Finding and Editing Multi-Modal Neurons in Pre-Trained Transformer

Multi-modal large language models (LLM) have achieved powerful capabilities for visual semantic understanding in recent years. However, little is known about how LLMs comprehend visual information and interpret different modalities of features. In this paper, we propose a new method for identifying multi-modal neurons in transformer-based multi-modal LLMs. Through a series of experiments, We highlight three critical properties of multi-modal neurons by four well-designed quantitative evaluation metrics. Furthermore, we introduce a knowledge editing method based on the identified multi-modal neurons, for modifying a specific token to another designative token. We hope our findings can inspire further explanatory researches on understanding mechanisms of multi-modal LLMs

Stiffness of Substrate Influences the Distribution but not the Synthesis of Autophagosomes in Human Liver (LO2) Cells

Extracellular matrix (ECM) often becomes stiffer during tumor development, which not only gives the tumor's hardness feel but also actively contributes to the tumor formation. A good example is hepatocellular carcinoma (HCC) that usually develops within chronically stiffened liver tissues due to fibrosis and cirrhosis. On the other hand, HCC cells exhibit reduced autophagy in a malignancy dependent manner, suggesting autophagy is suppressed during tumor development. However, it is not known whether ECM stiffness would influence autophagy during tumor development. To investigate this issue, We cultured the human liver (LO2) cells that stably expressed autophagosome indicator LC3 on polydimethylsiloxane (PDMS) gels with stiffness varying from 11 to 1220 kPa. and on plastic cell culture dish as controls for up to 48h. We found that the total protein level of LC3-II in LO2 cells was not affected by the substrate stiffness. However the autophagosomes in LO2 cells cultured on the soft substrate (11 kPa PDMS gel) were localized and accumulated around the nucleus, while those on the stiff substrate (1220 kPa PDMS gel or plastic dish surface) were dispersed throughout the cytoplasmic space. Therefore, our data suggest that ECM stiffness may not directly synthesize nascent autophagosomes, but instead influence the location/translocation and ultimately distribution of autophagosomes in the cells

HE3^3DB: An Efficient and Elastic Encrypted Database Via Arithmetic-And-Logic Fully Homomorphic Encryption

As concerns are increasingly raised about data privacy, encrypted database management system (DBMS) based on fully homomorphic encryption (FHE) attracts increasing research attention, as FHE permits DBMS to be directly outsourced to cloud servers without revealing any plaintext data. However, the real-world deployment of FHE-based DBMS faces two main challenges: i) high computational latency, and ii) lack of elastic query processing capability, both of which stem from the inherent limitations of the underlying FHE operators. Here, we introduce HE$^3$DB, a fully homomorphically encrypted, efficient and elastic DBMS framework based on a new FHE infrastructure. By proposing and integrating new arithmetic and logic homomorphic operators, we devise fast and high-precision homomorphic comparison and aggregation algorithms that enable a variety of SQL queries to be applied over FHE ciphertexts, e.g., compound filter-aggregation, sorting, grouping, and joining. In addition, in contrast to existing encrypted DBMS that only support aggregated information retrieval, our framework permits further server-side analytical processing over the queried FHE ciphertexts, such as private decision tree evaluation. In the experiment, we rigorously study the efficiency and flexibility of HE$^3$DB. We show that, compared to the state-of-the-art techniques,HE$^3$DB can homomorphically evaluate end-to-end SQL queries as much as $41\times$ -$299\times$ faster than the state-of-the-art solution, completing a TPC-H query over a 16-bit 10K-row database within 241 seconds

Inhibition of RhoA-Subfamily GTPases Suppresses Schwann Cell Proliferation Through Regulating AKT Pathway Rather Than ROCK Pathway

Inhibiting RhoA-subfamily GTPases by C3 transferase is widely recognized as a prospective strategy to enhance axonal regeneration. When C3 transferase is administered for treating the injured peripheral nerves, Schwann cells (SCs, important glial cells in peripheral nerve) are inevitably impacted and therefore SC bioeffects on nerve regeneration might be influenced. However, the potential role of C3 transferase on SCs remains elusive. Assessed by cell counting, EdU and water-soluble tetrazolium salt-1 (WST-1) assays as well as western blotting with PCNA antibody, herein we first found that CT04 (a cell permeable C3 transferase) treatment could significantly suppress SC proliferation. Unexpectedly, using Y27632 to inhibit ROCK (the well-accepted downstream signal molecule of RhoA subfamily) did not impact SC proliferation. Further studies indicated that CT04 could inactivate AKT pathway by altering the expression levels of phosphorylated AKT (p-AKT), PI3K and PTEN, while activating AKT pathway by IGF-1 or SC79 could reverse the inhibitory effect of CT04 on SC proliferation. Based on present data, we concluded that inhibition of RhoA-subfamily GTPases could suppress SC proliferation, and this effect is independent of conventional ROCK pathway but involves inactivation of AKT pathway

