we meant by "irreversible" here was that there was a permanent increase of immune activity by the larval IMD activation. It would have been inappropriate to describe the phenotype, so we would avoid this word in the revised manuscript.

Alp results are interesting. Does IAP expression decrease in adults as they age? The authors used "sustained Alp supplementation" to rescue the reduced lifespan phenotype in adults. How long were the flies treated with Alp? This should be mentioned in the materials and methods

Response3-15: According to the literature, IAP expression is decreased during ageing in (Kühn F et al., JCI insight, 2020). In this experiment, we used life-long IAP supplementation (from day 2 onward). This would be mentioned in the revised manuscript.

The description of antibiotic cocktail treatment in the materials and methods should not be under the stocks and husbandry section, as it implies that all flies used were all the time maintained on an antibiotic cocktail.<br> In the qRT-PCR section, the analysis method could be added (copy number method/ΔΔCt)<br> Line 49-50 is missing a reference<br> Line 81, PGAM5 is mentioned without further explaining what it is<br> Line 229 - what is meant by inflammatory vicious cycles?<br> Line 314 - what is meant by thrifty phenotype?<br> In figures showing lifespan, a different color code could be used where yellow and orange/red lines represent different genotypes/treatments; it is hard to visually distinguish the colors that are used at the moment<br> Figure legend for Fig. 4C - AP could be written out as alkaline phosphatase already here. Also in the legend for Fig. 4 it says E twice (instead of E and then F)<br> Fig. 5A - a title for x-axis could be added to make it clearer that this represents the proportion of the bacterial taxa in the gut<br> Fig. S2A - LacZ is mentioned in the description but not shown in the figure

Response3-16: We would amend these in the revised manuscript.

Were there possible cross tissue contaminations in the adult gut samples? where possible contaminations checked e.g. with fatbody specific primers? This should be checked as fatbody is known to produce more AMPs when immune activated, than the gut tissue.

Response3-17: We are well-trained in the dissection of the gut. All the fat body was carefully removed by dissection. Especially when abdominal samples do not show any difference in Fig. 4B, we did not agree that the contamination would explain the data.

CFU analysis: were the flies surface sterilized briefly in ethanol prior dissections?

Response3-18: Yes, flies were surface sterilized by serial washes of 3% bleach and 70% ethanol. We add this procedure in the method section.

Fig2 B-C, the differences between the females and males are not drastic enough to decide to use only males later on. E. typo in starvation. DA>IMD males have decreased starvation resistance without and with the mifepristone treatment?

Response3-19: We decided to use males as females have a slight negative side effect of RU486. DaGS>IMDCA have increased starvation resistance only with the mifepristone treatment. We apologise that our figure caption is not clear. We would amend this in the revised manuscript.

Significance

The topic presented in this manuscript is interesting and relevant for both the fields of aging and immunology and partially explains why early life experiences are important for the wellbeing of the individual later in life. Some of the findings presented in the manuscript are novel, at the same time some of these same issues have been examined in papers related to immune priming/training/memory. The reported findings of the manuscript would be of interest for an audience that is interested about aging and lifespan related issues, as well as immunology and metabolism.

Response3-19: This reviewer's evaluation of the significance of the study is very encouraging. We believe that the phenotypes observed in the manuscript would give wide interest to the biologist working on this hot topic: how early-life event induces later-life health.

Field of expertise: Innate Immunity; Drosophila; Metabolism; Host-Pathogen Interactions; Biomedicine

This statement is completely valid. I know so many people who gravitate towards literature for the main purpose of finding a set of circumstances or a specific character that is going through similar things as they are. The main reason is because we often tend to look for outside resources as a way of justifying our behavior, our lifestyles, or really just as a way of saying, "Look, this person is kind of messed up too, and that's okay." I know that this is not always a great thing, especially when it comes to the point of being more inclusive, but from the perspective of someone who is familiar with why people do this, I think that it is normally for the individual's own self-gain in regards to personality and circumstances that a character goes through, rather than the idea that the character's background is the main factor in determining who reads what. And, I also believe that this idea of gravitating towards writers in which they see themselves can be true for individuals of all races, not just white critics specifically.

It's a bit presumptuous to assume that the most complex object in the universe just happens to be in our heads.

isn't just a lecture to the straights, it's also diagnosing a problem within the LGBTQ+ community that hasn't gone away with time

WAYYY big voerdramatization. makes father and whole situation seems suspicious. does give insight to how Gregor spends his time though

Just git status | less -R worked for me without any additional trickery, but I see now that's because I told it to "always" use color in my .gitconfig:

.[color]
  ui = always
  status = always

I tried disabling that and then trying the

0<&- script -qfc "git status" /dev/null | less -R

trick, but it didn't work for me. It didn't show any output and I couldn't exit out with Ctrl-C or anything I tried. Had to force kill from another terminal.

But it's a good example of the related but different problems:

1. forcing less to respect colors (easy)
2. force/trick git status to think it has a terminal
3. force/trick it so you can control keyboard with less

So you think it's better to make people post a new "answer" (as if it were actually a distinct, unrelated answer) instead of just letting them comment on the answer that they actually want to comment on? Yuck.

I sent this proposal recently to a photographer friend in his early 40s and this is what he wrote in response:

Wow! Did you ever go forward / get funding with this project? I really can't imagine a better introduction and tutorial series for learning photography when you were proposing this! The entire arc of the tutorial was great: introducing the technical aspects of photography, then raising the idea of learning how to see and think photographically, then featuring several acclaimed photographers' work with the laserdisc's visual quality at the time was a great idea.

I think that would have been an excellent at-home learning option for people at the time. You ask about today's state of the art, and from what I've seen, it's still the model y'all were pointing at. What has changed, of course, is the ease of producing the content, and therefore being much more inclusive of different modes and styles, the presentation mechanisms, and the interactivity options available, but I don't think the training structure has advanced from the basic form you articulated here.

