In these lines we learn about whenever ,you use the term text in composition courses , its mean communication ,of text movie , social media post ,essay, website ,podcast and the other list goes on .mean we can consider diffrent texts in the multimodal

In this chapter we learn about introduces multimodal composing and five strategies for creating a multimodal text .so we also learn about the beginning with the introduction of the new London Group and offers three reasons of skills learning ,why its important to learn about the multimodal composing

his part helped me understand that multimodal composing isn’t just about adding pictures or videos for decoration. It’s about thinking intentionally about how different modes communicate meaning. I never really thought about writing like that before, like choosing tools based on what helps the reader.

The gesture mode is something that I found interesting and would like to apply to my writings

Before this class i never really realized i was using some of the writing methods

Definitely only remember using the 5 paragraph essay method

Důvěřují nám + pls correct it in the whole web, so I don´t have to write it again and again... :)

the same as on page https://test2025.mitkoforevents.cz/nuzkove-stany/

the same as on page https://test2025.mitkoforevents.cz/nuzkove-stany/

use the banner "Nejste si čímkoliv jistí..."

use the banner "Zeptejte se nás na cokoliv"

This study highlights the true complexity of protein processing, trafficking, and its ultimate function! I think it could benefit from some orthogonal methods of analysis - would be it be possible to try to isolate specific 'states' of processed protein (like you did with the CHX treatment) or using subcellular localization or IPs to identify exactly which glycosylation sites or cleavages have been made? Excited to see what comes next!

Some Lamp1 staining for lysosome localization could contribute to the above IF figures as well!

I wonder if there might be a more straightforward way to probe this interaction. It seems difficult to study the interaction between RNF13 and IDS because there are so many different precursors or processed forms of IDS. Perhaps a strategic approach could be to either isolate the process (in cells) for which the interaction is most important, and then determine which processed form of IDS is involved. Or maybe purify different forms of IDS and determine using binding assays, since IPs are less capable of identifying 'direct interactions'.

This is a clever way to probe protein processing! It might be useful to do some western blotting with this treatment to look at the impact on processing that way as well.

This is a very neat result! I'm wondering if it might be interesting to repeat an IP with different fractions - like a lysosome-enriched fraction vs a whole lysate. There are some pretty crude lysosome preps that could give some nice connections between forms that are trafficked, the maturation data you have, and the localization data you have below.

What is your hypothesis for this interaction, then? Does RNF13 interact with both species, throughout the whole processing stage? Or predominantly with one species?

This second stanza, instead, completely opposes the first one, and focuses on the present moment and life.

By using the term body, the author implies that the calf is already dead; having a deformity means that his life-span will be shorter.

Notice how the author uses he instead of it to refer to the calf. Maybe this stylistic choice is used to let the reader identify themselves with the calf; it could also be used to give more humanity to the animal, instead of referring to him with the pronoun used for objects.

decoupling caps table

I would nationalize all of them. Make them run on a not for profit model. These sites are so essential to the connections that our generations have with each other so I would consider them an inelastic demand. Because if I can't be in instagram I can't get the address for this house show or I can't keep up with my local activism group about meetings. I think that these services of connection should be centralized so they can be regulated and stripped of greed.

If I could design a new social media, I would like to make an app that allows people to chat with friends, like snapchat. But this app won't only have messaging, it can also allow users to pay, see the locations of friends(with permission), and post. In China, WeChat already has all the functions above, so people don't need to bring cash and cards. All they need to take with is just a phone. I would also add some mini-programs for entertainment and official accounts.

Even worse than before! I don’t want to post anything on social media anymore, not for a long time, at least. I don’t know what the future will bring, but I will definitely not get involved in writing negative comments toward creators, and I’ll be more mindful when using social media.

The text book reinforces a lot of my preexisting opinions about the internet and cemented information I already knew. The general negativity of the internet was apparent to me through my extensive usage of it, along with hearing stories about other cases and their consequences.

This article draws similarities between McKinsey the consulting firm and AI as a whole. I honestly don't think its a very good analogy but I'll do my best. They say similar to McKinsey normalizing mass layoffs as a firm AI is going to take away a lot of jobs. I think that McKinsey is way, way worse because those are actual people being evil not an Ai that may tell you to do something evil.

This article outlines the impact and importance of Black Twitter as a space for Black people to share customs and culture and freely find community. The article goes into the history of Black Twitter from its creation and what it has meant during its time of existence. The article also summarizes the statements made by many Black Twitter users that Black Twitter is now dead after the purchase of Twitter by Elon Musk.

After checking out Coded Bias, I was honestly surprised how much everyday technology relies on algorithms that were never tested on diverse groups of people. The documentary shows how facial recognition failed on darker-skinned women, which made me think about how “neutral” tech isn’t neutral at all. What really got me is how the developers didn’t seem to think about these consequences until people called them out. It connects perfectly to the chapter’s theme that innovation often ignores ethics until harm already happens. It also made me wonder how many other systems we use every day have hidden biases we just haven’t noticed yet.

This article is about an ex-twitter engineer, Steve Krenzel's experience of rejecting selling identifiable user data and some predictions about twitter's future. There was one telco company that wanted to buy the data about users' privacy such as what time the users leave their home, and Steve Krenzel refused this. And after Elon Musk bought twitter, he worried about Elon Musk would do worse things with these datas. This article reflects the importance of ethics that we learned in info 103. As an internet user, and maybe tech worker in the future, it's really important to be ethical and respectful to users' privacy and rights.

I’m glad that we, as humans, still have ethics that limit us from doing things that could potentially harm others, especially people who might want to take too much of our personal information. It can be very difficult for people to control themselves when they feel the temptation of what they might gain.

The way in twitter operates is less the fault of twitter itself and the people that created it but more the fact that twitter is under a cooperation and as such needs to continuously make money. It monetization method relies on user engagement, and without it, the platform will quickly die out. To achieve this, twitter prays on the human psychic, showing the user what interests or draws them in the most, in most cases it might be something negative.

By using the term body, the author implies that the calf is already dead; having a deformity means that his life-span will be shorter.

Notice how the author uses he instead of it to refer to the calf. Maybe this stylistic choice is used to let the reader identify themselves with the calf; it could also be used to give more humanity to the animal, instead of referring to him with the pronoun used for objects.

I would like to recommend OER to continuing ed instructors who usually don't have paid prep time - it could save some time. Yet the constant review also seems so time consuming. It's not quite an easy sell. It's so much easier to keep your own materials current when they are your own and you are actively working in the field - you know exactly what to update, and where.

eLife Assessment

This study presents a fundamental discovery of how cerebellar climbing fibers modulate plastic changes in the somatosensory cortex by identifying both the responsible cortical circuit and the anatomical pathways. The evidence supporting the conclusions is convincing and well supported by modern neuroscience methodologies. Overall, this work represents a significant contribution that will be of broad interest to neuroscientists, especially those studying the long-distance cerebellar influence on non-motor brain functions.

Reviewer #1 (Public review):

Summary:

Silbaugh, Koster and Hansel investigated how the cerebellar climbing fiber (CF) signals influence neuronal activity and plasticity in mouse primary somatosensory (S1) cortex. They found that optogenetic activation of CFs in the cerebellum modulates responses of cortical neurons to whisker stimulation in a cell-type-specific manner and suppresses potentiation of layer 2/3 pyramidal neurons induced by repeated whisker stimulation. This suppression of plasticity by CF activation is mediated through modulation of VIP- and SST-positive interneurons. Using transsynaptic tracing and chemogenetic approaches, the authors identified a pathway from the cerebellum through the zona incerta and the thalamic posterior medial (POm) nucleus to the S1 cortex, which underlies this functional modulation.

The authors have addressed all the necessary points.

Reviewer #2 (Public review):

Summary:

The authors examined long-distance influence of climbing fiber (CF) signaling in the somatosensory cortex by manipulating whiskers through stimulation. Also, they examined CF signaling using two-photon imaging and mapped projections from the cerebellum to somatosensory cortex using transsynaptic tracing. As a final manipulation, they used chemogenetics to perturb parvalbumin positive neurons in the zona incerta and recorded from climbing fibers.

Strengths:

There are several strengths to this paper. The recordings were carefully performed and AAVs used were selective and specific for the cell-types and pathways being analyzed. In addition, the authors used multiple approaches that support climbing fiber pathways to distal regions of the brain. This work will impact the field and describes nice methods to target difficult to reach brain regions, such as the inferior olive.

No weaknesses noted.

Reviewer #3 (Public review):

Summary:

The authors developed an interesting novel paradigm to probe the effects of cerebellar climbing fiber activation on short-term adaptation of somatosensory neocortical activity during repetitive whisker stimulation. Normally, RWS potentiated whisker responses in pyramidal cells and weakly suppressed them in interneruons, lasting for at least 1h. Crusii Optogenetic climbing fiber activation during RWS reduced or inverted these adaptive changes. This effect was generally mimicked or blocked with chemogenetic SST or VIP activation/suppression as predicted based on their "sign" in the circuit.

Strengths:

The central finding about CF modulation of S1 response adaptation is interesting, important, and convincing, and provides a jumping-off point for the field to start to think carefully about cerebellar modulation of neocortical plasticity.

