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Proceedings of the 37th International Conference on Neural Information Processing systems

作者： Chaofei Fan Nick Hahn Foram Kamdar Donald Avansino Guy H. Wilson Leigh Hochberg Krishna V. Shenoy Jaimie M. Henderson Francis R. Willett Department of Computer Science Stanford University Department of Neurosurgery Stanford University Howard Hughes Medical Institute at Stanford University Department of Neuroscience Stanford University School of Engineering and Carney Institute for Brain Science Brown University and VA RR & D Center for Neurorestoration and Neurotechnology VA Providence Healthcare System and Center for Neurotechnology and Neurorecovery Department of Neurology Massachusetts General Hospital Harvard Medical School Bio-X Program Stanford University and Department of Neurobiology Stanford University and Department of Bioengineering Stanford University and Wu Tsai Neurosciences Institute Stanford University and Howard Hughes Medical Institute at Stanford University and Department of Electrical Engineering Stanford University Department of Neurosurgery Stanford University and Wu Tsai Neurosciences Institute Stanford University

Intracortical brain-computer interfaces (iBCIs) have shown promise for restoring rapid communication to people with neurological disorders such as amyotrophic lateral sclerosis (ALS). However, to maintain high performance over time, iBCIs typically need frequent recalibration to combat changes in the neural recordings that accrue over days. This requires iBCI users to stop using the iBCI and engage in supervised data collection, making the iBCI system hard to use. In this paper, we propose a method that enables self-recalibration of communication iBCIs without interrupting the user. Our method leverages large language models (LMs) to automatically correct errors in iBCI outputs. The self-recalibration process uses these corrected outputs ("pseudo-labels") to continually update the iBCI decoder online. Over a period of more than one year (403 days), we evaluated our Continual Online Recalibration with Pseudo-labels (CORP) framework with one clinical trial participant. CORP achieved a stable decoding accuracy of 93.84% in an online handwriting iBCI task, significantly outperforming other baseline methods. Notably, this is the longest-running iBCI stability demonstration involving a human participant. Our results provide the first evidence for long-term stabilization of a plug-and-play, high-performance communication iBCI, addressing a major barrier for the clinical translation of iBCIs.

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CRISPR/Cas9 mediated somatic gene therapy for insertional mutations:the vibrator mouse model

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Precision Clinical Medicine 2021年第3期4卷 168-175页

作者： Xin Fu Jie Zhu Yaou Duan Paul Lu Kang Zhang Spine Center Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Guangzhou Women and Children’s Medical Center Guangzhou Medical UniversityGuangzhou 510623China Department of Nanoengineering Chemical Engineering Programand Moores Cancer CenterUniversity of California at San DiegoLa JollaCA 92093USA VA-San Diego Healthcare System San DiegoCA 92161USA Department of Neurosciences University of California at San DiegoLa JollaCA 92093USA Center for Biomedicine and Innovations Faculty of MedicineMacao University of Science and TechnologyMacaoChina

Somatic gene therapy remains technically challenging,especially in the central nervous system(CNS).Efficiency of gene delivery,efficacy in recipient cells,and proportion of cells required for overall benefit are the key points needed to be considered in any therapeutic *** efforts have demonstrated the efficacy of RNA-guided nucleases such as CRISPR/Cas9 in correcting point mutations or removing dominant *** we used viral delivered Cas9 plasmid and two guide RNAs to remove a recessive insertional mutation,vibrator(vb),in the mouse *** vb mice expressed∼20%of normal levels of phosphatidylinositol transfer protein,α(PITPα)RNA and protein due to an endogenous retrovirus inserted in intron 4,resulting in early-onset tremor,degeneration of brainstem and spinal cord neurons,and juvenile *** in situ CRISPR/Cas9 viral treatment effectively delayed neurodegeneration,attenuated tremor,and bypassed juvenile *** studies demonstrate the potential of CRISPR/Cas9-mediated gene therapy for insertional mutations in the postnatal brain.

