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The de novo design of three protein chains that associate to form a heterotrimer (but not any of the possible two-chain heterodimers) and that can drive the assembly of higher-order branching structures is an important challenge for protein design. We designed helical heterotrimers with specificity conferred by buried hydrogen bond networks and large aromatic residues to enhance shape complementary packing. We obtained ten designs for which all three chains cooperatively assembled into heterotrimers with few or no other species present. Crystal structures of a helical bundle heterotrimer and extended versions, with helical repeat proteins fused to individual subunits, showed all three chains assembling in the designed orientation. We used these heterotrimers as building blocks to construct larger cyclic oligomers, which were structurally validated by electron microscopy. Our three-way junction designs provide new routes to complex protein nanostructures and enable the scaffolding of three distinct ligands for modulation of cell signaling.

The maritime domain, largely comprised of international ‘commons’ covering more than 70% of the Earth’s surface, presents some unique challenges in identifying, much less reconciling, applicable International Environmental Law (IEL) and International Humanitarian Law (IHL) principles. This article posits that the 1982 United Nations Convention on the Law of the Sea, particularly its prescriptive and enforcement jurisdictional apportionments to nations relating to the prevention and control of pollution, establishes the peacetime IEL normative framework at sea. After exploring this normative framework, this article furthers the symposium’s overall theme by examining the interplay between this IEL framework and the relatively sparse and sporadic IHL regime at sea. As will be seen, this interplay is largely a question of the extent to which, if at all, these jurisdictional apportionments survive during periods of armed conflict. As such, it aligns more closely with the ‘application process’ for impacting the regulation of armed conflict, in which IEL applies alongside IHL to activities related to armed conflict, than with the ‘interpretation process’, whereby IHL is interpreted in light of IEL.

Context Intermittent rivers make up more than 50% of the world’s rivers. Refuge waterholes in these systems are critical for survival of fish populations. Aim This study investigated the effect that angling pressure imparts on native fish within refuge waterholes. Methods Golden perch (Macquaria ambigua) size structure was analysed in eight refuge waterholes across three catchments of the northern Murray–Darling Basin. Waterhole characteristics were recorded, with town proximity or remoteness being adopted as a surrogate variable for angling pressure. Key results Remoteness was found to be significantly correlated with median length, biomass, and proportion of legal-sized fish, but not with fish density. Sampling occurred after widespread connective flows, and the strength of remoteness as a predictor of median length suggests that redistribution of legal-sized golden perch on these flows was minimal. Legal-sized fish were poorly represented in the length–frequency distributions of near-town waterholes, and smaller size classes were well represented in most waterholes. Conclusion This study suggests that populations of golden perch in refuge waterholes near towns face significant angling pressure, with impacts on size structure at a local level. Implications These findings may have wider implications for the long-term resilience of the species.

Hegel is not an author who plays a starring role in Cavell’s work like that of Austin, Wittgenstein, or Emerson. Cavell mentions him rarely, and almost always in passing. This is hardly surprising. Given that Cavell draws as heavily as he does upon Kant, whom Hegel regularly attacks, and Kierkegaard, who regularly attacks Hegel, one might expect that Hegel’s more important claims and ideas would be uncongenial to Cavell, and incompatible with the main lines of his work. Moreover, Cavell’s early and lasting embrace of Romanticism would seem to preclude the embrace of an author who lambasts the leading Jena Romantic Friedrich von Schlegel as the purveyor of a corrosive amoral subjectivism. Appearances, however, can be deceiving, and in the essay that follows I demonstrate that there are good reasons to believe that Hegel has influenced Cavell considerably more than one might suppose.

Propagation of sound through a non-uniform medium without scattering is possible, in principle, if the density and acoustic compressibility assume complex values, requiring passive and active mechanisms, also known as Hermitian and non-Hermitian solutions, respectively. Two types of constant intensity wave conditions are identified: in the first the propagating acoustic pressure has constant amplitude, while in the second the energy flux remains constant. The fundamental problem of transmission across an impedance discontinuity without reflection or energy loss is solved using a combination of monopole and dipole resonators in parallel. The solution depends on an arbitrary phase angle which can be chosen to give a unique acoustic metamaterial with both resonators undamped and passive, requiring purely Hermitian acoustic elements. For other phase angles one of the two elements must be active and the other passive, resulting in a gain/loss non-Hermitian system. These results prove that uni-directional and reciprocal transmission through a slab separating two half spaces is possible using passive Hermitian acoustic elements without the need to resort to active gain/loss energetic mechanisms., Comment: 8 pages, 3 figures

