AFM nanoindentation to quantify mechanical properties of nano- and micron-sized crystals of a metal-organic framework material

The mechanical properties of individual nanocrystals and small micron-sized single crystals of metal-organic frameworks (MOFs), hitherto, cannot be measured directly by employing the conventional instrumented nanoindentation approach. Here we propose the application of atomic force microscopy (AFM)-based nanoindentation technique, equipped with a calibrated diamond cube-corner indenter tip to quantify the Young's modulus, hardness, adhesion energy, and interfacial and fracture strengths of a zeolitic imidazolate framework (ZIF-8) porous material. We use ZIF-8 as a model MOF system to develop AFM nanoindentation leveraging the concept of unloading strain rate, enabling us to critically assess the practicality and technical limitations of AFM to achieve quantitative measurements of fine-scale MOF crystals. We demonstrate the advantages of using a high unloading strain rate (ε̇ > 60 s-1) to yield reliable force-displacement data in the few μN load range, corresponding to a shallow indentation depth of ∼10s nm. We found that the Young's moduli (∼3-4 GPa) determined by AFM nanoindentation of the nanocrystals (<500 nm) and micron-sized crystals (∼2 μm) are in agreement with magnitudes derived previously from other techniques, namely instrumented nanoindentation and Brillouin spectroscopy (however, these methods requiring large 100-μm sized crystals) and also in line with density functional theory predictions of an idealized ZIF-8 crystal

In situ micropillar compression of an anisotropic metal-organic framework single crystal

Understanding of the complex mechanical behavior of metal-organic frameworks (MOF) beyond their elastic limit will allow the design of real-world applications in chemical engineering, optoelectronics, energy conversion apparatus, and sensing devices. Through in situ compression of micropillars, the uniaxial stress-strain curves of a copper paddlewheel MOF (HKUST-1) were determined along two unique crystallographic directions, namely the (100) and (111) facets. We show strongly anisotropic elastic response where the ratio of the Young’s moduli are E(111) ≈ 3.6 × E(100), followed by extensive plastic flows. Likewise, the yield strengths are considerably different, in which Y(111) ≈ 2 × Y(100) because of the underlying framework anisotropy. We measure the fracture toughness using micropillar splitting. While in situ tests revealed differential cracking behavior, the resultant toughness values of the two facets are comparable, yielding Kc ~ 0.5 MPam√m. This work provides insights of porous framework ductility at the micron scale under compression and failure by bonds breakage

A Multidisciplinary Investigation to Determine the Structure and Source of Dimeric Impurities in AMG 517 Drug Substance

In the initial scale-up batches of the experimental drug substance AMG 517, a pair of unexpected impurities was observed by HPLC. Analysis of data from initial LC-MS experiments indicated the presence of two dimer-like molecules. One impurity had an additional sulfur atom incorporated into its structure relative to the other impurity. Isolation of the impurities was performed, and further structural elucidation experiments were conducted with high-resolution LC-MS and 2D NMR. The dimeric structures were confirmed, with one of the impurities having an unexpected C-S-C linkage. Based on the synthetic route of AMG 517, it was unlikely that these impurities were generated during the last two steps of the process. Stress studies on the enriched impurities were carried out to further confirm the existence of the C-S-C linkage in the benzothiazole portion of AMG 517. Further investigation revealed that these two dimeric impurities originated from existing impurities in the AMG 517 starting material, N-acetyl benzothiazole. The characterization of these two dimeric impurities allowed for better quality control of new batches of the N-acetyl benzothiazole starting material. As a result, subsequent batches of AMG 517 contained no reportable levels of these two impuritie

The NF-κB multidimer system model: A knowledge base to explore diverse biological contexts

The nuclear factor κB (NF-κB) system is critical for various biological functions in numerous cell types, including the inflammatory response, cell proliferation, survival, differentiation, and pathogenic responses. Each cell type is characterized by a subset of 15 NF-κB dimers whose activity is regulated in a stimulus-responsive manner. Numerous studies have produced different mathematical models that account for cell type-specific NF-κB activities. However, whereas the concentrations or abundances of NF-κB subunits may differ between cell types, the biochemical interactions that constitute the NF-κB signaling system do not. Here, we synthesized a consensus mathematical model of the NF-κB multidimer system, which could account for the cell type-specific repertoires of NF-κB dimers and their cell type-specific activation and cross-talk. Our review demonstrates that these distinct cell type-specific properties of NF-κB signaling can be explained largely as emergent effects of the cell type-specific expression of NF-κB monomers. The consensus systems model represents a knowledge base that may be used to gain insights into the control and function of NF-κB in diverse physiological and pathological scenarios and that describes a path for generating similar regulatory knowledge bases for other pleiotropic signaling systems

Radiation hardness study of BC408 plastic scintillator under 80 MeV proton beam irradiations

