The Basal Thermal Sensitivity of the TRPV1 Ion Channel Is Determined by PKCβII

Copyright © 2014 the authors 0270-6474/14/348246-13$15.00/0.Peer reviewedPublisher PD

Towards Zero-Shot Personalized Table-to-Text Generation with Contrastive Persona Distillation

Existing neural methods have shown great potentials towards generating informative text from structured tabular data as well as maintaining high content fidelity. However, few of them shed light on generating personalized expressions, which often requires well-aligned persona-table-text datasets that are difficult to obtain. To overcome these obstacles, we explore personalized table-to-text generation under a zero-shot setting, by assuming no well-aligned persona-table-text triples are required during training. To this end, we firstly collect a set of unpaired persona information and then propose a semi-supervised approach with contrastive persona distillation (S2P-CPD) to generate personalized context. Specifically, tabular data and persona information are firstly represented as latent variables separately. Then, we devise a latent space fusion technique to distill persona information into the table representation. Besides, a contrastive-based discriminator is employed to guarantee the style consistency between the generated context and its corresponding persona. Experimental results on two benchmarks demonstrate S2P-CPD's ability on keeping both content fidelity and personalized expressions.Comment: Accepted by ICASSP 202

Scalable wavelength-multiplexing photonic reservoir computing

Photonic reservoir computing (PRC) is a special hardware recurrent neural network, which is featured with fast training speed and low training cost. This work shows a wavelength-multiplexing PRC architecture, taking advantage of the numerous longitudinal modes in a Fabry-Perot semiconductor laser. These modes construct connected physical neurons in parallel, while an optical feedback loop provides interactive virtual neurons in series. We experimentally demonstrate a four-channel wavelength-multiplexing PRC, which runs four times faster than the single-channel case. It is proved that the multiplexing PRC exhibits superior performance on the task of signal equalization in an optical fiber communication link. Particularly, this scheme is highly scalable owing to the rich mode resources in Fabry-Perot lasers

Direct inhibition of the cold-activated TRPM8 ion channel by Gαq

Activation of the TRPM8 ion channel in sensory nerve endings produces a sensation of pleasant coolness. Here we show that inflammatory mediators such as bradykinin and histamine inhibit TRPM8 in intact sensory nerves, but do not do so through conventional signalling pathways. The G-protein subunit Gα(q) instead binds to TRPM8 and when activated by a Gq-coupled receptor directly inhibits ion channel activity. Deletion of Gα(q) largely abolished inhibition of TRPM8, and inhibition was rescued by a Gα(q) chimaera whose ability to activate downstream signalling pathways was completely ablated. Activated Gα(q) protein, but not Gβγ, potently inhibits TRPM8 in excised patches. We conclude that Gα(q) pre-forms a complex with TRPM8 and inhibits activation of TRPM8, following activation of G-protein-coupled receptors, by a direct action. This signalling mechanism may underlie the abnormal cold sensation caused by inflammation

Excitation and modulation of TRPA1, TRPV1, and TRPM8 channel-expressing sensory neurons by the pruritogen chloroquine

The sensations of pain, itch, and cold often interact with each other. Pain inhibits itch, whereas cold inhibits both pain and itch. TRPV1 and TRPA1 channels transduce pain and itch, whereas TRPM8 transduces cold. The pruritogen chloroquine (CQ) was reported to excite TRPA1, leading to the sensation of itch. It is unclear how CQ excites and modulates TRPA1+, TRPV1+, and TRPM8+ neurons and thus affects the sensations of pain, itch, and cold. Here, we show that only 43% of CQ-excited dorsal root ganglion neurons expressed TRPA1; as expected, the responses of these neurons were completely prevented by the TRPA1 antagonist HC-030031. The remaining 57% of CQ-excited neurons did not express TRPA1, and excitation was not prevented by either a TRPA1 or TRPV1 antagonist but was prevented by the general transient receptor potential canonical (TRPC) channel blocker BTP2 and the selective TRPC3 inhibitor Pyr3. Furthermore, CQ caused potent sensitization of TRPV1 in 51.9% of TRPV1+ neurons and concomitant inhibition of TRPM8 in 48.8% of TRPM8+ dorsal root ganglion neurons. Sensitization of TRPV1 is caused mainly by activation of the phospholipase C-PKC pathway following activation of the CQ receptor MrgprA3. By contrast, inhibition of TRPM8 is caused by a direct action of activated Gαq independent of the phospholipase C pathway. Our data suggest the involvement of the TRPC3 channel acting together with TRPA1 to mediate CQ-induced itch. CQ not only elicits itch by directly exciting itch-encoding neurons but also exerts previously unappreciated widespread actions on pain-, itch-, and cold-sensing neurons, leading to enhanced pain and itch