Weaknesses:

The SST and VIP results appeared slightly weaker statistically, but I do not personally think this detracts from the importance of the initial finding (if there are multiple underlying mechanisms, modulating one may reproduce only a fraction of the effect size). I found the suggestion that zona incerta may be responsible for the cerebellar effects on S1 to be a more speculative result (it is not so easy with existing technology to effectively modulate this type of polysynaptic pathway), but this may be an interesting topic for the authors to follow up on in more detail in the future.

Comments on revisions:

The authors have appropriately addressed my comments.

Author response:

The following is the authors’ response to the original reviews

Public Reviews:

Reviewer #1 (Public review):

Summary:

Silbaugh, Koster, and Hansel investigated how the cerebellar climbing fiber (CF) signals influence neuronal activity and plasticity in mouse primary somatosensory (S1) cortex. They found that optogenetic activation of CFs in the cerebellum modulates responses of cortical neurons to whisker stimulation in a cell-type-specific manner and suppresses potentiation of layer 2/3 pyramidal neurons induced by repeated whisker stimulation. This suppression of plasticity by CF activation is mediated through modulation of VIP- and SST-positive interneurons. Using transsynaptic tracing and chemogenetic approaches, the authors identified a pathway from the cerebellum through the zona incerta and the thalamic posterior medial (POm) nucleus to the S1 cortex, which underlies this functional modulation.

Strengths:

This study employed a combination of modern neuroscientific techniques, including two-photon imaging, opto- and chemo-genetic approaches, and transsynaptic tracing. The experiments were thoroughly conducted, and the results were clearly and systematically described. The interplay between the cerebellum and other brain regions - and its functional implications - is one of the major topics in this field. This study provides solid evidence for an instructive role of the cerebellum in experience-dependent plasticity in the S1 cortex.

Weaknesses:

There may be some methodological limitations, and the physiological relevance of the CFinduced plasticity modulation in the S1 cortex remains unclear. In particular, it has not been elucidated how CF activity influences the firing patterns of downstream neurons along the pathway to the S1 cortex during stimulation.

Our study addresses the important question of whether CF signaling can influence the activity and plasticity of neurons outside the olivocerebellar system, and further identifies the mechanism through which this indeed occurs. We provide a detailed description of the involvement of specific neuron subtypes and how they are modulated by climbing fiber activation to impact S1 plasticity. We also identify at least one critical pathway from the cerebellar output to the S1 circuit. It is indeed correct that we did not investigate how the specific firing patterns of all of these downstream neurons are affected, or the natural behaviors in which this mechanism is involved. Now that it is established that CF signaling can impact activity and plasticity outside the olivocerebellar system -- and even in the primary somatosensory cortex -- these questions will be important to further investigate in future studies.

(1) Optogenetic stimulation may have activated a large population of CFs synchronously, potentially leading to strong suppression followed by massive activation in numerous cerebellar nuclear (CN) neurons. Given that there is no quantitative estimation of the stimulated area or number of activated CFs, observed effects are difficult to interpret directly. The authors should at least provide the basic stimulation parameters (coordinates of stim location, power density, spot size, estimated number of Purkinje cells included, etc.).

As discussed in the paper, we indeed expect that synchronous CF activation is needed to allow for an effect on S1 circuits under natural or optogenetic activation conditions. The basic optogenetic stimulation parameters (also stated in the methods) are as follows: 470 nm LED; Ø200 µm core, 0.39 NA rotary joint patch cable; absolute power output of 2.5 mW; spot size at the surface of the cortex 0.6 mm; estimated power density 8 mW/mm2. A serious estimate of the number of Purkinje cells that are activated is difficult to provide, in particular as ‘activation’ would refer to climbing fiber inputs, not Purkinje cells directly.

(2) There are CF collaterals directly innervating CN (PMID:10982464). Therefore, antidromic spikes induced by optogenetic stimulation may directly activate CN neurons. On the other hand, a previous study reported that CN neurons exhibit only weak responses to CF collateral inputs (PMID: 27047344). The authors should discuss these possibilities and the potential influence of CF collaterals on the interpretation of the results.

A direct activation of CN neurons by antidromic spikes in CF collaterals cannot be ruled out. However, we believe that this effect will not be substantial. The activation of the multi-synaptic pathway that we describe in this study is more likely to require a strong nudge as resulting from synchronized Purkinje cell input and subsequent rebound activation in CN neurons (PMID: 22198670), rather than small-amplitude input provided by CF collaterals (PMID: 27047344). A requirement for CF/PC synchronization would also set a threshold for activation of this suppressive pathway.

(3) The rationale behind the plasticity induction protocol for RWS+CF (50 ms light pulses at 1 Hz during 5 min of RWS, with a 45 ms delay relative to the onset of whisker stimulation) is unclear.

a) The authors state that 1 Hz was chosen to match the spontaneous CF firing rate (line 107); however, they also introduced a delay to mimic the CF response to whisker stimulation (line 108). This is confusing, and requires further clarification, specifically, whether the protocol was designed to reproduce spontaneous or sensory-evoked CF activity.

This protocol was designed to mimic sensory-evoked CF activity as reported in Bosman et al (J. Physiol. 588, 2010; PMID: 20724365).

b) Was the timing of delivering light pulses constant or random? Given the stochastic nature of CF firing, randomly timed light pulses with an average rate of 1Hz would be more physiologically relevant. At the very least, the authors should provide a clear explanation of how the stimulation timing was implemented.

Light pulses were delivered at a constant 1 Hz. Our goal was to isolate synchrony as the variable distinguishing sensory-evoked from spontaneous CF activity; additionally varying stochasticity, rate, or amplitude would have confounded this. Future studies could explore how these additional parameters shape S1 responses.

(4) CF activation modulates inhibitory interneurons in the S1 cortex (Figure 2): responses of interneurons in S1 to whisker stimulation were enhanced upon CF coactivation (Figure 2C), and these neurons were predominantly SST- and PV-positive interneurons (Figure 2H, I). In contrast, VIP-positive neurons were suppressed only in the late time window of 650-850 ms (Figure 2G). If the authors' hypothesis-that the activity of VIP neurons regulates SST- and PVneuron activity during RWS+CF-is correct, then the activity of SST- and PV-neurons should also be increased during this late time window. The authors should clarify whether such temporal dynamics were observed or could be inferred from their data.

Yes, we see a significant activity increase in PV neurons in this late time window (see updates to Data S2). Activity was also increased in SST neurons, though this did not reach statistical significance (Data S2). One reason might be that – given the small effect size overall – such an effect would only be seen in paired recordings. Chemogenetic activity modulation in VIP neurons, which provides a more crude test, shows, however, that SST- and PV-positive interneurons are indeed regulated via inhibition from VIP-positive interneurons (Fig. 5).

(5) Transsynaptic tracing from CN nicely identified zona incerta (ZI) neurons and their axon terminals in both POm and S1 (Figure 6 and Figure S7).

a) Which part of the CN (medial, interposed, or lateral) is involved in this pathway is unclear.

We used a dual-injection transsynaptic tracing approach to specifically label the outputs of ZI neurons that receive input from the deep cerebellar nuclei. The anterograde viral vector injected into the CN is unlabeled (no fluorophore) and therefore, it is not possible to reliably assess the extent of viral spread in those experiments as performed. However, we have previously performed similar injections into the deep cerebellar nuclei and post hoc histology suggest all three nuclei will have at least some viral expression (Koster and Sherman, 2024). Due to size and injection location, we will mostly have reached the lateral (dentate) nuclei, but cannot exclude partial transsynaptic tracing from the interposed and medial nuclei.  

b) Were the electrophysiological properties of these ZI neurons consistent with those of PV neurons?

Although most recorded cells demonstrated electrophysiological properties consistent with PV+ interneurons in other brain regions (i.e. fast spiking, narrow spike width, non-adapting; see Tremblay et al., 2016), interneuron subtypes in the ZI have been incompletely characterized, with SST+ cells showing similar features to those typically associated with PV+ cells (if interested, compare Fig. 4 in DOI: 10.1126/sciadv.abf6709 vs. Fig. S10 in https://doi.org/10.1016/j.neuron.2020.04.027). Therefore, we did not attempt to delineate cell identity based on these characteristics.

c) There appears to be a considerable number of axons of these ZI neurons projecting to the S1 cortex (Figure S7C). Would it be possible to estimate the relative density of axons projecting to the POm versus those projecting to S1? In addition, the authors should discuss the potential functional role of this direct pathway from the ZI to the S1 cortex.

An absolute quantification is difficult to provide based on the images that we obtained. However, any crude estimate would indicate the relative density of projections to POm is higher than the density of projections to S1 (this is apparent from the images themselves). While the anatomical and functional connections from POm to S1 have been described in detail (Audette et al., 2018), this is not the case for the direct projections to ZI. A direct ZI to S1 projection would potentially involve a different recruitment of neurons in the S1 circuit. Any discussion on the specific consequences of the activation of this direct pathway would be purely speculative.

