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The Traf2 and NcK interacting kinase inhibitor NCB-0846 suppresses seizure activity involving the decrease of GRIA1

Genes & Diseases 2024年第3期11卷 452-467页

作者： Min Wang Yixue Gu Qiubo Li Bangzhe Feng Xinke Lv Hao Zhang Qingxia Kong Zhifang Dong Xin Tian Yanke Zhang Department of Neurology Affiliated Hospital of Jining Medical UniversityJiningShandong 272000China Department of Neurology The First Affiliated Hospital of Chongqing Medical UniversityChongqing Key Laboratory of NeurologyChongqing 400016China Department of Pediatrics Affiliated Hospital of Jining Medical UniversityJiningShandong 272000China Department of Neurosurgery Affliated Hospital of Jining Medical UniversityJiningShandong 272000China Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China

Epilepsy,one of the most common neurological disorders,is characterized by spon-taneous recurrent *** lobe epilepsy(TLE)is one of the most common medically intractable seizure ***2-and NcK-interacting kinase(TNIK)has recently attracted attention as a critical modulation target of many neurological and psychiatric disorders,but its role in epilepsy remains *** this study,we hypothesized the involvement of TNIK in epilepsy and investigated TNIK expression in patients with intractable TLE and in a pilocarpineinduced rat model of epilepsy by western blotting,immunofluorescence,and immunohistochemistry.A pentylenetetrazole(PTZ)-induced epilepsy rat model was used to determine the effect of the TNIK inhibitor NCB-0846 on behavioral manifestations of ***(Co-IP)/mass spectrometry(MS)was used to identify the potential *** Co-IP,we detected and confirmed the main potential TNIK *** fractionation was used to establish the effect of NCB-0846 on the expression of the main interactors in postsynaptic density(PSD)*** found that TNIK was primarily located in neurons and decreased significantly in epilepsy model rats and TLE patients compared with ***-0846 delayed kindling progression and decreased seizure ***-IP/MS identified 63 candidate TNIK interactors in rat hippocampi,notably ***-IP showed that TNIK might correlate with endogenous GRIA1,SYN2,PSD-95,CaMKIV,GABRG1,and *** addition,the significant decrease in GRIA1 in hippocampal total lysate and PSDs after NCB-0846 treatment might help modify the progression of PTZ *** results suggest that TNIK contributes to epileptic pathology and is a potential antiepileptic drug target.

关键词： Epilepsy NCB-0846 Rat TLE TNIK Traf2-and NcK-interacting kinase

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Optimal Design of WET Etching Bath for 3D Flash Memories Using Multi-Objective Bayesian Optimization

Optimal Design of WET Etching Bath for 3D Flash Memories Usi...

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Joint e-Manufacturing and Design Collaboration Symposium (eMDC) & International Symposium on Semiconductor Manufacturing (ISSM)

作者： Miyuki Kouda Yumi Mori Tomohiko Sugita Youyang Ng AI & System Research Center Frontier Technology R&D Institute KIOXIA Corporation Yokkaichi-shi Japan AI & System Research Center Frontier Technology R&D Institute KIOXIA Corporation Yokohama-shi Japan Advanced Memory Process Development Center Memory Division KIOXIA Corporation Yokkaichi-shi Japan

ISBN: (数字)9798331510589

ISBN: (纸本)9798331510596

In recent years, the complexity of semiconductor manufacturing processes has increased, leading to a growing need for the high-precision optimization of device structures. For example, in batch-type wet etching devices, the flow of chemical liquids within the process bath can vary depending on the device structure, causing variations in the etching state of the wafer. This issue is addressed using a feedback mechanism that iteratively adjusts the device structure based on the results of an etching experiment, thereby achieving more uniform etching conditions. However, this approach requires a large number of trial experiments. In the fabrication process of 3D flash memories, word-line formation in the silicon substrate requires precise control of the silicon concentration in the etching solution. However, this concentration can fluctuate due to the dissolution of the SiN film during the etching process. This fluctuation may cause various problems. This study introduces an innovative method utilizing multi-objective Bayesian optimization to derive optimal wet etching bath design parameters; this method is informed by image and physical-quantity data from fluid dynamics simulations [1]. This approach is validated through simulation experiments, whose results are used to identify the best possible wet etching bath designs effectively.

