Investigation of hydrate slurry flow behaviors in deep-sea pipes with different inclination angles

The marine area is the main direction of the development of oil and gas resources in the world. The pipeline transportation technology of natural gas hydrate slurry plays an important role in the exploitation of marine oil and gas and the exploitation of marine gas hydrate resources. In order to study the influence of pipe inclination on pipeline transportation, population balance model based on hydrate particle aggregation dynamics was coupled with the Eulerian–Eulerian two-fluid multiphase flow model to simulate the flow behaviors of hydrate slurry flow in pipes with different inclination angles. In the study, three variables of inclination, flow rate and initial particle size were considered. The results show that tilted pipes are beneficial to hydrate slurry transport rather than harmful. Meanwhile, higher flow rates and lower initial particle sizes are beneficial for promoting the flow safety of hydrate slurry transport. However, the flow pressure drop of the hydrate slurry increases with the increase of the flow rate and the decrease of the initial particle size, which is not conducive to the economics of mining. The research results in this paper can provide reference for the research of hydrate slurry flow safety and parameter guidance for hydrate solid fluidized mining

Advancing Transformer Architecture in Long-Context Large Language Models: A Comprehensive Survey

Transformer-based Large Language Models (LLMs) have been applied in diverse areas such as knowledge bases, human interfaces, and dynamic agents, and marking a stride towards achieving Artificial General Intelligence (AGI). However, current LLMs are predominantly pretrained on short text snippets, which compromises their effectiveness in processing the long-context prompts that are frequently encountered in practical scenarios. This article offers a comprehensive survey of the recent advancement in Transformer-based LLM architectures aimed at enhancing the long-context capabilities of LLMs throughout the entire model lifecycle, from pre-training through to inference. We first delineate and analyze the problems of handling long-context input and output with the current Transformer-based models. We then provide a taxonomy and the landscape of upgrades on Transformer architecture to solve these problems. Afterwards, we provide an investigation on wildly used evaluation necessities tailored for long-context LLMs, including datasets, metrics, and baseline models, as well as optimization toolkits such as libraries, frameworks, and compilers to boost the efficacy of LLMs across different stages in runtime. Finally, we discuss the challenges and potential avenues for future research. A curated repository of relevant literature, continuously updated, is available at https://github.com/Strivin0311/long-llms-learning.Comment: 40 pages, 3 figures, 4 table

Pathological Comparisons of the Hippocampal Changes in the Transient and Permanent Middle Cerebral Artery Occlusion Rat Models

© Copyright © 2019 Shah, Li, Kury, Zeb, Khatoon, Liu, Yang, Liu, Yao, Khan, Koh, Jiang and Li. Ischemic strokes are categorized by permanent or transient obstruction of blood flow, which impedes delivery of oxygen and essential nutrients to brain. In the last decade, the therapeutic window for tPA has increased from 3 to 5–6 h, and a new technique, involving the mechanical removal of the clot (endovascular thrombectomy) to allow reperfusion of the injured area, is being used more often. This last therapeutic approach can be done until 24 h after stroke onset. Due to this fact, more acute ischemic stroke patients are now being recanalized, and so tMCAO is probably the “best” model to address these patients that have a potential good outcome in terms of survival and functional recovery. However, permanent occlusion patients are also important, not only to increase survival rate but also to improve functional outcomes, although these are more difficult to achieve. So, both models are important, and which target different stroke patients in the clinical scenario. Hippocampus has a vital role in memory and cognition, is prone to ischemic induced neurodegeneration. This study was designed to delineate the molecular, pathological, and neurological changes in rat models of t-MCAO, permanent MCAO (pMCAO), and pMCAO with diabetic conditions in hippocampal tissue. Our results showed that these three models showed distinct discrepancies at numerous pathological process, including key signaling molecules involved in neuronal apoptosis, glutamate induced excitotoxicity, neuroinflammation, oxidative stress, and neurotrophic changes. Our result suggests that the two commonly used MCAO models exhibited tremendous differences in terms of neuronal cell loss, glutamate excitotoxic related signaling, synaptic transmission markers, neuron inflammatory and oxidative stress molecules. These differences may reflect the variations in different models, which may provide valuable information for mechanistic and therapeutic inconsistences as experienced in both preclinical models and clinical trials

The correlation between fruit intake and all-cause mortality in hypertensive patients: a 10-year follow-up study