Homo-oligomeric ligand-activated proteins are ubiquitous in biology. The functions of such molecules are commonly regulated by allosteric coupling between ligand-binding sites. Understanding the basis for this regulation requires both quantifying the free energy ΔG transduced between sites, and the structural basis by which it is transduced. We consider allostery in three variants of the model ring-shaped homo-oligomeric trp RNA-binding attenuation protein (TRAP). First, we developed a nearest-neighbor statistical thermodynamic binding model comprising microscopic free energies for ligand binding to isolated sites ΔG

The phrase, “epistemology of moods,” appears in Stanley Cavell’s writings in the late 1970’s, as The Claim of Reason is published and Cavell begins the direct engagement with Emerson around which his work will pivot for the rest of his career. Indeed, it is as an “epistemologist of moods” that Emerson first appeals to Cavell in his own right, and not as merely a “second-hand Thoreau.” The phrase is an odd one. Most of us would not think that knowledge and mood are connected in the way it suggests: my foul mood may make it difficult for me to concentrate on, say, my taxes, but it does not appear to otherwise affect my ability to know how much or how little I owe—and the same could be said of Sextus’ honey, Descartes’ ball of wax, Price’s tomato, and Clarke’s block of cheese. The oddity of the phrase is, if anything, even more marked when coming from Cavell: though Cavell is deeply interested in questions of self-knowledge, and of our ability to speak for one another and in that sense know one another, he is not an epistemologist; and when he writes of epistemology he often uses phrases like traditional epistemology or classical epistemology that distance him from it. Cavell does not share the traditional epistemologist’s interest in determining what, if anything, might warrant our claims to knowledge of the empirical world or the existence of “other minds”; and “the truth of skepticism” that he announces and explores is not the truth of the claims of the epistemological skeptic regarding such matters. While the epistemologist seeks to assure himself of the certainty of his knowledge, Cavell seeks to understand our disappointment with the knowledge we have. What, then, does Cavell mean by this phrase? What is the epistemology of moods?

Homo-oligomeric ligand-activated proteins are ubiquitous in biology. The functions of such molecules are commonly regulated by allosteric coupling between ligand binding sites. Understanding the basis for this regulation requires both quantifying the free energy ΔG transduced between sites, and the structural basis by which it is transduced. We consider allostery in three variants of the model ring-shaped homo-oligomeric trpRNA binding attenuation protein, TRAP. First, we developed nearest-neighbor statistical thermodynamic binding models comprising microscopic free energies for ligand binding to isolated sites ΔGN0, and for coupling between one or both adjacent sites, ΔGN1 and ΔGN2. Using the resulting partition function (PF) we explored the effects of these parameters on simulated population distributions for the 2N possible liganded states. We then experimentally monitored liganddependent population shifts using conventional spectroscopic and calorimetric methods, and using native mass spectrometry (MS). By resolving species with differing numbers of bound ligands by their mass, native MS revealed striking differences in their ligand-dependent population shifts. Fitting the populations to a binding polynomial derived from the PF yielded coupling free energy terms corresponding to orders of magnitude differences in cooperativity. Uniquely, this approach predicts which of the possible 2N liganded states are populated at different ligand concentrations, providing necessary insights into regulation. The combination of statistical thermodynamic modeling with native MS may provide the thermodynamic foundation for a meaningful understanding of the structure-thermodynamic linkage that drives cooperativity.TOC Figure (draft)TOC Figure.Ligand (Trp) binding to multiple sites on homo-oligomeric ring-shaped proteins like TRAP alters their functional states. Homotropic cooperativity is expected to alter the activation pathway in response to cellular ligand concentration. In the presence of positive nearest-neighbor cooperativity, ligand binding is favored at adjacent sites, whereas in the absence of cooperativity, a random “Normal” distribution is expected.