Reviewer #2 (Public review):

Summary:

The authors examined long-distance influence of climbing fiber (CF) signaling in the somatosensory cortex by manipulating whiskers through stimulation. Also, they examined CF signaling using two-photon imaging and mapped projections from the cerebellum to the somatosensory cortex using transsynaptic tracing. As a final manipulation, they used chemogenetics to perturb parvalbumin-positive neurons in the zona incerta and recorded from climbing fibers.

Strengths:

There are several strengths to this paper. The recordings were carefully performed, and AAVs used were selective and specific for the cell types and pathways being analyzed. In addition, the authors used multiple approaches that support climbing fiber pathways to distal regions of the brain. This work will impact the field and describes nice methods to target difficult-to-reach brain regions, such as the inferior olive.

Weaknesses:

There are some details in the methods that could be explained further. The discussion was very short and could connect the findings in a broader way.

In the revised manuscript, we provide more methodological details, as requested. We provided as simple as possible explanations in the discussion, so as not to bias further investigations into this novel phenomenon. In particular, we avoid an extended discussion of the gating effect of CF activity on S1 plasticity. While this is the effect on plasticity specifically observed here, we believe that the consequences of CF signaling on S1 activity may entirely depend on the contexts in which CF signals are naturally recruited, the ongoing activity of other brain regions, and behavioral state. Our key finding is that such modulation of neocortical plasticity can occur. How CF signaling controls plasticity of the neocortex in all contexts remains unknown, but needs to be thoughtfully tested in the future.

Reviewer #3 (Public review):

Summary:

The authors developed an interesting novel paradigm to probe the effects of cerebellar climbing fiber activation on short-term adaptation of somatosensory neocortical activity during repetitive whisker stimulation. Normally, RWS potentiated whisker responses in pyramidal cells and weakly suppressed them in interneurons, lasting for at least 1h. Crusii Optogenetic climbing fiber activation during RWS reduced or inverted these adaptive changes. This effect was generally mimicked or blocked with chemogenetic SST or VIP activation/suppression as predicted based on their "sign" in the circuit.

Strengths:

The central finding about CF modulation of S1 response adaptation is interesting, important, and convincing, and provides a jumping-off point for the field to start to think carefully about cerebellar modulation of neocortical plasticity.

Weaknesses:

The SST and VIP results appeared slightly weaker statistically, but I do not personally think this detracts from the importance of the initial finding (if there are multiple underlying mechanisms, modulating one may reproduce only a fraction of the effect size). I found the suggestion that zona incerta may be responsible for the cerebellar effects on S1 to be a more speculative result (it is not so easy with existing technology to effectively modulate this type of polysynaptic pathway), but this may be an interesting topic for the authors to follow up on in more detail in the future.

Our interpretation of the anatomical and physiological findings is that a pathway via the ZI is indeed critical for the observed effects. This pathway also represents perhaps the most direct pathway (i.e. least number of synapses connecting the cerebellar nuclei to S1). However, several other direct and indirect pathways are plausible as well and we expect distinct activation requirements and consequences for neurons in the S1 circuit. These are indeed interesting topics for future investigation.

Recommendations for the authors:

Reviewer #1 (Recommendations for the authors):

(1) Line 77: "CF transients" is not a standard or widely recognized term. Please use a more precise expression, such as "CF-induced calcium transients."

We now avoid the use of the term “CF transients” and replaced it with “CF-induced calcium transients.”

(2) Titer of AAVs injected should be provided.

AAV titers have been included in an additional data table (Data S9).

(3) Several citations to the figures are incorrect (for example, "Supplementary Data 2a (Line 398)" does not exist).

We apologize for the mistakes in this version of the article. Incorrect citations to the figures have been corrected.

(4) Line 627-628: "The tip of the patch cable was centered over Crus II in all optogenetic stimulation experiments." The stereotaxic coordinate of the tip position should be provided.

The stereotaxic coordinate of the tip position has been provided in the methods.

(5) Line 629: "Blue light pulses were delivered with a 470 nm Fiber-Coupled LED (Thorlabs catalog: M470F3)." The size of the light stim and estimated power density (W/mm^2) at the surface of the cortex should be provided.

The spot size and estimated power density at the surface of the cortex has been provided in the methods.

(6) Line 702-706: References for DCZ should be cited.

We now cited Nagai et al, Nat. Neurosci. 23 (2020) as the original reference.

(7) Two-photon image processing (Line 807-809): The rationale for normalizing ∆F/F traces to a pre-stimulus baseline is unclear because ∆F/F is, by definition, already normalized to baseline fluorescence: (Ft-F0)/F0. The authors should clarify why this additional normalization step was necessary and how it affected the interpretation of the data.

A single baseline fluorescence value (F₀) was computed for each neuron across the entire recording session, which lasted ~120-minutes. However, some S1 neurons exhibit fluctuations in baseline fluorescence over time—often related to locomotive activity or spontaneous network oscillations—which can obscure stimulus-evoked changes. To isolate fluorescence changes specifically attributable to whisker stimulation, we normalized each ∆F/F trace to the prestimulus baseline for that trial. This additional normalization allowed us to quantify potentiation or depression of sensory responses themselves, independently of spontaneous oscillations or locomotion-related changes in the ongoing neural activity.

Reviewer #2 (Recommendations for the authors):

(1) Did the climbing fiber stimulation for Figure 1 result in any changes to motor activity? Can you make any additional comments on other behaviors that were observed during these manipulations?

Acute CF stimulation did not cause any changes in locomotive or whisking activity. The CF stimulation also did not influence the overall level of locomotion or whisking during plasticity induction.

(2) Figure 3B and F- it is very difficult to see the SST+ neurons. Can this be enhanced?

We linearly adjusted the brightness and contrast for the bottom images in Figure 3B and F to improve visualization of SST+ neurons. Note the expression of both hM3D(Gq) and hM4D(Gi) in SST+ neurons is sparse, which was necessary to avoid off-target effects.

(3) Can you be more specific about the subregions of cerebellar nuclei and cell types that are targeted in the tracing studies? Discussions of the cerebellar nuclei subregions are missing and would be interesting, as others have shown discrete pathways between cerebellar nuclei subregions and long-distance projections.

See our response to comment 5a from Reviewer 1 (copied again here): we used a dual-injection transsynaptic tracing approach to specifically label the outputs of ZI neurons that receive input from the deep cerebellar nuclei. The anterograde viral vector injected into the CN is unlabeled (no fluorophone) and therefore, it is not possible to reliably assess the extent of viral spread in those experiments as performed. However, we have previously performed similar injections into the deep cerebellar nuclei and post hoc histology suggest all three nuclei will have at least some viral expression (Koster and Sherman, 2024). Due to size and injection location, we will mostly have reached the lateral (dentate) nuclei, but cannot exclude partial transsynaptic tracing from the interposed and medial nuclei.  

It would indeed be interesting to further investigate the effect of CFs residing in different cerebellar lobules, which preferentially target different cerebellar nuclei, on targets of these nuclei.

(4) Did you see any connection to the ventral tegmental area? Can you comment on whether dopamine pathways are influenced by CF and in your manipulations?

We did not specifically look at these pathways and thus are not able to comment on this.

(5) These are intensive surgeries, do you think glia could have influenced any results?

This was not tested and seems unlikely, but we cannot exclude such possibility.

(6) It is unclear in the methods how long animals were recorded for in each experiment. Can you add more detail?

Additional detail was added to the methods. Recordings for all experimental configurations did not last more than 120 minutes in total. All data were analyzed across identical time windows for each experiment.

(7) In the methods it was mentioned that recording length can differ between animals. Can this influence the results, and if so, how was that controlled for?

There was a variance in recording length within experimental groups, but no systematic difference between groups.

(8) I do not see any mention of animal sex throughout this manuscript. If animals were mixed groups, were sex differences considered? Would it be expected that CF activity would be different in male and female mice?

As mentioned in the Methods (Animals), mice of either sex were used. No sex-dependent differences were observed.

(9) Transsynaptic tracing results of the zona incerta are very interesting. The zona incerta is highly understudied, but has been linked to feeding, locomotion, arousal, and novelty seeking. Do you think this pathway would explain some of the behavioral results found through other studies of cerebellar lobule perturbations? Some discussion of how this brain region would be important as a cerebellar connection in animal behavior would be interesting.

Since the multi-synaptic pathway from the cerebellum to S1 involves several brain regions with their own inputs and modulatory influences, it seems plausible to assume that behaviors controlled by these regions or affecting signaling pathways that regulate them would show some level of interaction. Our study does not address these interactions, but this will be an interesting question to be addressed in future work.

Reviewer #3 (Recommendations for the authors):

General comments on the data presentation:

I'm not a huge fan of taking areas under curves ('AUC' throughout the study) when the integral of the quantity has no physical meaning - 'normalizing' the AUC (1I,L etc) is even stranger, because of course if you instead normalize the AUC by the # of data points, you literally just get the mean (which is probably what should be used instead).

