A Multi-Arm Two-Stage (MATS) Design for Proof-of-Concept and Dose Optimization in Early-Phase Oncology Trials

The Project Optimus initiative by the FDA's Oncology Center of Excellence is widely viewed as a groundbreaking effort to change the $\textit{status quo}$ of conventional dose-finding strategies in oncology. Unlike in other therapeutic areas where multiple doses are evaluated thoroughly in dose ranging studies, early-phase oncology dose-finding studies are characterized by the practice of identifying a single dose, such as the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D). Following the spirit of Project Optimus, we propose an Multi-Arm Two-Stage (MATS) design for proof-of-concept (PoC) and dose optimization that allows the evaluation of two selected doses from a dose-escalation trial. The design assess the higher dose first across multiple indications in the first stage, and adaptively enters the second stage for an indication if the higher dose exhibits promising anti-tumor activities. In the second stage, a randomized comparison between the higher and lower doses is conducted to achieve proof-of-concept (PoC) and dose optimization. A Bayesian hierarchical model governs the statistical inference and decision making by borrowing information across doses, indications, and stages. Our simulation studies show that the proposed MATS design yield desirable performance. An R Shiny application has been developed and made available at https://matsdesign.shinyapps.io/mats/

Micro-Spherical Sulfur/Graphene Oxide Composite via Spray Drying for High Performance Lithium Sulfur Batteries

An efficient, industry-accepted spray drying method was used to synthesize microspherical sulfur/graphene oxide (S/GO) composites as cathode materials within lithium sulfur batteries. The as-designed wrapping of the sulfur-nanoparticles, with wrinkled GO composites, was characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The unique morphological design of this material enabled superior discharge capacity and cycling performance, demonstrating a high initial discharge capacity of 1400 mAh g1 at 0.1 C. The discharge capacity remained at 828 mAh g1 after 150 cycles. The superior electrochemical performance indicates that the S/GO composite improves electrical conductivity and alleviates the shuttle effect. This study represents the first time such a facile spray drying method has been adopted for lithium sulfur batteries and used in the fabrication of S/GO composite

Low-dimensional perovskite nanoplatelet synthesis using in situ photophysical monitoring to establish controlled growth.

Perovskite nanoparticles have attracted the attention of research groups around the world for their impressive photophysical properties, facile synthesis and versatile surface chemistry. Here, we report a synthetic route that takes advantage of a suite of soluble precursors to generate CsPbBr3 perovskite nanoplatelets with fine control over size, thickness and optical properties. We demonstrate near unit cell precision, creating well characterized materials with sharp, narrow emission lines at 430, 460 and 490 nm corresponding to nanoplatelets that are 2, 4, and 6 unit cells thick, respectively. Nanoplatelets were characterized with optical spectroscopy, atomic force microscopy, scanning electron microscopy and transmission electron microscopy to explicitly correlate growth conditions, thickness and resulting photophysical properties. Detailed in situ photoluminescence spectroscopic studies were carried out to understand and optimize particle growth by correlating light emission with nanoplatelet growth across a range of synthetic conditions. It was found that nanoplatelet thickness and emission wavelength increase as the ratio of oleic acid to oleyl amine or the reaction temperature is increased. Using this information, we control the lateral size, width and corresponding emission wavelength of the desired nanoplatelets by modulating the temperature and ratios of the ligand

Advancing LLM Reasoning Generalists with Preference Trees

We introduce Eurus, a suite of large language models (LLMs) optimized for reasoning. Finetuned from Mistral-7B and CodeLlama-70B, Eurus models achieve state-of-the-art results among open-source models on a diverse set of benchmarks covering mathematics, code generation, and logical reasoning problems. Notably, Eurus-70B beats GPT-3.5 Turbo in reasoning through a comprehensive benchmarking across 12 tests covering five tasks, and achieves a 33.3% pass@1 accuracy on LeetCode and 32.6% on TheoremQA, two challenging benchmarks, substantially outperforming existing open-source models by margins more than 13.3%. The strong performance of Eurus can be primarily attributed to UltraInteract, our newly-curated large-scale, high-quality alignment dataset specifically designed for complex reasoning tasks. UltraInteract can be used in both supervised fine-tuning and preference learning. For each instruction, it includes a preference tree consisting of (1) reasoning chains with diverse planning strategies in a unified format, (2) multi-turn interaction trajectories with the environment and the critique, and (3) pairwise data to facilitate preference learning. UltraInteract allows us to conduct an in-depth exploration of preference learning for reasoning tasks. Our investigation reveals that some well-established preference learning algorithms may be less suitable for reasoning tasks compared to their effectiveness in general conversations. Inspired by this, we derive a novel reward modeling objective which, together with UltraInteract, leads to a strong reward model.Comment: Models and data are available at https://github.com/OpenBMB/Euru