And I think that's a real testament to your and Arthur's vision for this project.

Photography also means something much wider scope today than it did before. I think KelbyOne.com is probably the top site for training in this wide scope sense, but I also think they’re just a supercharged version of your vision here (but again, with today's enhanced technologies and vastly expanded production/distribution/interactivity options).

When I reading through the project it made me think about when I was learning photography. and how it was very different than most people I know from my age and olders, who came of age either before or just at the beginning of the internet and its vast content options. I think the excellent model you and Arthur had developed was a great way of presenting this material, but I’m not sure it would have found me at the time. And I think that points to something interesting in how not only passions get formed and molded, but how one learns can directly impact what one learns… especially within particular technical infrastructures, political economies, and theory productions. I think I told you this before, but I developed my love of photography only after my love for cinema and cinematography. I never took an in-depth photography course in person, and then I finally started to study it, it was through the New York Institute of Photography's at-home course that was all done through the mail! Remember all those learning by mail options for things? 😊

I got these booklets in the mail, mostly printed in b&W, where they went through the technical side of things, but it was still mostly reading and following instructions in the booklets. The printed materials' production quality had all the problems you identified in your proposal about the difficulties in high-quality photographic rendering. And those production issues meant that certain styles of photography would be better presented than others. For example, most B&W works came through better colorwork. In reading the booklets, I was often drawn to the B&W work because it was better represented, but also it reminded me of my favorite B&W cinematographers like Toland, Nykvist, and Alton.

I completed the assignments by mailing my prints to the school, and my assigned mentor would then send me cassette tapes of his review of my work. From my first assignment, and nearly every one of his reviews after it, would have something like, "Joe, your images have this really stark, severe tonal quality to them. They almost feel like film noir to me." Or: "Your compositions and framing feels widescreen sometimes, or like your weighing your frames really different than a lot of other students."

So here was this voice on a tape of a person I never met, who knew nothing about me, whom I never had a conversation with, referencing how he noticed cinematography influenced and informed my own photographic seeing in a way that seemed to surprise him. And this influence is something that likely wouldn’t be a part of a traditional photography pedagogy. (This could also mean I’m just a hack who merely regurgitates his limited influences, but I’ll stick with my deeper point 😊. HAHA. )

I bring this up because I think the model you were proposing was excellent in traditional photography pedagogy. And that model, especially at the time you were proposing it, would have been informed not only by the technical infrastructure and the political economy of the time in how you could present and distribute it, but in the thinking and theorizing of what photography itself was an artform, and what should be a part of the discussion in teaching it.

This is not remotely a criticism! I think this project was awesome. But I think it’s interesting in thinking how these projects are necessarily shaped by the times in which they’re being considered..

What do you think about the project now? In reading it through, what do you think you would change now?

When teachers teach students the idea that there is a way to learn to write in general it is setting them up for failure. It is frustrating to other teachers and employers when teachers try to teach students one specific way to write because there is not one single way to write, it all depends on audience and setting.

While I agree that it is not possible to "write in generaI", I disagree with the sentiment that the skills are never transferrable because I believe the overall writing techniques and conventions learned in English can be applied to other subjects. While the papers may not all be structured in the same way, I think there are general writing themes that remain consistent (thesis, evidence, conclusion). These attributes of a paper will always be relevant, no matter the subject. While not all papers are argumentative per se, I do believe they are in some sense. In nearly every essay I have written, I have been trying to back up a claim through references and evidence that my claim holds true. In other words, defending my point.

Amazing! It's true, so many things factor in to societies and their customs. It was a brilliant idea to start a program for boys and change their thinking to something healthier toward women and girls. When you grow up believing one thing, it can be hard to change, but educating them while they're young makes so much sense! I love how she's thinking outside the box and finding ways to change things for the better in wildly inventive ways that many people wouldn't have even thought of! It's interesting to see just how much of an impact some of these things really have, whether it's educating boys on gender equality, or showing a father how amazing his daughter is. One person or one million, it makes a difference, and that matters!

I love this statement. You don't have to cure cancer to deserve an education, a better life, a say in your life. Everyone deserves those things, but not everyone gets them. It really is true that some people have to fight for things that should be a right. And it's sad. It's awful! I'm so glad there's a program to help these kids and it's amazing that it just keeps getting bigger! I also feel like it really does matter when mothers and grandmothers encourage their daughters and granddaughters. They are the first female role models they have and, not only that, but without their help and guidance, they may not ever have a chance anyway. In a culture such as that, it can be hard for a small child, especially a girl to make their voice heard. It must be hard to live in a place where your whole life is planned for you. Especially when the plans aren't so great. This story was so amazing and inspirational!

This is great but it's a sideshow as far as universities are concerned. Because they're subsidised by publication of the final product. A researcher who only shared their process and even products in the open doesn't generate the subsidy that universities rely on.

I think this is a really important factor to weigh when implementing any new ed tech. It's true that the tech may meet our goals and enhance student learning, but that may only be the case if everyone has the time and energy to learn the new tech. Timing is important!

This seems like black and white thinking. People negotiate for living the way they desire in the face of difficult practical circumstances all the time.

This has always been the case, especially in Hollywood. The problem becomes that everyone thinks they can become rich and famous too. Talent shows like American Idol show us that this is rarely the case. Building a platform for oneself is not an easy thing to do, even if you've got the talent.

I often wonder why he chose the word "deferred" but the phrase a "dream deferred" and the alliteration of it also creates a musical element that sticks in your head easier. His jazz background shines through in this poem, as his word choices are intentional and critical in providing movement to the poem. A "dream deferred" rolls off the tongue easier and can be committed to memory better and I also think the words appear casual and harmless, when, just like a dream that is deferred, it's impact lies beneath the surface.

