1. Last 7 days
    1. RRID:AB_940405

      Traceback (most recent call last): File "/home/ubuntu/dashboard/py/create_release_tables.py", line 54, in format_anno_for_release parsedanno = HypothesisAnnotation(anno) File "/home/ubuntu/dashboard/py/hypothesis.py", line 231, in init self.links = row['document']['link'] TypeError: string indices must be integers

    2. RRID:AB_2614304

      Traceback (most recent call last): File "/home/ubuntu/dashboard/py/create_release_tables.py", line 54, in format_anno_for_release parsedanno = HypothesisAnnotation(anno) File "/home/ubuntu/dashboard/py/hypothesis.py", line 231, in init self.links = row['document']['link'] TypeError: string indices must be integers

    3. Jackson Laboratory Cat_032276

      Traceback (most recent call last): File "/home/ubuntu/dashboard/py/create_release_tables.py", line 54, in format_anno_for_release parsedanno = HypothesisAnnotation(anno) File "/home/ubuntu/dashboard/py/hypothesis.py", line 231, in init self.links = row['document']['link'] TypeError: string indices must be integers

    1. plasmid_8454

      Traceback (most recent call last): File "/home/ubuntu/dashboard/py/create_release_tables.py", line 54, in format_anno_for_release parsedanno = HypothesisAnnotation(anno) File "/home/ubuntu/dashboard/py/hypothesis.py", line 231, in init self.links = row['document']['link'] TypeError: string indices must be integers

    2. RRID:SCR_021756

      Traceback (most recent call last): File "/home/ubuntu/dashboard/py/create_release_tables.py", line 54, in format_anno_for_release parsedanno = HypothesisAnnotation(anno) File "/home/ubuntu/dashboard/py/hypothesis.py", line 231, in init self.links = row['document']['link'] TypeError: string indices must be integers

    1. RRID:SCR_019060

      Traceback (most recent call last): File "/home/ubuntu/dashboard/py/create_release_tables.py", line 54, in format_anno_for_release parsedanno = HypothesisAnnotation(anno) File "/home/ubuntu/dashboard/py/hypothesis.py", line 231, in init self.links = row['document']['link'] TypeError: string indices must be integers

    1. RRID:IMSR_JAX

      Traceback (most recent call last): File "/home/ubuntu/dashboard/py/create_release_tables.py", line 54, in format_anno_for_release parsedanno = HypothesisAnnotation(anno) File "/home/ubuntu/dashboard/py/hypothesis.py", line 231, in init self.links = row['document']['link'] TypeError: string indices must be integers

    1. MMRRC:033000

      Traceback (most recent call last): File "/home/ubuntu/dashboard/py/create_release_tables.py", line 54, in format_anno_for_release parsedanno = HypothesisAnnotation(anno) File "/home/ubuntu/dashboard/py/hypothesis.py", line 231, in init self.links = row['document']['link'] TypeError: string indices must be integers

    2. MMRRC:032999

      Traceback (most recent call last): File "/home/ubuntu/dashboard/py/create_release_tables.py", line 54, in format_anno_for_release parsedanno = HypothesisAnnotation(anno) File "/home/ubuntu/dashboard/py/hypothesis.py", line 231, in init self.links = row['document']['link'] TypeError: string indices must be integers

    3. MMRRC:032998

      Traceback (most recent call last): File "/home/ubuntu/dashboard/py/create_release_tables.py", line 54, in format_anno_for_release parsedanno = HypothesisAnnotation(anno) File "/home/ubuntu/dashboard/py/hypothesis.py", line 231, in init self.links = row['document']['link'] TypeError: string indices must be integers

    1. MMRRC:000041

      Traceback (most recent call last): File "/home/ubuntu/dashboard/py/create_release_tables.py", line 54, in format_anno_for_release parsedanno = HypothesisAnnotation(anno) File "/home/ubuntu/dashboard/py/hypothesis.py", line 231, in init self.links = row['document']['link'] TypeError: string indices must be integers

    1. La note est trop affirmative et me semble incorrecte. Les règles budgétaires ne recommandent pas une trajectoire mais elles fiixent un ajustement minimum pluriannuel. Un ajustement fort au debut permet un ajustement moindre plus tard, c'est au pays de décider. Il faut etre plus informatif.

      "Les règles européennes demandent un ajustement moyen de l'ordre de 0.8 point de PIB par an sur plusieurs années. Les mesures issues du PLF impliquaient donc un ajustement supérieur en pour 2025."

    1. his 1683 edition of Plutarch's Lives Translated From the Greek by Several Hands in which he introduced the word 'biography' to English readers;

      via https://en.wikipedia.org/wiki/John_Dryden

      John Dryden apparently coined the English word 'biography' in his 1683 edition of Plutarch's Lives.

      Does the OED bear this out?

