S3^{3}: Increasing GPU Utilization during Generative Inference for Higher Throughput

Generating texts with a large language model (LLM) consumes massive amounts of memory. Apart from the already-large model parameters, the key/value (KV) cache that holds information about previous tokens in a sequence can grow to be even larger than the model itself. This problem is exacerbated in one of the current LLM serving frameworks which reserves the maximum sequence length of memory for the KV cache to guarantee generating a complete sequence as they do not know the output sequence length. This restricts us to use a smaller batch size leading to lower GPU utilization and above all, lower throughput. We argue that designing a system with a priori knowledge of the output sequence can mitigate this problem. To this end, we propose S$^{3}$, which predicts the output sequence length, schedules generation queries based on the prediction to increase device resource utilization and throughput, and handle mispredictions. Our proposed method achieves 6.49$\times$ throughput over those systems that assume the worst case for the output sequence length

SpeedLimit: Neural Architecture Search for Quantized Transformer Models

While research in the field of transformer models has primarily focused on enhancing performance metrics such as accuracy and perplexity, practical applications in industry often necessitate a rigorous consideration of inference latency constraints. Addressing this challenge, we introduce SpeedLimit, a novel Neural Architecture Search (NAS) technique that optimizes accuracy whilst adhering to an upper-bound latency constraint. Our method incorporates 8-bit integer quantization in the search process to outperform the current state-of-the-art technique. Our results underline the feasibility and efficacy of seeking an optimal balance between performance and latency, providing new avenues for deploying state-of-the-art transformer models in latency-sensitive environments

Molecular interactions of autophagy with the immune system and cancer

Autophagy is a highly conserved catabolic mechanism that mediates the degradation of damaged cellular components by inducing their fusion with lysosomes. This process provides cells with an alternative source of energy for the synthesis of new proteins and the maintenance of metabolic homeostasis in stressful environments. Autophagy protects against cancer by mediating both innate and adaptive immune responses. Innate immune receptors and lymphocytes (T and B) are modulated by autophagy, which represent innate and adaptive immune responses, respectively. Numerous studies have demonstrated beneficial roles for autophagy induction as well as its suppression of cancer cells. Autophagy may induce either survival or death depending on the cell/tissue type. Radiation therapy is commonly used to treat cancer by inducing autophagy in human cancer cell lines. Additionally, melatonin appears to affect cancer cell death by regulating programmed cell death. In this review, we summarize the current understanding of autophagy and its regulation in cancer

Deep-Learning-Based Algorithm for the Removal of Electromagnetic Interference Noise in Photoacoustic Endoscopic Image Processing

Despite all the expectations for photoacoustic endoscopy (PAE), there are still several technical issues that must be resolved before the technique can be successfully translated into clinics. Among these, electromagnetic interference (EMI) noise, in addition to the limited signal-to-noise ratio (SNR), have hindered the rapid development of related technologies. Unlike endoscopic ultrasound, in which the SNR can be increased by simply applying a higher pulsing voltage, there is a fundamental limitation in leveraging the SNR of PAE signals because they are mostly determined by the optical pulse energy applied, which must be within the safety limits. Moreover, a typical PAE hardware situation requires a wide separation between the ultrasonic sensor and the amplifier, meaning that it is not easy to build an ideal PAE system that would be unaffected by EMI noise. With the intention of expediting the progress of related research, in this study, we investigated the feasibility of deep-learning-based EMI noise removal involved in PAE image processing. In particular, we selected four fully convolutional neural network architectures, U-Net, Segnet, FCN-16s, and FCN-8s, and observed that a modified U-Net architecture outperformed the other architectures in the EMI noise removal. Classical filter methods were also compared to confirm the superiority of the deep-learning-based approach. Still, it was by the U-Net architecture that we were able to successfully produce a denoised 3D vasculature map that could even depict the mesh-like capillary networks distributed in the wall of a rat colorectum. As the development of a low-cost laser diode or LED-based photoacoustic tomography (PAT) system is now emerging as one of the important topics in PAT, we expect that the presented AI strategy for the removal of EMI noise could be broadly applicable to many areas of PAT, in which the ability to apply a hardware-based prevention method is limited and thus EMI noise appears more prominently due to poor SNR

Diode Laser—Can It Replace the Electrical Current Used in Endoscopic Submucosal Dissection?

Background/Aims A new medical fiber-guided diode laser system (FDLS) is expected to offer high-precision cutting with simultaneous hemostasis. Thus, this study aimed to evaluate the feasibility of using the 1,940-nm FDLS to perform endoscopic submucosal dissection (ESD) in the gastrointestinal tract of an animal model. Methods In this prospective animal pilot study, gastric and colorectal ESD using the FDLS was performed in ex vivo and in vivo porcine models. The completeness of en bloc resection, the procedure time, intraprocedural bleeding, histological injuries to the muscularis propria (MP) layer, and perforation were assessed. Results The en bloc resection and perforation rates in the ex vivo study were 100% (10/10) and 10% (1/10), respectively; those in the in vivo study were 100% (4/4) and 0% for gastric ESD and 100% (4/4) and 25% (1/4) for rectal ESD, respectively. Deep MP layer injuries tended to occur more frequently in the rectal than in the gastric ESD cases, and no intraprocedural bleeding occurred in either group. Conclusions The 1,940-nm FDLS was capable of yielding high en bloc resection rates without intraprocedural bleeding during gastric and colorectal ESD in animal models

Methylation-dependent regulation of HIF-1 alpha stability restricts retinal and tumour angiogenesis

