Classification of Quantum Hall Universality Classes by $\ W_{1+\infty}\ $ symmetry

We show how two-dimensional incompressible quantum fluids and their excitations can be viewed as $\ W_{1+\infty}\$ edge conformal field theories, thereby providing an algebraic characterization of incompressibility. The Kac-Radul representation theory of the $\ W_{1+\infty}\$ algebra leads then to a purely algebraic complete classification of hierarchical quantum Hall states, which encompasses all measured fractions. Spin-polarized electrons in single-layer devices can only have Abelian anyon excitations.Comment: 11 pages, RevTeX 3.0, MPI-Ph/93-75 DFTT 65/9

Regularized extremal shift in problems of stable control

We discuss a technical approach, based on the method of regularized extremal shift (RES), intended to help solve problems of stable control of uncertain dynamical systems. Our goal is to demonstrate the essence and abilities of the RES technique; for this purpose we construct feedback controller for approximate tracking a prescribed trajectory of an inaccurately observed system described by a parabolic equation. The controller is "resource-saving" in a sense that control resource spent for approximate tracking do not exceed those needed for tracking in an "ideal" situation where the current values of the input disturbance are fully observable. © 2013 IFIP International Federation for Information Processing.German Sci. Found. (DFG) Eur. Sci. Found. (ESF);Natl. Inst. Res. Comput. Sci. Control France (INRIA);DFG Research Center MATHEON;Weierstrass Institute for Applied Analysis and Stochastics (WIAS);European Patent Offic

Cytosolic Fc receptor TRIM21 inhibits seeded tau aggregation

Alzheimer's disease (AD) and other neurodegenerative disorders are associated with the cytoplasmic aggregation of microtubule-associated protein tau. Recent evidence supports transcellular transfer of tau misfolding (seeding) as the mechanism of spread within an affected brain, a process reminiscent of viral infection. However, whereas microbial pathogens can be recognized as nonself by immune receptors, misfolded protein assemblies evade detection, as they are host-derived. Here, we show that when misfolded tau assemblies enter the cell, they can be detected and neutralized via a danger response mediated by tau-associated antibodies and the cytosolic Fc receptor tripartite motif protein 21 (TRIM21). We developed fluorescent, morphology-based seeding assays that allow the formation of pathological tau aggregates to be measured in situ within 24 h in the presence of picomolar concentrations of tau seeds. We found that anti-tau antibodies accompany tau seeds into the cell, where they recruit TRIM21 shortly after entry. After binding, TRIM21 neutralizes tau seeds through the activity of the proteasome and the AAA ATPase p97/VCP in a similar manner to infectious viruses. These results establish that intracellular antiviral immunity can be redirected against host-origin endopathogens involved in neurodegeneration

Sigma models as perturbed conformal field theories

We show that two-dimensional sigma models are equivalent to certain perturbed conformal field theories. When the fields in the sigma model take values in a space G/H for a group G and a maximal subgroup H, the corresponding conformal field theory is the $k\to\infty$ limit of the coset model $(G/H)_k$, and the perturbation is related to the current of G. This correspondence allows us for example to find the free energy for the "O(n)" (=O(n)/O(n-1)) sigma model at non-zero temperature. It also results in a new approach to the CP^{n} model.Comment: 4 pages. v2: corrects typos (including several in the published version

Integrability of Coupled Conformal Field Theories

The massive phase of two-layer integrable systems is studied by means of RSOS restrictions of affine Toda theories. A general classification of all possible integrable perturbations of coupled minimal models is pursued by an analysis of the (extended) Dynkin diagrams. The models considered in most detail are coupled minimal models which interpolate between magnetically coupled Ising models and Heisenberg spin-ladders along the $c<1$ discrete series.Comment: 23 pages, four figure

Single-dose immunisation with a multimerised SARS-CoV-2 receptor binding domain (RBD) induces an enhanced and protective response in mice.

The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, has triggered a worldwide health emergency. Here, we show that ferritin-like Dps from hyperthermophilic Sulfolobus islandicus, covalently coupled with SARS-CoV-2 antigens via the SpyCatcher system, forms stable multivalent dodecameric vaccine nanoparticles that remain intact even after lyophilisation. Immunisation experiments in mice demonstrated that the SARS-CoV-2 receptor binding domain (RBD) coupled to Dps (RBD-S-Dps) elicited a higher antibody titre and an enhanced neutralising antibody response compared to monomeric RBD. A single immunisation with RBD-S-Dps completely protected hACE2-expressing mice from serious illness and led to viral clearance from the lungs upon SARS-CoV-2 infection. Our data highlight that multimerised SARS-CoV-2 subunit vaccines are a highly efficacious modality, particularly when combined with an ultra-stable scaffold

Tau assemblies do not behave like independently acting prion-like particles in mouse neural tissue

Funder: Wellcome Trust; doi: http://dx.doi.org/10.13039/100004440Funder: DRIFunder: Medical Research Council; doi: http://dx.doi.org/10.13039/501100000265Funder: Takeda Pharmaceuticals U.S.A.; doi: http://dx.doi.org/10.13039/100007723Abstract: A fundamental property of infectious agents is their particulate nature: infectivity arises from independently-acting particles rather than as a result of collective action. Assemblies of the protein tau can exhibit seeding behaviour, potentially underlying the apparent spread of tau aggregation in many neurodegenerative diseases. Here we ask whether tau assemblies share with classical pathogens the characteristic of particulate behaviour. We used organotypic hippocampal slice cultures from P301S tau transgenic mice in order to precisely control the concentration of extracellular tau assemblies in neural tissue. Whilst untreated slices displayed no overt signs of pathology, exposure to recombinant tau assemblies could result in the formation of intraneuronal, hyperphosphorylated tau structures. However, seeding ability of tau assemblies did not titrate in a one-hit manner in neural tissue. The results suggest that seeding behaviour of tau arises at high concentrations, with implications for the interpretation of high-dose intracranial challenge experiments and the possible contribution of seeded aggregation to human disease

Tau assemblies do not behave like independently acting prion-like particles in mouse neural tissue

Funder: Wellcome Trust; doi: http://dx.doi.org/10.13039/100004440Funder: DRIFunder: Medical Research Council; doi: http://dx.doi.org/10.13039/501100000265Funder: Takeda Pharmaceuticals U.S.A.; doi: http://dx.doi.org/10.13039/100007723Abstract: A fundamental property of infectious agents is their particulate nature: infectivity arises from independently-acting particles rather than as a result of collective action. Assemblies of the protein tau can exhibit seeding behaviour, potentially underlying the apparent spread of tau aggregation in many neurodegenerative diseases. Here we ask whether tau assemblies share with classical pathogens the characteristic of particulate behaviour. We used organotypic hippocampal slice cultures from P301S tau transgenic mice in order to precisely control the concentration of extracellular tau assemblies in neural tissue. Whilst untreated slices displayed no overt signs of pathology, exposure to recombinant tau assemblies could result in the formation of intraneuronal, hyperphosphorylated tau structures. However, seeding ability of tau assemblies did not titrate in a one-hit manner in neural tissue. The results suggest that seeding behaviour of tau arises at high concentrations, with implications for the interpretation of high-dose intracranial challenge experiments and the possible contribution of seeded aggregation to human disease