    1. eLife Assessment

      This important study investigates the role of vasopressin in modulating same-sex affiliative relationships in the context of linear dominance hierarchies. It provides convincing evidence that vasopressin signaling is involved in modulating aspects of affiliative behavior, although the evidence that affiliative relationships specifically arise from the triadic interaction study design is incomplete. Nevertheless, its focus on broadening the types of social relationships and species studied in this area makes it of interest to both neuroendocrinologists and colleagues studying the evolution and mechanisms underlying social affiliation.

    2. Reviewer #1 (Public review):

      Summary:

      The authors seek to establish whether triadic interaction can promote affiliative relationships in the context of strict dominance hierarchies, and whether the vasopressinergic system is involved in such affiliations. To address this, they experimentally examine how male same-sex affiliations form by testing triadic cohabitation in large-billed crows, a species where males are known to develop and maintain same-sex affiliative relationships within a strict linear social hierarchy. They show a reduction in aggressive behavior over time with cohabitation and the formation of affiliative relationships, as measured by reciprocal allopreening, between two members (dyad) of the triad. The authors then administer a V1aR antagonist to each member of the triad, finding that allopreening decreases and dominance/submissive behaviors reemerge only in the dyad that developed an affiliated relationship ("affiliated dyad") with blockade of V1aR, demonstrating that V1aR mediates maintenance of affiliative peer relationships. The questions of how peer affiliations form, particularly in the context of dominance hierarchies, and the role of V1aR in regulating these behaviors are impactful for the field of social behavior. While the experimental paradigm provides a new way of approaching these questions, we have outlined below our concerns regarding the collection and interpretation of the data that limit the impact of this particular study.

      Strengths:

      (1) The authors develop a behavioral paradigm and experimental sequence using large-billed crows that allows them to identify the formation of stable, affiliated dyads within triadic groups that are robust to subsequent testing and are sensitive to pharmacological manipulation.

      (2) The effects of V1aR antagonism on allopreening and respective dominance or submissive behaviors appear significant and specific to the affiliated dyad, which supports the view that V1aR plays a role in context-dependent, flexible regulation of aggressive behaviors across species. However, these results are difficult to interpret with respect to the authors' main claims given the weaknesses outlined below.

      Weaknesses:

      (1) The authors claim that the data demonstrates that a triadic social group facilitates the formation of affiliative dyads and go further to claim that these relationships have relevance to understanding coalition formation. It is difficult to say whether the triadic structure actually facilitates or promotes the formation of these affiliative interactions as stated without direct comparisons to alternately sized groupings. Further, the relevance to coalitions is weak without expanded behavioral testing.

      (2) Aspects of the experimental design introduce confounding factors that make it difficult to interpret the resulting data. In experiment 1, 6 of the 18 animals that are used for testing are part of multiple triads. This is not accounted for in either the experimental design (wash-out period prior to reuse of animals) or statistical analysis (including repeated testing as a factor in the model) or is not described. Further, while the authors do randomize and counterbalance the two dose trials for the antagonist, vehicle vs drug exposure is not randomized.

      (3) The re-emergence of dominance-related agonistic behaviors with V1aR antagonism specifically in the affiliated dyads is interesting, but difficult to interpret without further description and analysis of the dyadic behavior, particularly given the absence of dominance-related behaviors in either affiliated or unaffiliated dyads during the cohabitation period. In addition, the current data does not support the hypothesis that V1aR is also required to form affiliative relationships, as stated in the discussion (Lines 464-5, 472, 494), since the authors did not administer V1aR antagonist during the initial period of triadic cohabitation.

      (4) Sentences are often repetitive or duplicated (lines 424-426), and paragraphs should be condensed for easier reading, especially in the discussion. Further, some of the discussion might be better presented in an "Ideas and Speculation" subsection, which would help readers appropriately assess the validity of the conclusions based on the data vs the larger implications suggested by the authors.

    3. Reviewer #2 (Public review):

      Seguchi and Izawa provide robust evidence for the role of vasopressin in modulating same-sex affiliative relationships. Especially striking is that these effects appear to be selective to key relationships within a triadic social context. Overall, this is an interesting and rich dataset with compelling results. I largely have some clarifying questions.

      Experiment 1 Comments:

      (1) The primary argument/finding in this experiment is that a triadic situation/environment facilitates the development of male-male reciprocal social relationships. Overall, this effect appears striking in that male-male affiliative bonds (defined as reciprocal allopreening) formed in 6 of the 8 triads tested. However, there is no comparison group of dyads to determine whether co-housing for 2 weeks could also support the formation of male-male social bonds. This lack of a comparison group makes it unclear to what extent the triad is the key aspect of the environment that supports social bonding.