Human Rad52 protein binds to ssDNA and promotes the annealing of complementary strands. This activity is central to multiple DNA repair pathways and Rad52 is a target for cancer therapeutics. Previous crystal structures of the DNA binding domain of Rad52 revealed an 11-mer ring that binds to ssDNA in an extended conformation with the bases exposed for homology recognition. While this complex is likely involved in the early stages of annealing, there is no structure of Rad52 with two strands of DNA bound simultaneously, and its mechanism of annealing is poorly understood. To approach this problem, we have turned to the RecT/Redβ family of annealing proteins from bacteriophage, which are distant homologs of Rad52 that form stable complexes with a duplex intermediate of annealing. We have used single particle cryo-electron microscopy (cryo-EM) to determine a 3.4 Å structure of a RecT homolog from a prophage of Listeria innocua (LiRecT) in complex with two complementary 83-mer oligonucleotides that were added to the protein sequentially. The structure reveals a left-handed helical filament of the protein bound to a novel conformation of DNA duplex that is highly extended and under-wound. The duplex is bound at a stoichiometry of 5 bp/monomer to a deep, narrow, positively-charged groove that runs along the outer surface of the filament. Data from native mass spectrometry confirm that the filament complex seen by cryo-EM also exists in solution. Collectively, these data provide new insights into the mechanism of annealing by LiRecT and by homologous proteins including human Rad52.

BX1 from Zea mays (zmBX1) is an enzyme of plant secondary metabolism that generates indole for the synthesis of plant defensins. It is a homologue of the tryptophan synthase α-subunit, TrpA. Whereas TrpA itself is a monomer in solution, zmBX1 is dimeric, confirmed in our work by native MS. Using cross-linking and mutagenesis, we identified the physiological dimerization interface of zmBX1. We found that homodimerization has only minor effects on catalysis and stability. A comparison of the zmBX1-zmBX1 homodimer and zmTrpA-zmTrpB heterodimer interfaces suggest that homodimerization in zmBX1 might, at an early point in evolution, have served as a mechanism to exclude the interaction with the tryptophan synthase β-subunit (zmTrpB), marking its transition from primary to secondary metabolism.

Degradation of instream habitats in the northern Murray–Darling Basin has occurred through numerous stressors, including siltation, clearing of bankside vegetation, intrusion of livestock and impacts of pest species. A better understanding of habitat preferences of native fish species could help guide future instream habitat restoration actions. The habitat choices of seven native fish species, juvenile Murray Cod (Maccullochella peelii), juvenile Golden Perch (Macquaria ambigua ambigua), juvenile Silver Perch (Bidyanus bidyanus), adult Murray–Darling Rainbowfish (Melanotaenia fluviatilis), adult Olive Perchlet (Ambassis agassizii), adult Un‐specked Hardyhead (Craterocephalus stercusmuscarum fulvus) and adult carp gudgeons (Hypseleotris spp.) were tested in preference troughs to help inform potential habitat restoration actions in the Condamine catchment. Each species was given a choice between pair combinations of open sandy habitat, submerged macrophytes, emergent plants and rocky rubble. Habitat preferences varied between species. Murray Cod, Golden Perch, carp gudgeons and Olive Perchlets preferred structure over open sandy habitat, whilst juvenile Silver Perch, Un‐specked Hardyhead and Murray–Darling Rainbowfish did not avoid open sandy habitats. Juvenile Murray Cod preferred rocky rubble habitat over all other habitat choices. Use of complex rock piles to provide nursery habitat for Murray Cod populations is a potential restoration option. Introduction of rock could also benefit Golden Perch and carp gudgeons. Use of emergent plants, submerged macrophytes and rocky rubble for habitat restoration all appear to have merit for one or more species of small‐bodied fishes or juvenile stages of larger sized fishes. Rocky rubble or floating attached macrophytes could be viable restoration options in areas too turbid to establish submerged macrophytes. These habitat interventions would complement existing actions such as re‐snagging and provision of fish passage to assist with sustainable management of native fish populations.