关键词： Wet etching Three-dimensional displays Fluid dynamics Semiconductor device manufacture Silicon Bayes methods Flash memories Optimization Silicon dioxide Substrates

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Exchange stiffness proportional to power of magnetization in permalloy co-doped with Mo and Cu

arXiv

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arXiv 2023年

作者： Nakamura, Shiho Umetsu, Nobuyuki Quinsat, Michael Kado, Masaki Institute of Memory Technology Research and Development Kioxia Corporation 3-13-1 Moriya-cho Kanagawa-ku Yokohama221-0022 Japan

The exchange stiffness of magnetic materials is one of the essential parameters governing magnetic texture and its dynamics in magnetic devices. The effect of single-element doping on exchange stiffness has been investigated for several doping elements for permalloy (NiFe alloy), a soft magnetic material whose soft magnetic properties can be controlled by doping. However, the impact of more practical multi-element doping on the exchange stiffness of permalloy is unknown. This study investigates the typical magnetic properties, including exchange stiffness, of permalloy systematically co-doped with Mo and Cu using broadband ferromagnetic resonance spectroscopy. We find that the exchange stiffness, which decreases with increasing doping levels, is proportional to a power of magnetization, which also decreases with increasing doping levels. The magnetization, Ms, dependence of the exchange stiffness constant, A, of all the investigated samples, irrespective of the doping levels of each element, lies on a single curve expressed as A∝Msn with exponent n close to 2. This empirical power-law relationship provides a guideline for predicting unknown exchange stiffness in nonmagnetic element-doped permalloy systems. Copyright © 2023, The Authors. All rights reserved.

关键词： Ferromagnetic materials

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Preventing method of volume expansion of polymer after metal infiltration 38

Preventing method of volume expansion of polymer after metal...

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Advances in Patterning Materials and Processes XXXVIII 2020

作者： Sasao, Norikatsu Sugimura, Shinobu Asakawa, Koji Institute of Memory Technology Research and Development Kioxia Corporation 1 Komukai-Toshiba-Cho Saiwai-Ku Kawasaki212-0001 Japan

ISBN: (数字)9781510640580

ISBN: (纸本)9781510640573

Polymeric materials have been utilized in semiconductor industries such as pattern formation materials. One of the drawbacks of such polymers is the lack of etch resistance. Metal infiltration into polymer matrices is an emerging technology that could overcome the issue. The gaseous organo-metal precursors penetrate into polymer matrices where they are oxidized to form stable metal oxides. Thus formed organic-inorganic hybrid material shows superior etch-resistance which enables to form patterns with high aspect ratio [1]. One of the most commonly studied processes is the infiltration of trimethylaluminium (TMA) into polymethylmethacrylate (PMMA). One of the issues of this technology is that increase in volume of the polymer after the infiltration is inevitable, since metal oxides are added to the polymer. For example, we observed over 10 % of volume expansion for the combination of PMMA and TMA [2]. If this technology was dedicated to small feature sizes, it would be preferable to maintain its original shape. Poly(tert-butylmethacrylate) (PtBuMA) has a similar structure to PMMA except that it has a tert-butyl group on its side-chain instead of a methyl group. This polymer is known to decompose above 180 degree Celsius, releasing the butyl group in form of 2-butene. If the out-going of tert-butyl group and the in-coming of TMA occurs simultaneously under ambient temperature, we can expect to see a balance of volumetric shrinkage and expansion. In this paper, a concept using PtBuMA to compensate the volume increase after metal infiltration is described. © SPIE. Downloading of the abstract is permitted for personal use only.

关键词： Aspect ratio

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Multi-field imprint technology: Enabling the productivity enhancement of NIL

Multi-field imprint technology: Enabling the productivity en...

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Novel Patterning Technologies 2021

作者： Nakasugi, Tetsuro Inanami, Ryoichi Fukuhara, Kazuya Komori, Motofumi Arae, Sadanori Inoue, Soichi Hashimoto, Koji Process Technology Research and Development Center Institute of Memory Technology Research and Development Kioxia Corporation 8 Shinsugita-cho Isogo-ku Yokohama235-0032 Japan 800 Yamanoisshiki-cho Yokkaichi512-8550 Japan

ISBN: (数字)9781510640542

ISBN: (纸本)9781510640535

We have developed Multi-Field Imprint (MFI) technology to improve the productivity of for nano-imprint lithography (NIL). Using the template having the imprinting size of 46 mm x 28 mm for MFI and the latest NIL system NZ2C (Canon Corp.), we successfully achieved multi-field imprinting on a 300 mm wafer. The throughput being equivalent to 160 wafers per hour was demonstrated using throughput enhancement solutions, such as gas permeable spin-on-carbon and multi field dispense. The overlay accuracy around 7 nm was also obtained. In this report, we'll report about the performance of MFI technology: patterning ability, throughput, and overlay accuracy and discuss the future outlook. © 2021 SPIE.