      (2) More specifically, the authors argue that it is not just that triads support affiliative male-male bonds, but that bonds form between the second "middle" (dominant/subordinate) and third "low" (subordinate/subordinate) individuals in each triad. However, it was difficult to assess this from the results.<br /> a) For example, in Figure 3B is each data point the average of two individuals, since in each triad there are two dominant and two subordinate individuals?<br /> b) For me, using more precise language beyond dominant and subordinate (e.g. middle and low), and more clearly displaying the results of allopreening for each pairwise dyad within a triad would improve the impact of the results and support the authors' argument.

      (3) Experiment 2 Comments:<br /> The results here are quite striking, despite the low sample size. In Figure 4, it appears that in every instance of administration V1aRA low and high administration decreased allopreening for both dominant and subordinate individuals.

      (4) Some methodological questions:<br /> a) Can you clarify whether the duration of the post-test was also 30 min?<br /> b) As in Experiment 1, how are individual birds represented in the triad? Was the second "Middle" bird (dominant/subordinate) tested as both a dominant and subordinate bird? My understanding is that the dominant and subordinate birds in Figure 4 are different individuals but that they are the same individuals represented between the affiliated dyad and unaffiliated dyad.

      (5) Throughout the manuscript (Lines 57-67; 557-566) the authors argue that the role of VP in regulating gregariousness can be extrapolated to understand the role of same-sex affiliative bonding. Importantly, gregariousness does not necessarily reflect affiliative bonding. While allopreening is specifically associated with social bonding (e.g. monogamous pair bonds) independent of broader social systems, gregariousness in general, and specifically as defined in many of the references cited, is independent of social bonds - in fact, it is assessed primarily in novel social contexts.

      (6) To clarify, adult prairie voles in the wild do not engage in same-sex affiliative behavior commonly. In fact one of the primary components of opposite-sex pair bonding is same-sex aggression. Thus, while mechanistic studies on the neurobiology of same-sex peer bonds are relevant for this work, I am less convinced that you can make comparisons between the ultimate function of same-sex affiliative relationships in prairie voles.

      (17) The results here are consistent with VP having an anxiolytic effect, as has been suggested in birds, with the consequences on social behaviors being directly or indirectly related. This may be a useful point to draw on in the discussion when considering your findings.

    4. Reviewer #3 (Public review):

      Summary:

      In this study, Seguchi & Izawa investigate the formation of male-male affiliative relationships within triads of large-billed crows. They then administered a vasopressin 1a receptor (V1aR) antagonist to either the dominant or subordinate individual within affiliative dyads, to examine whether blocking V1aR disrupts affiliative behavior. They discovered that affiliative dyads can be induced in large-billed crows by housing them in triads. They also found that blocking V1aRs significantly decreased allopreening (an affiliative behavior) within dyads. In addition, it increased aggression by dominant individuals and submissive calls by subordinate individuals.

      Strengths:

      This manuscript uses an especially interesting species - a highly intelligent and highly social corvid, with complex dominance hierarchies - to extend previous work into the effects of the oxytocin and vasopressin peptides hormones on social behaviors. The results are surprisingly clear, despite a small sample size. The authors use the correct statistical approaches to account for a complex, nested design. The introduction and discussion both reflect a strong understanding of the relevant literature, including the limitations of extrapolating from peripheral (intramuscular) versus central (into the brain) injections of the V1aR antagonist. In addition, the authors appear to have been transparent about the data and results, accounting for some of the challenges and limitations of the data and study.

      Weaknesses:

      There are two major concerns. First, the study has a very low sample size (8 triads for Experiment 1, and only 5 triads for Experiment 2). Despite the surprisingly convincing findings, the sample size is too small to support the claim that the vasopressin system "universally mediates same sex relationships. Secondly, the study does not account for the effects of V1aR on non-social behaviors. This is especially true because vasopressin/V1aR (and the particular antagonist used in this study) is known to have effects on osmotic balance, food intake, and stress, including in birds. My concern is that the behavioral effects could be accounted before by differences in general stress or activity levels. Allopreening is usually an activity performed in periods of relative inactivity with aggression being more characterized by high activity levels. The authors discuss these different effects of vasopressin/V1aR in the Discussion, but they do not account for these effects in the study design.

    1. Plutarch’s highest merit as a biographer. He is no historian;
    2. It has taken its place on the clockshelf, with only the Bible, the “Pilgrim's Progress,” and the Almanac for its companions. No other classic author, with, perhaps, the single exception of Æsop, has been so widely read in modern times; and the popular knowledge of the men of Greece and Rome is derived more from Plutarch than from all other ancient authors put together.

      importance of Plutarch's Lives

    3. But the chief interest of this translation at the present day, except what it possesses as a storehouse of good mother-English, comes from the fact that it was one of the books of Shakespeare’s moderate library, and one which he had thoroughly read, as is manifest from the use that he made of it in his own works, especially in "Coriolanus,” “Julius Ca;sar,” and “Antony and Cleopatra.”