Mechanistic understanding of the structural basis for DNA recombination in the Cre-loxP system has largely been guided by crystallographic structures of tetrameric synaptic complexes (intasomes). These structural and biochemical studies have suggested that conformational changes and DNA bending in presynaptic complexes underlie site-selection and activation mechanisms of Cre recombinase. Here we used protein engineering and various DNA substrates to isolate the Cre-loxP (54 kDa), Cre2-loxP (110 kDa), and Cre4-loxP2 assembly intermediates, and determined their structures using cryo-EM to resolutions of 3.9 Å, 4.5 Å, and 3.2 Å, respectively. Progressive DNA bending along the assembly pathway enables formation of increasingly intimate protein-protein interfaces. Insufficient stabilization of important protein motifs observed during the assembly process provides a compelling explanation for the observed half-the-sites activity, and preferential bottom strand cleavage of loxP sequences. We found that selection of loxP sites is largely dependent on Cre’s ability to bend and stabilize the spacer region between two recombinase binding elements. Application of 3D variability analysis to the tetramer data reveals a propensity for motion along the pathway between protomer activation and Holliday junction isomerization. These findings help us to better understand loxP site specificity, controlled activation of alternating protomers, the basis for the observed bias of strand cleavage order, and the importance of conformational sampling, especially with regards to site-selection and activity among Cre variants. Furthermore, our findings provide invaluable information for the rational development of designer, site-specific recombinases for use as gene editing technologies.HighlightsCryo-EM structures of Cre-loxP assembly intermediates (monomer, dimer, and tetramer) provide insights into mechanisms of site recognition, half-the-sites activity, strand cleavage order, and concerted strand cleavageSelectivity of loxP sites arises from few base-specific contacts made by each protomer and is mainly driven by formation of phosphate contacts and DNA deformations that are maximal in the fully assembled “active” tetramerCis and trans interactions of the β2-3 loop (i) define which sites are “active” and (ii) ensure half-the-sites activityProtein flexibility plays a central role in enabling DNA sequence scanning, recruitment of a second protein to form a dimer, synapsis, control of activity, as well as subsequent recombination stepsConformational sampling within the tetrameric complex was uncovered using 3D variability analysis and revealed the importance of protein-protein interfaces for site- selection and activation of Cre-loxP complexes

COVID-19 was declared a pandemic by the WHO in 2020. In light of the global shortage of PPE and concerns regarding the safety of healthcare providers, clinicians have resorted to the use of novel protective barriers, such as aerosol boxes and plastic sheets, during aerosol generating procedures, especially tracheal intubation. We compared the effect of these barriers on the tracheal intubation of simulated patients with severe COVID-19 in a crossover study. The study was approved by the Ethics Committee of King Faisal Specialist Hospital, and the procedures were compliant with the COVID-19 airway management guidelines of the Saudi Anesthesia Society. The time to intubation was our primary outcome. Secondary outcomes included number of optimization maneuvers, number of intubation attempts, time to glottic view and ventilation of the lungs, and damage to PPE. Thirteen consultant anesthetists performed 39 tracheal intubations on a manikin using each of three approaches (aerosol box, plastic sheet, and no-barrier). Data were collected via direct and video observation. The plastic sheet approach demonstrated the highest time to intubation (mean ± StE [95% CI]: 33.3s ± 3.5 [25.8– 40.9]) compared to the aerosol box (22.0s ± 2.5 [16.5 – 27.5], P < 0.01) and no-barrier approaches (16.1s ± 1.1 [13.7 – 18.4], P < 0.0001). Similarly, the plastic sheet approach had the highest time to glottic view, and ventilation intervals compared to the other two approaches, while the no-barrier approach had the shortest time intervals. There were no failed intubations or damage to the PPE sustained during the use of any of the three approaches. The aerosol box does not impose a significant delay in tracheal intubation using video laryngoscopy, unlike the plastic sheet barrier. Further research on the aerosolization risk is warranted before these protective barriers can be considered as mainstay approaches during aerosol generating procedures.

Redβ is a single strand annealing protein from bacteriophage λ that binds loosely to ssDNA, not at all to pre-formed dsDNA, but tightly to a duplex intermediate of annealing. As viewed by electron microscopy, Redβ forms oligomeric rings on ssDNA substrate, and helical filaments on the annealed duplex intermediate. However, it is not clear if these are the functional forms of the protein in vivo. We have used size-exclusion chromatography coupled with multi-angle light scattering, analytical ultracentrifugation and native mass spectrometry (nMS) to characterize the size of the oligomers formed by Redβ in its different DNA-bound states. The nMS data, which resolve species with the highest resolution, reveal that Redβ forms an oligomer of 12 subunits in the absence of DNA, complexes ranging from 4 to 14 subunits on 38-mer ssDNA, and a much more distinct and stable complex of 11 subunits on 38-mer annealed duplex. We also measure the concentration of Redβ in cells active for recombination and find it to range from 7 to 27 μM. Collectively, these data provide new insights into the dynamic nature of the complex on ssDNA, and the more stable and defined complex on annealed duplex.

