Reflexion: Language Agents with Verbal Reinforcement Learning

Large language models (LLMs) have been increasingly used to interact with external environments (e.g., games, compilers, APIs) as goal-driven agents. However, it remains challenging for these language agents to quickly and efficiently learn from trial-and-error as traditional reinforcement learning methods require extensive training samples and expensive model fine-tuning. We propose Reflexion, a novel framework to reinforce language agents not by updating weights, but instead through linguistic feedback. Concretely, Reflexion agents verbally reflect on task feedback signals, then maintain their own reflective text in an episodic memory buffer to induce better decision-making in subsequent trials. Reflexion is flexible enough to incorporate various types (scalar values or free-form language) and sources (external or internally simulated) of feedback signals, and obtains significant improvements over a baseline agent across diverse tasks (sequential decision-making, coding, language reasoning). For example, Reflexion achieves a 91% pass@1 accuracy on the HumanEval coding benchmark, surpassing the previous state-of-the-art GPT-4 that achieves 80%. We also conduct ablation and analysis studies using different feedback signals, feedback incorporation methods, and agent types, and provide insights into how they affect performance.Comment: v4 contains a few additional experiment

Low-cost, bottom-up fabrication of large-scale single-molecule nanoarrays by DNA origami placement

Large-scale nanoarrays of single biomolecules enable high-throughput assays while unmasking the underlying heterogeneity within ensemble populations. Until recently, creating such grids which combine the unique advantages of microarrays and single-molecule experiments (SMEs) has been particularly challenging due to the mismatch between the size of these molecules and the resolution of top-down fabrication techniques. DNA Origami Placement (DOP) combines two powerful techniques to address this issue: (i) DNA origami, which provides a 100-nm self-assembled template for single-molecule organization with 5 nm resolution, and (ii) top-down lithography, which patterns these DNA nanostructures, transforming them into functional nanodevices via large-scale integration with arbitrary substrates. Presently, this technique relies on state-of-the-art infrastructure and highly-trained personnel, making it prohibitively expensive for researchers. Here, we introduce a bench-top technique to create meso-to-macro-scale DNA origami nanoarrays using self-assembled colloidal nanoparticles, thereby circumventing the need for top-down fabrication. We report a maximum yield of 74%, two-fold higher than the statistical limit of 37% imposed on non-specific molecular loading alternatives. Furthermore, we provide a proof-of-principle for the ability of this nanoarray platform to transform traditionally low-throughput, stochastic, single-molecule assays into high-throughput, deterministic ones, without compromising data quality. Our approach has the potential to democratize single-molecule nanoarrays and demonstrates their utility as a tool for biophysical assays and diagnostics

Plasmonic nanostructures through DNA-assisted lithography

Programmable self-assembly of nucleic acids enables the fabrication of custom, precise objects with nanoscale dimensions. These structures can be further harnessed as templates to build novel materials such as metallic nanostructures, which are widely used and explored because of their unique optical properties and their potency to serve as components of novel metamaterials. However, approaches to transfer the spatial information of DNA constructions to metal nanostructures remain a challenge. We report a DNA-assisted lithography (DALI) method that combines the structural versatility of DNA origami with conventional lithography techniques to create discrete, well-defined, and entirely metallic nanostructures with designed plasmonic properties. DALI is a parallel, high-throughput fabrication method compatible with transparent substrates, thus providing an additional advantage for optical measurements, and yields structures with a feature size of ~10 nm. We demonstrate its feasibility by producing metal nanostructures with a chiral plasmonic response and bowtie-shaped nanoantennas for surface-enhanced Raman spectroscopy. We envisage that DALI can be generalized to large substrates, which would subsequently enable scale-up production of diverse metallic nanostructures with tailored plasmonic features.Peer reviewe

Absolute and arbitrary orientation of single molecule shapes

DNA origami is a modular platform for the combination of molecular and colloidal components to create optical, electronic, and biological devices. Integration of such nanoscale devices with microfabricated connectors and circuits is challenging: large numbers of freely diffusing devices must be fixed at desired locations with desired alignment. We present a DNA origami molecule whose energy landscape on lithographic binding sites has a unique maximum. This property enables device alignment within 3.2∘ on SiO_2. Orientation is absolute (all degrees of freedom are specified) and arbitrary (every molecule's orientation is independently specified). The use of orientation to optimize device performance is shown by aligning fluorescent emission dipoles within microfabricated optical cavities. Large-scale integration is demonstrated via an array of 3,456 DNA origami with 12 distinct orientations, which indicates the polarization of excitation light

Low-cost, bottom-up fabrication of large-scale single-molecule nanoarrays by DNA origami placement

Large-scale nanoarrays of single biomolecules enable high-throughput assays while unmasking the underlying heterogeneity within ensemble populations. Until recently, creating such grids which combine the unique advantages of microarrays and single-molecule experiments (SMEs) has been particularly challenging due to the mismatch between the size of these molecules and the resolution of top-down fabrication techniques. DNA Origami Placement (DOP) combines two powerful techniques to address this issue: (i) DNA origami, which provides a 100-nm self-assembled template for single-molecule organization with 5 nm resolution, and (ii) top-down lithography, which patterns these DNA nanostructures, transforming them into functional nanodevices via large-scale integration with arbitrary substrates. Presently, this technique relies on state-of-the-art infrastructure and highly-trained personnel, making it prohibitively expensive for researchers. Here, we introduce a bench-top technique to create meso-to-macro-scale DNA origami nanoarrays using self-assembled colloidal nanoparticles, thereby circumventing the need for top-down fabrication. We report a maximum yield of 74%, two-fold higher than the statistical limit of 37% imposed on non-specific molecular loading alternatives. Furthermore, we provide a proof-of-principle for the ability of this nanoarray platform to transform traditionally low-throughput, stochastic, single-molecule assays into high-throughput, deterministic ones, without compromising data quality. Our approach has the potential to democratize single-molecule nanoarrays and demonstrates their utility as a tool for biophysical assays and diagnostics

