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A superconducting quantum simulator based on a photonic-bandgap metamaterial
No full textSynthesizing many-body quantum systems with various ranges of interactions facilitates the study of quantum chaotic dynamics. Such extended interaction range can be enabled by using nonlocal degrees of freedom such as photonic modes in an otherwise locally connected structure. Here, we present a superconducting quantum simulator in which qubits are connected through an extensible photonic-bandgap metamaterial, thus realizing a one-dimensional Bose-Hubbard model with tunable hopping range and on-site interaction. Using individual site control and readout, we characterize the statistics of measurement outcomes from many-body quench dynamics, which enables in situ Hamiltonian learning. Further, the outcome statistics reveal the effect of increased hopping range, showing the predicted crossover from integrability to ergodicity. Our work enables the study of emergent randomness from chaotic many-body evolution and, more broadly, expands the accessible Hamiltonians for quantum simulation using superconducting circuits
A rapid, multiplex digital PCR assay for EGFR, KRAS, BRAF, ERBB2 variants and ALK, RET, ROS1, NTRK1 gene fusions in non-small cell lung cancer
No full textDigital PCR (dPCR) is emerging as an ideal platform for the detection and tracking of genomic variants in cancer due to its high sensitivity and simple workflow. The growing number of clinically-actionable cancer biomarkers creates a need for fast, accessible methods that allow for dense information content and high accuracy. Here, we describe a proof-of-concept amplitude modulation based multiplex dPCR assay capable of detecting 12 single nucleotide and indel variants in EGFR, KRAS, BRAF, and ERBB2, 14 gene fusions in ALK, RET, ROS1, NTRK1, and MET exon 14 skipping present in non-small cell lung cancer (NSCLC). We also demonstrate the use of multi-spectral target signal encoding to improve the specificity of variant detection by reducing background noise up to 11-fold. The assay reported an overall 100% PPA and 98.5% NPA compared to a sequencing-based assay in a cohort of 62 human FFPE samples. In addition, the dPCR assay rescued actionable information in 10 samples that failed to sequence, highlighting the utility of a multiplexed digital assay as a potential reflex solution for challenging NSCLC samples
Pervasive, conserved secondary structure in highly charged protein regions
No full textUnderstanding how protein sequences confer function remains a defining challenge in molecular biology. Two approaches have yielded enormous insight yet are often pursued separately: structure-based, where sequence-encoded structures mediate function, and disorder-based, where sequences dictate physicochemical and dynamical properties which determine function in the absence of stable structure. Here we study highly charged protein regions (>40% charged residues), which are routinely presumed to be disordered. Using recent advances in structure prediction and experimental structures, we show that roughly 40% of these regions form well-structured helices. Features often used to predict disorder—high charge density, low hydrophobicity, low sequence complexity, and evolutionarily varying length—are also compatible with solvated, variable-length helices. We show that a simple composition classifier predicts the existence of structure far better than well-established heuristics based on charge and hydropathy. We show that helical structure is more prevalent than previously appreciated in highly charged regions of diverse proteomes and characterize the conservation of highly charged regions. Our results underscore the importance of integrating, rather than choosing between, structure- and disorder-based approaches
Large-scale brain-wide neural recording in nonhuman primates
No full textHigh-density, integrated silicon electrodes have begun to transform systems neuroscience, by enabling large-scale neural population recordings with single cell resolution. Existing technologies, however, have provided limited functionality in nonhuman primate species such as macaques, which offer close models of human cognition and behavior. Here, we report the design, fabrication, and performance of Neuropixels 1.0-NHP, a high channel count linear electrode array designed to enable large-scale simultaneous recording in superficial and deep structures within the macaque or other large animal brain. These devices were fabricated in two versions: 4416 electrodes along a 45 mm shank, and 2496 along a 25 mm shank. For both versions, users can programmably select 384 channels, enabling simultaneous multi-area recording with a single probe. We demonstrate recording from over 3000 single neurons within a session, and simultaneous recordings from over 1000 neurons using multiple probes. This technology represents a significant increase in recording access and scalability relative to existing technologies, and enables new classes of experiments involving fine-grained electrophysiological characterization of brain areas, functional connectivity between cells, and simultaneous brain-wide recording at scale
Stringy Dynamics from an Amplitudes Bootstrap
No full textWe describe an analytic procedure whereby scattering amplitudes are bootstrapped directly from an input mass spectrum and a handful of physical constraints: crossing symmetry, boundedness at high energies, and finiteness of exchanged spins. For an integer spectrum, this procedure gives a first principles derivation of a new infinite parameter generalization of the Veneziano amplitude that is unitary while exhibiting dual resonance and consistent high-energy behavior. Lifting to a q-deformed integer spectrum, we derive the Coon amplitude and its analogous generalizations. Finally, we apply this logic to derive an infinite class of deformed Virasoro-Shapiro amplitudes
Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamics
No full textSARS-CoV-2 emergent variants are characterized by increased viral fitness and each shows multiple mutations predominantly localized to the spike (S) protein. Here, amide hydrogen/deuterium exchange mass spectrometry has been applied to track changes in S dynamics from multiple SARS-CoV-2 variants. Our results highlight large differences across variants at two loci with impacts on S dynamics and stability. A significant enhancement in stabilization first occurred with the emergence of D614G S followed by smaller, progressive stabilization in subsequent variants. Stabilization preceded altered dynamics in the N-terminal domain, wherein Omicron BA.1 S showed the largest magnitude increases relative to other preceding variants. Changes in stabilization and dynamics resulting from S mutations detail the evolutionary trajectory of S in emerging variants. These carry major implications for SARS-CoV-2 viral fitness and offer new insights into variant-specific therapeutic development
Identification of potential solid-state Li-ion conductors with semi-supervised learning
No full textDespite ongoing efforts to identify high-performance electrolytes for solid-state Li-ion batteries, thousands of prospective Li-containing structures remain unexplored. Here, we employ a semi-supervised learning approach to expedite identification of ionic conductors. We screen 180 unique descriptor representations and use agglomerative clustering to cluster ~26,000 Li-containing structures. The clusters are then labeled with experimental ionic conductivity data to assess the fitness of the descriptors. By inspecting clusters containing the highest conductivity labels, we identify 212 promising structures that are further screened using bond valence site energy and nudged elastic band calculations. Li₃BS₃ is identified as a potential high-conductivity material and selected for experimental characterization. With sufficient defect engineering, we show that Li₃BS₃ is a superionic conductor with room temperature ionic conductivity greater than 1 mS cm⁻¹. While the semi-supervised method shows promise for identification of superionic conductors, the results illustrate a continued need for descriptors that explicitly encode for defects
A User-friendly Graphical User Interface for Dynamic Light Scattering Data Analysis
No full textDynamic light scattering (DLS) is a commonly used analytical tool for characterizing the size distribution of colloids in a dispersion or a solution. Typically, the intensity of a scattering produced from the sample at a fixed angle from an incident laser beam is recorded as a function of time and converted into time autocorrelation data, which can be inverted to estimate the distribution of colloid diffusivity to estimate the colloid size distribution. For polydisperse samples, this inversion problem, being a Fredholm integral equation of the first kind, is ill-posed and is typically handled using cumulant expansions or regularization methods. Here, we introduce a user-friendly graphical user interface (GUI) for analyzing the measured scattering intensity time autocorrelation data using both the cumulant expansion method and regularization methods, with the latter implemented using various commonly employed algorithms including NNLS, CONTIN, REPES, and DYNALS. Additionally, the GUI also enables a comparison of the size distributions generated by various algorithms and an evaluation of their performance. We present the fit results obtained from the GUI for model monomodal and bimodal dispersions to highlight the strengths, limitations, and scope of applicability of these algorithms for analyzing time autocorrelation data from DLS
A High-resolution Optical Survey of Upper Sco: Evidence for Coevolution of Accretion and Disk Winds
No full textMagnetohydrodynamic (MHD) and photoevaporative winds are thought to play an important role in the evolution and dispersal of planet-forming disks. Here, we analyze high-resolution (Δv ∼ 7 km s⁻¹) optical spectra from a sample of 115 T Tauri stars in the ∼5–10 Myr Upper Sco association and focus on the [O I] λ6300 and Hα lines to trace disk winds and accretion, respectively. Our sample covers a large range of spectral types and we divide it into warm (G0-M3) and cool (later than M3) to facilitate comparison with younger regions. We detect the [O I] λ6300 line in 45 out of 87 Upper Sco sources with protoplanetary disks and 32 out of 45 are accreting based on Hα profiles and equivalent widths. All [O I] λ6300 Upper Sco profiles have low-velocity (centroid < −30 km s⁻¹; low-velocity component (LVC)) emission and most (36/45) can be fit by a single Gaussian (SC). The single-component (SC) distribution of centroid velocities and FWHMs is consistent with MHD disk winds. We also find that the Upper Sco sample follows the same accretion luminosity−LVC [O I] λ6300 relation and the same anticorrelation between SC FWHM and Wide-field Infrared Survey Explorer W3-W4 spectral indices as the younger samples. These results indicate that accretion and disk winds coevolve and that, as inner disks clear out, wind emission arises further away from the star. Finally, our large spectral range coverage reveals that cool stars have larger FWHMs normalized by stellar mass than warm stars indicating that [O I] λ6300 emission arises closer in toward lower-mass/lower luminosity stars
Controls on Wintertime Ventilation in Southern Drake Passage
No full textDrake Passage is a key region for transport between the surface and interior ocean, but a mechanistic understanding of this exchange remains immature. Here, we present wintertime, submesoscale-resolving hydrographic transects spanning the southern boundary of the Antarctic Circumpolar Current and the Polar Front (PF). Despite the strong surface wind and buoyancy forcing, a freshwater lens suppresses surface-interior exchange south of the PF; ventilation is instead localized to the PF. Multiple lines of the analysis suggest submesoscale processes contribute to ventilation at the PF, including small-scale, O(10 km), frontal structure in water mass properties below the mixed layer and modulation of a surface eddy diffusivity at sub-50 km scales. These results show that ventilation is sensitive to both submesoscale properties near fronts and non-local processes, for example, sea-ice melt, that set stratification and mixed layer properties. This highlights the need for adaptive observing strategies to constrain Southern Ocean heat and carbon budgets