BX1 from Zea mays (zmBX1) is an enzyme of plant secondary metabolism that generates indole for the synthesis of plant defensins. It is a homolog of the tryptophan synthase α-subunit, TrpA. Whereas TrpA itself is a monomer in solution, zmBX1 is dimeric, confirmed in our work by native MS. Using cross-linking and mutagenesis, we identified the physiological dimerization interface of zmBX1. We found that homodimerization has only minor effects on catalysis and stability. A comparison of the zmBX1–zmBX1 homodimer and zmTrpA–zmTrpB heterodimer interfaces suggest that homodimerization in zmBX1 might, at an early point in evolution, have served as a mechanism to exclude the interaction with the tryptophan synthase β-subunit (zmTrpB), marking its transition from primary to secondary metabolism.

Dual topological materials are unique topological phases that host coexisting surface states of different topological nature on the same or on different material facets. Here, we show that Bi2TeI is a dual topological insulator. It exhibits band inversions at two time reversal symmetry points of the bulk band, which classify it as a weak topological insulator with metallic states on its 'side' surfaces. The mirror symmetry of the crystal structure concurrently classifies it as a topological crystalline insulator. We investigated Bi2TeI spectroscopically to show the existence of both two-dimensional Dirac surface states, which are susceptible to mirror symmetry breaking, and one-dimensional channels that reside along the step edges. Their mutual coexistence on the step edge, where both facets join, is facilitated by momentum and energy segregation. Our observation of a dual topological insulator should stimulate investigations of other dual topology classes with distinct surface manifestations coexisting at their boundaries.

In this article I compare and contrast Hannah Arendt’s and Stanley Cavell’s understandings of critique, focusing in each case upon the role played in it by skepticism. Both writers are decisively influenced by the later Heidegger’s thought that thinking as such is, first, the necessary turn to a practice adequate to our situation and, second, something that we shun. They also share the desire to take up this Heideggerian thought in Kantian terms: what is at stake is critical thinking. It is here, however, that they part ways, with Arendt insisting that critique is as incompatible with skepticism as it is with dogmatism, and Cavell insisting that skepticism is the central moment within critique. Arendt’s attempt to ban skepticism from critique forces her into the contradictory position of at once denying and affirming the role of dogma in critical thinking. Cavell, in contrast, is able to shed light consistently upon the question of how citizens might best respond to the new – a task, ironically, that is as central to Arendt’s work as it is to Cavell’s. My argument thus functions as an immanent critique of Arendt, an attempt to demonstrate the need to read her in light of Cavell.

The manuscript describes the use of chemical cross-linking/mass spectrometry and mutagenesis to investigate the dimeric interface of the tryptophan synthase α-subunit homolog, BX1. This work indicates that BX1 homodimerization might have served as a mechanism to exclude an interaction with the tryptophan synthase β-subunit, TrpB, at an early time in evolution, thereby eliminating cross-talk between primary and secondary metabolism. This work would be of interest to mass spectrometrists and structural biologist as it presents a workflow to determine the physiological protein-protein interactions within crystal structures using chemical cross-linking/mass spectrometry and mutagenesis as complementary structural biology techniques, thereby eliminating ambiguity and potential mis-assignments due to the presence of additional (artificial) protein contacts formed during the crystallization process.

To fulfill their biological functions, proteins must interact with their specific binding partners and often function as large assemblies composed of multiple proteins or proteins plus other biomolecules. Structural characterization of these complexes, including identification of all binding partners, their relative binding affinities, and complex topology, is integral for understanding function. Understanding how proteins assemble and how subunits in a complex interact is a cornerstone of structural biology. Here we report a native mass spectrometry (MS)-based method to characterize subunit interactions in globular protein complexes. We demonstrate that dissociation of protein complexes by surface collisions, at the lower end of the typical surface-induced dissociation (SID) collision energy range, consistently cleaves the weakest protein:protein interfaces, producing products that are reflective of the known structure. We present here combined results for multiple complexes as a training set, two validation cases, and four computational models. We show that SID appearance energies can be predicted from structures via a computationally derived expression containing three terms (number of residues in a given interface, unsatisfied hydrogen bonds, and a rigidity factor).