Langston Hughes uses the symbol of rivers often in his poetry. In "The Negro Speaks of Rivers" Hughes writes about the rivers Black people have known throughout history. He then compares his soul to a river. Just as this river is old, deep and flowing so is the Black soul.

The river is often used in Black American spirituals as a sign of freedom. To pass through the river to freedom, to be carried by the river to freedom etc.

In Hughes' poem "Suicide's Note," he writes:

The calm, Cool face of the river Asked me for a kiss.

Here we see the river providing freedom in different a way. Through the taking of ones life. It is a very dark poem, that has little hope in comparison to songs like "Deep River and poems like "The Negro Speaks of Rivers," while the speaker finds freedom, it's because they could no longer persevere.

not sure how lewis can say the growing attention is reasonable and sensible just to say that it's political and makes her uncomfortable. racism and stereotyping is not political

As we become more educated and hear more from our “experts” nothing seems to be consistent. Why? Do they really know or is this just their “expert” opinion? Sometimes we just need to make our own decisions and do what’s best for ourselves while taking accountability for our affect on others.

Скорее всего, вы уже слышали что-то о том, кто такие анархисты и во что они должны верить. Скорее всего, все, что вы слышали, - ерунда. Многие люди, кажется, думают, что анархисты являются сторонниками насилия, хаоса и разрушения, что они против всех форм порядка и организации или что они сумасшедшие нигилисты, которые просто хотят все взорвать. В действительности нет ничего более далекого от истины. Анархисты - это просто люди, которые верят, что люди способны вести себя разумно, не будучи принужденными к этому. Это действительно очень простое понятие. Но это то, что богатые и могущественные всегда считали чрезвычайно опасным.

It's interesting to note that Winslow's first instinct when hearing a gunshot was defend the kin, instead of anyone or anything else. This shows the innate bias these people had to protect their kin and how important their kin were to them

poetry just the way it is

the way we operate around downership

liquify leap that abys

It's apparent that the internet archive has websites cataloged ranging from the educational websites they just listed to something as random as a kickstarter page.

One of my favourite techniques... And one I set up in a simple way.

I typically have some form of weekly contribution which is posted publicly and assessed by other members of the class. Basically: the output of low-stakes assignments are posts in a forum and students rate one another using a simple scale (eg. satisfactory, excellent, unsatisfactory). The aggregate ratings make up that grade. And there's a grade for those peer-ratings.

A basic need this technique fulfills is about getting continuous feedback. Though shallow, ratings tend to satisfy some of the most grade-obsessed students, Which makes it easier for me to focus on the learning process.

What's more interesting, though, is that it gets learners to pay attention to each other's work. Unlike the typical "I need you to comment on five posts", it's more of a nudge. The effect is that there's a lot more reference to what others have said and, in some cases, it really contributes to the community-building aspect of my teaching. Sure, it's just one part of the whole process. But it does help.

So... For me, peer-assessment is almost a way to placate the grading spirits”.

Which might be the opposite of ungrading.

Ah, well...

Upon further research, I discovered that Cognizant has left the content moderation world. In the article (linked below) it's said that, "The professional services firm Cognizant will exit the content moderation business." After The Verge started two follow up investigations on the well-being of Cognizant employees, the company ended its partnership with Facebook when their 2020 contract was up.

I don't want to believe that the founders/higher ups at Cognizant are all corrupt people, but brushing their accusations under the rug isn't making the company look professional or respectable.

What caused the work place environment to get this out of hand? Being signed by the massive company, Facebook, I would think that Facebook would have nothing but the best for its employees.

Why are content moderators being treated so poorly when they are essential in keeping Facebook appear to be its family friendly, connective, and social platform it is?

Read more about the investigation and Cognizant's exit following this link:

https://www.theverge.com/2019/10/30/20940956/cognizant-facebook-content-moderation-exit-business-conditions-investigation

Call me naïve...

...I always thought that gaining diverse insight was a basic principle throughout UX and specifically what makes HCD what it is.

It's so very surprising when you find out that the question bears asking. Yet, like Mannan, I've been in situations where UX and/or HCD people have needed to ponder that question.

It is interesting how this pill is talked about in a way that is so taboo. This illustrates the fine line that many have to walk when discussing the terms of a diy abortion.

I agree with this general sentiment, but...

NFTs are not a way of promoting sustainable and great art. Just look at Beeple's Everydays, they aren't what anyone would call high art.

Art is a very very old profession and it has never been all that lucrative for the artists. Only in very recent times have a few musicians been monetarily successful and still fewer other types of artists. This seems like trying to not only solve a technical problem but a societal one. I don't recognize that societal problem.

I think art is essential, I promote art appreciation, I always give money to street performers and support local artists, but it's simply not very lucrative to to be an artist because artists are not businessmen and neither are the customers. The vast majority of profit goes to the person who can manage the logistics of the whole thing. In an NFT world that would be the certifiers I guess.

You can try to abstract that management logistical role away, but I don't think that will be very easy. IMO rich patrons are the way to go. Their contribution is altruistically providing the platform.

Perhaps, rich patrons could provide centralized NFT platforms and sponsor artists by giving them a spot on their platforms where those select artists would be able to control their art and profit. That would bring attention to the artist and provide a scalable solution. Win-win.

This whole situation for artists shouldn't necessarily be different. Who are we to question the market? There could be arguments made that artists have slowly been becoming more successful and in charge of their art as it were, but I think that is a characteristic of fiat money.

Yes, but very few people are buying things that are at risk of being forged. I'm personally not a collector, I'm aware it's pretty big business. I'd assume here that this depends on the item. A person might have incentive to buy a good forgery that they can sell higher later. And on and on it goes.

You could also sign the actual digital art right? Like put your signature in the art itself.

This is incorrect. The equivocation of "value" from above is coming back to bite you. What are you talking about, subjective value or exchange value?