      Shakespeare's versions of Coriolanus, Julius Caesar, and Anthony and Cleopatra origininate from Plutarch's Lives by way of the English translations of Thomas North who was translating from the French version of Jacques Amyrot.

    4. The learned Dr. Guy Patin says: “On dit que M. de Meziriac avoit corrigé dans son Amyot huit mille fautes, et qu’Amyot n’avoit pas de bons exemplaires, ou qu’il n’avoit pas bien entendu le Grec de Plutarque.”3

      Translation: It is said that M. de Meziriac had corrected eight thousand mistakes in his Amyot, and that Amyot did not have good copies, or that he had not understood Plutarch's Greek well.

    5. The book is interesting from Dryden’s connection with it, but still more so — considering how slight that connection was, his only contribution to it being the Life of Plutarch—from the fact, that the translations of some of the Lives were made by famous men, as that of Alcibiades by Lord Chancellor Somers, and that of Alexander by the excellent John Evelyn ; while others were made by men who, if not famous, are at least well remembered by the lovers of the literature of the time,—as that of Numa by Sir Paul Rycaut, the Turkey merchant, and the continuer of Dr. Johnson's favorite history of the Turks,—that of Otho by Pope’s friend, the medical poet, Dr. Garth,—that of Solon by Creech, the translator of Lucretius,—that of Lysander by the Honorable Charles Boyle, whose name is preserved in the alcohol of Bentley's classical satire, — and that of Themistocles by Edward, the son of Sir Thomas Browne.

      Dryden didn't translate Plutarch himself, but edited it and relied on translation by others, including his friends and acquaintances.

    1. eLife Assessment

      In their valuable study, Lee et al. explore a role for the Hippo signaling pathway, specifically wts-1/LATS and the downstream regulator yap, in age-dependent neurodegeneration and microtubule dynamics using C. elegans mechanosensory neurons as a model. The authors demonstrate that disruption of wts-1/LATS leads to age-associated morphological and functional neuronal abnormalities, linked to enhanced microtubule stabilization, and shows a genetic connection between yap and microtubule stability. Despite some mechanistic gaps, the study employs robust genetic and molecular approaches to reveal a convincing link between the Hippo pathway, microtubule dynamics, and neurodegeneration.

    2. Reviewer #1 (Public review):

      Summary:

      In this manuscript, the authors investigate the role of microtubule dynamics and its effects on neuronal aging. Using C. elegans as a model, the authors investigate the role of evolutionarily conserved Hippo pathway in microtubule dynamics of touch receptor neurons (TRNs) in an age-dependent manner. Using genetic, molecular, behavioral, and pharmacological approaches, the authors show that age-dependent loss of microtubule dynamics might underlie structural and functional aging of TRNs. Further, the authors show that the Hippo pathway specifically functions in these neurons to regulate microtubule dynamics. Specifically, authors show that hyperactivation of YAP-1, a downstream component of the Hippo pathway that is usually inhibited by the kinase activity of the upstream components of the pathway, results in microtubule stabilization and that might underlie the structural and functional decline of TRNs with age. However, how the Hippo pathway regulates microtubule dynamics and neuronal aging was not investigated by the authors.

      Strengths:

      This is a well-conducted and well-controlled study, and the authors have used multiple approaches to address different questions.

      Weaknesses:

      There are no major weaknesses identified, except that the effect of the Hippo pathway seems to be specific to only a subset of neurons. I would like the authors to address the specificity of the effect of the Hippo pathway in TRNs, in their resubmission.

    3. Reviewer #2 (Public review):

      Summary:

      This study examines a novel role of the Hpo signaling pathway, specifically of wts-1/LATS and the downstream regulator of gene expression, yap, in age-related neurodegeneration in C. elegans touch-responsive mechanosensory neurons, ALM and PLM. The study shows that knockdown or deletion of wts-1/LATS causes age-associated morphological abnormalities of these neurons, accompanied by functional loss of touch responsiveness. This is further associated with enhanced, abnormal, microtubule stabilization in these neurons.

      Strengths:

      This study examines a novel role of the Hpo signaling pathway, specifically of wts-1/LATS and the downstream regulator of gene expression, yap, in age-related neurodegeneration in C. elegans touch-responsive mechanosensory neurons, ALM and PLM. The study shows that knockdown or deletion of wts-1/LATS causes age-associated morphological abnormalities of these neurons, accompanied by functional loss of touch responsiveness. This is further associated with enhanced, abnormal, microtubule stabilization in these neurons. Strong pharmacological and especially genetic manipulations of MT-stabilizing or severing proteins show a strong genetic link between yap and regulation of MTs stability. The study is strong and uses robust approaches, especially strong genetics. The demonstrations on the aging-related roles of the Hpo signaling pathway, and the link to MTs, are novel and compelling. Nevertheless, the study also has mechanistic weaknesses (see below).