Common carp (Cyprinus carpio) are one of the world's most destructive vertebrate pests. In Australia, they dominate many aquatic ecosystems causing a severe threat to aquatic plants, invertebrates, water quality, native fish and social amenity. The Australian Government is considering release of cyprinid herpesvirus-3 (CyHV-3) as a control measure and consequently a robust, continental-scale estimate of the carp population and biomass is essential to inform planning and risk management. Here, we pioneer a novel model-based approach to provide the first estimate of carp density (no/ha) and biomass density (kg/ha) at river reach/waterbody, basin and continental scales. We built a spatial layer of rivers and waterbodies, classified aquatic habitats and calculated the area of each throughout the range of carp in Australia. We then developed a database of fishery-independent electrofishing catch-per-unit-effort (CPUE) for habitat types, containing catch information for 574,145 carp caught at 4831 sites. Eastern Australia accounted for 96% of carp biomass and 92% of the total available wetted habitat area (16,686 km2) was occupied. To correct these data for variable detection efficiencies, we used existing electrofishing data and undertook additional field experiments to establish relationships between relative and absolute abundances. We then scaled-up site-based estimates to habitat types to generate continental estimates. The number of carp was estimated at 199.2 M (95%Crl: 106 M to 357.6 M) for an ‘average’ hydrological scenario and 357.5 M (95%Crl: 178.9 M to 685.1 M) for a ‘wet’ hydrological scenario. In eastern Australia, these numbers correspond with biomasses of 205,774 t (95%Crl: 117,532–356,482 t) (average scenario) and 368,357 t (95%Crl: 184,234–705,630 t) (wet scenario). At a continental scale the total biomass was estimated at 215,456 t for an ‘average’ hydrological scenario. Perennial lowland rivers had the highest CPUE and greatest biomass density (up to 826 kg/ha) and the modelled biomass exceeded a density-impact threshold of 80–100 kg/ha in 54% of wetlands and 97% of stream area in large lowland rivers. The continental-scale biomass estimates provide a baseline for focusing national conservation strategies to reduce carp populations below thresholds needed to restore aquatic ecosystems at a range of spatial scales.

Michael Oakeshott provides the best articulation of the widespread view that the moral foundations of the modern state limit it to the defense and maintenance of a system of formal rules governing individuals and non-state enterprises. While this understanding of the proper relation between individual and state has been challenged by liberals of a more Rawlsian persuasion, these criticisms have persuaded few to change their minds, as they rest upon assumptions that are plainly incompatible with the view under consideration. I argue that, rightly understood, central and attractive features of Oakeshott’s own conception of understanding, philosophy, individuality, and education lead to significantly different conclusions than those embraced by Oakeshott himself. The “morality of individuality” upon which Oakeshott rests his strict restrictions on the use of state power requires that we be open to the use of that power to guarantee that all receive the education postulated by individuality.

Graphene is a suitable substrate to study organic films due to the chemical stability of graphene derived from its structure and the low density of states around the Fermi level (Dirac point for neutral graphene). These two characteristics result in a reduced perturbation on the adsorbed molecules. There are few examples showing the unperturbed frontier molecular orbitals for individual molecules adsorbed on graphene or the formation of unperturbed intermolecular bands in self-assembled molecular overlayers. Simultaneously noncovalent functionalization using molecules has been suggested as a means of tailoring graphene’s band structure without compromising its overall excellent electron properties.

In this essay I ask what Wittgenstein means when he writes in the introductory section of his “Remarks on Frazer’s Golden Bough,” “I must plunge into the water of doubt again and again.” This comment is both significant and obscure. Although Wittgenstein did not himself publish the “Remarks,” he took care to organize them, and rejected other introductory comments in favor of the ones that now open the “Remarks” and which conclude with this sentence. But it is not clear what role doubt plays in the “Remarks,” as Wittgenstein neither mentions it again not assumes a doubtful posture towards what he describes as Frazer’s errors. I argue that the sentence is meant to apply first and foremost not to Frazer but to Wittgenstein himself, and that, when read carefully, it refers to a kind of baptism. Appreciating this should decisively shape our understanding of the “Remarks” and has implications for our understanding of the Philosophical Investigations, which echoes and repeats many of the central ideas and even formulations of the earlier text. In particular, it underscores the importance of the idea of disorientation to Wittgenstein’s later work. Being doubtful or disoriented is not just a difficulty to be solved or avoided, but a beneficial process through which one must pass, as Wittgenstein says, again and again.