For your part 1) "holders believe their coins have value", is not the case. They either KNOW their coins have exchange value, or KNOW their coins have personal subjective value. There is no belief.

The opposite act of applying the digital signature (what this section is concerned with), namely holding, is a calculated act based in part on belief and in part on experience.

Your second point 2) is worded in a confusing way. People take part in exchange because they subjectively value the other thing more than the thing they already possess. If a person values sats more than the item they are trading for it, of course they are willing. In free exchange there are no unwilling parties.

Of course, this goes the other way. The person giving up sats in exchange for another item values the sats less than the item they are giving up. They are willing to do the reverse.

Your third point 3) is the part I have the biggest problem with. Perhaps I don't understand exactly what you are saying here. There are several ways you can transfer bitcoin, not all require a digital signature from the sender. Big example, Opendime.

The digital signature needed to spend bitcoins on the network are part of a broad whole network. If one invalid signature goes through, it's all over. Everyone depends on every signature.

Signatures in bitcoin are not tied to an originator. They are totally fungible within a transaction, IOW no specific entity must sign, it doesn't matter if Adam Back signed some tainted coins 20 transactions ago that are now in my possession, and I couldn't tell anyway. Signatures not signers. Signatures are fungible in bitcoin, where they are not fungible in NFTs. In fact, that is what makes NFTs non-fungible, the signature alone from the originator.

What does it mean to Tae-yul that he is working on this bicycle with his uncle? How does he feel about his uncle?

This is super interesting to me. What makes something structurally impossible in biology? Is it that it's so extreme that there is no way it could be advantageous, or is it that genetically, it's just not possible

This is a great example of how services like Facebook can be like the abusive significant other you can never leave.

it's difficult to look at this diagram without comparing it to a model using W3C DID and a ledger. The verifiers are going to know to interconnect to the local/regional PHA then it asserts that the UVCI is still valid (presuming that it could be voided or cancelled, revoked) and that call requires a call to a centralized (within the jurisdiction) PHA service, potentially processing millions of SVC verifications a day, and punting the international ones to a foreign PHA when it's not resolved locally. So the PKI repo only distributes PKI but does not distribute the revocation or validity of the UVCI? This architecture is daunting and the coordination required to create this PHA network is huge. Does the architecture contemplate a network of PHAs within a single country, or what the term Int PHA just meant to convey not the local PHA? Is there a discovery protocol contemplated for resolving to the PHA?

You are describing some powerful stuff about encoded texts and practices that signal membership or affiliation.

This is one of the easiest ways to find people who share similar interests online. It's so much easier to find a community who share the same ideas, interests, hobbies, etc. It's really cool to see how big these online communities grow and in a way that offline ones can't do. With the help of social media, those from all around the world are able to connect and not limiting it to just one place or area.

Huh, it's pretty's interesting that media was named this way initially to mean a broad definition of just something that delivers data and information.

While news media is still prevalent, I find it interesting how media has become more closely associated with entertainment such as referencing a Facebook feed or a video game pertaining to a form of media.

That's a tough one. I can see it both ways.

So scientists from Asia countries don't speak to each other in their native languages because they know they'll be targeted. Sounds like racism to me.

What is the significance of this scene? Why does the author include his memory of a baseball game as his last memory before he dies? Is this the author's way of telling Anders' life story? Could the author mean that childhood is very important, and one's entire life is affected during childhood? Coyle's cousin saying "they is" sparked an interest in words to Anders, and as the readers know, Anders became a book critic (a savage one at that).

People saying it really isn't that bad, and it's optional anyway. The charge is neutral, it's a tool.

Uncomfortable? I like uncomfortable. It's beyond time to get uncomfortable.

Gee, a very large uncomfortable truth... and not as though it isn't well known and documented... is that Black America, as well as Black Britain, and extending to Black Everywhere, performs at a substantially lower mental efficiency than White Everywhere. Now why is that?

It's because Nature Is Racist. WHAT!! Say it ain't so. Uh-Uh, can't do that. That would violate a principle tenet not found in Algore's "An Uncomfortable Truth", namely that snow will be here for ever.

All over the world Blacks have a lower AVERAGE IQ than do Whites Hey! I din't do it, okay? I'm just reporting the fact.

So what does this mean? Among other things it means that Blacks in a largely white society are going to be frozen out of the jobs that require higher IQs, like doctors, scientists, engineers, mathematicians, to name a few at the top level of IQ requirement.

But there's a way out. Loose the 'tude. Black IQs in the US South are lower than in the North. Exposure to more things and ideas in the North than in the South shows the way. That said, school age Blacks need, really need, to stop thinking that a fellow Black who wants to get ahead is "Just tryin' to be white".

In 1900 the literacy rate among Blacks in the US was higher than it is today. They need to recapture that and go beyond. The brain is flexible and can be stuffed with knowledge at any age, knowledge that leads to good careers and high paying jobs... and a better self image.

You want to go a fur piece in ending the "institutionalized racism" you've helped to bring upon yourselves? You want to be a somebody? Then assign your brains the task of improvement so that you'll be a better fit in a modern techno-society.

Mr. Boffin loves playing the villain. He's done this for the entire book, and he seems to enjoy it. It's good that it is just for show.

I agree with this, although I have never taken a class with this type of grading scheme I feel like I will enjoy it. The author describes what I think my feelings towards it will be.

I'm reminded of the research implied by Arthur Conan Doyle's writing about Sherlock Holmes. We hear about the time and effort spent studying the smallest things, but we don't see it, instead we see the mythical application of it at the "right" times to solve cases in spectacular fashion.

No one focuses on the time spent studying and learning and instead we mythologize the effects at the other end.

Another example of this is the fêting of Andrew Wiles's proof of Fermat's last theorem, while simultaneously ignoring the decades of work he poured into studying and solving it not to mention the work of thousands before him to help give him a platform on which to see things differently.