Indeed, AUC is equal to the average response in the time window used, multiplied by the window duration (thus, AUC is directly proportional to the mean). We choose to report AUC, a descriptive statistic, rather than the mean within this window. In 1I and L, we normalize the AUC across animals, essentially removing the variability across animals in the ‘Pre’ condition for visualization. Note the significance of these comparisons are consistent whether or not we normalize to the ‘Pre’ condition (non-normalized RWS data in I shows a significant increase in PN activity, p = 0.0068, signrank test; non-normalized RWS+CF data in I shows a significant decrease in PN activity, p = 0.0135, paired t-test; non-normalized RWS data in L shows a significant decrease in IN activity, p <0.001, paired t-test; non-normalized RWS+CF data in L shows no significant change in IN activity, p = 0.7789, paired t-test).

I think unadorned bar charts are generally excluded from most journals now. Consider replacing these with something that shows the raw datapoints if not too many, or the distribution across points.

We have replaced bar charts with box plots and violin plots. We have avoided plotting individual data points due to the quantity of points.

In various places, the statistics produce various questionable outcomes that will draw unwanted reader scrutiny. Many of the examples below involve tiny differences in means with overlapping error bars that are "significant" or a few cases of nonoverlapping error bars that are "not significant." I think replacing the bar charts may help to resolve things here if we can see the whole distribution or the raw data points. As importantly, I think a big problem is that the statistical tests all seem to be nonparametric (they are ambiguously described in Table S3 as "Wilcoxon," which should be clarified, since there is an unpaired Wilcoxon test [rank sum] and a paired Wilcoxon test [sign rank]), and thus based on differences in the *median* whereas the bar charts are based on the *mean* (and SEM rather than MAD or IQR or other medianappropriate measure of spread). This should be fixed (either change the test or change the plots), which will hopefully allay many of the items below.

We thank the reviewer for this important point. As mentioned in the Statistics and quantification section, Wilcoxon signed rank tests were used for non-normal data. We have replaced the bar charts with box plots which show the IQR and median, which indeed allays may of the items below.

Here are some specific points on the statistics presentation:

(1) 1G, the test says that following RWS+CF, the decrease in PN response is not significant. In 1I, the same data, but now over time, shows a highly significant decrease. This probably means that either the first test should be reconsidered (was this a paired comparison, which would "build in" the normalization subsequently used automatically?) or the second test should be reconsidered. It's especially strange because the n value in G, if based on cells, would seem to be ~50-times higher than that in I if based on mice.

In Figure 1G, the analysis tests whether individual pyramidal neurons significantly changed their responses before vs. after RWS+CF stimulation. This is a paired comparison at the single-cell level, and here indicates that the average per-neuron response did not reliably decrease after RWS+CF when comparing each cell’s pre- and post-values directly. In contrast, Figure 1I examines the same dataset analyzed across time bins using a two-way ANOVA, which tests for effects of time, group (RWS vs. RWS+CF), and their interaction. The analysis showed a significant group effect (p < 0.001), indicating that the overall level of activity across all time points differed between RWS and RWS+CF conditions. The difference in significance between these two analyses arises because the first test (Fig. 1G) assesses within-neuron changes (paired), whereas the second test (Fig. 1I) assesses overall population-level differences between groups over time (independent groups). Thus, the tests address related but distinct questions—one about per-cell response changes, the other about how activity differs across experimental conditions.

(2) 1J RWS+CF then shows a much smaller difference with overlapping error bars than the ns difference with nonoverlapping errors in 1G, but J gets three asterisks (same n-values).

Bar graphs have been replaced with box plots.

(3) 1K, it is very unclear what is under the asterisk could possibly be significant here, since the black and white dots overlap and trade places multiple times.

See response to point 1. A significant group effect will exist if the aggregate difference across all time bins exceeds within-group variability. The asterisk therefore reflects a statistically significant main group effect (RWS versus RWS+CF) rather than differences at any single time point. Note, however, the very small effect size here.

(4) 2B, 2G, 2H, 2I, 3G, 3H, 5C etc, again, significance with overlapping error bars, see suggestions above.

Bar graphs have been replaced with box plots.

(5) Time windows: e.g., L149-153 / 2B - this section reads weirdly. I think it would be less offputting to show a time-varying significance, if you want to make this point (there are various approaches to this floating around), or a decay rate, or something else.

Here, we wanted to understand the overall direction of influence of CFs on VIP activity. We find that CFs exert a suppressive effect on VIP activity, which is statistically significant in this later time window. The specific effect of CF modulation on the activity of S1 neurons across multiple time points will be described in more detail in future investigations.

(6) 4G, 6I, these asterisks again seem impossible (as currently presented).

Bar graphs have been replaced with box plots.

The writing is in generally ok shape, but needs tightening/clarifying:

(1) L45 "mechanistic capacity" not clear.

We have simplified this term to “capacity.” We use the term here to express that the central question we pose is whether CF signals are able to impact S1 circuits. We demonstrate CF signals indeed influence S1 circuits and further describe the mechanism through which this occurs, but we do not yet know all of the natural conditions in which this may occur. We feel that “capacity” describes the question we pose -- and our findings -- very well.

(2) L48-58 there's a lot of material here, not clear how much is essential to the present study.

We would like to give an overview of the literature on instructive CF signaling within the cerebellum. Here, we feel it is important to describe how CFs supervise learning in the cerebellum via coincident activation of parallel fiber inputs and CF inputs. Our results demonstrate CFs have the capacity to supervise learning in the neocortex in a similar manner, as coincident CF activation with sensory input modulates plasticity of S1 neurons.

(3) L59 "has the capacity to" maybe just "can".

This has been adopted. We agree that “can” is a more straightforward way of saying “has the capacity to” here. In this sentence, “can” and “has the capacity to” both mean a general ability to do something, without explicit knowledge about the conditions of use.

(4) L61-62 some of this is circular "observation that CF regulates plasticity in S1..has consequences for plasticity in S1".

We now changed this to read “…consequences for input processing in S1.”

(5) L91 "already existing whisker input" although I get it, strictly speaking, not clear what this means.

This sentence has been reworded for clarity.

(6) L94 "this form of plasticity" what form?

Edited to read “sensory-evoked plasticity.”

(7) L119 should say "to test the".

This has been corrected.

(8) L120 should say "well-suited to measure receptive fields".

We agree; this wording has been adopted.

(9) L130 should say "optical imaging demonstrated that receptive field".

This has been adopted.

(10) L138, the disclaimer is helpful, but wouldn't it be less confusing to just pick a different set of terms? Response potentiation etc.

Perhaps, but we want to stress that components of LTP and LTD (traditionally tested using electrophysiological methods to specifically measure synaptic gain changes) can be optically measured as long as it is specified what is recorded.

(11) L140, this whole section is not very clear. What was the experiment? What was done and how?

The text in this section has been updated.

(12) L154, 156, 158, 160, 960, what is a "basic response"? Is this supposed to contrast with RWS? If so, I would just say "we measured the response to whisker stimulation without first performing RWS, and compared this to the whisker stimulation with simultaneous CF activation."

What we meant by “basic response” was the acute response of S1 neurons to a single 100 ms air puff. Here, we indeed measured the acute responses of S1 neurons to whisker stimulation (100 ms air puff) and compared them to whisker stimulation with simultaneous CF activation (100 ms air puff with a 50 ms light pulse; the light pulse was delayed 45 ms with respect to the air puff). This paragraph has been reworded for clarity.

(13) L156 "comprised of a majority" unclear. You mean most of the nonspecific IN group is either PV or SST?

Yes, that was meant here. This paragraph has been reworded for clarity.

(14) L165 tense. "are activated" "we tested" prob should be "were activated."

This sentence was reworded.

(15) L173 Not requesting additional experiments, but demonstrating that the effect is mimicked by directly activating SST or suppressing VIP questions the specificity of CF activation per se, versus presumably many other pathways upstream of the same mechanisms, which might be worth acknowledging in the text.

We indeed observe that directly activating SST or suppressing VIP neurons in S1 is sufficient to mediate the effect of CF activation on S1 pyramidal neurons, implicating SST and VIP neurons as the local effectors of CF signaling. In the text, we wrote “...the notion of sufficiency does not exclude potential effects of plasticity processes elsewhere that might well modulate effector activation in this context and others not yet tested.” Here, we mean that CFs are certainly not the only modulators of the inhibitory network in S1. One example we highlight in the discussion is that projections from M1 are known to modulate this disinhibitory VIP-to-SST-to-PN microcircuit in S1. We conclude from our chemogenetic manipulation experiments that CFs ultimately have the capacity to modulate S1 interneurons, which must occur indirectly (either through the thalamus or “upstream” regions as this reviewer points out). The fact that many other brain regions may also modulate the interneuron network in S1 -- or be modulated by CF activity themselves -- only expands the capacity of CFs to exert a variety of effects on S1 neurons in different contexts.

(16) L247 "induced ChR2" awkward.

We changed this to read “we expressed ChR2.”

(17) 6C, what are the three colors supposed to represent?