SPHINX: The Joint Mixing of Weights, Tasks, and Visual Embeddings for Multi-modal Large Language Models

We present SPHINX, a versatile multi-modal large language model (MLLM) with a joint mixing of model weights, tuning tasks, and visual embeddings. First, for stronger vision-language alignment, we unfreeze the large language model (LLM) during pre-training, and introduce a weight mix strategy between LLMs trained by real-world and synthetic data. By directly integrating the weights from two domains, the mixed LLM can efficiently incorporate diverse semantics with favorable robustness. Then, to enable multi-purpose capabilities, we mix a variety of tasks for joint visual instruction tuning, and design task-specific instructions to avoid inter-task conflict. In addition to the basic visual question answering, we include more challenging tasks such as region-level understanding, caption grounding, document layout detection, and human pose estimation, contributing to mutual enhancement over different scenarios. Additionally, we propose to extract comprehensive visual embeddings from various network architectures, pre-training paradigms, and information granularity, providing language models with more robust image representations. Based on our proposed joint mixing, SPHINX exhibits superior multi-modal understanding capabilities on a wide range of applications. On top of this, we further propose an efficient strategy aiming to better capture fine-grained appearances of high-resolution images. With a mixing of different scales and high-resolution sub-images, SPHINX attains exceptional visual parsing and reasoning performance on existing evaluation benchmarks. We hope our work may cast a light on the exploration of joint mixing in future MLLM research. Code is released at https://github.com/Alpha-VLLM/LLaMA2-Accessory.Comment: Work in progress. Code and demos are released at https://github.com/Alpha-VLLM/LLaMA2-Accessor

Proinflammatory mediators modulate the heat-activated ion channel TRPV1 via the scaffolding protein AKAP79/150

Peer reviewedPostprin

Ndrg2 regulates vertebral specification in differentiating somites

AbstractIt is generally thought that vertebral patterning and identity are globally determined prior to somite formation. Relatively little is known about the regulators of vertebral specification after somite segmentation. Here, we demonstrated that Ndrg2, a tumor suppressor gene, was dynamically expressed in the presomitic mesoderm (PSM) and at early stage of differentiating somites. Loss of Ndrg2 in mice resulted in vertebral homeotic transformations in thoracic/lumbar and lumbar/sacral transitional regions in a dose-dependent manner. Interestingly, the inactivation of Ndrg2 in osteoblasts or chondrocytes caused defects resembling those observed in Ndrg2−/− mice, with a lower penetrance. In addition, forced overexpression of Ndrg2 in osteoblasts or chondrocytes also conferred vertebral defects, which were distinct from those in Ndrg2−/− mice. These genetic analyses revealed that Ndrg2 modulates vertebral identity in segmented somites rather than in the PSM. At the molecular level, combinatory alterations of the amount of Hoxc8-11 gene transcripts were detected in the differentiating somites of Ndrg2−/− embryos, which may partially account for the vertebral defects in Ndrg2 mutants. Nevertheless, Bmp/Smad signaling activity was elevated in the differentiating somites of Ndrg2−/− embryos. Collectively, our findings unveiled Ndrg2 as a novel regulator of vertebral specification in differentiating somites