Dual topological materials are unique topological phases that host coexisting surface states of different topological nature on the same or on different material facets. Here, we show that Bi

This chapter addresses Cavell’s understanding skepticism, demonstrating that Cavell neither affirms the correctness of the skeptic’s claims nor refutes them, but provides a critique of epistemology. Skepticism is an expression of our deep discomfort with our finitude, our resistance to accepting the world and acknowledging those with whom we share it. And it is a particularly pure example of a more general attempt to speak without accepting responsibility for the conditions that make speech intelligible—an attempt to disown the criteria of our language, to speak without speaking to someone, to speak without being someone who needs or wants to speak, and who wants and needs to be addressed. This chapter draws heavily upon Wittgenstein and Heidegger in its account of this aspect of Cavell’s work, as other commentators have as well and upon Thompson Clarke, as they have not.

This chapter evaluates Cavell’s reception of Austin’s ordinary language philosophy, showing it to be more critical than it has been understood to be. For Austin, the ordinary language philosopher speaks in the first-person plural to remind other philosophers of “what we say when” so as to correct the mistakes those philosophers have made in writing about ethics, epistemology, etc. But Austin cannot give a compelling explanation of why those other philosophers require such reminders: how can they have been wrong about their language and its implications, since they too are one of us who speak the language? On Cavell’s account, we forget what we say when—or, what comes to the same thing, fail to mean what we say—because we evade ourselves. Ordinary language philosophy does not correct mistakes but addresses the uncanny nature of the ordinary, that it is not yet what it is.

This chapter presents Cavell’s Emersonian perfectionism as a response to and interpretation of Kant. For Cavell, receptivity is the key to Emerson’s inheritance of Kant’s theoretical philosophy, as partiality is the key to his inheritance of Kant’s practical philosophy. Partiality for Emerson names both the individual agent’s inherent lack and its want for change and growth. The shameful experience of lack is the precondition for the transformative encounter with an exemplary other who enables the self’s conversion of the nihilistic conformity of everyday life as it is now lived. The chapter argues that Cavell’s insistence that Emersonian perfectionism sets itself against any idea of ultimate perfection does not condemn Cavell’s agents to an endless and hence nihilistic pursuit of an unrealizable telos, as it might seem, but instead furnishes the basis for democratic hope.

This chapter analyzes Cavell’s reception of Rousseau’s theory of the general will and the manner in which he uses it to counter dominant conceptions of democracy, freedom, rhetoric, and public reason. Central here is Rousseau’s idea that the virtuous citizen can speak for fellow citizens—articulate their shared general will—in much the same way, and with the same limitations, as the ordinary language philosopher who articulates “what we say when.” Cavell develops this in his account of the political “claim to community,” and argues that certain archetypical forms of injustice are best explained by the failure of their perpetrators to properly articulate their own will. The problem here is not one of sincerity, but of self-knowledge. In reviewing these matters, this chapter also clarifies as neither previous commentators nor Cavell himself have the nature and worth of Cavell’s critique of the dominant model of contract theory, that of John Rawls.

While a number of books and many articles have been written on the work of Stanley Cavell, this is the first monograph on his contribution to politics and practical philosophy. Though skepticism is Cavell’s central topic, he understands it not as an epistemological problem or position but as an existential one. The central question is not what we know or fail to know, but to what extent we have made our lives our own, or failed to do so. Accordingly, Cavell’s reception of Austin and Wittgenstein highlights, as other readings of these figures do not, the uncanny nature of the ordinary, the extent to which we ordinarily fail to mean what we say. Bringing this out highlights Cavell’s debts to Heidegger and Thompson Clarke, even as it allows for a deeper appreciation of the extent to which Cavell’s perfectionism is a rewriting of Rousseau’s and Kant’s theories of autonomy. This in turn opens up a way of understanding citizenship and political discourse that develops points made more elliptically in the work of Hannah Arendt, and that contrasts in important ways with the positions of liberal thinkers like John Rawls and Jürgen Habermas on the one hand, and radical democrats like Ernesto Laclau and Chantal Mouffe on the other.