This sentence stood out to me because it puts into perspective exactly how much waste is created in a year. I found it interesting that the amount of waste created in one year is equivalent to every commercial aircraft that has been ever built throughout history. I mainly found it interesting because it's hard to put something of that amount of weight into perspective and this sentence does a great way of explaining it.

Here is the image link:

the problem of self-driving cars

“这是不可预料的，也是令人惊讶的——同时，我本人也是异常地激动。事实上，从某种程度来说我已经为此努力了将近50年，但就是在近几个月，这些东西才终于结合在一起成为现实。它比我想象的更美妙、更美丽！”

I have to admit that I'm totally making excuses here. Really, at the time of publication, I was just eager to get something out there, and I was (and am) not entirely motivated or sure of how to fully document the subject in the "literate" style. (Although it has to be said [see Kartik on Knuth] that it's possible no one else, even LP practitioners, really grok how to use LP, either.)

Factors to keep in mind as you evaluate continued performance of the startup

<br>

Analytic Note: We noted in the article that, according to Akbar Etemad, the founder of the Iranian nuclear program under the Shah, the Islamic Republic resumed the program under Rafsanjani’s presidency, which began in the summer of 1989. However, other accounts of Iran’s nuclear efforts indicate that it was during the war and Khamenei’s, not Rafsanjani’s, presidency, that Tehran resumed the program. Available sources suggest that the latter account is more likely to be accurate. We did not discuss this point in the article, but wanted to address it here and to note that, despite the discrepancy, Etemad’s insights remain very valuable given his involvement in Iran’s nuclear program. The following excerpt is the full section on that issue from the interview with him conducted over the phone on June 10, 2014, followed by the Iran’s Primer’s account of Iran’s nuclear progress in the mid-1980s.

Source Excerpt 1: Q: So, you started working on the nuclear program and then the revolution happened and changed everything. At first, the revolutionaries decided to halt the nuclear program because they thought it was yet another western imposition. But then, the program was resumed in the 1980s. At that point, you were no longer formally involved in the program, but did you have any contact with decision-makers at that point? Can you describe what was going on in Tehran, what the new leadership was thinking about the nuclear program?

A: The first few years, the AEOI was destroyed. The theory, at that point, like many other things at that time, was that the United States had imposed nuclear energy on us. This was until Rafsanjani’s presidency. He was the one who made the decision to resume the program. I was in France. For years, they wanted to negotiate with me to go back. But I didn’t want to. I didn’t think working in Iran would be possible. I didn’t go. The first person they picked for the organization was someone who didn’t even know anything about the atom. They went and bought centrifuges from Pakistan, and tried to enrich Uranium.

Source Excerpt 2: Q: Iran obviously claims that it’s never gone after nuclear weapons, just energy. Based on the communications you had with them at the time, what is your assessment of that?

A: From the beginning, they wanted to have all the options. And they were right. I’ll tell you why I say this. The reason is that they only went after enrichment. Nothing else, just enrichment.

Source Excerpt 3: According to the Iran Primer’s account, however, A 2009 internal IAEA working document reports that in April 1984, then President Ali Khamenei announced to top Iranian officials that Khomeini had decided to launch a nuclear weapons program as the only way to secure the Islamic Revolution from the schemes of its enemies, especially the United States and Israel.

Iran began developing a gas centrifuge program in 1985, according to IAEA reports but realized that it needed foreign assistance to make progress on centrifuges. Iranians visited potential suppliers abroad in order to acquire and learn how to operate key centrifuge equipment. In 1987, Iran acquired key components from the A.Q. Khan network, a rogue nuclear supply network operating out of Pakistan’s state-run nuclear weapons program. The components included: • A starter kit for a gas centrifuge plant • A set of technical drawings for a P-1 (Pakistani) centrifuge • Samples of centrifuge components • And instructions for enriching uranium to weapon-grade levels. (Weapon-grade uranium is the most desirable highly enriched uranium for fission nuclear weapons and is over 90 percent enriched.)

Full Citation: David Albright and Andrea Stricker, “Iran Nuclear Program,” The Iran Primer (2010/ Updated in 2015), http://iranprimer.usip.org/resource/irans-nuclear-program <br> Permanent link: https://perma.cc/E3F4-A7DS <br>

I just have an idea that you can consider comparing this point with the idea of Benjamin that you explain in the following paragraph because it's similar in general topic but quite different in details.

Didn't understand it at first, but now I think it's a pretty clever/decent solution.

Just a bit more verbose than one might like...

At first I had reservations about the fact that this requires you to pass a hash ... or rather, once you start using a hash as your "list", you can't just "switch back" to an array (a "problem" I've noticed in RSpec, where you have some tags that are symbols, and some that are hashes: you have to list the symbols first: describe 'thing', :happy_path, driver: :chrome):

{}.bury(users: Array, 0, 'Value')

But I think that's okay in practice. Just use a hash for all "elements" in your list:

{}.bury(users: Array, 0 => 'Value')

Reviewer #3 (Public Review):

As the authors lay out, there are a number of theoretical perspectives that expect that male features that are sexually dimorphic and, hence, vary in their levels of "masculinity" (or perhaps less sex-anchored, vary along a male-female dimension) within human males, to have been under sexual selection historically (if not now), which may in part explain their sexual dimorphism. The target article examines associations between a number of such traits that have been examined-bodily strength and muscularity, facial masculinity, vocal pitch, 2nd to 4th digit ratio (2D:4D), height, and testosterone levels-with measures of mating "success" (e.g., sexual partner number) and reproductive outcomes (e.g., reproductive success). With traits keyed such that more positive values reflect greater "maleness," virtually all associations with putative fitness components were found to be positive, though not all associations had confidence intervals that do not cross the zero-point (i.e., not all are "significant").