关键词： somatic gene editing neurodegenerative disease vibrator mouse model CRISPR/Cas9 Pitpna

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Agastache rugosa Extract Combined With Voluntary Wheel Exercise Affects the Improvement of Skeletal Muscle Homeostasis in Aged C57BL/6J Mice

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Current Developments in Nutrition 2022年 6卷 520-520页

作者： Lee, Hyejoon Lee, Jisang Kim, Hye Jin Kwon, Oran Ewha Womans University Department of Nutritional Science and Food Management Graduate Program in System Health Science and Engineering The Research Institute for Veterinary Science College of Veterinary Medicine Seoul National University

Objectives:This study aimed to investigate the beneficial effects of Agastache rugosa (AR) combined with wheel running exercise on maintaining muscle homeostasis in aged skeletal muscle. Methods:Male 38-week-old C57BL/6J mice were divided into five groups (n = 8/group): control (CON), Low-dose AR-treated (ARL, 100 mg/kg/day), High-dose AR-treated (ARH, 200 mg/kg/day), exercise (EXC), and EXC + ARH (EXH) group. After 2 weeks of acclimation period, AR-treated groups were fed AR extract by oral administration for 4 weeks. The daily voluntary wheel running (VWR) distance was recorded using a counter machine. In the gastrocnemius (GAS) muscle sample, muscle homeostasis-related genes and protein were analyzed by qPCR and western blotting, respectively. Results:The weight of GAS in ARH and EXH increased significantly, compared to CON ( p < 0.05). qPCR analysis showed that AR and exercise affected both oxidative and glycolytic muscle fibers. mRNA levels of Myh7 and Myh1 in EXH were remarkably higher than in CON ( p < 0.05). Skeletal muscle atrophy ( Atrogin-1 and MuRF-1) and hypertrophy ( myogenin) related genes were up-regulated in EXC compared to CON ( p < 0.05). Meanwhile, EXH dramatically downregulated Atrogin-1 and MuRF-1 and up-regulated < > ( p < 0.05). Western blotting analysis indicated that the hypertrophy-related protein p70S6 showed high levels in both exercise groups, but there was no statistically significant difference. In contrast, atrophy-related protein FOXO3a and MuRF-1 levels were remarkably lower in the EXC and EXH ( p < 0.05). Conclusions:Taken together, this study demonstrated that AR with VWR exercise enhanced muscle homeostasis via regulation of skeletal muscle protein synthesis and degradation markers in aged hindlimb muscles. In conclusion, AR could be a promising candidate for maintaining muscle homeostasis and further alleviating sarcopenia. Funding Sources:This work was supported by the BK21 FOUR (Fostering Outstanding Universities for Research

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Quality index design for online monitoring injection molding process 77

Quality index design for online monitoring injection molding...

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77th Annual Technical Conference of the Society of Plastics Engineers, ANTEC 2019

作者： Chen, Jian-Yu Huang, Ming-Shyan Nian, Shih-Chih Tseng, Chien-Chou Bachelor Program of Precision System Design Feng Chia University Taiwan Dept. of Mechanical and Automation Engineering National Kaohsiung University of Science and Technology Taiwan Dept. of Power Mechanical Engineering National Taitung College Taiwan

Quality control is a crucial issue in the injection molding process with target of obtaining a high yield rate and reducing production cost. However, conventional injection molding acts like a black-box in which the flowing behavior of polymer melt within cavities is unseen, and the tuning of process parameters is heavily relied on operators' experience, design of experimental methods, or even trial- and-error. Such approaches are not only time-consuming but also lack of assuring consistent injection molding qualities and quality control is then required. Nowadays with the advance of sensing technology, many sensors are available to detect the flowing behavior of polymer melt within mold cavities. Particularly the pressure, velocity, and temperature that affect the flowing ability of polymer melt can be detected in time. In other words, injection molding now has been transformed into a grey-box and a scientific viewpoint to tune process parameters can be realized. In this research, a quality index extracted from pressure profile is aimed for online quality monitoring. In addition, the clamping force increment quality index extracted from the tie-bar elongation which is detected by strain gauges attached on tie bars, free of invading injection mold structure, is paid much attention. To verify the feasibility of the designed quality index using to prediction the injection molded quality, varying barrel temperature, back pressure and rotational speed of plasticizing screw those can affect the plasticizing quality of raw materials are conducted in this investigation. Experimental results reveals that the clamping force increment as well as pressure peak index extracted from injection system pressure, nozzle pressure, end-of-filling cavity pressure profiles during injection molding are highly correlated with injection-molded qualities and thereby are feasible to be a good quality indicator. © 2019 Society of Plastics Engineers. All rights reserved.

