Language models for protein design.

The recent surge of large language models has shown that machines are capable of reading, understanding, and communicating through language, even sometimes displaying capabilities surpassing those of humans. Proteins can be represented as strings of amino acids akin to words in a sentence, and the same principles of language modeling can be used to learn informative representations for protein structure prediction, design, and property prediction. In this review, we will focus on applications of language modeling to protein design.

Superfluid stiffness of twisted trilayer graphene superconductors.

The robustness of the macroscopic quantum nature of a superconductor can be characterized by the superfluid stiffness, ρ, a quantity that describes the energy required to vary the phase of the macroscopic quantum wavefunction. In unconventional superconductors, such as cuprates, the low-temperature behaviour of ρ markedly differs from that of conventional superconductors owing to quasiparticle excitations from gapless points (nodes) in momentum space. Intensive research on the recently discovered magic-angle twisted graphene family has revealed, in addition to superconducting states, strongly correlated electronic states associated with spontaneously broken symmetries, inviting the study of ρ to uncover the potentially unconventional nature of its superconductivity.

Double-sided van der Waals epitaxy of topological insulators across an atomically thin membrane.

Atomically thin van der Waals (vdW) films provide a material platform for the epitaxial growth of quantum heterostructures. However, unlike the remote epitaxial growth of three-dimensional bulk crystals, the growth of two-dimensional material heterostructures across atomic layers has been limited due to the weak vdW interaction. Here we report the double-sided epitaxy of vdW layered materials through atomic membranes.

FlowPacker: protein side-chain packing with torsional flow matching.

Motivation: Accurate prediction of protein side-chain conformations is necessary to understand protein folding, protein-protein interactions and facilitate de novo protein design.

Results: Here, we apply torsional flow matching and equivariant graph attention to develop FlowPacker, a fast and performant model to predict protein side-chain conformations conditioned on the protein sequence and backbone. We show that FlowPacker outperforms previous state-of-the-art baselines across most metrics with improved runtime.

A High-Throughput Method for Screening Peptide Activators of G-Protein-Coupled Receptors.

Here, we describe an innovative and efficient method for screening peptide activators of G-protein-coupled receptors (GPCRs) utilizing a protein-protein interaction (PPI) approach. We designed a library of 92,918 peptides fused with transmembrane domains of glycosylphosphatidylinositol-anchored proteins (GPI-APs). We employed a pooled lentiviral system to promote the expression of these proteins at the cellular membrane and evaluate their ability to activate GPCRs.

UOTe: Kondo-Interacting Topological Antiferromagnet in a Van der Waals Lattice.

Since the initial discovery of 2D van der Waals (vdW) materials, significant effort has been made to incorporate the three properties of magnetism, band structure topology, and strong electron correlations-to leverage emergent quantum phenomena and expand their potential applications. However, the discovery of a single vdW material that intrinsically hosts all three ingredients has remained an outstanding challenge. Here, the discovery of a Kondo-interacting topological antiferromagnet is reported in the vdW 5f electron system UOTe.

EuDockScore: Euclidean graph neural networks for scoring protein-protein interfaces.

Motivation: Protein-protein interactions are essential for a variety of biological phenomena including mediating biochemical reactions, cell signaling, and the immune response. Proteins seek to form interfaces which reduce overall system energy. Although determination of single polypeptide chain protein structures has been revolutionized by deep learning techniques, complex prediction has still not been perfected.

Twelve-month results from a randomized controlled trial comparing differential target multiplexed spinal cord stimulation and conventional spinal cord stimulation in subjects with chronic refractory axial low back pain not eligible for spine surgery.

Background: Successful treatments for intractable chronic low back pain (CLBP) in patients who are not eligible for surgical interventions are scarce. The superior efficacy of differential target multiplexed spinal cord stimulation (DTM SCS) to conventional SCS (Conv-SCS) on the treatment of CLBP in patients with persistent spinal pain syndrome (PSPS) who have failed surgical interventions (PSPS-T2) motivated the evaluation of DTM SCS versus Conv-SCS on PSPS patients who are non-surgical candidates (PSPS-T1).

