On Computational Complexity of Clifford Algebra

After a brief discussion of the computational complexity of Clifford algebras, we present a new basis for even Clifford algebra Cl(2m) that simplifies greatly the actual calculations and, without resorting to the conventional matrix isomorphism formulation, obtains the same complexity. In the last part we apply these results to the Clifford algebra formulation of the NP-complete problem of the maximum clique of a graph introduced in a previous paper.Comment: 13 page

Electrochromic Polymer Ink Derived from a Sidechain-Modified EDOT for Electrochromic Devices with Colorless Bright State

AbstractPrintable organic electrochromic materials are the key component of flexible low power and low weight displays and dynamic shading systems. A vast number of more or less well‐performing materials is reported in the literature, but only a very limited number of them have been tested in an industrially‐relevant environment so far. Upscaling requires simplicity of synthesis, overall sustainability, low cost and compatibility with simple and high throughput wet‐chemical deposition techniques, such as slot‐die coating or inkjet printing. In the present paper, an original process is described that enables the controlled oxidative polymerization of a water insoluble, functionalized 3,4‐ethylene dioxythiophene (EDOT) derivative. This process leads to the formation of an ink that consists solely of active polymeric material (no dispersing agents) and has suitable rheological properties for use in roll‐to‐roll slot‐die coating or ink‐jet printing. The straightforward deposition, followed by a simple thermal treatment, directly yields stable and homogeneous thin films with state‐of‐the‐art electrochromic performance

Quality-Diversity through AI Feedback

In many text-generation problems, users may prefer not only a single response, but a diverse range of high-quality outputs from which to choose. Quality-diversity (QD) search algorithms aim at such outcomes, by continually improving and diversifying a population of candidates. However, the applicability of QD to qualitative domains, like creative writing, has been limited by the difficulty of algorithmically specifying measures of quality and diversity. Interestingly, recent developments in language models (LMs) have enabled guiding search through AI feedback, wherein LMs are prompted in natural language to evaluate qualitative aspects of text. Leveraging this development, we introduce Quality-Diversity through AI Feedback (QDAIF), wherein an evolutionary algorithm applies LMs to both generate variation and evaluate the quality and diversity of candidate text. When assessed on creative writing domains, QDAIF covers more of a specified search space with high-quality samples than do non-QD controls. Further, human evaluation of QDAIF-generated creative texts validates reasonable agreement between AI and human evaluation. Our results thus highlight the potential of AI feedback to guide open-ended search for creative and original solutions, providing a recipe that seemingly generalizes to many domains and modalities. In this way, QDAIF is a step towards AI systems that can independently search, diversify, evaluate, and improve, which are among the core skills underlying human society's capacity for innovation.Comment: minor additions to supplementary result

New Roll‐to‐Roll Processable PEDOT‐Based Polymer with Colorless Bleached State for Flexible Electrochromic Devices

Conjugated electrochromic (EC) polymers for flexible EC devices (ECDs) generally lack a fully colorless bleached state. A strategy to overcome this drawback is the implementation of a new sidechain-modified poly(3,4-ethylene dioxythiophene) derivative that can be deposited in thin-film form in a customized high-throughput and large-area roll-to-roll polymerization process. The sidechain modification provides enhanced EC properties in terms of visible light transmittance change, Δτv = 59% (ΔL* = 54.1), contrast ratio (CR = 15.8), coloration efficiency (η = 530 cm² C−1), and color neutrality (L* = 83.8, a* = −4.3, b* = −4.1) in the bleached state. The intense blue-colored polymer thin films exhibit high cycle stability (10 000 cycles) and fast response times. The design, synthesis, and polymerization of the modified 3,4-ethylene dioxythiophene derivative are discussed along with a detailed optical, electrochemical, and spectroelectrochemical characterization of the resulting EC thin films. Finally, a flexible see-through ECD with a visible light transmittance change of Δτv = 47% (ΔL* = 51.9) and a neutral-colored bleached state is developed

A small molecule restores function to TRPML1 mutant isoforms responsible for mucolipidosis type IV