关键词： Polymer melts

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Hybrid Particle Swarm and Conjugate Gradient Optimization in Neural Network for Prediction of Suspended Particulate Matter 4

Hybrid Particle Swarm and Conjugate Gradient Optimization in...

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4th International Conference on Energy, Environment, Epidemiology and Information system, ICENIS 2019

作者： Warsito, Budi Prahutama, Alan Yasin, Hasbi Sumiyati, Sri Department of Statistics Faculty of Sciences and Mathematics Diponegoro University Semarang Indonesia Master Program of Information System School of Postgraduate Studies Diponegoro University Semarang Indonesia Department of Environmental Engineering Faculty of Engineering Diponegoro University Semarang Indonesia

The scope of this research is the use of artificial neural network models and meta-heuristic optimization of Particle Swarm Optimization (PSO) for the prediction of ambient air pollution parameter data at air quality monitoring stations in the city of Semarang, Central Java. The observed parameter is an indicator of ambient air quality, Suspended Particulate Matter (SPM). Based on air quality parameter data in previous times which is a time series data, modeling is done using Neural Networks (NN). Estimation of weights from NN is done using a hybrid method between meta-heuristic and gradient optimization. The meta-heuristic optimization method used is Particle Swarm Optimization (PSO) while the gradient based method is the Conjugate Gradient. Optimization with PSO is done first, then proceed with optimization using the Conjugate Gradient. Four scenarios of iteration selection at the PSO stage are 10, 25, 50 and 100. At the Conjugate Gradient, stage iteration is carried out up to 1000 epohs. The predicted results were compared with the PSOs and Conjugate Gradient respectively. The results show that the hybrid method provides better predictions. The number of iterations needed at the PSO stage is not too much so it is efficient in combining the two methods. © The Authors, published by EDP Sciences, 2019.

关键词： Forecasting

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Tie-bar elongation based prediction of injection molding quality 77

Tie-bar elongation based prediction of injection molding qua...

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77th Annual Technical Conference of the Society of Plastics Engineers, ANTEC 2019

作者： Huang, Ming-Shyan Nian, Shih-Chih Chen, Jian-Yu Dept. of Mechanical and Automation Engineering National Kaohsiung University of Science and Technology Taiwan Dept. of Power Mechanical Engineering National Taitung College Taiwan Bachelor Program in Precision System Design Feng Chia University Taiwan

Filling-to-packing switchover (also called as V/P switchover) is critical for assuring injection molding quality. An improper filling-to-packing switchover setting may result in various defects of injection-molded parts, such as excessive residual stress, flash, short shot, and warpage, etc. To enhance consistent molding quality, recent V/P switchover approach applies cavity pressure profiles requiring sensors embedded in mold cavities, which is invasive to mold cavities and even expensive. Instead of using cavity pressure sensors, this study thereby proposes a novel approach of identifying ideal V/P switchover timing using a tie-bar elongation profile. In this investigation, a dumbbell testing specimen mold is applied to experimentally verify the feasibility of the proposed method. The results showthat the mold filling and packing stages can be observed along the tie-bar elongation profile detected by mounting strain gauges on tie bars. Moreover, the varying process parameter settings including injection speed, filling-to-packing switchover point, and holding pressure, can be reflected in these profiles. By extracting their characteristics, the decision of filling-to-packing switchover is proved to be realistic. © 2019 Society of Plastics Engineers. All rights reserved.

关键词： Filling

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Saca chip enabled circulating tumor cell clusters phenotyping for cancer immunotherapy response monitoring 24

Saca chip enabled circulating tumor cell clusters phenotypin...