Methods: This is a prospective, open label, crossover, post-market randomized controlled trial in 20 centers across the United States.

Antibody-SGM, a Score-Based Generative Model for Antibody Heavy-Chain Design.

Traditional computational methods for antibody design involved random mutagenesis followed by energy function assessment for candidate selection. Recently, diffusion models have garnered considerable attention as cutting-edge generative models, lauded for their remarkable performance. However, these methods often focus solely on the backbone or sequence, resulting in the incomplete depiction of the overall structure and necessitating additional techniques to predict the missing component.

Controlled interlayer exciton ionization in an electrostatic trap in atomically thin heterostructures.

Atomically thin semiconductor heterostructures provide a two-dimensional (2D) device platform for creating high densities of cold, controllable excitons. Interlayer excitons (IEs), bound electrons and holes localized to separate 2D quantum well layers, have permanent out-of-plane dipole moments and long lifetimes, allowing their spatial distribution to be tuned on demand. Here, we employ electrostatic gates to trap IEs and control their density.

Strongly coupled edge states in a graphene quantum Hall interferometer.

Electronic interferometers using the chiral, one-dimensional (1D) edge channels of the quantum Hall effect (QHE) can demonstrate a wealth of fundamental phenomena. The recent observation of phase jumps in a Fabry-Pérot (FP) interferometer revealed anyonic quasiparticle exchange statistics in the fractional QHE. When multiple integer edge channels are involved, FP interferometers have exhibited anomalous Aharonov-Bohm (AB) interference frequency doubling, suggesting putative pairing of electrons into quasiparticles.

Differential Target Multiplexed Spinal Cord Stimulation for the Treatment of Chronic Intractable Upper Limb Pain: 12-Month Results From a Prospective, Multicenter Study.

Objectives: This prospective, open-label, single-arm, multicenter study evaluated the use of differential target multiplexed (DTM) spinal cord stimulation (SCS) therapy for chronic upper limb pain (ULP).

Materials And Methods: A total of 58 candidates for SCS who had chronic ULP were enrolled at 11 sites in the USA. The safety and effectiveness of DTM SCS for treating chronic intractable ULP were evaluated over 12 months.

In situ via Contact to hBN-Encapsulated Air-Sensitive Atomically Thin Semiconductors.

Establishing reliable electrical contacts to atomically thin materials is a prerequisite for both fundamental studies and applications yet remains a challenge. In particular, the development of contact techniques for air-sensitive monolayers has lagged behind, despite their unique properties and significant potential for applications. Here, we present a robust method to create contacts to device layers encapsulated within hexagonal boron nitride (hBN).

Magneto-Thermoelectric Transport in Graphene Quantum Dot with Strong Correlations.

Disorder at etched edges of graphene quantum dots (GQD) enables random all-to-all interactions between localized charges in partially filled Landau levels, providing a potential platform to realize the Sachdev-Ye-Kitaev (SYK) model. We use quantum Hall edge states in the graphene electrodes to measure electrical conductance and thermoelectric power across the GQD. In specific temperature ranges, we observe a suppression of electric conductance fluctuations and slowly decreasing thermoelectric power across the GQD with increasing temperature, consistent with recent theory for the SYK regime.

A two-site Kitaev chain in a two-dimensional electron gas.

Artificial Kitaev chains can be used to engineer Majorana bound states (MBSs) in superconductor-semiconductor hybrids. In this work, we realize a two-site Kitaev chain in a two-dimensional electron gas by coupling two quantum dots through a region proximitized by a superconductor. We demonstrate systematic control over inter-dot couplings through in-plane rotations of the magnetic field and via electrostatic gating of the proximitized region.

Targeted Nerve Root Stimulation Alleviates Intractable Chronic Limb Pain Associated with Complex Regional Pain Syndrome - A Prospective Multi-Center Feasibility Study.

Background: There are limited therapeutic options to treat complex regional pain syndrome (CRPS). Spinal cord stimulation and dorsal root ganglion stimulation are proven therapies for treating chronic low limb pain in CRPS patients. There is limited evidence that stimulation of dorsal nerve roots can also provide relief of lower limb pain in these patients.

Engineering a Rigid Nucleic Acid Structure to Improve the Limit of Detection for Genetic Assays.

Detecting nucleic acids at ultralow concentrations is critical for research and clinical applications. Particle-based assays are commonly used to detect nucleic acids. However, DNA hybridization on particle surfaces is inefficient due to the instability of tethered sequences, which negatively influences the assay's detection sensitivity.

Transport Study of Charge-Carrier Scattering in Monolayer WSe_{2}.

Employing flux-grown single crystal WSe_{2}, we report charge-carrier scattering behaviors measured in h-BN encapsulated monolayer field effect transistors. We observe a nonmonotonic change of transport mobility as a function of hole density in the degenerately doped sample, which can be explained by energy dependent scattering amplitude of strong defects calculated using the T-matrix approximation. Utilizing long mean-free path (>500  nm), we also demonstrate the high quality of our electronic devices by showing quantized conductance steps from an electrostatically defined quantum point contact, showing the potential for creating ultrahigh quality quantum optoelectronic devices based on atomically thin semiconductors.

Two-dimensional heavy fermions in the van der Waals metal CeSiI.

Heavy-fermion metals are prototype systems for observing emergent quantum phases driven by electronic interactions. A long-standing aspiration is the dimensional reduction of these materials to exert control over their quantum phases, which remains a significant challenge because traditional intermetallic heavy-fermion compounds have three-dimensional atomic and electronic structures. Here we report comprehensive thermodynamic and spectroscopic evidence of an antiferromagnetically ordered heavy-fermion ground state in CeSiI, an intermetallic comprising two-dimensional (2D) metallic sheets held together by weak interlayer van der Waals (vdW) interactions.

Score-based generative modeling for de novo protein design.

The generation of de novo protein structures with predefined functions and properties remains a challenging problem in protein design. Diffusion models, also known as score-based generative models (SGMs), have recently exhibited astounding empirical performance in image synthesis. Here we use image-based representations of protein structure to develop ProteinSGM, a score-based generative model that produces realistic de novo proteins.

Drug-Free Noninvasive Thermal Nerve Block: Validation of Sham Devices.

Headache is a leading cause of disability and suffering. One major challenge in developing device treatments is demonstrating their efficacy given devices' often-high placebo rate. This paper reviews the importance of validating sham devices as part of finalizing the design for larger-scale prospective randomized controlled trials in patients with chronic headache as well as the results of a prospective, single-blind trial to validate two potential sham noninvasive thermal nerve block devices.

Time-reversal symmetry breaking superconductivity between twisted cuprate superconductors.

Twisted interfaces between stacked van der Waals (vdW) cuprate crystals present a platform for engineering superconducting order parameters by adjusting stacking angles. Using a cryogenic assembly technique, we construct twisted vdW Josephson junctions (JJs) at atomically sharp interfaces between BiSrCaCuO crystals, with quality approaching the limit set by intrinsic JJs. Near 45° twist angle, we observe fractional Shapiro steps and Fraunhofer patterns, consistent with the existence of two degenerate Josephson ground states related by time-reversal symmetry (TRS).

Evaluation of a STAT MRI Protocol for Patients with Optic Disc Edema.

Background: Evaluating patients with potentially sight-threatening conditions frequently involves urgent neuroimaging, and some providers recommend expediting emergency department (ED) evaluation. However, several factors may limit the practicality of ED evaluation. This pilot study assessed the feasibility and safety of a STAT magnetic resonance imaging (MRI) protocol, designed to facilitate outpatient MRI within 48 hours of referral, compared with ED evaluation for patients with optic disc edema.