To investigate the 1.6 GeV high-energy proton beam detector utilized in the CSNS Phase-II upgrade project, a plastic scintillator detector presents a viable option due to its superior radiation hardness. This study investigates the effects of irradiation damage on a BC408 plastic scintillator induced by 80 MeV protons, including absorption and fluorescence spectroscopy, and light yield tests of BC408 pre- and post-proton irradiation, with a focus on determining the radiation resistance threshold of BC408. The results indicate that the performance of BC408 remains unimpaired at absorbed doses up to 5.14*10^3 Gy/cm3, demonstrating its ability to absorb 1.63*10^13 p/cm3 1.6 GeV protons while maintaining stability. This suggests that BC408 could potentially be used as the 1.6 GeV high-energy proton beam detector in the CSNS Phase-II upgrade project

Carve3D: Improving Multi-view Reconstruction Consistency for Diffusion Models with RL Finetuning

Multi-view diffusion models, obtained by applying Supervised Finetuning (SFT) to text-to-image diffusion models, have driven recent breakthroughs in text-to-3D research. However, due to the limited size and quality of existing 3D datasets, they still suffer from multi-view inconsistencies and Neural Radiance Field (NeRF) reconstruction artifacts. We argue that multi-view diffusion models can benefit from further Reinforcement Learning Finetuning (RLFT), which allows models to learn from the data generated by themselves and improve beyond their dataset limitations during SFT. To this end, we introduce Carve3D, an improved RLFT algorithm coupled with a novel Multi-view Reconstruction Consistency (MRC) metric, to enhance the consistency of multi-view diffusion models. To measure the MRC metric on a set of multi-view images, we compare them with their corresponding NeRF renderings at the same camera viewpoints. The resulting model, which we denote as Carve3DM, demonstrates superior multi-view consistency and NeRF reconstruction quality than existing models. Our results suggest that pairing SFT with Carve3D's RLFT is essential for developing multi-view-consistent diffusion models, mirroring the standard Large Language Model (LLM) alignment pipeline. Our code, training and testing data, and video results are available at: https://desaixie.github.io/carve-3d.Comment: 22 pages, 16 figures. Our code, training and testing data, and video results are available at: https://desaixie.github.io/carve-3d. This paper has been accepted to CVPR 2024. v2: incorporated changes from the CVPR 2024 camera-ready versio

Response of picophytoplankton to a warm eddy in the northern South China Sea

We investigated the distribution of several picophytoplankton groups (Prochlorococcus, Synechococcus, and picoeukaryotes) in relation to a warm eddy in the northern South China Sea in summer 2012. An anticyclonic eddy centered on 117°E longitude was identified during the sampling period using satellite data and hydrologic mapping. The layer of maximum Prochlorococcus and Synechococcus abundance within the eddy core dropped from 50 to 75 m, which was consistent with the subsurface chlorophyll a maximum. The water-column integrated abundance of Prochlorococcus, Synechococcus, and picoeukaryotes in the eddy core (9.67±0.23, 1.56±0.04, and 0.28±0.01 × 103 cells ml-1, respectively) was significantly lower (P&lt;0.05) than that of the reference stations (25.10±2.32, 2.71±0.63, and 0.92±0.15 × 103 cells ml-1, respectively), and the abundance of Prochlorococcus in the core was also significantly lower than that at eddy edges (15.75±1.78 × 103 cells ml-1). However, there were no differences in the water-column integrated Chl a between the eddy core and edge. Our findings show that the warm eddy led to the reduced picophytoplankton abundance, especially of Prochlorococcus and picoeukaryotes, causing the layer of maximum picophytoplankton abundance to differ from that of the subsurface Chl a maximum.We investigated the distribution of several picophytoplankton groups (Prochlorococcus, Synechococcus, and picoeukaryotes) in relation to a warm eddy in the northern South China Sea in summer 2012. An anticyclonic eddy centered on 117°E longitude was identified during the sampling period using satellite data and hydrologic mapping. The layer of maximum Prochlorococcus and Synechococcus abundance within the eddy core dropped from 50 to 75 m, which was consistent with the subsurface chlorophyll a maximum. The water-column integrated abundance of Prochlorococcus, Synechococcus, and picoeukaryotes in the eddy core (9.67±0.23, 1.56±0.04, and 0.28±0.01 × 103 cells ml-1, respectively) was significantly lower (P&lt;0.05) than that of the reference stations (25.10±2.32, 2.71±0.63, and 0.92±0.15 × 103 cells ml-1, respectively), and the abundance of Prochlorococcus in the core was also significantly lower than that at eddy edges (15.75±1.78 × 103 cells ml-1). However, there were no differences in the water-column integrated Chl a between the eddy core and edge. Our findings show that the warm eddy led to the reduced picophytoplankton abundance, especially of Prochlorococcus and picoeukaryotes, causing the layer of maximum picophytoplankton abundance to differ from that of the subsurface Chl a maximum