Absolute and arbitrary orientation of single-molecule shapes

Introduction: Molecular and particulate nanodevices such as carbon nanotubes and semiconductor nanowires exhibit properties that are difficult to achieve with conventional silicon microfabrication. Unfortunately, most such devices must be synthesized or processed in solution. To combine nanodevices into larger circuits, or simply to connect them with the macroscopic world, scientists use a range of directed self-assembly techniques to deposit them at specific locations on microfabricated chips. Many such methods work well with spherical devices for which orientation is irrelevant. For linear wire-like devices, flow or field alignment works for applications involving a single global orientation. However, a general solution for multiple orientations or less symmetric devices (e.g., diodes or transistors) has remained elusive. Rationale: Single-molecule DNA origami shapes can simultaneously act as templates to create nanodevices and as adaptors to integrate them onto chips. With 200 attachment sites just 5 nm apart, origami can organize any material that can be linked to DNA; for example, carbon nanotube crosses have been templated to yield field-effect transistors. With ~100-nm outlines, origami are large enough that shape-matched binding sites can be written at arbitrary positions on chips using electron-beam lithography. Our prior work used equilateral triangles that stuck to binding sites in six degenerate orientations. Here, we asked whether origami shapes could provide both absolute orientation (to uniquely orient asymmetric devices) and arbitrary orientation (to independently orient each device). Success depended on finding a suitably asymmetric shape. Results: To break up-down symmetry and to ensure that each shape was deposited right-side up, we added adhesion-decreasing single-stranded DNAs to one side of each origami. The binding of asymmetric right triangles to shape-matched sites gave orientation distributions consistent with strong kinetic trapping, as predicted by the volumes of basins of attraction around local minima. This motivated the design of a “small moon” shape whose energy landscape has a single minimum. Fluorescent molecular dipoles fixed to small moons served as model nanodevices and allowed us to measure variability in orientation (±3.2°) by polarization microscopy. Large-scale integration was demonstrated by an array of 3456 small moons in 12 orientations, which we used as a fluorescence polarimeter to indicate excitation polarization. The utility of orientation for optimizing device performance was shown by aligning fluorescent dipoles within microfabricated optical cavities, which showed a factor of 4.5 increase in emission. Conclusion: Control over optical dipole orientation may enable metal nanorod metasurfaces at visible wavelengths, optimized coupling of emitters to nanoantennas, lumped nanocircuits, and coherence effects between small numbers of emitters. Still, these applications and the devices we present do not demonstrate the full power of the small moons: Dipolar devices can rotate 180° and still function. Completely asymmetric nanodevices requiring absolute orientation (e.g., molecular bipolar junction transistors) have yet to be developed; now that orientation can be controlled, there is motivation to invent them. In the meantime, the wiring of existing devices into circuits may be greatly simplified

Optical gaps, mode patterns and dipole radiation in two-dimensional aperiodic photonic structures

Based on the rigorous generalized Mie theory solution of Maxwell's equations for dielectric cylinders we theoretically investigate the optical properties of two-dimensional deterministic structures based on the Fibonacci, Thue-Morse and Rudin-Shapiro aperiodic sequences. In particular, we investigate band-gap formation and mode localization properties in aperiodic photonic structures based on the accurate calculation of their Local Density of States (LDOS). In addition, we explore the potential of photonic structures based on aperiodic order for the engineering of radiative rates and emission patterns in Erbium-doped silicon-rich nitride photonic structures.Comment: 4 pages with 5 figures (to appear in Physica E, 40, 2008

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Optimized Assembly and Covalent Coupling of Single-Molecule DNA Origami Nanoarrays

Artificial DNA nanostructures, such as DNA origami, have great potential as templates for the bottom-up fabrication of both biological and nonbiological nanodevices at a resolution unachievable by conventional top-down approaches. However, because origami are synthesized in solution, origami-templated devices cannot easily be studied or integrated into larger on-chip architectures. Electrostatic self-assembly of origami onto lithographically defined binding sites on Si/SiO₂ substrates has been achieved, but conditions for optimal assembly have not been characterized, and the method requires high Mg²⁺ concentrations at which most devices aggregate. We present a quantitative study of parameters affecting origami placement, reproducibly achieving single-origami binding at 94 ± 4% of sites, with 90% of these origami having an orientation within ±10° of their target orientation. Further, we introduce two techniques for converting electrostatic DNA–surface bonds to covalent bonds, allowing origami arrays to be used under a wide variety of Mg²⁺-free solution conditions

Optimized Assembly and Covalent Coupling of Single-Molecule DNA Origami Nanoarrays

Artificial DNA nanostructures, such as DNA origami, have great potential as templates for the bottom-up fabrication of both biological and nonbiological nanodevices at a resolution unachievable by conventional top-down approaches. However, because origami are synthesized in solution, origami-templated devices cannot easily be studied or integrated into larger on-chip architectures. Electrostatic self-assembly of origami onto lithographically defined binding sites on Si/SiO₂ substrates has been achieved, but conditions for optimal assembly have not been characterized, and the method requires high Mg²⁺ concentrations at which most devices aggregate. We present a quantitative study of parameters affecting origami placement, reproducibly achieving single-origami binding at 94 ± 4% of sites, with 90% of these origami having an orientation within ±10° of their target orientation. Further, we introduce two techniques for converting electrostatic DNA–surface bonds to covalent bonds, allowing origami arrays to be used under a wide variety of Mg²⁺-free solution conditions