The strongest associations were with body masculinity. Specific measures included strength, body shape, and muscle or non-fat body mass (though the associations are not broken down by indicator type). In the mating domain, the overall correlation was .13 (.14 in the behavior domain, perhaps most related to mating "success"). In the reproductive domain, the mean correlation was .14, and .16 in high fertility samples (a subset of which may represent natural fertility populations). Especially when strength (e.g., grip strength) was used as the measure of body masculinity, these associations are likely underestimated, due to imperfect validity of the masculinity/muscularity indicator.

Associations with voice pitch were, on average, nearly identical to those involving body masculinity: .13 overall in the mating domain and .14 overall in the reproductive domain. But due to smaller sample size, the confidence interval around the correlation in the reproductive domain included zero.

The next grouping of traits, in terms of strength of association, contains facial masculinity and testosterone levels. There, associations were .09 and .08 in the mating domain and .09 and .04 in the reproductive domain, respectively. Once again, not all confidence intervals were exclusively above zero.

Associations with both 2D:4D and height were weaker: .03 and .06 in the mating domain and .07 and .01 in the reproductive domain, respectively.

I offer a few observations.

First, the meta-analysis, to my mind, offers some interesting data. We need to be aware of its limitations. Many samples are drawn from WEIRD populations (Henrich et al., 2010). It remains unclear to what extent fertility and reproductive success in these samples, even when drawn from high fertility populations, reflect processes that would have operated in ancestral human groups. It makes sense that some of these features may well have been variably associated with fitness components in ancestral populations, but potential key moderator variables (e.g., pathogen prevalence, level of paternal provisioning, level of intergroup violence, degree of female choice [vs. arranged marriages]) may not be available to examination here. To the extent moderation exists, mean levels in this meta-analysis are less meaningful (though not meaningless), as we do not know whether the distribution of moderators in this sample of samples is representative of populations of interest. (E.g., due to advances in modern medicine, these samples may be much healthier than ancestral populations in which these features were subject to selection.) And that is just a partial list of caveats we need to keep in mind. Nonetheless, with those limitations kept in mind, these findings are interesting to reflect upon.

Second, the associations of course do not tell us what processes drive them. They are correlations. Indeed, we do not know whether the traits themselves were directly implicated in the processes leading to their associations with fitness outcomes. (2D:4D surely wasn't-it's a marker of other causal variables-but its associations are among the weakest seen here.) It makes some sense that the stronger the associations, the more likely the trait in question was directly causally implicated in these processes. And again, that may be particularly true of body masculinity, as associations with it may be underestimated due to fallible indicator validity. But even then, we cannot rule out other mediating traits. Perhaps more muscular men exhibit greater confidence and gain leadership roles more readily than less muscular men, giving them an edge in intrasexual competition or intersexual choice due to associated behavior or status. Or maybe they ultimately gain greater control of resources, giving them advantages in competition for mates or provisioning of offspring. This is not to deny that muscularity may well have been (and be) under sexual selection; but it may have been selected along with other traits rather than the direct target of selection itself.

Third, then, we do not know what intrasexual or intersexual selection processes may have been involved historically, even if these traits have directly been under sexual selection. To what extent are these associations due to advantages in intrasexual competition? To what extent might they be due to female preferences and choice? Naturally, as the authors note, these processes are not mutually exclusive. After all, in lekking species, males compete with one another for a symbolic spatial position, which, because it represents the outcome of the competition, leads to mating success via female choice. Still, we might be interested in knowing what processes led to the associations found, and how they speak to sexual selection and mating processes in humans.

Once again, however, the associations reported are interesting to reflect upon. And they could, either directly or indirectly (by stimulating additional research), lead to better answers to issues raised above. One key outcome that relatively little data currently speak to, for instance, is mortality rate of offspring. As the authors note, men who are more successful with respect to mating effort may invest lower amounts of parental investment in offspring. In theory, then, their greater offspring number could be offset to an extent by lower survival rates. In the relatively few data the authors aggregated from the literature, that was not clearly the case. But more data may be needed, especially with respect to the strongest predictors of mating success, and especially in more traditional societies.

Paternal investment in offspring, however, need not pay off just in terms of offspring survival rates; paternal provisioning may permit greater rates of reproduction via shortening of interbirth intervals in traditional societies. The data here show that, at least with respect to body masculinity, more masculine men have greater mating success and greater reproductive success. Yet the data do not necessarily tell us that the female partners of these men have greater reproductive success. More masculine men's rates of offspring production could be spread over more female mates than that of less masculine men. Knowing whether female partners of more masculine men benefit reproductively by mating with masculine men is pertinent to addressing whether the reproductive success of masculine men has been mediated, in part, by female mate choice.

Reviewer #2 (Public Review):

Summary:

Frey et al develop an automated decoding method, based on convolutional neural networks, for wideband neural activity recordings. This allows the entire neural signal (across all frequency bands) to be used as decoding inputs, as opposed to spike sorting or using specific LFP frequency bands. They show improved decoding accuracy relative to standard Bayesian decoder, and then demonstrate how their method can find the frequency bands that are important for decoding a given variable. This can help researchers to determine what aspects of the neural signal relate to given variables.

Impact:

I think this is a tool that has the potential to be widely useful for neuroscientists as part of their data analysis pipelines. The authors have publicly available code on github and Colab notebooks that make it easy to get started using their method.

Relation to other methods:

This paper takes the following 3 methods used in machine learning and signal processing, and combines them in a very useful way. 1) Frequency-based representations based on spectrograms or wavelet decompositions (e.g. Golshan et al, Journal of Neuroscience Methods, 2020; Vilamala et al, 2017 IEEE international workshop on on machine learning for signal processing). This is used for preprocessing the neural data; 2) Convolutional neural networks (many examples in Livezey and Glaser, Briefings in Bioinformatics, 2020). This is used to predict the decoding output; 3) Permutation feature importance, aka a shuffle analysis (https://scikit-learn.org/stable/modules/permutation_importance.htmlhttps://compstat-lmu.github.io/iml_methods_limitations/pfi.html). This is used to determine which input features are important. I think the authors could slightly improve their discussion/referencing of the connection to the related literature.