      Weaknesses:

      Specific comments:

      (1) The study demonstrates age-specific roles of the Hpo pathway, specifically of wts-1/LATS and yap, specifically in TRN mechanosensory neurons, without observing developmental defects in these neurons, or effects in other neurons. This is a strong demonstration. Nevertheless, the study does not address whether there is a correlation of Hpo signaling pathway activity decline specifically in these neurons, and not other neurons, and at the observed L4 stage and onwards (including the first day of adulthood, 1DA stage). Such demonstrations of spatio-temporal regulation of the Hpo signaling pathway and its activation seem important for linking the Hpo pathway with the observed age-related neurodegeneration. Can this age-related response be correlated to indeed a decline in Hpo signaling during adulthood? Especially at L4 and onwards? It will be informative to measure this by examining the decline in wts1 as well as yap levels and yap nuclear localization.

      (2) The Hpo pathway eventually activates gene expression via yap. Although the study uses robust genetic manipulations of yap and wts-1/LATS, it is not clear whether the observed effects are attributed to yap-mediated regulation of gene expression (see 3).

      (3) The observations on the abnormal MT stabilization, and the subsequent genetic examinations of MT-stability/severing genes, are a significant strength of the study. Nevertheless, despite the strong genetic links to yap and wts-1/LATS, it is not clear whether MT-regulatory genes are regulated by transcription downstream of the Hpo pathway, thus not enabling a strong causal link between MT regulation and Hpo-mediated gene expression, making this strong part of the study mechanistically circumstantial. Specifically, it will be good to examine whether the genes addressed herein, for example, Spastin, are transcriptionally regulated downstream of the Hpo pathway. This comment is augmented by the finding that in the wts-1/ yap-1 double mutants, MT abnormality, and subsequent neuronal morphology and touch responses are restored, clearly indicating that there is an associated transcriptional regulation

      Other comments:

      (1) The TRN-specific knockdown of wts-1 and yap-1 is a clear strength. Nevertheless, these do not necessarily show cell-autonomous effects, as the yap transcription factor may regulate the expression of external cues, secreted or otherwise, thus generating non-cell autonomous effects. For example, it is known that yap regulates TGF-beat expression and signaling.

      (2) Continuing from comment (3) above, it seems that many of the MT-regulators chosen here for genetic examinations were chosen based on demonstrated roles in neurodegeneration in other studies. It would be good to show whether these MT-associated genes are directly regulated by transcription by the Hpo pathway.

      (3) The impairment of the touch response may not be robust: it is only a 30-40% reduction at L4, and even less reduction at 1DA. It would be good to offer possible explanations for this finding.

    1. Career impact

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    7. Start Learning Get all the information about the course and pricing in our live webinar with Q&A

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    8. 4.67

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    9. AWS Cloud Solutions Architect COURSE

      Please maintain casing consistency.

    1. Open source technology, now responsible for 80% of all used software

      for - stats - 80% of all used software is open source - from Substack article - The Cosmo-Local Plan for our Next Civilization - Michel Bauwens - 2024, Dec 20

    2. current techno-logical conditions make such a shift eminently imaginable

      for - adjacency - factor of 20 - town anywhere

    3. ‘factor 20’ movement can be imagined, in fact, already exists, which aims to reduce energy usage by 95%, coupled with significant savings in the use of materials. This movement is already active in various European cities

      for - research further - EU movement - factor of 20 - from Substack article - The Cosmo-Local Plan for our Next Civilization - Michel Bauwens - 2024, Dec 20

    4. mutualizing forms of governance and ownership, can also have extraordinary effects on the amount of needed energy and materials. For example, in the context of shared transport, one shared car can replace 9 to 13 private cars, without any loss of mobility.

      for - stats - climate crisis - example - positive impacts of mutualisation / sharing - car sharing - 1 Shared car can replace 9 to 13 cars without loss of mobility - from Substack article - The Cosmo-Local Plan for our Next Civilization - Michel Bauwens - 2024, Dec 20

    5. This is what we have called ‘True Accelerationism’.

      for - definition - accelerationism - from Substack article - The Cosmo-Local Plan for our Next Civilization - Michel Bauwens - 2024, Dec 20

    6. this means that the switch in growth from towards exclusive efficiency

      for - grammar - 'from towards' - I think you meant 'from'

    7. current system is ‘closed source’, and is carried out by competitive agents that do not share innovations for very long time periods; the competitiveness of these agents requires behaviors that externalize costs

      for - examples - closed source IP externalises cost - from Substack article - The Cosmo-Local Plan for our Next Civilization - Michel Bauwens - 2024, Dec 20

      examples - closed source IP externalises cost - closed source circular economy is much more challenging than open source circular economy because - if inputs are kept secret and proprietary, reuse of End of life products are difficult to break down and reuse as input in a re-manufacturing process - closed IP creates fragmented and completing de facto standards that make interoperability impossible