We apologize for the missing labels in this version of the manuscript. Figure 6C and the figure legend have been updated.

eLife Assessment

This study presents important findings on the role of Slit-Robo signaling in cardiac innervation. The evidence supporting the main claims of the authors is convincing. The use of several mouse models including constitutive and cell type specific knockout models make the findings more robust. The scope of the presented studies is fitting, as they primarily focus on evaluating the phenotypic changes in cardiac innervation following the loss of various Slit or Robo genes

Reviewer #1 (Public review):

The study aims to determine the role of Slit-Robo signaling in the development and patterning of cardiac innervation, a key process in heart development. Despite the well-studied roles of Slit axon guidance molecules in the development of the central nervous system, their roles in the peripheral nervous system are less clear. Thus, the present study addresses an important question. The study uses genetic knockout models to investigate how Slit2, Slit3, Robo1, and Robo2 contribute to cardiac innervation

Using constitutive and cell type-specific knockout mouse models, they show that the loss of endothelial-derived Slit2 reduces cardiac innervation. Additionally, Robo1 knockout, but not Robo2 knockout, recapitulated the Slit2 knockout effect on cardiac innervation, leading to the conclusion that Slit2-Robo1 signaling drives sympathetic innervation in the heart. Finally, the authors also show a reduction in isoproterenol-stimulated heart rate but not basal heart rate in the absence of endothelial Slit2.

The conclusions of this paper are mostly well supported by the data, but there are several limitations:

(1) It is well established that Slit ligands undergo proteolytic cleavage, generating N- and C-terminal fragments with distinct biological functions. Full-length Slit proteins and their fragments differ in cell association, with the N-terminal fragment typically remaining membrane-bound, while the C-terminal fragment is more diffusible. This distinction is crucial when evaluating the role of Slit proteins secreted by different cell types in the heart. However, this study does not examine or discuss the specific contributions of different Slit2 fragments, limiting its mechanistic insight into how Slit2 regulates cardiac innervation. While these points are mentioned in the discussion, they are not incorporated into the interpretation of the data or the presented model.

(2) The endothelial-specific deletion of Slit2 leads to its loss in endothelial cells across various organs and tissues in the developing embryo. Therefore, the phenotypes observed in the heart may be influenced by defects in other parts of the embryo, such as the CNS or sympathetic ganglia, and this possibility cannot be ruled out. The data presented in the manuscript does not dissect the relative contributions of endothelial Slit2 loss in the heart versus secondary effects arising from other organ systems. Without tissue-specific rescue or complementary conditional models, it remains unclear whether the observed cardiac phenotypes are a direct consequence of local endothelial Slit2 deficiency or an indirect outcome of broader developmental perturbations.

Reviewer #2 (Public review):

The aims of investigating Slit-Robo signaling in cardiac innervation were achieved by the experiments designed. The authors demonstrate that endothelial Slit2 signaling through Robo1 drives sympathetic innervation. While questions remain regarding signal regulation and interplay between established axon guidance signals and the further role of other Slit ligands and Robo expression in endothelium, the results strongly support the conclusions drawn.<br /> Writing and presentation are easy to follow and well structured. Appropriate controls are used, statistical analysis applied appropriately, and experiments directly test aims following a logical story.<br /> The authors demonstrate a novel mechanism for Slit-Robo signaling in cardiac sympathetic innervation. The data establishes a framework for future studies.

The authors have updated their discussion to highlight the need for investigation of the role of proteolytic cleavage of Slit2 as well as the potential for defects in other tissues due to endothelial knockout of Slit2 influencing cardiac innervation.

Author response:

The following is the authors’ response to the original reviews

Public Reviews:

Reviewer #1 (Public review):

The study aims to determine the role of Slit-Robo signaling in the development and patterning of cardiac innervation, a key process in heart development. Despite the well-studied roles of Slit axon guidance molecules in the development of the central nervous system, their roles in the peripheral nervous system are less clear. Thus, the present study addresses an important question. The study uses genetic knockout models to investigate how Slit2, Slit3, Robo1, and Robo2 contribute to cardiac innervation.

Using constitutive and cell type-specific knockout mouse models, they show that the loss of endothelial-derived Slit2 reduces cardiac innervation. Additionally, Robo1 knockout, but not Robo2 knockout, recapitulated the Slit2 knockout effect on cardiac innervation, leading to the conclusion that Slit2-Robo1 signaling drives sympathetic innervation in the heart. Finally, the authors also show a reduction in isoproterenol-stimulated heart rate but not basal heart rate in the absence of endothelial Slit2.

The conclusions of this paper are mostly well supported by the data, but some should be modified to account for the study's limitations and discussed in the context of previous literature.

We would like to thank the reviewer for their positive evaluation of our manuscript and in response to the reviewer’s comments we have extended the discussion as indicated below.

(1) It is well established that Slit ligands undergo proteolytic cleavage, generating N- and C-terminal fragments with distinct biological functions. Full-length Slit proteins and their fragments differ in cell association, with the N-terminal fragment typically remaining membrane-bound, while the C-terminal fragment is more diffusible. This distinction is crucial when evaluating the role of Slit proteins secreted by different cell types in the heart. However, this study does not examine or discuss the specific contributions of different Slit2 fragments, limiting its mechanistic insight into how Slit2 regulates cardiac innervation.

This is a valid point and it will be of interest for future studies to investigate the specific effects of the full length versus N- and C-terminal fragments in the context of cardiac innervation development. We have updated our discussion with a clearer reference to the proteolytic cleavage of Slit2.

(2) The endothelial-specific deletion of Slit2 leads to its loss in endothelial cells across various organs and tissues in the developing embryo. Therefore, the phenotypes observed in the heart may be influenced by defects in other parts of the embryo, such as the CNS or sympathetic ganglia, and this possibility cannot be ruled out.

We agree and we have now added this possibility to the discussion.

Reviewer #2 (Public review):

The aims of investigating Slit-Robo signaling in cardiac innervation were achieved by the experiments designed. While questions remain regarding signal regulation and interplay between established axon guidance signals and further role of other Slit ligands and Robo expression in endothelium, the results strongly support the conclusions drawn.

Writing and presentation are easy to follow and well structured, Appropriate controls are used, statistical analysis applied appropriately, and experiments directly test aims following a logical story.

The authors demonstrate a novel mechanism for Slit-Robo signaling in cardiac sympathetic innervation. The data establishes a framework for future studies.

We would like to thank the reviewer for these positive comments.

Recommendations:

Further assessment of interplay between Slit ligands as well as other signaling pathways (Semaphorin, NGF, etc) could be investigated. Is it possible to rescue the phenotype by modulation of other signaling pathways? Can combined Slit2/Slit3 KO rescue? Additionally, as the authors state, conditional Robo1 knockouts will be important to validate the findings of constitutive knockout.

Our study has provided the first data on the role of Slit-Robo signalling during cardiac innervation development and a base for exploring the interesting further questions the reviewer raises.  

Recommendations for the authors:

Reviewer #1 (Recommendations for the authors):

There is a typo on line 83 (disease).

This has been corrected.

she was suicidal

Pískové závaží Závaží vč. náplně 16 kg se připevňuje ke stanové noze.

+ put there the correct picture of 16 kg sand ballast

Konkurenční výhody

+ can you put this part at the very TOP of this page?

same banner "Zeptejte se nás na cokoliv" from the party-stany page

prices into "Cena od" in the shared doc

The import of Network is missing:

from pyvis.network import Network

Reordenar el párrafo: Por un lado, (desarrollar toda la idea: capability centered). Mientras que por otro, (attitudinal approaches).

Esto es resultado

testear la posibilidad? Redactar más directo

Reformular en torno a la comparabilidad como eje central.

redacción

Cita a Lytheratis y Van Dijker, digital divide de segundo orden (dentro de la cual entran las diferencias de autoeficacia)

No es así, mayor spec DSE = menor cil; la general si tiene una relación al menos en ICILS. Al respecto Campos y Scherer

The dimensions of the DSE are not only relevant to contrast for theoretical reasons, but also because the application of this approach has an impact on the distribution among groups

Differential item functioning (DIF) es el término especializado

Creo que como está escrito se entiende que el marco de competencias se encuadra en la autoeficacia bidimensional, cuando es al revés. Quizás se podría plantear la frase al contrario: The problem is that the bidimensional aproach to self-efficacy is no longer suitable with recent definitions of Digital competence

Creo que acá es esencial mencionar el rol de ICILS como estudio de vanguardia en proponer y validar esta medición. Sumado a esto, sería importante citar más fuentes que apliquen el enfoque bidimensional, ya que la aceveración "broad consensus" es bastante fuerte (o bajarle el grado).

Rohatgi, A., Scherer, R., & Hatlevik, O. E. (2016). The role of ICT self-efficacy for students’ ICT use and their achievement in a computer and information literacy test. Computers & Education, 102, 103-116. https://doi.org/10.1016/j.compedu.2016.08.001

Está rara la redacción. Propuesta: Originally formulated by Bandura (1982), self-efficacy is defined as “judgments of how well one can execute courses of action required to deal with prospective situations” (p. 122). This construct is fundamental to human agency, as it help to understand how individuals approach challenges, persist despite setbacks, and develop competence in complex domains. It does so by facilitating the establishment of standards and the attainment of performance accomplishments across learning activities (Bandura, 1995; Bandura, 1997; Steele & Aronson, 1995).