The introduction examines why Cavell’s contribution to our understanding of politics and practical philosophy has not yet received extensive examination in book form and why it merits such examination and such a book. It then briefly reviews Cavell’s unique approach to philosophy in general and to practical philosophy in particular. It concludes by summarizing the five chapters of the book, and their accounts of Cavell’s understanding of, in turn, ordinary language, skepticism, the nature of political claims, Thoreau’s achievement in Walden, and the manner in which what he terms Emersonian perfectionism represents a radical reworking of Kant’s theory of autonomy.

This chapter turns to Cavell’s first encounter with American transcendentalism and his initial exploration of views he would later characterize as “Emersonian perfectionism.” As read by Cavell, Thoreau’s Walden is a sustained attempt to wake his readers that bears comparison with Socrates’s attempt to wake his fellow citizens. Thoreau’s attempt is a provocative one in the sense that he must at once attract and disturb or repel his reader. Cavell’s reading of Thoreau both brings out and draws upon hitherto unnoticed resemblances between Walden and Being and Time. The chapter concludes by considering the manner in which a proper understanding of these works throws into high relief the profound differences between their authors’ respective understanding of politics and of the place of philosophy in public life.

The higher the energy of a particle is above equilibrium, the faster it relaxes because of the growing phase space of available electronic states it can interact with. In the relaxation process, phase coherence is lost, thus limiting high-energy quantum control and manipulation. In one-dimensional systems, high relaxation rates are expected to destabilize electronic quasiparticles. Here, we show that the decoherence induced by relaxation of hot electrons in one-dimensional semiconducting nanowires evolves nonmonotonically with energy such that above a certain threshold hot electrons regain stability with increasing energy. We directly observe this phenomenon by visualizing, for the first time, the interference patterns of the quasi-one-dimensional electrons using scanning tunneling microscopy. We visualize the phase coherence length of the one-dimensional electrons, as well as their phase coherence time, captured by crystallographic Fabry-Pèrot resonators. A remarkable agreement with a theoretical model reveals that the nonmonotonic behavior is driven by the unique manner in which one-dimensional hot electrons interact with the cold electrons occupying the Fermi sea. This newly discovered relaxation profile suggests a high-energy regime for operating quantum applications that necessitate extended coherence or long thermalization times, and may stabilize electronic quasiparticles in one dimension.

Recent examinations of the culture of consumption in different periods of literary history have interrogated the connections between incorporation and introjection while redefining orality as the space where speech and food meet and interact. This introduction presents an overview of the key concepts discussed in the subsequent chapters of this book. The book has affinities with some of Ellmann's attempts to delineate a general poetics of hunger that serves to raise questions about authority and political representation. By looking at the different acts of visceral, affective and ideological resistance performed by the starving body, the authors hope to open further avenues of research into areas which exceed the dominant paradigms of food and hunger studies, whether of the aesthetic or the cultural/sociological variety. Dealing with hunger and starvation as a cultural phenomenon calls for a maximalist method that uses themes, ideas and tropes as the structuring, transversal blocks.

‘Demonstration reaches’ are sections of river where multiple threats to native fish are addressed through river rehabilitation and strong community participation. They are an important way of promoting the key driving actions of the Murray-Darling Basin Authority's Native Fish Strategy (NFS) by using on-ground community-driven rehabilitation. Measuring rehabilitation success against well-defined targets and using this information to adaptively mange activities is fundamental to the demonstration reach philosophy. Seven years on from the establishment of the first demonstration reach, there are now seven throughout the Murray-Darling Basin (MDB), all in differing states of maturation and but all applying a standardised framework for monitoring native fish outcomes. In this study, we reflect on the role that demonstration reaches have played within the NFS, synthesise some key findings from 32 monitoring and evaluation outputs, and highlight some of the successes and barriers to success. We make recommendations as to how to strengthen the demonstration reach model to ensure it remains a relevant approach for fish habitat rehabilitation beyond the NFS and MDB.