关键词： Productivity

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Cryogenic Operation of 3D Flash memory for New Applications and Bit Cost Scaling with 6-Bit per Cell (HLC) and Beyond

Cryogenic Operation of 3D Flash Memory for New Applications ...

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IEEE Electron Devices technology and Manufacturing Conference (EDTM)

作者： Yuta Aiba Hitomi Tanaka Takashi Maeda Keiichi Sawa Fumie Kikushima Masayuki Miura Toshio Fujisawa Mie Matsuo Tomoya Sanuki Institute of Memory Technology Research & Development Memory Div. Kioxia Corporation

This report is the first to introduce a cryogenic operation and characteristics of 3D Flash memory at 77 K in the liquid nitrogen. It was found that read, program and erase operations were fully functional. The read noise was significantly minimized at 77 K, the cycle endurance was improved over 10 times compared to that at 300 K, and the data retention was greatly improved. In addition, we show the successful demonstration of 6-bit per cell (HLC). The cryogenic operation of 3D Flash memory opens the door for new application and becomes a strong candidate for future storage device enabling further bit cost scaling.

关键词： Electric potential Three-dimensional displays Quantum computing Liquid nitrogen Aerospace electronics Manufacturing Flash memories

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COSINE:A web server for clonal and subclonal structure inference and evolution in cancer genomics

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Zoological research 2022年第1期43卷 75-77页

作者： Xi-Guo Yuan Yuan Zhao Yang Guo Lin-Mei Ge Wei Liu Shi-Yu Wen Qi Li Zhang-Bo Wan Pei-Na Zheng Tao Guo Zhi-Da Li Martin Peifer Yu-Peng Cun School of Computer Science and Technology Xidian UniversityXi'anShaanxi 710071China iFlora Bioinformatics Center Germplasm Bank of Wild SpeciesKunming Institute of BotanyChinese Academy of SciencesKunmingYunan 650201China Yuxi Rongjian Information Technology Co. Ltd.YuxiYunan 653100China Center for Molecular Medicine Cologne(CMMC) University of CologneCologne 50931Germany Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren’s Hospital of Chongqing Medical UniversityChongqing 400014China

Cancer cell genomes originate from single-cell mutation with sequential clonal and subclonal expansion of somatic mutation acquisition during pathogenesis,thus exhibiting a Darwinian evolutionary process(Gerstung et al.,2020;Nik-Zainal et al.,2012).Through next-generation sequencing of tumor tissue,this evolutionary process can be characterized by statistical modelling,which can identify the clonal state,somatic mutation order,and evolutionary process(Gerstung et al.,2020;Mcgranahan&Swanton,2017).Inference of clonal and subclonal structure from bulk or single-cell tumor genomic sequencing data has a huge impact on studying cancer *** state and mutation order can provide detailed insight into tumor origin and future *** the past decade,various methods for subclonal reconstruction using bulk tumor sequencing data have been ***,these methods had different programming languages and data input formats,which limited their use and ***,we established a web server for Clonal and Subclonal Structure Inference and Evolution(COSINE)of cancer genomic data,which incorporated twelve popular subclonal reconstruction *** deconstructed each method to provide a detailed workflow of single processing steps with a user-friendly *** the best of our knowledge,this is the first web server providing online subclonal inference based on the integration of most popular subclonal reconstruction *** is freely accessible at ***.

关键词： .net server COSINE

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Multi-omics analysis reveals the evolutionary origin of diterpenoid alkaloid biosynthesis pathways in Aconitum

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Journal of Integrative Plant Biology 2023年第10期65卷 2320-2335页