Me hace ruido la segunda afirmación. No tenemos una hipótesis sobre el efecto de la operacionalización de los constructos. El fallo de la invarianza puede deberse a muchas cosas (diferencias culturales, fallos de aplicación, errores de medición, países muy disímiles con el resto), y creo que esto plantea algo binario (o es consistente o está mal operacionalizado).

Creo que en este párrafo vendría muy bien una cita de la relación entre autoeficacia digital y alfabetización digital en estudiantes. Al respecto, Hatlevik et al. (2018)

this code is not needed. you only need: net.show("x.html") --> you will create the name

the

It's good, we can ask AI help us to have some idea or summary before our reading, but after that we should read the whole, because after our reading we will give summary how we understand, not how AI analyzed at that moment. Brief description can help students given by AI, but analyzation should be done by ourselves.

In fact, in some subjects from literature and linguisticsa areas, the use of AI is useful when we came up to certain terms that we don not know. One example can be found in today's translation lesson. We were talking about acronyms and its translation into Spanish or English and we rely on AI in order to indetify which entity did the A

Diversification Methods

You already know that studying full-time helps you finish faster but takes more money and time, while part-time or online classes are easier to balance but take longer. You also know that starting a family now may make school harder, and waiting could give you more stability. What you still need to know includes the exact cost of a four-year program, your financial aid options, how much a degree improves job opportunities, and how your work schedule can change. You can get this information by talking to your college adviser, checking financial aid offices, researching game-design careers, and discussing schedules with your wife. The pros of continuing school are better skills, more career options, and long-term growth; the cons are higher cost, more stress, and less free time. The pros of delaying school are more stability and less pressure, while the cons are slower career progress and fewer opportunities in the short term.

You have several good options for each part of the problem. For money, you could use financial aid or wait until you save more. For time, you could study part-time or full-time. To balance work and school, you could change your work hours or take fewer classes. For starting a family, you could begin now and move through school slowly, or wait until after you finish your degree. For your career, you could get the four-year degree for more skills, or learn through online courses and personal projects instead.

Here’s a small, clear paragraph:

The problem can be broken into a few manageable parts: figuring out the financial impact of continuing your education, understanding the time commitment needed for a four-year degree, determining how school will fit with your work and your wife’s schedule, considering how starting a family soon will affect your availability, and weighing how much a four-year degree will actually improve your chances of becoming a video game designer. By breaking it down this way, each part becomes easier to evaluate.

The core problem is deciding whether to pursue a four-year degree to better prepare for a career in video game design while also balancing work, finances, and plans to start a family soon. Related issues include the cost of more schooling, the time commitment, and how it will affect your home life and future stability. A successful solution must support your career goals, remain financially realistic, and still allow room for family responsibilities. A good metaphor for this situation is choosing between two paths—one easier and shorter now, and one longer but potentially leading to greater opportunities.

After doing three ten-minute brainstorming sessions with my group and comparing them to my own ideas, I noticed that the group came up with more ideas and they were generally more creative. Working together helped us build on each other’s suggestions, which made the ideas more unique and interesting. My individual ideas were simpler, while the group had more innovative ones.

words are mixed up - not everyone agrees on whats what

borrowing = do not need to be fluent to use, mixing = need to be bilingual somewhat understand

Mixing kinda becomes its own language

Mixing is more about identity, showing who your comfortable with

Switching depending on situation, like changing languages depending on who you talk to

shows how people switch/mix differently depending on the situation

But in this method the opposite is done ? Maybe order does not matter in this approach cuz of decoupling

It detects both the type of object (class label) and also creates masks as well

hiphop, download, usa,

hiphop, download, usa,

hiphop, download, usa,

hiphop, download, usa,

The purpose of an accuracy test is to confirm that the information is fully correct. This means it must be:

Up to date: current and not outdated

Factual: based on verified facts

Detailed: containing enough information

Exact: precise and without errors

Comprehensive: covering the whole topic, not missing important aspects.

LiDA101

delighted to see my annotation 5 years ago showing up here

Ever since I learned about hypothesis in 2017 I worked to follow hypothesis example of making

Reading active and social

to "lock the web open" and make Colaborative Writing and interpersonal collaboration linked to annotation possible.

Use hypothesis as a an interpersonal search engine

[INT] Example of the lawyer only valuing his employees for their work force.

Referencing code: [INT]: Personal comments, interpretations [STY]: Stylistic comments [SCH]: Scholarly comments

Scholarly Works Cited - Kuebrich, David. “Melville’s Doctrine of Assumptions: The Hidden Ideology of Capitalist Production in ‘Bartleby.’” The New England Quarterly, vol. 69, no. 3, 1996, pp. 381–405. - Ngai, Sianne. Ugly Feelings. Harvard UP, 2005. - Ngai, Sianne. Theory of the Gimmick. Harvard University Press, 2017 - Tseng, Chia-Chieh Mavis. “The Poetics of Refusal: Bartleby’s Language and the Violence of Signification in ‘Bartleby, the Scrivener.’” Journal of Interdisciplinary Cultural Studies, vol. 2, 2025, pp. 305–313. - Verdicchio, Massimo. “‘Bartleby the Scrivener’: An Allegory of Reading.” Canadian Review of Comparative Literature / Revue Canadienne de Littérature Comparée, Sept. 2018. - Žižek, Slavoj. The Parallax View. MIT Press, 2006.

[INT/SCH] The lawyer encourages the separartion between him and his subordinate. Yet, as Ngai has illustrated exactly Bartleby's nothingness makes him so attainable: "Indeed, the aversion that Bartleby elicits from the Lawyer, which the Lawyer is then compelled to manage with the affects of conviviality and charity, involves a disattendability so exaggerated that the disattendability itself comes to demand attention. We might say that for all his passivity, Bartleby is finding a way to make to make himself intolerable" (Ngai "Ugly Feelings", 337).

[INT] Though his passivity angers the lawyer, Bartleby's behavior still mesmerizes him. This is a prime example of Bartleby as a stuplime figure, who dumbfounds the people around him but leaves them with an "open feeling" (Ngai "Ugly Feelings", 284).

[INT / SCH] The lawyer acknowledges the triviality of the work he puts upon his clerks, yet he is utterly dumbfounded if one of them does not comply. As Žižek proclaimes, Bartleby's passive refusal showcases how the system is failing with nonparticipation (384).

[INT / SCH] Nippers could be described in Ngai's terms as "gimmicky": The Gimmick, for Ngai, is an inherently capitalist aesthetic; the gimmick encapsulates tensions in how labor, time and value are perceived under capitalism and its alluring drive for efficiency ("Gimmick", e.g., 468, 505).

[INT] Introduction of Bartleby as an uncommon copyist.

Oiginaly annotated the IPFS version https://bafybeig7nrhxx3nyb5rfmuj7cfy5xbl4ldtwr57ol6lykibww625qkxnke.ipfs.dweb.link/?filename=hyperpost-0.html

the one showing should be the canonical

Honestly, I kinda disagree with this one. Women shouldn't have to just "cope". That's the male playbook. We should strictly get rid of accusations, of insults, of "you are only there because of X male"... psych support entails giving in to meritocracy's zero sum game. Competition for the gain, at any cost. No. Players shouldn't feel burned out period.

Indeed! Reminds me of cherry picked Islamophobic assault compilations. Ragebait. Polarisation devices. This can also lead perhaps not too trauma, but to imposter syndrome, to loss of confidence, to de-motivation, and burnout. Surely, males experience these too, but less frequently, and notably, on their own. Not sharing and taking a stoic toxic masculinity stance then builds up to projection, hate, impotency, outward attacks not so much as inner pitying (it's others who are wrong, and I must defend myself). There is a certain dread and anguish I feel sorry males have to go through, much unhealthier than fems.

It's harder to train hard without communal motivation, without relatives to play with. It's hard to improve without someone to best, without being allowed to play with people with high technical knowledge, communicative skills, and professional trainers + diet (enhancements) behind. It's even more complicated if basic game layers, like communication, chat, friends, are systematically barred for you. If doing so risks being insulted, harassed.

This. There is a layer of inheritance already in place. Past streamers were male, many of whom pro-players. They go on to train male teams, have male friends, they played more, and they can change games if needed. This is market saturation. Women will get no place because future places are occupated in advance. Who gets the early trial, previews, beta sponsored invitations (think Apex)? It's not her.

Yet, this is the case exactly why? It doesn't just happen. It's because of the way the streamers talk, the examples they give, the banter they use, and the difference of having a masculine idol for male viewers, and a feminine one. I'd argue boys don't choose female celebrities as reference period.

To be fair, there are many less women players, but still 7% is a notable difference at least in high leagues. Wouldn't say noticeable for most viewers, though.

DOI: 10.1038/s41590-025-02279-4

Resource: (MMRRC Cat# 010466-UCD,RRID:MMRRC_010466-UCD)

Curator: @AleksanderDrozdz

SciCrunch record: RRID:MMRRC_010466-UCD

What is this?

DOI: 10.1158/0008-5472.CAN-24-3477

Resource: The Cancer Genome Atlas (RRID:SCR_003193)

Curator: @scibot

SciCrunch record: RRID:SCR_003193

What is this?

DOI: 10.1158/0008-5472.CAN-23-1851

Resource: The European Genome-phenome Archive (EGA) (RRID:SCR_004944)

Curator: @scibot

SciCrunch record: RRID:SCR_004944

What is this?

изучающие данную проблему люди отмечают ограниченность возможностей искусственного интеллекта, однако общество продолжает активно использовать его, не задумываясь о последствиях

Введение в тематику статьи и обнаружение проблемы на примере использования искусственного интеллекта повсеместно

https://youtube.com/watch?v=TAQ7yBLRZ3U&feature=shared

Certainly! Here’s a detailed summary and key insights from the YouTube talk “Use.GPU - Declarative/Reactive 3D Graphics by Steven Wittens #LambdaConf2024” (link to video):

Overview

Steven Wittens introduces Use.GPU, a TypeScript library for driving WebGPU with a declarative and reactive programming model. The talk explores the motivation, design, and technical underpinnings of Use.GPU, emphasizing productivity, maintainability, and the bridging of web and graphics paradigms.

Key Topics Covered

1. The Problem with Traditional 3D Graphics Development

• High Complexity & Maintenance Cost: Building custom 3D graphics (e.g., configurators, data visualizations, CAD apps) is often slow, expensive, and results in code that’s hard for teams to maintain.
• Specialization Barrier: The field is so specialized that many companies avoid using advanced GPU graphics due to the expertise required.

2. The Permutation Problem

• Example: A 3D house configurator requires manually assembling assets and coding every possible combination of options, leading to exponential complexity.
• Customization Pain: Existing visualization libraries (like Deck.gl) are hard to deeply customize without forking and maintaining complex codebases.

3. The Web vs. Graphics Divide

• Graphics World: Driven by games/CAD, large teams, offline delivery, monolithic codebases, and focus on rendering performance.
• Web World: Driven by SaaS, small teams, continuous delivery, focus on compatibility, composition, and reuse.
• Different Priorities: These differences make it hard to bring GPU graphics into mainstream web development.

4. Live: A React-like Runtime

• What is Live? A React-inspired, incremental, and reactive runtime that allows for declarative UI and graphics code.
• Key Features:
• Incremental updates: Only re-executes code in response to changes.
• Implicit, one-way data flow.
• Declarative side effects: Auto-mounting and disposal.
• Enables features like undo/redo and multiplayer state management.
• Unique Twist: Live allows data to flow back from child to parent components—something not possible in React—which is crucial for certain graphics/data workflows.

5. Use.GPU: Declarative WebGPU

• Goal: Make GPU graphics as easy to use and maintain as modern web UIs.
• Approach: Use familiar JSX-like syntax and React-style components to describe 3D scenes and behaviors.
• Incremental Rendering: The system is designed as if rendering one frame, and only reruns necessary parts for interactivity/animation.
• Bridging the Gap: By combining Live’s reactive model with WebGPU, Use.GPU makes advanced graphics accessible to web developers.

6. Technical Insights

• Immediate vs. Retained Mode:
• Immediate mode (e.g., Canvas): Easy but doesn’t scale for complex interactivity.
• Retained mode (e.g., GPU): More efficient but much harder to program and maintain.
• GPU as a Pure Function Applicator: The challenge is efficiently feeding unique data to millions of parallel shader invocations, with memory bandwidth as a key constraint.
• Use.GPU’s Innovation: Abstracts away much of the boilerplate and complexity, letting developers focus on high-level structure and reactivity.

Why This Matters

• Productivity: Use.GPU aims to democratize GPU programming for web developers, reducing the need for deep graphics expertise.
• Maintainability: Declarative, reactive patterns make complex interactive graphics more maintainable and composable.
• New Possibilities: Opens the door for more sophisticated, interactive, and visually rich web applications.

Further Resources

• Use.GPU Project: GitHub link (if available, check video description) (replace with actual link if different)
• Steven Wittens’ Website: acko.net (famous for its interactive header)
• LambdaConf: LambdaConf 2025 Tickets

TL;DR

Use.GPU is a new TypeScript/WebGPU library that brings React-style declarative, reactive programming to 3D graphics in the browser. Built on the “Live” runtime, it enables maintainable, high-performance graphics apps with familiar web development patterns—potentially revolutionizing how interactive graphics are built on the web.

If you want a specific section of the talk summarized, or code examples from Use.GPU, let me know!

Citations: [1] watch?v=TAQ7yBLRZ3U https://www.youtube.com/watch?v=TAQ7yBLRZ3U

Det singulære og unikke - det har en stor værdi for forbrugeren at vide at andre forbrugere ikke bare kan gå ud og anskaffe sig præcist det samme

What stood out to me is how every generation thinks new technology is going to ruin everything, whether it’s writing, machines, or even social media today. It makes me wonder if our fears about tech—like AI or algorithms—are actually about the tech itself or more about us not wanting to adapt. At the same time, I don’t think these concerns are pointless. The examples of Eli Whitney and Alfred Nobel show that even good intentions can lead to huge negative consequences. So I feel like the real issue isn’t whether technology is good or bad, but whether the people creating it are actually thinking ahead about the impact. Honestly, most of the time it feels like they’re not, especially when companies rush to build something new just because they can. It makes me question: what current tech are we going to look back on in 20 years and say, “Wow, that messed things up more than we expected”?

Transparent Peer Review

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Joe Starks, despite his obsession with control, ironically loses control of his own emotions.

Joe is a control freak due to his anxieties and insecurities. Now, he sees Janie's defiance of him, and the townspeople's ridicule, as an existential threat to his control. This brings his deep-seated fear of losing control back up to the forefront of his mind.

As a social media user, going forward, this class encouraged me to think about the ethics of social media, specifically the ethics behind AI-driven social media algorithms that promote user engagement and profit, and disregard the damage that these algorithms do to users' mental health.

I am not necessarily cautious about anything regarding the film. It is about about the horrors of slavery so I believe that everyone should be prepared to see exactly that. I am concerned however that they will insensitivity portray the Africans. There are many negative stereotypes and misunderstandings about Africans in general and it will be disappointing to see any of those in the film.

I am most interested to see how they dramatize the court proceedings of the case. Many movies get how courts function in real life wrong. They do this, I believe, to make sure the audience remains engaged and entertained which is fine unless they begin to misconstrue the facts of what occurred.

I like this point—it reminds me that digital literacies go beyond just knowing how to use tools. They include understanding the social, ethical, and practical context of technology use. #LiDA101

(Loble and Stephens 372)

The net contact wrench cone (CWC) is the friction cone of the net contact wrench acting on a robot making multiple contacts, i.e. the sum of all contact wrenches. It can be represented as a set of feasible wrenches:

Cartesian forces:

A Cartesian coordinate system is a plane or space defined by two or three perpendicular axes, where every point is uniquely specified by an ordered pair (or triple) of real numbers representing its distances from the fixed axes, allowing geometric problems to be described algebraically.

Systemic harm can't be resolved through individual accountability, but instead requires structural change for misogyny, racism and victim blaming. Systemic harm needs structural change, not just statements (Combahee River Collective 1983).

Does "established" mean in practice? However, they don’t explain what functioning actually looks like in practice. “Established” might only mean legally. but not clear if survivors are being helped or if the system just created a committee and called it progress.

Intersecting identities such as race, gender identity, sexuality, etc. can shape an individuals choice/ability to report. identity shapes who feels safe engaging with the police. For Indigenous, people of colour, or queer survivors, reporting is shaped by power, history, and fear of mistrust (Crenshaw 1991).

Terminology matters. Calling individuals as "victim" rather than "survivor" constructs survivors to feel less than empowered and strong for coming forward. Sara Ahmed states how words can shape feelings and shapes power, therefore, by using “survivor” it recognizes agency (Ahmed 2014).

I never thought about home ownership as a colonial benefit. Their reflection made visible how property is structurally tied to settler privilege.

I was not taught about Indigenous queerness and two-spirit identities in school; I had to learn about it myself. https://youtu.be/A4lBibGzUnE

"Diversity" without structural change reinforces colonization and reproduces Western settler ideology. This connects to the to Combahee River Collective (2022) critique of liberal inclusion politics. It emphasizes the importance of intersectionality; recognizing each part of a person’s identity as relational and important.

This showcases gender regulation as a tool of genocide. It reminds me of the unproportioned violence rates against Indigenous queer people and Two-Spirit individuals. Link to the article: https://www.gbvlearningnetwork.ca/our-work/backgrounders/GBV%20Against%20Two%20Spirit%20Indigenous%20Peoples/index.html

These good intentions replicate the same oppression that is trying to be resisted. Jordan (2003) critiques white innocence and unearned solidarity, which focuses solely on inclusion of marginalized groups and not accountability from the privileged groups.

This is classic feminist killjoy work: naming histories that disrupt White settler comfort. Ahmed (2017) says naming oppression is read as “killing joy,” but is necessary to live ethically.

This is exactly what TallBear (2022) discusses: Indigenous kinship vs. the imposed nuclear family model. The nuclear family is a settler colonial tool used to privatize care and restructure land relations. Lenon’s (2015) discussion of monogamy as a nation-building tool helps frame why resisting normative family models is decolonial. The very act of parenting in this way is resisting settler norms. By raising a child with anti-racist, anti-settler frameworks, Cindy resists the reproduction of the settler nuclear family model.

As Jordan (2003) states, there is danger in assuming automatic connection, when privileged women assume solidarity without accountability. This highlights the danger of white benevolence; helping without dismantling power. It also echoes the warning that ‘good intentions’ reproduce colonial harm.

The privileged must take responsibility and accountability for recognizing that they are privileged within society; the burden is on them, not the marginalized people, to work towards connection. This connects to Jordan's (2003) emphasis that privilege distorts relationships and cannot be erased through superficial “connection.” Even though there can be shared connection through certain aspects of identity, oftentimes it is not enough to unite for a shared struggle.

Lorde (2022) insists difference should be “a fund of necessary polarities,” not erased. And theory in the flesh (Moraga & Anzaldúa, 2022) shows lived multiplicity as a form of resistance. Both texts refuse binary thinking: gender, race, belonging. This is shown through Indigenous gender systems and through the body (for theory in the flesh).

This directly echoes the idea of heteropatriarchy: settlers enforced patriarchal nuclear family structures to reorganize Indigenous kinship (Maile, Tuck, and Morrill, 2013). Whitehead (2022) and Maracle (1996) argue that settler colonialism violently replaces Indigenous relational gender systems with patriarchal ones; this article gives a lived, interpersonal example of that statement.

This is not true for everyone. The authors are challenging the idea that activism happens "out there", echoing Ahmed's (2017) idea of feminist practice as homework. This is also a perfect example of Ahmed’s feminist killjoy—discomfort enters the “home,” revealing sexism, racism, or colonialism where they are usually hidden (2017).

If decolonization needs to be place-based, how do queer settlers avoid symbolic belonging on land they occupy?

Being queer isn’t just an identity label; it is an active practice that challenges norms, structures, and power. Queerness is an action, a verb: it is about resisting norms.

This echoes Anzaldúa (2022): “The act of writing is the act of making soul.” As well as theory in the flesh where lived stories produce political knowledge (Anzaldúa and Moraga, 2022).

In a certain work place especially in the United Stated it may be expected to only write and speak in standard English. If you cannot then you may not be able to be hired.

The way some students speak or write may be incorrect in the classroom but from how or where they grew up it makes sense and is not incorrect from their perspective.

Students may not agree but they can find it to be helpful. Mastering it may even be a necessity to some.

I believe it’s not right as well, but it also doesn’t change the way things work for most careers or even schools.

I do see parts of the Elizabethan aspects, but I felt it was more futuristic and majestical. I know the Midsummer play is meant to be fantastical so maybe it is the right mix of past and present. Maybe this is something we could discuss?

I found it so interesting how often the author used the term "lust" to describe the plot. Not only is the repetition slightly annoying, but it almost reduces the struggles down to teenage hormones and struggles with emotions. When in reality, it's more about a feeling of belonging and acceptance, not just sex.

The first thing I think of when I watched this scene was our first movie, Stagebeauty. I think we forget how different gender roles were hundreds of years ago, and especially during peak Shakespearian times. In the past it was due to power struggles, but now it seems to be more rooted in homophobia.

She is totally the conspiring character, or perhaps the engineer. She totally sets everything up literally for the play, but also for Timothy personally. I feel it's important for all students to have a teacher in high school who supports you and promotes your success.

I think that the separation of church and state is an important standard that our government should follow, i also think that the way the writer uses the text to show this really helps to prove that point

I really like how this table is set up, its a great source of media that really shows how a writer should think and what questions they should ask themselves while they write.

I think that this is a great way for a writer to make their writing more interesting and for some to make more academic writing sound more professional

I think as a writer one of the most important things you can do is make sure you writing is not only relevant but also relatable to the reader

I've never really thought of trying to do this but i think that this would be a great way to make my writing better

Acquiring standard English gives one more opportunity to fulfill more.

Standard forms in the united stated may differ from another country.

While I do agree that the rate of formation of N2O2 = k1[NO]^2, I don’t agree that [N2O2]=k1[NO]^2. Am I wrong?

This is super interesting. This is what the class is all about - RESISTANCE

Very good definitions

!!!!! LOOK HERE

Important distinction

This is simply untrue

More important numbers

Important numbers

This is a very significant detail. It dictates where certain people and groups live, where wealth was accumulated, what ownership of land truly meant etc.

the rebuttal

Interesting. I need to be wary of this well being poisoned. Of course I knew that this subject would have ill-intentioned scholarship but I naively assumed that I would not fall victim to it. So it is critical to remember that the yeomen did exist and were a significant class, but that they were certainly not larger than poor whites.

So how did the poor whites themselves respond?

Another intriguing figure that I should look in to

Very interesting. Here we have a callback to the importance of liberty in the southern mind.

Immigration is an interesting facet. These are not all people who are familiar with slavery

I think I prefer the term "state transition".

What is this hypermedia contract, then?

Bronze armor was highly valuable, as shown in The Iliad, where battles often revolve around looting it. Those who could produce large quantities of bronze could equip armies. This made bronze production a key factor in military power.

The oldest tin mines were in Anatolia, but by 4,500 years ago, tin was also mined in Cornwall, and later in Germany and Portugal. Its scarcity and importance for making bronze made these regions key trade hubs. This drove long-distance trade networks across Europe.

The Gilgamesh story highlights the contrast between city life and the wild countryside. It explores tensions between civilization and nature, order and chaos. This theme is central to understanding the characters and their journeys.

The Minoans of Crete used Linear A around 3,800 years ago, a logographic-syllabic writing system. About 3,450 years ago, it evolved into Linear B, which was used by the Mycenaeans. This shows the development and continuity of writing in the region.

The city had two main temple sites and 19 additional temple complexes nearby in the Supe Valley. This indicates a strong religious or ceremonial focus in the region. It reflects the importance of ritual in their society.

I agree—that’s really fascinating! The absence of battlements or weapons suggests these sites weren’t focused on warfare. Instead, the discovery of so many flutes and wind instruments points to a strong emphasis on music and ritual. It really highlights the cultural and ceremonial importance in that society.

Absolutely! Longshan was truly China’s first urban culture, and Liangchengzhen’s population of around 40,000 shows how developed it was. It’s fascinating to see such early urban growth along the Yellow River. This highlights how complex societies emerged independently in different parts of the world.

I completely agree! The Indus Valley Civilization does seem remarkably egalitarian compared to Egypt or Uruk. Its uniform housing and advanced sewer systems suggest a society where resources and infrastructure were widely shared. It’s impressive how organized and community-focused their cities were.

Yes, that makes sense! Hierakonpolis really was Egypt’s first city, with elites controlling key trade routes. They accessed resources like shells, obsidian, gold, and copper, and later even luxury goods like cedar and lapis. It shows how early urban centers were tied to both power and trade.

Sardinian islanders, being relatively isolated from later migrations, kept the highest proportion of Anatolian Early European Farmer ancestry in Europe. This makes them a key population for studying early European farming genetics. Their heritage reflects the legacy of the continent’s first farmers.

The earliest farmers in Europe appeared in the eastern Mediterranean around 8,500 years ago. Sites like Franchthi Cave in Greece and the Starčevo-Körös-Criș culture in the Balkans show they used pottery, polished stone tools, and lived in villages. These communities mark the beginning of settled farming life in Europe.

Aurochs were the ancestors of today’s cattle, towering over six feet tall with long, curved horns. They were hunted by humans for thousands of years. These wild bovines are now extinct, but they played a key role in the development of modern cattle.

I wonder how this became, because is it like the mother is well known rather than the father but this is a interesting concept

I wonder what technology they used

Man-in-the-middle wifi uplink

Can Flock footage be challenged in court?

rice is the best food, so versatile

Instead of shipping early shipping often

or "Get IT Right First time"

Get the IT right first.

If you do that IT can self-host and self-realize the IT

as a Conversations

After all Software is a Symmathetic Conversaiton creating the Medium, the Sweet spot, just above the threshold that is trully required.

Proving that the "Worse IS Not Better"

Need the Jewel like Diamond approach

This is truly working in the Open Learning Commons

creating the Indy (Mutual) Learning Commons

The work is not only Open Souce

developing Open constructs

easy to emulate compelling to do and etend expand exapt

but it shipf with Open Sauce

i

☑️The most up to date version will be the canonical version that will point to the latest version using IPNS

all versions thus will be available via links

My to do list is on the annotation margins

use hypothesis search to see a reverse chronological listing of todo tasks

https://jonudell.info/h/facet/?user=gyuri&max=50&exactTagSearch=true&addQuoteContext=true&any=%E2%98%91%EF%B8%8F

This annotation is at the top of that list when this annotation was made

We have instructional coaches at our school for hum, STEM, and ELD. The tricky part is SPED. We have a person assigned which is nice and they are great but you can tell it is an after thought. It is not someone that is certified or has experience.

we are working on student voice, active listening, and thinking right now in our classes.

sometimes happens because a language doesn't have a specific word

Cultural identity and belonging

switched: Family vs business

private argument