    8. The current system of production is based on mass production, and requires the constant creation of new desires and needs, which need to be created through advertising, and require massive forms of potentially unnecessary material production

      for - addendum - add ecological footprint of advertising industry to material waste generated by consumer culture - from Substack article - The Cosmo-Local Plan for our Next Civilization - Michel Bauwens - 2024, Dec 20

      addendum - add ecological footprint of advertising industry to material waste generated by consumer culture - The advertising industry itself has a huge ecological footprint as well, in addition to the extra, unneeded material that planned obsolescence creates - references to be added

    9. The current global system of production and trade is reported to use three times more of its resource use for transport, not for making. This creates a profound ‘ecological’, i.e. biophysical and thermodynamic, rationale for relocalizing production

      for - stats - motivation for cosmolocal - high inefficacy of resource and energy use - 3x for transport as for production - from Substack article - The Cosmo-Local Plan for our Next Civilization - Michel Bauwens - 2024, Dec 20

    10. worder

      for - typo - 'worder' should be 'order'

    11. for - Substack article - The Cosmo-Local Plan for our Next Civilization - Michel Bauwens - 2024, Dec 20 - adjacency - web 3 and Blockchain / crypto technology - communities engaged in regeneration and relocalization - tinkering at the edge - missed opportunity - cosmolocal strategy as leverage point - safe and just cross scale translation of earth system boundaries - Tipping Point Festival - Web 4 - Indyweb

      Summary adjacency between - web 3 and crypto / Blockchain technology - communities engaged in regeneration and relocalization - tinkering at the edge - missed opportunity - cosmolocal lens and framework as a leverage point for synthesis - cosmolocal projects as leverage points - cross scale translated safe and just earth system boundaries as necessary cosmolocal accounting system - meme: sync global, act local - new relationship - This article explores the untapped potential and leverage point offered by recognising a new adjacency and concomitant synthesis of - globalising Web 3 and crypto/Blockchain technology - communities engaged in regenerative and relocation interventions - The fragmentation between these areas keeps activists working in each respective one - tinkering at the edge - severely constraining their potential impact - This is a case of the whole Berlin car greater than the sun of its parts - By joining forces in a global, strategic and systemic way, each can achieve fast more through their mutual support - A cosmolocal lens offers a perspective and framework that makes joining forces make sense<br /> - Projects that recognize that the adjacency between - the globalizing technologies of web 3 and Blockchains and - interventions at the local community level - offer a significant leverage point to bottom up efforts to drive a rapid transition are themselves a leverage point - In this regard, incorporation of an equitable accounting system such as safe and just earth system boundaries that can be cross scale translated to - bioregional, - city and - community, district and ward scale - are an important cosmolocal component of a system designed for rapid transition - Global bottom up community scale events such as the Tipping Point Festival can help rapidly advocate for a cosmolocal lens, framework and strategy - At the same time, Web 4 technology that's goes beyond decentralising into people-centered can contribute another dimension to humanizing technology

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    7. Nail the Embedded Software Engineering Interview

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    6. Best suited for Current or Former Business Analysts/Data Analysts/Product Analysts/Business Intelligence Analysts/Business Intelligence Engineers

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    7. Nail the Data Analyst & Business Analyst Interview

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    1. Career impact

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  2. math.libretexts.org math.libretexts.org
    1. R1−R2→R1,R3+3R2→R3R1−R2→R1,R3+3R2→R3R_1 - R_2 \rightarrow R_1, \;\; R_3 + 3R_2 \rightarrow R_3\nonumber ⎛⎝⎜⎜1001131−1−12−1−1⎞⎠⎟⎟

      Isn't R3 + 3R2 ->R3 going to give you a 6 in the R3C2 position? Someone, please help explain...

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    1. Welcome back and in this lesson I want to cover IPsec fundamentals.

      So I want to talk about what IPsec is, why it matters and how IPsec works at a fundamental level.

      Now we have a lot of theory to cover so let's jump in and get started.

      At a foundational level IPsec is a group of protocols which work together.

      Their aim is to set up secure networking tunnels across insecure networks.

      For example, connecting two secure networks or more specifically their routers called PIRS across the public internet.

      Now you might use this if you're a business with multiple sites spread around geographically and want to connect them together.

      Or if you have infrastructure in AWS or another cloud platform and want to connect to that infrastructure.

      IPsec provides authentication so that only PIRS which are known to each other and can authenticate with each other can connect.

      And any traffic which is carried by the IPsec protocols is encrypted which means to unlockers the secure data which has been carried is ciphertext.

      It can't be viewed and it can't be altered without being detected.

      Now architecturally it looks like this.

      We have the public internet which is an insecure network full of goblins looking to steal your data.

      Over this insecure network we create IPsec tunnels between PIRS.