作者： Dake Zhao Ya Zhang Huanxing Ren Yana Shi Ding Dong Zonghang Li Guanghong Cui Yong Shen Zongmin Mou Edward JKennelly Luqi Huang Jue Ruan Suiyun Chen Diqiu Yu Yupeng Cun School of Ecology and Environmental Science Yunnan UniversityKunming 650500China Agricultural Genomics Institute at Shenzhen Chinese Academy of Agricultural SciencesShenzhen 518000China Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders Pediatric Research InstituteMinistry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Germplasm Bank of Wild Species Kunming Institute of BotanyChinese Academy of SciencesKunming 650201China Faculty of Life Science and Technology Kunming University of Science and TechnologyKunming 650500China National Resource Center for Chinese Materia Medica Chinese Academy of Chinese Medical SciencesBeijing 100700China College of Agriculture and Biotechnology Yunnan Agricultural UniversityKunming 650201China Department of Biological Sciences Lehman CollegeCity University of New YorkBronx 10468New YorkUSA Graduate Center City University of New YorkBronx 10468New YorkUSA State Key Laboratory for Conservation and Utilization of Bio‐resources in Yunnan Yunnan UniversityKunming 650500China

Diterpenoid alkaloids(DAs) have been often utilized in clinical practice due to their analgesic and anti-infammatory properties. Natural DAs are prevalent in the family Ranunculaceae, notably in the Aconitum genus. Nevertheless, the evolutionary origin of the biosynthesis pathway responsible for DA production remains *** this study, we successfully assembled a highquality, pseudochromosome-level genome of the DA-rich species Aconitum vilmorinianum(***)(5.76 Gb). An A. vilmorinianumspecific whole-genome duplication event was discovered using comparative genomic analysis,which may aid in the evolution of the DA biosynthesis pathway. We identified several genes involved in DA biosynthesis via integrated genomic, transcriptomic, and metabolomic analyses. These genes included enzymes encoding target ent-kaurene oxidases and aminotransferases, which facilitated the activation of diterpenes and insertion of nitrogen atoms into diterpene skeletons, thereby mediating the transformation of diterpenes into DAs. The divergence periods of these genes in A. vilmorinianum were further assessed, and it was shown that two major types of genes were involved in the establishment of the DA biosynthesis pathway. Our integrated analysis offers fresh insights into the evolutionary origin of DAs in *** as well as suggestions for engineering the biosynthetic pathways to obtain desired DAs.

关键词： Aconitum vilmorinianum acute toxicity biosynthetic pathway diterpenoid alkaloid evolutionary origin genome assembly

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Challenges of Flash memory for Next Decade

Challenges of Flash Memory for Next Decade

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Annual International Symposium on Reliability Physics

作者： Kazunari Ishimaru Institute of Memory Technology Research and Development Kioxia Corporation Yokkaichi Japan

It was more than 50 years ago, the first floating gate MOS transistor was proposed and 30 years has passed after the first NAND flash memory was commercialized. The NAND flash memory kept increasing its capacity by introducing new technology with dimensional scaling. In the past, the market was mainly driven by consumer electronics, but in today's information explosion, data center, automobiles and industrial equipment are growing markets and reliability is very important. There is a trade-off between improving reliability and reducing manufacturing cost. Since capacity expansion continues, how to realize both reliability and cost requirement under the complex manufacturing process has been a major issue. It becomes increasingly important to improve the reliability not only by memory device itself but also from the entire system point of view.

关键词： MOSFET Data centers Manufacturing processes Nonvolatile memory Explosions Manufacturing Reliability

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Adaptive Quantization Method for CNN with Computational-Complexity-Aware Regularization

Adaptive Quantization Method for CNN with Computational-Comp...

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IEEE International Symposium on Circuits and Systems

作者： Kengo Nakata Daisuke Miyashita Jun Deguchi Ryuichi Fujimoto Kioxia Corporation Institute of Memory Technology Research & Development Kawasaki Japan

Quantization is a typical approach toward reducing processing time for inference of convolutional neural networks (CNNs). The key to reducing inference times without drastic decreases in accuracy is allocating optimal bit widths according to each layer or filter. One of the most promising ways to find optimal bit allocations is to learn quantization step size and weight parameters through gradient descent. The conventional method optimizes those parameters under the constraint for model size or memory footprint of CNN. However, the bit allocations obtained by the conventional method are not always optimal for inference time because the arithmetic intensity of CNN is significantly high, and the time spent on computing is a bottleneck for the inference time. In this paper, we propose a regularization method using a computational-complexity metric (which we call MACxbit) that is correlated with the inference time of quantized CNN models. The proposed method can obtain an optimal bit allocation that achieves better recognition accuracy under a specified computational-complexity target than the conventional method. For similar recognition accuracy on the optimized ResNet-18 model, the proposed method achieves 21.0% less inference time compared to the conventional method.

关键词： Measurement Adaptation models Quantization (signal) Target recognition Computational modeling Bit rate Integrated circuit modeling

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