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24th International Conference on Miniaturized systems for Chemistry and Life Sciences, MicroTAS 2020

作者： Hsu, Chun-Jieh Kan, Yu-Chia Lee, Chun-Wei Wu, Jen-Kuei Lee, Kang-Yun Feng, Po-Hao Chang, Wei-Chiao Tseng, Fan-Gang Department of Engineering and System Science National Tsing Hua University Taiwan Nano Science and Technology Program International Graduate Program Academia Sinica Taiwan Research Center for Applied Sciences Academia Sinica Taiwan Division of Pulmonary Medicine Department of Internal Medicine Shuang Ho Hospital Taipei Medical University Taiwan Division of Pulmonary Medicine Department of Internal Medicine School of Medicine College of Medicine Taipei Taiwan School of Pharmacy Department of Clinical Pharmacy Taipei Medical University Taiwan

ISBN: (纸本)9781733419017

In the present study, we indicated that the detection of specific subtypes of circulating tumor microemboli (CTM) in post-operative patients could help predict cancer recurrence. By using conventional strategies for detection of non-small-cell lung cancer (NSCLC) circulating tumor cells, is significantly limited due to inherently heterogeneous and dynamic expression of EpCAM, and degradation of cytokeratins during epithelial-tomesenchymal transition. These lead to non-negligible false negative detection of "uncapturable and invisible" single CTCs. To solve the problem, we investigated the clinical significance of CTM subtypes, including single CTCs, multi-CTCs cluster, and WBC-CTCs cluster on SACA chip for studying cancer metastasis and recurrence in patients with lung adenocarcinoma. © 2020 CBMS-0001

关键词： Tumors

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Induction of diabetes in cynomolgus monkey with one shot of analytical grade streptozotocin

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Animal Models and Experimental Medicine 2020年第1期3卷 79-86页

作者： Zhengzhao Liu Ying Lu Wenbao Hu Hidetaka Hara Yifan Dai Zhiming Cai Lisha Mou Shenzhen Xenotransplantation Medical Engineering Research and Development Center Institute of Translational MedicineShenzhen Second People's HospitalThe First Affiliated Hospital of Shenzhen UniversityHealth Science CenterShenzhenChina Movement System Injury and Repair Research Center Xiangya Hospital of Central South UniversityChangshaChina Jiangsu Key Laboratory of Xenotransplantation Nanjing Medical UniversityNanjingChina Xenotransplantation Program/Department of Surgery The University of Alabama at BirminghamBirminghamALUSA

Backgrounds:Streptozotocin(STZ)-induced diabetic monkey is a wide used preclinical animal model for the investigation of diabetes such as islet transplantation and development of diabetic *** are serious side effects of this method,including nausea,emesis,weight loss,liver damage,renal failure,and metabolic *** order to reduce the side effects,diabetic monkeys were induced using clinicalgrade ***,clinical-grade STZ is not available in ***,we establised a method by using 100 mg/kg analytical-grade STZ to induce complete diabetes in cynomolgus monkey without generating adverse effects to liver and ***:Three cynomolgus monkeys were used in this study.100 mg/kg STZ dissolved in normal saline and infused through vein line in 5 minutes after indwelling catheter in the carotid artery and jugular *** the STZ administration,blood glucose levels were examined every 1 or 2 hours in the first 48 ***,blood glucose levels were examined twice per day during the first week after the STZ *** and C-peptide levels were measured by *** chemistry of hepatic and renal function tests were *** and glucagon expression in the islet of diabetic monkey and normal monkey were examined by immunohistochemistry ***:The stimulated C-peptide level(Intravenous glucose tolerance test)which is less than 0.5 ng/mL,the triphasic blood glucose response and the destroyed β cell suggested the complete induction of diabetes *** apparent adverse effects were observed including no signs of vomiting and toxicity after STZ ***:In summary,we established a safe and reproducible STZ-induced diabetic cynomolgus monkey model for islet transplantation which will be used to develop novel approaches for the treatment of diabetes.

关键词： analytical grade diabetic model nonhuman primate STZ

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Spatiotemporal changes in land cover land use in protected areas of Serra da Mantiqueira, Southeastern Brazil

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Environmental Challenges 2021年 4卷

作者： da Silva, Ismael Aparecido Dupas, Francisco Antonio Costa, Carlos Wilmer Medeiros, Grasiela de Oliveira Rodrigues de Souza, Alessandra Ribeiro Graduate Program in Energy Engineering Federal University of Itajubá Itajubá Minas Gerais Brazil Graduate Program in Environmental Sciences Federal University of São Carlos São Paulo Brazil Department of Civil Engineering Federal University of Rio Grande do Norte Natal Rio Grande do Norte Brazil Earth System Science Center National Institute of Spacial Research São José dos Campos São Paulo Brazil