ObjectiveExtensive research has consistently shown the beneficial impact of fruit consumption on overall health. While some studies have proposed a potential association between fruit consumption and hypertension management, the influence of fruit consumption on mortality rates among hypertensive individuals remains uncertain. Consequently, aim of this study is to evaluate whether fruit consumption is associated with all-cause mortality among hypertensive patients.MethodsData were obtained from the National Health and Nutrition Examination Survey (NHANES), conducted between 2003 and 2006. Ten-year follow-up data from the National Death Index (NDI) were used to assess all-cause mortality. Cox proportional hazard model was utilized to explore the impact of fruit intake on all-cause mortality among hypertensive individuals.ResultsThe study included a cohort of 2,480 patients diagnosed with hypertension, and during the follow-up period, a total of 658 deaths from various causes were recorded. The COX regression analysis demonstrated that hypertensive patients who consumed apples three to six times per week exhibited a significantly reduced risk of all-cause mortality (HR = 0.60, 95%CI: 0.45–0.78, p < 0.001) in comparison to those who consumed apples less than once per month. Likewise, consuming bananas three to six times per week also led to a comparable outcome (HR = 0.76, 95%CI: 0.59–0.97, p = 0.027). Moreover, Combined consumption of bananas and apples three to six times per week exhibited a noteworthy decrease in all-cause mortality (HR = 0.57, 95%CI: 0.39–0.84, p = 0.005) when compared to individuals who consumed these fruits less frequently. Conversely, no significant association was found between the consumption of other fruits, including pears, pineapples, and grapes, and all-cause mortality.ConclusionThe study discovered that moderate consumption of apples and bananas was associated with a reduced risk of all-cause mortality in patients with hypertension

Chronic salmon calcitonin exerts an antidepressant effect via modulating the p38 MAPK signaling pathway

Depression is a common recurrent psychiatric disorder with a high lifetime prevalence and suicide rate. At present, although several traditional clinical drugs such as fluoxetine and ketamine, are widely used, medications with a high efficiency and reduced side effects are of urgent need. Our group has recently reported that a single administration of salmon calcitonin (sCT) could ameliorate a depressive-like phenotype via the amylin signaling pathway in a mouse model established by chronic restraint stress (CRS). However, the molecular mechanism underlying the antidepressant effect needs to be addressed. In this study, we investigated the antidepressant potential of sCT applied chronically and its underlying mechanism. In addition, using transcriptomics, we found the MAPK signaling pathway was upregulated in the hippocampus of CRS-treated mice. Further phosphorylation levels of ERK/p38/JNK kinases were also enhanced, and sCT treatment was able only to downregulate the phosphorylation level of p38/JNK, with phosphorylated ERK level unaffected. Finally, we found that the antidepressant effect of sCT was blocked by p38 agonists rather than JNK agonists. These results provide a mechanistic explanation of the antidepressant effect of sCT, suggesting its potential for treating the depressive disorder in the clinic

IL-2-Free Tumor-Infiltrating Lymphocyte Therapy With PD-1 Blockade Demonstrates Potent Efficacy in Advanced Gynecologic Cancer

BACKGROUND: Tumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of an innovative modified regimen in patients with advanced gynecologic cancer. METHODS: Patient-derived xenografts (PDX) were established from a local recurrent cervical cancer patient. TILs were expanded ex vivo from minced tumors without feeder cells in the modified TIL therapy regimen. Patients underwent low-dose cyclophosphamide lymphodepletion followed by TIL infusion without intravenous IL-2. The primary endpoint was safety; the secondary endpoints included objective response rate, duration of response, and T cell persistence. RESULTS: In matched patient-derived xenografts (PDX) models, homologous TILs efficiently reduced tumor size (p \u3c 0.0001) and underwent IL-2 absence in vivo. In the clinical section, all enrolled patients received TIL infusion using a modified TIL therapy regimen successfully with a manageable safety profile. Five (36%, 95% CI 16.3-61.2) out of 14 evaluable patients experienced objective responses, and three complete responses were ongoing at 19.5, 15.4, and 5.2 months, respectively. Responders had longer overall survival (OS) than non-responders (p = 0.036). Infused TILs showed continuous proliferation and long-term persistence in all patients and showed greater proliferation in responders which was indicated by the Morisita overlap index (MOI) of TCR clonotypes between infused TILs and peripheral T cells on day 14 (p = 0.004) and day 30 (p = 0.004). Higher alteration of the CD8 CONCLUSIONS: Our modified TIL therapy regimen demonstrated manageable safety, and TILs could survive and proliferate without IL-2 intravenous administration, showing potent efficacy in patients with advanced gynecologic cancer