      Now these tunnels exist as they're required.

      Within IPsec VPNs there's the concept of interesting traffic.

      Now interesting traffic is simply traffic which matches certain rules.

      And these could be based on network prefixes or match more complex traffic types.

      Regardless of the rules if data matches any of those rules it's classified as interesting traffic.

      And a VPN tunnel is created to carry traffic through to its destination.

      Now if there's no interesting traffic then tunnels are eventually torn down only to be reestablished when the system next detects interesting traffic.

      The key thing to understand is that even though those tunnels use the public internet for transit any data within the tunnels is encrypted while transiting over that insecure network.

      It's protected.

      Now to understand the nuance of what IPsec does we need to refresh a few key pieces of knowledge.

      In my fundamental section I talked about the different types of encryption.

      I mentioned symmetric and asymmetric encryption.

      Now symmetric encryption is fast.

      It's generally really easy to perform on any modern CPU and it has pretty low overhead.

      But exchanging keys is a challenge.

      The same keys are used to encrypt and decrypt.

      So how can you get the key from one entity to another securely?

      Do you transmit it in advance over a different medium or do you encrypt it?

      If so you run into a catch-22 situation how do you securely transmit the encrypted key?

      That's why asymmetric encryption is really valuable.

      Now it's slower so we don't want to be using it all the time.

      But it makes exchanging keys really simple because different keys are used for encryption and decryption.

      Now a public key is used to encrypt data and only the corresponding private key can decrypt that data.

      And this means that you can safely exchange the public key while keeping the private key private.

      So the aim of most protocols which handle the encryption of data over the internet is to start with asymmetric encryption.

      Use this to securely exchange symmetric keys and then use those for ongoing encryption.

      Now I mentioned that because it will help you understand exactly how IPsec VPN works.

      So let's go through it.

      IPsec has two main phases.

      If you work with VPNs you're going to hear a lot of talk about phase one or phase two.

      It's going to make sense why these are needed by the end of this lesson.

      But understand there are two phases in setting up a given VPN connection.

      The first is known as Ike phase one.

      Ike or internet key exchange as the name suggests is a protocol for how keys are exchanged in this context within a VPN.

      There are two versions.

      Ike version one and Ike version two.

      Version one logically is older.

      Version two is newer and comes with more features.

      Now you don't need to know all the detail right now.

      Just understand that the protocol is about exchanging keys.

      Ike phase one is the slow and heavy part of the process.

      It's where you initially authenticate using a pre-shared key.

      So a password of sorts or a certificate.

      It's where asymmetric encryption is used to agree on, create and share symmetric keys which are used in phase two.

      The end of this phase is what's known as an Ike phase one tunnel or a security association known as an SA.

      There's lots of jargon being thrown around and I'll be showing you how this all works visually in just a moment.

      But at the end of phase one you have a phase one tunnel and the heavy work of moving towards symmetric keys which can be used for encryption has been completed.

      The next step is Ike phase two which is faster and much more agile because much of the heavy lifting has been done in phase one.

      Technically the phase one keys are used as a starting point for phase two.

      Phase two is built on top of phase one and is concerned with agreeing encryption methods and the keys used for the bulk transfer of data.

      The end result is an IPsec security association, a phase two tunnel which runs over phase one.

      Now the reason why these different phases are split up is that it's possible for phase one to be established, then a phase two tunnel created, used and then torn down when no more interesting traffic occurs, but the phase one tunnel stays.

      It means that establishing a new phase two tunnel is much faster and less work.

      It's an elegant and well designed architecture.

      So let's look at how this all works together visually.

      So this is Ike phase one.

      The architecture is a simple one.

      Two business sites, site one on the left with the user Bob and site two on the right with the user Julie and in the middle the public internet.

      The very first step of this process is that the routers, the two peers at either side of this architecture need to authenticate, essentially prove their identity which is done either using certificates or pre-shared keys.

      Now it's important to understand that this isn't yet about encryption, it's about proving identity, proving that both sides agree that the other side should be part of this VPN.

      No keys are exchanged, it's just about identity.

      Once the identity has been confirmed then we move on to the next stage of Ike phase one.

      In this stage we use a process called Diffie-Hellman Key Exchange.

      Now again, I'm sorry about the jargon but try your best to remember Diffie-Hellman known as DH.

      What happens is that each side creates a Diffie-Hellman private key.

      This key is used to decrypt data and to sign things.

      You should remember this from the encryption fundamentals lesson.

      In addition, each side uses that private key and derives a corresponding public key.

      Now the public key can be used to encrypt data that only that private key can decrypt.

      So at this point each side has a private key as well as a corresponding public key.

      At this point these public keys are exchanged.

      So Bob has Julie's public key and Julie has Bob's public key.

      Remember these public keys are not sensitive and can only be used normally to encrypt data for decryption by the corresponding private key.