Effect of progestin on thyroid function in female Wistar rats

IntroductionTo characterize the influence of female-specific hormones on women’s thyroid function, the study investigated the influence of extra progestin from oral contraceptives on inducing thyroid dysfunction.MethodsSixty female Wistar rats were divided into six groups based on levonorgestrel or desogestrel administration as the main active agents: control, low (0.0039 mg*20-fold), medium (0.0039 mg*100-fold), high (0.0318 mg*100-fold) levonorgestrel (pure product); and low (0.0083 mg*20-fold) and high (0.0083 mg*100-fold) desogestrel (pure product). Progestin was administered by gavage every 4 days for 1 month. Statistical analysis was performed using one-way analysis of variance and the Kruskal–Wallis test.ResultsFollowing levonorgestrel gavage, serum free T4 and thyroidstimulating hormone levels were significantly lower in the experimental group than that in the control group (p=0.013 and 0.043). After desogestrel gavage, the serum free T4 and free T3 levels were lower in the experimental group than that in the control group (p=0.019 and 0.030). Thyroid hormone antibody concentrations were lower in rats administered levonorgestrel and desogestrel than that in control rats. Moreover, exposure to progestin upregulated the expression of the thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid.DiscussionProgestin stimulation enhanced the proliferation of follicular epithelial cells in rat thyroid tissues. Progestin exposure could cause thyroid dysfunction by upregulating the transcription of thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid, thus inducing pathomorphological changes in rats’ thyroid

Ascorbic Acid Facilitates Neural Regeneration After Sciatic Nerve Crush Injury

Ascorbic acid (AA) is an essential micronutrient that has been safely used in the clinic for many years. The present study indicates that AA has an unexpected function in facilitating nerve regeneration. Using a mouse model of sciatic nerve crush injury, we found that AA can significantly accelerate axonal regrowth in the early stage [3 days post-injury (dpi)], a finding that was revealed by immunostaining and Western blotting for antibodies against GAP-43 and SCG10. On day 28 post-injury, histomorphometric assessments demonstrated that AA treatment increased the density, size, and remyelination of regenerated axons in the injured nerve and alleviated myoatrophy in the gastrocnemius. Moreover, the results from various behavioral tests and electrophysiological assays revealed that nerve injury-derived functional defects in motor and sensory behavior as well as in nerve conduction were significantly attenuated by treatment with AA. The potential mechanisms of AA in nerve regeneration were further explored by investigating the effects of AA on three types of cells involved in this process [neurons, Schwann cells (SCs) and macrophages] through a series of experiments. Overall, the data illustrated that AA treatment in cultured dorsal root ganglionic neurons resulted in increased neurite growth and lower expression of RhoA, which is an important inhibitory factor in neural regeneration. In SCs, proliferation, phagocytosis, and neurotrophin expression were all enhanced by AA. Meanwhile, AA treatment also improved proliferation, migration, phagocytosis, and anti-inflammatory polarization in macrophages. In conclusion, this study demonstrated that treatment with AA can promote the morphological and functional recovery of injured peripheral nerves and that this effect is potentially due to AA’s bioeffects on neurons, SCs and macrophages, three of most important types of cells involved in nerve injury and regeneration

A SPectroscopic Survey of Biased Halos in the Reionization Era (ASPIRE): A First Look at the Rest-frame Optical Spectra of z > 6.5 Quasars Using JWST

© 2023. The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the Creative Commons Attribution License, to view a copy of the license, see: https://creativecommons.org/licenses/by/4.0/Studies of rest-frame optical emission in quasars at z > 6 have historically been limited by the wavelengths accessible by ground-based telescopes. The James Webb Space Telescope (JWST) now offers the opportunity to probe this emission deep into the reionization epoch. We report the observations of eight quasars at z > 6.5 using the JWST/NIRCam Wide Field Slitless Spectroscopy as a part of the “A SPectroscopic survey of biased halos In the Reionization Era (ASPIRE)” program. Our JWST spectra cover the quasars’ emission between rest frame ∼4100 and 5100 Å. The profiles of these quasars’ broad Hβ emission lines span a full width at half maximum from 3000 to 6000 km s−1. The Hβ-based virial black hole (BH) masses, ranging from 0.6 to 2.1 billion solar masses, are generally consistent with their Mg ii-based BH masses. The new measurements based on the more reliable Hβ tracer thus confirm the existence of a billion solar-mass BHs in the reionization epoch. In the observed [O iii] λ λ 4960,5008 doublets of these luminous quasars, broad components are more common than narrow core components (≤ 1200 km s−1), and only one quasar shows stronger narrow components than broad. Two quasars exhibit significantly broad and blueshifted [O iii] emission, thought to trace galactic-scale outflows, with median velocities of −610 and −1430 km s−1 relative to the [C ii] 158 μm line. All eight quasars show strong optical Fe ii emission and follow the eigenvector 1 relations defined by low-redshift quasars. The entire ASPIRE program will eventually cover 25 quasars and provide a statistical sample for the studies of the BHs and quasar spectral properties.Peer reviewe

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe