AgentBench: Evaluating LLMs as Agents

Large Language Models (LLMs) are becoming increasingly smart and autonomous, targeting real-world pragmatic missions beyond traditional NLP tasks. As a result, there has been an urgent need to evaluate LLMs as agents on challenging tasks in interactive environments. We present AgentBench, a multi-dimensional evolving benchmark that currently consists of 8 distinct environments to assess LLM-as-Agent's reasoning and decision-making abilities in a multi-turn open-ended generation setting. Our extensive test over 27 API-based and open-sourced (OSS) LLMs shows that, while top commercial LLMs present a strong ability of acting as agents in complex environments, there is a significant disparity in performance between them and OSS competitors. We identify the typical reasons of failures in environments and LLMs, showing that poor long-term reasoning, decision-making, and instruction following abilities are the main obstacles for developing usable LLM agents. Training on code and high quality multi-turn alignment data could improve agent performance. Datasets, environments, and an integrated evaluation package for AgentBench are released at \url{https://github.com/THUDM/AgentBench}.Comment: 55 page

A forward genetic screen identifies modifiers of rocaglate responsiveness

Rocaglates are a class of eukaryotic translation initiation inhibitors that are being explored as chemotherapeutic agents. They function by targeting eukaryotic initiation factor (eIF) 4A, an RNA helicase critical for recruitment of the 40S ribosome (and associated factors) to mRNA templates. Rocaglates perturb eIF4A activity by imparting a gain-of-function activity to eIF4A and mediating clamping to RNA. To appreciate how rocaglates could best be enabled in the clinic, an understanding of resistance mechanisms is important, as this could inform on strategies to bypass such events as well as identify responsive tumor types. Here, we report on the results of a positive selection, ORFeome screen aimed at identifying cDNAs capable of conferring resistance to rocaglates. Two of the most potent modifiers of rocaglate response identified were the transcription factors FOXP3 and NR1I3, both of which have been implicated in ABCB1 regulation-the gene encoding P-glycoprotein (Pgp). Pgp has previously been implicated in conferring resistance to silvestrol, a naturally occurring rocaglate, and we show here that this extends to additional synthetic rocaglate derivatives. In addition, FOXP3 and NR1I3 impart a multi-drug resistant phenotype that is reversed upon inhibition of Pgp, suggesting a potential therapeutic combination strategy.R35 GM118173 - NIGMS NIH HHS; U01 TR002625 - NCATS NIH HHS; FDN-148366 - CIHRPublished versio

Reperfusion status and postoperative blood pressure in acute stroke patients after endovascular treatment

Background and purposeAn aggressive lowering of blood pressure (BP) could lead to neurological worsening, particularly of the area that has not been reperfused in acute stroke patients with large vessel occlusion (LVO). We sought to investigate the association of reperfusion status and BP course following mechanical thrombectomy (MT) with outcomes in LVO.Materials and methodsConsecutive patients with LVO treated with MT between Jan 2020 to Jun 2021 were enrolled in a retrospective cohort study. Hourly systolic BP (SBP) and diastolic BP (DBP) were recorded for 72 h following MT and maximum SBP and DBP levels were identified. The Extended Thrombolysis in Cerebral Infarction (eTICI) scale was used to assess reperfusion extent. LVO patients were stratified in 2 groups based on reperfusion status: complete reperfusion (eTICI 3) and incomplete reperfusion (eTICI 2b/c). Three-month functional independence was defined as a modified Rankin Scale score of 0–2.ResultsA total of 263 acute ischemic stroke patients with LVO were retrospectively evaluated. Complete reperfusion was achieved in 210 patients (79.8%). Post-MT maximum SBP over 160 mmHg was significantly related to worse functional outcome (38.1% vs. 55.7%, p = 0.006), higher likelihood of in-hospital mortality and 3-month mortality (19.0% vs. 6.9%, p = 0.004, 27.4% vs. 14.3%, p = 0.012). No statistical correlation was found between reperfusion status and blood pressure level (p > 0.05). In patients with complete reperfusion, patients with an average BP 120-140 mmHg tends to have worse functional outcome compared with 100-120 mmHg (OR = 1.77, 95%CI: 0.97–3.23, p = 0.061).ConclusionHigh maximum SBP levels following MT are associated with an increased likelihood of 3-month functional dependence and mortality. An average BP of 100–120 mmHg tends to have better functional independence in completely reperfused patients. The effect of intensive BP control on incomplete reperfusion still warrants further investigations

Sensitivities of Ozone Air Pollution in the Beijing-Tianjin-Hebei Area to Local and Upwind Precursor Emissions Using Adjoint Modeling

Effective mitigation of surface ozone pollution entails detailed knowledge of the contributing precursors' sources. We use the GEOS-Chem adjoint model to analyze the precursors contributing to surface ozone in the Beijing-Tianjin-Hebei area (BTH) of China on days of different ozone pollution severities in June 2019. We find that BTH ozone on heavily polluted days is sensitive to local emissions, as well as to precursors emitted from the provinces south of BTH (Shandong, Henan, and Jiangsu, collectively the SHJ area). Heavy ozone pollution in BTH can be mitigated effectively by reducing NOx (from industrial processes and transportation), ≥C3 alkenes (from on-road gasoline vehicles and industrial processes), and xylenes (from paint use) emitted from both BTH and SHJ, as well as by reducing CO (from industrial processes, transportation, and power generation) and ≥C4 alkanes (from industrial processes, paint and solvent use, and on-road gasoline vehicles) emissions from SHJ. In addition, reduction of NOx, xylene, and ≥C3 alkene emissions within BTH would effectively decrease the number of BTH ozone-exceedance days. Our analysis pinpoint the key areas and activities for locally and regionally coordinated emission control efforts to improve surface ozone air quality in BTH

Pre-existing chromatin accessibility and gene expression differences among naive CD4+ T cells influence effector potential

CD4+ T cells have a remarkable potential to differentiate into diverse effector lineages following activation. Here, we probe the heterogeneity present among naive CD4+ T cells before encountering their cognate antigen to ask whether their effector potential is modulated by pre-existing transcriptional and chromatin landscape differences. Single-cell RNA sequencing shows that key drivers of variability are genes involved in T cell receptor (TCR) signaling. Using CD5 expression as a readout of the strength of tonic TCR interactions with self-peptide MHC, and sorting on the ends of this self-reactivity spectrum, we find that pre-existing transcriptional differences among naive CD4+ T cells impact follicular helper T (TFH) cell versus non-TFH effector lineage choice. Moreover, our data implicate TCR signal strength during thymic development in establishing differences in naive CD4+ T cell chromatin landscapes that ultimately shape their effector potential

Regulating the proximity effect of heterocycle-containing AIEgens

Abstract Proximity effect, which refers to the low-lying (n,π*) and (π,π*) states with close energy levels, usually plays a negative role in the luminescent behaviors of heterocyclic luminogens. However, no systematic study attempts to reveal and manipulate proximity effect on luminescent properties. Here, we report a series of methylquinoxaline derivatives with different electron-donating groups, which show different photophysical properties and aggregation-induced emission behaviors. Experimental results and theoretical calculation reveal the gradually changed energy levels and different coupling effects of the closely related (n,π*) and (π,π*) states, which intrinsically regulate proximity effect and aggregation-induced emission behaviors of these luminogens. With the intrinsic nature of heterocycle-containing compounds, they are utilized for sensors and information encryption with dynamic responses to acid/base stimuli. This work reveals both positive and negative impacts of proximity effect in heterocyclic aggregation-induced emission systems and provides a perspective to develop functional and responsive luminogens with aggregation-induced emission properties

Nonreciprocal coherent coupling of nanomagnets by exchange spin waves

Nanomagnets are widely used to store information in non-volatile spintronic devices. Spin waves can transfer information with low-power consumption as their propagations are independent of charge transport. However, to dynamically couple two distant nanomagnets via spin waves remains a major challenge for magnonics. Here we experimentally demonstrate coherent coupling of two distant Co nanowires by fast propagating spin waves in an yttrium iron garnet thin film with sub-50 nm wavelengths. Magnons in two nanomagnets are unidirectionally phase-locked with phase shifts controlled by magnon spin torque and spin-wave propagation. The coupled system is finally formulated by an analytical theory in terms of an effective non-Hermitian Hamiltonian. Our results are attractive for analog neuromorphic computing that requires unidirectional information transmission. [Figure not available: see fulltext.]</p

Secondary Through-Space Interactions: Achieving Single-Molecule White-Light Emission from Clusteroluminogens with Isolated Phenyl Rings

Clusteroluminogens (CLgens) refer to some non-conjugated molecules that show visible light due to the formation of aggregates and unique electronic properties with through-space interactions (TSI). Although mature and systematic theories of molecular photophysics have been developed to study conventional conjugated chromophores, it is still challenging to endow CLgens with designed photophysical properties by manipulating TSI. Herein, three CLgens with non-conjugated donor-acceptor structures and different halide substituents with secondary TSI are designed and synthesized. These molecules show multiple emissions and even white-light emission in the crystalline state and the intensity ratio of these multiple emission peaks is easily manipulated by changing the halide atom and excitation wavelength. Experimental and theoretical results successfully disclose the electronic nature of these multiple emissions: through-space conjugation for short-wavelength fluorescence, through-space charge transfer based on secondary TSI for long-wavelength fluorescence, and room-temperature phosphorescence. The introduction of secondary TSI to CLgens not only enriches their varieties of photophysical properties but also inspires the establishment of novel aggregate photophysics for clusteroluminescence

Water‐Soluble Aggregation‐Induced Emission Luminogens with Near‐Infrared Emission for Advanced Phototheranostics

The development of water‐soluble aggregation‐induced emission luminogens (AIEgens) emitting in the near‐infrared (NIR) window holds promise for efficient biomedical applications. Nevertheless, synthesizing water‐soluble counterparts of NIR AIEgens presents difficulties due to their intrinsic hydrophobic properties. To address this issue, researchers have developed various molecular design strategies to improve the water solubility of NIR AIEgens. The integration of hydrophilic groups and targeting moieties is a crucial aspect of achieving precise phototheranostics. Here, diverse approaches to attain water‐soluble NIR AIEgens for biomedical applications are presented, and three commonly used strategies that involve decorating NIR AIEgens with positively or negatively charged groups, hydrophilic chains, and bioactive moieties are elaborated. These rational design strategies are believed to provide solutions for enhancing the water solubility and biological performance of NIR AIEgens in a single action. The remaining challenges and opportunities in this field are also discussed. The aim is to provide new insights into the design of water‐soluble NIR AIEgens and inspire more researchers to make significant contributions to this promising research area