A universal programmable Gaussian Boson Sampler for drug discovery

Gaussian Boson Sampling (GBS) exhibits a unique ability to solve graph problems, such as finding cliques in complex graphs. It is noteworthy that many drug discovery tasks can be viewed as the clique-finding process, making them potentially suitable for quantum computation. However, to perform these tasks in their quantum-enhanced form, a large-scale quantum hardware with universal programmability is essential, which is yet to be achieved even with the most advanced GBS devices. Here, we construct a time-bin encoded GBS photonic quantum processor that is universal, programmable, and software-scalable. Our processor features freely adjustable squeezing parameters and can implement arbitrary unitary operations with a programmable interferometer. Using our processor, we have demonstrated the clique-finding task in a 32-node graph, where we found the maximum weighted clique with approximately twice the probability of success compared to classical sampling. Furthermore, a multifunctional quantum pharmaceutical platform is developed. This GBS processor is successfully used to execute two different drug discovery methods, namely molecular docking and RNA folding prediction. Our work achieves the state-of-the-art in GBS circuitry with its distinctive universal and programmable architecture which advances GBS towards real-world applications.Comment: 10 pages, 5 figure

Observation of a charged charmoniumlike structure in e+e−→(D∗Dˉ∗)±π∓e^+e^- \to (D^{*} \bar{D}^{*})^{\pm} \pi^\mp at s=4.26\sqrt{s}=4.26GeV

We study the process $e^+e^- \to (D^{*} \bar{D}^{*})^{\pm} \pi^\mp$ at a center-of-mass energy of 4.26GeV using a 827pb$^{-1}$ data sample obtained with the BESIII detector at the Beijing Electron Positron Collider. Based on a partial reconstruction technique, the Born cross section is measured to be $(137\pm9\pm15)$pb. We observe a structure near the $(D^{*} \bar{D}^{*})^{\pm}$ threshold in the $\pi^\mp$ recoil mass spectrum, which we denote as the $Z^{\pm}_c(4025)$. The measured mass and width of the structure are $(4026.3\pm2.6\pm3.7)$MeV/c$^2$ and $(24.8\pm5.6\pm7.7)$MeV, respectively. Its production ratio $\frac{\sigma(e^+e^-\to Z^{\pm}_c(4025)\pi^\mp \to (D^{*} \bar{D}^{*})^{\pm} \pi^\mp)}{\sigma(e^+e^-\to (D^{*} \bar{D}^{*})^{\pm} \pi^\mp)}$ is determined to be $0.65\pm0.09\pm0.06$. The first uncertainties are statistical and the second are systematic.Comment: 7 pages, 4 figures, 1 table; version accepted to be published in PR

Search for the Lepton Flavor Violation Process J/ψ→eμJ/\psi \to e\mu at BESIII

We search for the lepton-flavor-violating decay of the $J/\psi$ into an electron and a muon using $(225.3\pm2.8)\times 10^{6}$ $J/\psi$ events collected with the BESIII detector at the BEPCII collider. Four candidate events are found in the signal region, consistent with background expectations. An upper limit on the branching fraction of $\mathcal{B}(J/\psi \to e\mu)< 1.5 \times 10^{-7}$ (90% C.L.) is obtained

Search for Baryonic Decays of \psi(3770) and \psi(4040)

By analyzing data samples of 2.9 fb^{-1} collected at \sqrt s=3.773 GeV, 482 pb^{-1} collected at \sqrt s=4.009 GeV and 67 pb^{-1} collected at \sqrt s=3.542, 3.554, 3.561, 3.600 and 3.650 GeV with the BESIII detector at the BEPCII storage ring, we search for \psi(3770) and \psi(4040) decay to baryonic final states, including \Lambda\bar\Lambda\pi^+\pi^-, \Lambda \bar\Lambda\pi^0, \Lambda\bar\Lambda\eta, \Sigma^+ \bar\Sigma^-, \Sigma^0 \bar\Sigma^0, \Xi^-\bar\Xi^+ and \Xi^0\bar\Xi^0 decays. None are observed, and upper limits are set at the 90% confidence level.Comment: 9 pages, 3 figure