An assessment of the dynamics of land cover and use in and around a Protected Area (PA) located in the Área de Preservação Ambiental da Serra da Mantiqueira (APASM;Mantiqueira Mountain Range Environmental Protection Area) and Parque Nacional do Itatiaia (PNI;Itatiaia National Park) has been developed. This PA is part of the Brazilian Mata Atlântica (MA;Atlantic Forest) biome, which is of great importance in providing water resources and in biodiversity maintenance since it is one of the largest and most populated urban centers in Brazil. In two contiguous drainage basins, with an area of 24,757.65 hectares (ha), proposals have been sought that lead to monitoring of forests pressured by anthropic actions that have as an inductor vehicle the roads built around the PA. Results obtained by Remote Sensing (RS) data show that pasture areas have grown 43% between 1985 and 2005 and forest areas have declined 20% in the same period. However, between 2005 and 2017, there was a 22% decline in pasture area and rehabilitation in forest areas by 26%. Urban spots have steadily grown by nearly 120% between 1985 and 2017. In a Geographic Information system (GIS) environment and using multiple-criteria decision analysis (MCDA) with a weighted sum to environmental attributes of roads and urban spots, it has also been verified that 85% of the study area is under high or very high pressure, which can jeopardize the maintenance of biodiversity and water resources in the region due to population increase induced by secondary roads and their paving, which moves towards the PNI limits. © 2021

关键词： Atlantic forest GIS National park Park road Remote sensing Territorial dynamics

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Microfluidic nanodevices for drug sensing and screening applications

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Biosensors and Bioelectronics 2023年 219卷 114783页

作者： Pal, Arnab Kaswan, Kuldeep Barman, Snigdha Roy Lin, Yu-Zih Chung, Jun-Hsuan Sharma, Manish Kumar Liu, Kuei-Lin Chen, Bo-Huan Wu, Chih-Cheng Lee, Sangmin Choi, Dongwhi Lin, Zong-Hong Institute of Biomedical Engineering National Tsing Hua University Hsinchu30013 Taiwan International Intercollegiate PhD Program National Tsing Hua University Hsinchu30013 Taiwan Department of Power Mechanical Engineering National Tsing Hua University Hsinchu30013 Taiwan Department of Materials Science and Engineering National Tsing Hua University Hsinchu30013 Taiwan Department of Chemistry National Tsing Hua University Hsinchu30013 Taiwan Frontier Research Center on Fundamental and Applied Sciences of Matters National Tsing Hua University Hsinchu30013 Taiwan Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital Linkou Medical Center Taoyuan333 Taiwan Center of Quality Management National Taiwan University Hospital Hsinchu Branch Hsinchu30059 Taiwan College of Medicine National Taiwan University Taipei10051 Taiwan Institute of Cellular and System Medicine National Health Research Institute Zhunan 35053 Taiwan School of Mechanical Engineering Chung-Ang University Seoul06974 Korea Republic of Kyung Hee University Gyeonggi 17104 Korea Republic of

The outbreak of pandemics (e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 in 2019), influenza A viruses (H1N1 in 2009), etc.), and worldwide spike in the aging population have created unprecedented urgency for developing new drugs to improve disease treatment. As a result, extensive efforts have been made to design novel techniques for efficient drug monitoring and screening, which form the backbone of drug development. Compared to traditional techniques, microfluidics-based platforms have emerged as promising alternatives for high-throughput drug screening due to their inherent miniaturization characteristics, low sample consumption, integration, and compatibility with diverse analytical strategies. Moreover, the microfluidic-based models utilizing human cells to produce in-vitro biomimetics of the human body pave new ways to predict more accurate drug effects in humans. This review provides a comprehensive summary of different microfluidics-based drug sensing and screening strategies and briefly discusses their advantages. Most importantly, an in-depth outlook of the commonly used detection techniques integrated with microfluidic chips for highly sensitive drug screening is provided. Then, the influence of critical parameters such as sensing materials and microfluidic platform geometries on screening performance is summarized. This review also outlines the recent applications of microfluidic approaches for screening therapeutic and illicit drugs. Moreover, the current challenges and the future perspective of this research field is elaborately highlighted, which we believe will contribute immensely towards significant achievements in all aspects of drug development. © 2022 Elsevier B.V.

关键词： Microfluidics

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