Hypoxia-inducible factor-1 alpha (HIF-1 alpha) mediates hypoxic responses and regulates gene expression involved in angiogenesis, invasion and metabolism. Among the various HIF-1 alpha posttranslational modifications, HIF-1 alpha methylation and its physiological role have not yet been elucidated. Here we show that HIF-1 alpha is methylated by SET7/9 methyltransferase, and that lysine-specific demethylase 1 reverses its methylation. The functional consequence of HIF-1 alpha methylation is the modulation of HIF-1 alpha stability primarily in the nucleus, independent of its proline hydroxylation, during long-term hypoxic and normoxic conditions. Knock-in mice bearing a methylation-defective Hif1a(KA/KA) allele exhibit enhanced retinal angiogenesis and tumour vascularization via HIF-1 alpha stabilization. Importantly, S28Y and R30Q mutations of HIF-1 alpha, found in human cancers, are involved in the altered HIF-1 alpha stability. Together, these results demonstrate a role for HIF-1 alpha methylation in regulating protein stability, thereby modulating biological output including retinal and tumour angiogenesis, with therapeutic implications in human cancer.1

G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast Cancer

Epigenetic abnormalities affect tumor progression, as well as gene expression and function. Among the diverse epigenetic modulators, the histone methyltransferase G9a has been focused on due to its role in accelerating tumorigenesis and metastasis. Although epigenetic dysregulation is closely related to tumor progression, reports regarding the relationship between G9a and its possible downstream factors regulating breast tumor growth are scarce. Therefore, we aimed to verify the role of G9a and its presumable downstream regulators during malignant progression of breast cancer. G9a-depleted MCF7 and T47D breast cancer cells exhibited suppressed motility, including migration and invasion, and an improved response to ionizing radiation. To identify the possible key factors underlying these effects, microarray analysis was performed, and a TGF-β superfamily member, BMP5, was selected as a prominent target gene. It was found that BMP5 expression was markedly increased by G9a knockdown. Moreover, reduction in the migration/invasion ability of MCF7 and T47D breast cancer cells was induced by BMP5. Interestingly, a G9a-depletion-mediated increase in BMP5 expression induced the phosphorylation of Smad proteins, which are the intracellular signaling mediators of BMP5. Accordingly, we concluded that the observed antitumor effects may be based on the G9a-depletion-mediated increase in BMP5 expression and the consequent facilitation of Smad protein phosphorylation

Synthesis and Reactivity of Nickel(II) Hydroxycarbonyl Species, NiCOOH-kappa C

Reactions of nickel complexes supported by an anionic PNP pincer ligand (PNP- = N[2-(PPr2)-Pr-i-4-Me-C6H3](2)) toward CO2 and CO are investigated, particularly for interrogating their C-O bond formation/cleavage chemistry. The formation of a nickel formate species (2) was accomplished by the reaction of (PNP)NiH with CO2, while the structural isomer complex (PNP)NiCOOH-kappa C (4) was successfully produced from the corresponding nickel hydroxyl compound by exposing it to CO(g). Its structurally unique character was gleaned by obtaining two solid-state structures for (PNP)NiCOOH-kappa C (4) and {(PNP)Ni}(2)-mu-CO2-kappa C-2,O (6); the latter was obtained from the reaction of 4 with a nickel hydroxyl complex. Both species possess a NiCOO-kappa C binding mode, which is reminiscent of the binding mode found at the carbon monoxide dehydrogenase (CODH) active site with its Ni-COO-Fe fragment. The cationic species {(PNP)NiCO}(+) (7) was also prepared via the protonation of 4, which then led to the investigation of the C-O bond formation in 7 by adding a nucleophile such as OH-

Identification and Characterization of an Isoform Antifreeze Protein from the Antarctic Marine Diatom, Chaetoceros neogracile and Suggestion of the Core Region

Antifreeze proteins (AFPs) protecting the cells against freezing are produced in response to extremely low temperatures in diverse psychrophilic organisms, and they are encoded by multiple gene families. The AFP of Antarctic marine diatom Chaetoceros neogracile is reported in our previous research, but like other microalgae, was considered to probably have additional genes coding AFPs. In this paper, we reported the cloning and characterization of additional AFP gene from C. neogracile (Cn-isoAFP). Cn-isoAFP protein is 74.6% identical to the previously reported Cn-AFP. The promoter sequence of Cn-isoAFP contains environmental stress responsive elements for cold, thermal, and high light conditions. Cn-isoAFP transcription levels increased dramatically when cells were exposed to freezing (−20 °C), thermal (10 °C), or high light (600 μmol photon m−2 s−1) stresses. The thermal hysteresis (TH) activity of recombinant Cn-isoAFP was 0.8 °C at a protein concentration of 5 mg/mL. Results from homology modeling and TH activity analysis of site-directed mutant proteins elucidated AFP mechanism to be a result of flatness of B-face maintained via hydrophobic interactions

Melatonin as an Oncostatic Molecule Based on Its Anti-Aromatase Role in Breast Cancer

Breast cancer is the most common type of cancer. In the developmental stages of breast cancer, estrogens are strongly involved. As estrogen synthesis is regulated by the enzyme aromatase, targeting the activity of this enzyme represents a therapeutic option. The pineal hormone melatonin may exert a suppressive role on aromatase activity, leading to reduced estrogen biosynthesis. A melatonin-mediated decrease in the expression of aromatase promoters and associated genes would provide suitable evidence of this molecule’s efficacy as an aromatase inhibitor. Furthermore, melatonin intensifies radiation-induced anti-aromatase effects and counteracts the unwanted disadvantages of chemotherapeutic agents. In this manner, this review summarizes the inhibitory role of melatonin in aromatase action, suggesting its role as a possible oncostatic molecule in breast cancer