Overall, I think this paper is a very useful contribution, but I do have a few concerns, as described below.

Concerns:

1) The interpretability of the method is not validated in simulations. To trust that this method uncovers the true frequency bands that matter for decoding a variable, I feel it's important to show the method discovers the truth when it is actually known (unlike in neural data). As a simple suggestion, you could take an actual wavelet decomposition, and create a simple linear mapping from a couple of the frequency bands to an imaginary variable; then, see whether your method determines these frequencies are the important ones. Even if the model does not recover the ground truth frequency bands perfectly (e.g. if it says correlated frequency bands matter, which is often a limitation of permutation feature importance), this would be very valuable for readers to be aware of.

2) It's unclear how much data is needed to accurately recover the frequency bands that matter for decoding, which may be an important consideration for someone wanting to use your method. This could be tested in simulations as described above, and by subsampling from your CA1 recordings to see how the relative influence plots change.

3)

a) It is not clear why your method leads to an increase in decoding accuracy (Fig. 1)? Is this simply because of the preprocessing you are using (using the Wavelet coefficients as inputs), or because of your convolutional neural network. Having a control where you provide the wavelet coefficients as inputs into a feedforward neural network would be useful, and a more meaningful comparison than the SVM. Side note - please provide more information on the SVM you are using for comparison (what is the kernel function, are you using regularization?).

b) Relatedly, because the reason for the increase in decoding accuracy is not clear, I don't think you can make the claim that "The high accuracy and efficiency of the model suggest that our model utilizes additional information contained in the LFP as well as from sub-threshold spikes and those that were not successfully clustered." (line 122). Based on the shown evidence, it seems to me that all of the benefits vs. the Bayesian decoder could just be due to the nonlinearities of the convolutional neural network.

支付是另一种交流形式，但它从来被如此看待，也从来没有被精心设计过，更是从来没有令人神奇的感觉。大约 90% 的美国人都带着信用卡，但很多商户并不接受信用卡付款。我们想平衡这一点，让支付的体验变得神奇。

I would say that we don't in the amount we currently use it, in general and in the classroom. Just because something is easier or newer does not mean it's better.

This is a phrase that people still use everyday and I think it's important that Claudia Rankine incorporated it in to the text. I love how she describes her take on it. The language she uses is so descriptive and really gets you thinking.

This is a great list of some common types of annotations for students just starting out, but it misses one key annotation that I think is the goal of all annotations:

New ideas from the reader that have been sparked by the writing.

Incidentally, this is also one of the more difficult types to create and it's also harder to model to students.

In some sense, many of these annotation types fall relatively neatly into Bloom's taxonomy with my addendum falling under the top level of the pyramid usually labeled "create".

It's so funny how people in power have the ability to just buy and take whenever they want to the point where it is a competition. I feel it would be better if people with that much money gave back, but they never seem to unless it is beneficial to them.

How is the phrase

including the production of meaning used in this article, yet the word "semantics" does not appear even once?

At least https://en.wikipedia.org/wiki/Meaning_(semiotics) ("semantics" appears exactly 1 time in that article) has a link to the article on semantics.

Seems like a missed opportunity to answer what to me is a very first immediate question that I wonder (and now I wonder if it really is a FAQ or if it's just me who wonders): how is semiotics different from semantics?

But I guess https://en.wikipedia.org/wiki/Semiotics is a better place to look for that answer, and it answers that when it says:

he defined semiotics as grouped into three branches:

1. Semantics: deals with the formal properties and interrelation of signs and symbols, without regard to meaning.
2. Syntactics/syntax: deals with the formal structures of signs, particularly the relation between signs and the objects to which they apply (i.e. signs to their designata, and the objects that they may or do denote).
3. Pragmatics: deals with the biotic aspects of semiosis, including all the psychological, biological, and sociological phenomena that occur in the functioning of signs. Pragmatics is concerned with the relation between the sign system and sign-using agents or interpreters (i.e., the human or animal users).

A reason why politicians can't fight back, or have to be careful about fighting back

Great conclusion material. Tries to make the ideas seem universal or bigger than the text.

As George Couros said if you use technology this way, a laptop just becomes a $1000 dollar replacement for pen and paper. It's not the technology itself. It's how you use it.

"We have some question, and data (network). Are people from the same school more connected than people from different schools. The data is X. That network is noisy, and we need quantitative procedures that account for the possibility of network uncertainty." Say specifically what the nodes and edges are. Be specific about what is uncertain. People are friends, but didn't add each other. People are not friends, but didn't remove each other (fight). In order to answer our question, we need to account for this uncertainty. Why not just use a t-test? It's a network, the assumptions for traditional statistical modeling don't make sense. It's one network, not n points in d-dimensions. Read ssg and statistical connectomics paper. Model ENTIRE network, not point-by-point. A realization is an entire network, an entirely new dataset. Make this point better in the example.

Bird's are super cool (and not at all controlled by the government)

everytime a wildfire is shown on the news I can't help but think about the Birds. It makes sense that due to their ability to fly, that they can persist and move easier than other species. A bear isn't going to out run a fire, but a bird may out fly it. Although birds do have an easier traveling ability, I still think it's wrong to over look them in terms of caring for and rescuing animals after habitat destruction. Yes, birds are able to fly away, but they are still meant for a specific habitat and just escaping does not ensure surviving and certainly does not ensure thriving.

I had no idea that this existed until this article. It's a service just to bookmark web pages...?

Reusing food and knowing how to do it is a great resource to have. Food places waste so much food everyday. It's actually pretty said because there are so many starving people in this world, and here we are just throwing away good food. Dunkin' Donuts is a great example. When I worked there we would throw away dozens of donuts that weren't sold. Such a waste.

Although I understand the point the speaker is trying to make here, I am a little uncomfortable with the fact that he keeps referring back to feeding pigs in order for it to benefit our society and economy. There are so so so many people around the world that die from the lack of food everyday, the focus should be on them. The focus should be on them not only to save the food that is being wasted, but to also be kind to each other. Not everything done on a global scale has to benefit the government and economy in some way. Sometimes, things are done to help other for the sake of just helping and supporting. This is what makes societies and people love each other, and want the best for each other. Nevertheless, this pure intention is something that is ideal, a wish you may say. Trying to change the intentions of a population is an almost impossible goal. So one can start small, like this speaker mentioned.

this is another good example and visual of just how food is wasted even before it makes it to public for consumption. Even at the early stage during harvest food is wasted due to industrial mishaps, food is also given to live stock at this stage to help with the supply of other foods such as meat and dairy like stated earlier. this shows that all wasted food is not directly thrown away it does has some use. but again the question arises why cant that same food be used to combat global hunger.

Food waste is one of the biggest silent problems in our world today. Not many people know how much it's being wasted and what it takes to drain all that wasted food. We waste natural resources such as land, water, and energy because we throw away food. People don't really think much about trashing the leftover food or just generally they throw it away because they don't want it anymore. It's ironic that we have so much food waste yet we still fighting world hunger. There are many simple ways that we can reduce this massive problem.

While it feels like common sense, I am still surprised I could have done this. Browning greens and rotten salad mix happens way too often in my house. Seeing damaged food, we have an instinct to throw it away. But, if you consider just going back to basics, we could have revived our greens. While we see our fresh produce turn different colors and change textures, we lose interest in them. We subconsciously view them as unedible or unworthy. If we were to just take a few extra steps, we could save so much fresh and healthy produce. Similar enough, expiration dates have controlled our eating for forever. These numbers have told us when we are allowed to eat something. When we go past that date, we instantly want to throw it away. But, if you taste it and deem it edible, don’t let those numbers let you purge food.

Makes no sense when there are people out there who would be extremely grateful and humbled to have what we call "waste" and because their not the "correct" shape is just absurd. It's crazy to think how our "trash" can be someone's treasure. When there is division between societies for example, by class, the upper or richest class easily decides for those below them. Taking away privilege's that a human should not have the authority to.

This is actual insanity. Who cares?! This waste is so unnecessary for our planet. No matter the shape or size, it's going to the place. It's eventually going to be eaten regardless. Not everything in this world has to look "perfect". Not every banana is going to look the same. What's the point of harvesting and picking the food but throwing it away because "it doesn't look right". That's absolutely crazy. It's the fact that they don't even donate it or give them to less fortunate people, they just throw it away.

I completely agree with this. It's so normalized to have fast food everyday, for breakfast, lunch and dinner. That can be caused by laziness, no knowledge of how to cook, whatever the case may be. But as humans, we should realize what we put into our bodies, especially for a necessity like food. Home-cooked meals are 10x better than fast food in many aspects. It's so much healthier. It can taste so much better. You can cook food to last several days. And you know exactly what you're putting into your body. Yes, of course there are people who can't cook out there but what else is life about? We learn something new everyday. Cooking is no different. And as time passes, you might even learn to love cooking. Cooking at home benefits not just you, but also the community.

I think it's insane how much food they invest into livestock alone. if livestock alone takes just as much food to raise as the insane amount we throw in the trash daily, steering away from meat might not only be in the best interest of the environment, but also the billions of people left hungry around the world.

问：所以你所描述的这种模式，基本上是通过各种不同的过程，把人们从一个收入水平连接到另一个更高的收入水平。我很好奇，你还能想象到有哪些其他的连接方式存在。

答：回答这个问题的方法是看看所有的短缺都在哪里，人们想在哪里招聘，而这些人却不存在？技术是一个很明显的问题，但在医疗保健和技术行业中到处都是。其实你可以从劳工部得到一个数据下载，包含我们现有人才库无法填补的所有角色。开始的时候，你只要把这些空缺填补上就可以了。随着时间的推移，你会得到更多的变化，并优化什么级别的程序员和其他具体的细节。但现在如果你是一个长途卡车司机，你会立即被雇用。你可以是一个从监狱里出来的重刑犯，你可以赚到 9 万美金，通过三个星期的培训，大多数人甚至不知道这是一个选择。这可能在 20 年后不是一个职业，谁知道自动驾驶汽车会发生什么，当这成为现实的时候，我们可能也应该有一个解决方案。

I like this idea of creating a space and causing a scene to pull people in.

Not too dissimilar to the aculturation Hollywood does to help normalize certain activities just by showing them increasingly.

Definitely want to circle back to this with additional examples and expand on it.

The yucca-moth makes me think of a Joshua Tree which I think is such a cool species! They are pollinated by yucca-moths, and if yucca moths over exploit them they will literally abort the ovary that the yucca moth laid it's eggs in. Their seeds were then distributed by giant ground sloths to more suitable habitat, and the extinction of the ground sloth is why the Joshua tree range is declining. I just think they're such a great species to describe so many interactions!

.c4

It is so sad to see that people have to justify everything that the public sees. People value this kind of information because they watched Tayshia and Zac's relationship unfold on national television.

It's hard to believe that the aborigines intentionally set fires to manage their ecosystems. The use of this method is fascinating in the least but is the increase in flammable grass biomass a good thing or bad thing when dealing with invasive native grasses? Does this practice seem to effect the natural plants? If this only effects the invasive species, could this practice be incorporated in places other than Australia? These are just some ideas that came to mind when reading this section.