Mucolipidosis type IV (MLIV) is an autosomal recessive lysosomal storage disorder often characterized by severe neurodevelopmental abnormalities and neuro-retinal degeneration. Mutations in the TRPML1 gene are causative for MLIV. We used lead optimization strategies to identify-and MLIV patient fibroblasts to test-small-molecule activators for their potential to restore TRPML1 mutant channel function. Using the whole-lysosome planar patch-clamp technique, we found that activation of MLIV mutant isoforms by the endogenous ligand PI(3, 5)P-2 is strongly reduced, while activity can be increased using synthetic ligands. We also found that the F465L mutation renders TRPML1 pH insensitive, while F408 Delta impacts synthetic ligand binding. Trafficking defects and accumulation of zinc in lysosomes of MLIV mutant fibroblasts can be rescued by the small molecule treatment. Collectively, our data demonstrate that small molecules can be used to restore channel function and rescue disease associated abnormalities in patient cells expressing specific MLIV point mutations

A small molecule restores function to TRPML1 mutant isoforms responsible for mucolipidosis type IV

Mucolipidosis type IV (MLIV) is an autosomal recessive lysosomal storage disorder often characterized by severe neurodevelopmental abnormalities and neuro-retinal degeneration. Mutations in the TRPML1 gene are causative for MLIV. We used lead optimization strategies to identify-and MLIV patient fibroblasts to test-small-molecule activators for their potential to restore TRPML1 mutant channel function. Using the whole-lysosome planar patch-clamp technique, we found that activation of MLIV mutant isoforms by the endogenous ligand PI(3, 5)P-2 is strongly reduced, while activity can be increased using synthetic ligands. We also found that the F465L mutation renders TRPML1 pH insensitive, while F408 Delta impacts synthetic ligand binding. Trafficking defects and accumulation of zinc in lysosomes of MLIV mutant fibroblasts can be rescued by the small molecule treatment. Collectively, our data demonstrate that small molecules can be used to restore channel function and rescue disease associated abnormalities in patient cells expressing specific MLIV point mutations

Genetic study of multimodal imaging Alzheimer’s disease progression score implicates novel loci

International audienc

Agonist-mediated switching of ion selectivity in TPC2 differentially promotes lysosomal function

Ion selectivity is a defining feature of a given ion channel and is considered immutable. Here we show that ion selectivity of the lysosomal ion channel TPC2, which is hotly debated (Calcraft et al., 2009;Guo et al., 2017;Jha et al., 2014;Ruas et al., 2015;Wang et al., 2012), depends on the activating ligand. A high-throughput screen identified two structurally distinct TPC2 agonists. One of these evoked robust Ca2+-signals and non-selective cation currents, the other weaker Ca2+-signals and Na+-selective currents. These properties were mirrored by the Ca2+ mobilizing messenger, NAADP and the phosphoinositide, PI(3,5)P-2, respectively. Agonist action was differentially inhibited by mutation of a single TPC2 residue and coupled to opposing changes in lysosomal pH and exocytosis. Our findings resolve conflicting reports on the permeability and gating properties of TPC2 and they establish a new paradigm whereby a single ion channel mediates distinct, functionally-relevant ionic signatures on demand

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Measurement of the quasi-elastic axial vector mass in neutrino-oxygen interactions

The weak nucleon axial-vector form factor for quasi-elastic interactions is determined using neutrino interaction data from the K2K Scintillating Fiber detector in the neutrino beam at KEK. More than 12,000 events are analyzed, of which half are charged-current quasi-elastic interactions nu-mu n to mu- p occurring primarily in oxygen nuclei. We use a relativistic Fermi gas model for oxygen and assume the form factor is approximately a dipole with one parameter, the axial vector mass M_A, and fit to the shape of the distribution of the square of the momentum transfer from the nucleon to the nucleus. Our best fit result for M_A = 1.20 \pm 0.12 GeV. Furthermore, this analysis includes updated vector form factors from recent electron scattering experiments and a discussion of the effects of the nucleon momentum on the shape of the fitted distributions.Comment: 14 pages, 10 figures, 6 table