      The next stage of the process is actually really complicated mathematics but at a fundamental level each side takes its own private key and the public key of the other side and uses this to derive what's known as the Diffie-Hellman key.

      The Diffie-Hellman key is the same at both sides but it's been independently generated.

      Now again the maths is something that's well beyond this lesson but it's at the core of how this phase of VPN works.

      And at this point it's used to exchange other key material and agreements.

      This part you can think of as a negotiation.

      The result is that each side again independently uses this DH key plus the exchanged key material to generate a final phase one symmetrical key.

      This key is what's used to encrypt anything passing through the phase one tunnel known as the Ike Security Association.

      Now if that process seems slow and heavy that's because it is.

      It's both complex and in some ways simplistically elegant at the same time but it means that both sides have the same symmetric key without that ever having been passed between them.

      And the phase ends with this security association in place and this can be used at phase two.

      So let's talk about that next.

      So in phase two we have a few things.

      First a DH key on both sides and the same phase one symmetric key also on both sides and then finally the established phase one tunnel.

      During this phase both of the peers are wanting to agree how the VPN itself will be constructed.

      The previous phase was about allowing this exchanging keys and allowing the peers to communicate.

      This phase so Ike phase two is about getting the VPN up and running being in a position to encrypt data.

      So agreeing how when and what.

      So the first part of this is that the symmetric key is used to encrypt and decrypt agreements and pass more key material between the peers.

      The idea is that one peer is informing the other about the range of Cypher suites that it supports basically encryption methods which it can perform.

      The other peer in this example the right one will then pick the best shared one.

      So the best method which it also supports and it will let the left peer know and this becomes the agreed method of communication.

      Next the DH key and the key material exchanged above is used to create a new key a symmetrical IP sec key.

      This is a key which is designed for large scale data transfer.

      It's an efficient and secure algorithm and the specific one is based on the negotiation which happened above in steps one and two of this phase.

      So it's this key which is used for the encryption and decryption of interesting traffic across the VPN tunnel.

      Across each phase one tunnel you actually have a pair of security associations one from right to left and one from left to right.

      And these are the security associations which are used to transfer the data between networks at either side of a VPN.

      Now there are actually two different types of VPN which you need to understand policy based VPNs and route based VPNs.

      The difference is how they match interesting traffic.

      Remember this is the traffic which gets sent over a VPN.

      So with policy based VPNs there are rules created which match traffic and based on this rule traffic is sent over a pair of security associations.

      One which is used for each direction of traffic.

      It means that you can have different rules for different types of traffic something which is great for more rigorous security environments.

      Now the other type of VPN are route based VPNs and these do target matching based on prefix.

      For example send traffic for 192.168.0.0/24 over this VPN.

      With this type of VPN you have a single pair of security associations for each network prefix.

      This means all traffic types between those networks use the same pair of security associations.

      Now this provides less functionality but it is much simpler to set up.

      To illustrate the differences between route based and policy based VPNs it's probably worth looking visually at the phase one and phase two architectures.

      Let's start with a simple route based VPN.

      The phase one tunnel is established using a phase one tunnel key.

      Now assuming that we're using a route based VPN then a single pair of security associations is created.

      One in each direction using a single IPsec key.

      So this means that we have a pair of security associations essentially a single phase two tunnel running over the phase one tunnel.

      That phase two or IPsec tunnel which is how we talk about the pair of security associations can be dropped when there is no more interesting traffic and recreated again on top of the same phase one tunnel when new traffic is detected.

      But the key thing to understand is that there's one phase one tunnel running one phase two tunnel based on routes.

      Running a policy based VPN is different.

      We still have the same phase one tunnel but over the top of this each policy match uses an essay pair with a unique IPsec key.

      And this allows us to have for the same network different security settings for different types of traffic.

      In this example infrastructure at the top CCTV in the middle and financial systems at the bottom.

      So policy based VPNs are more difficult to configure but do provide much more flexibility when it comes to using different security settings for different types of traffic.

      Now that at a very high level is how VPNs functions.

      So the security architecture of how everything interacts with everything else elsewhere in my course you'll be learning how AWS use VPNs within their product set.

      But for now that's everything that I wanted to cover.

      So go ahead and complete this video and then when you're ready I look forward to you joining me in the next.

    1. What to Expect at Front-end Engineer Interviews

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    2. Career impact

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    4. d

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    6. Meet your instructors

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    7. Program designed by FAANG+ leads Covering data structures, algorithms, interview-relevant topics, and career coaching Individualized teaching and 1:1 help Technical coaching, homework assistance, solutions discussion, and individual session Mock interviews with Silicon Valley engineers Live interview practice in real-life simulated environments with FAANG and top-tier interviewers

      There is no text alignment across the different headings. Can we edit the headings to better fit them here and make them aligned?