Journal articles: 'Brain on a chip'

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Service, Robert F. "The brain chip." Science 345, no. 6197 (August 7, 2014): 614–16. http://dx.doi.org/10.1126/science.345.6197.614.

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NAKADA, Tsutomu. "Brain Chip: A Hypothesis." Magnetic Resonance in Medical Sciences 3, no. 2 (2004): 51–63. http://dx.doi.org/10.2463/mrms.3.51.

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Leslie, M. "Chip off the Old Brain." Science of Aging Knowledge Environment 2003, no. 18 (May 7, 2003): 65nw—65. http://dx.doi.org/10.1126/sageke.2003.18.nw65.

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Bouzid, Hind, Julia Belk, Max Jan, Yanyan Qi, Chloé Sarnowski, Sara Wirth, Lisa Ma, et al. "Clonal Hematopoiesis is Associated with Reduced Risk of Alzheimer's Disease." Blood 138, Supplement 1 (November 5, 2021): 5. http://dx.doi.org/10.1182/blood-2021-151064.

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Abstract Clonal hematopoiesis of indeterminate potential (CHIP) occurs when hematopoietic stem cells (HSCs) acquire a mutation, most commonly a null variant in TET2 or DNMT3A, that confers a selective advantage. Blood cancers may result if additional cooperating mutations are acquired. However, CHIP may also cause atherosclerosis and other inflammatory diseases because these mutations alter the function or development of effector immune cells derived from the HSCs. Genome-wide association studies have implicated microglia, the resident myeloid cells in the brain, as key players in the biology of Alzheimer's disease (AD). Here, we asked whether CHIP associated with AD dementia or neuropathologic change, and whether mutant marrow-derived cells could be found in the brains of CHIP carriers. To test for an association, we used data from the Trans-omics for Precision Medicine project (TOPMed) and the Alzheimer's Disease Sequencing Project (ADSP), where whole genome or exome sequencing data as well as AD phenotype data was available on 5,730 persons. TOPMed contained population-based cohorts unselected for AD, while ADSP was a case-control study for AD. We surprisingly discovered that the presence of CHIP was associated with a reduced risk of AD dementia in both projects (fixed-effects meta-analysis odds ratio 0.64, p = 3.0 x 10-5, adjusted for age, sex and APOE genotype) (Figure 1). The protective effect of CHIP was strongest in those with APOE e3 or e4 alleles, but not seen in those with APOE e2 allele. No substantial differences in AD risk were seen based on mutated driver gene. In addition, the presence of CHIP was associated with a reduced burden of amyloid plaques and neurofibrillary tangles in the brains of those without dementia. In sum, our human genetic analyses indicated that CHIP was robustly associated with protection from AD dementia and AD-related neuropathologic changes. A causal link between CHIP and AD would be strengthened by finding the mutated cells infiltrating the brain. However, it is presumed that bone marrow progenitors have minimal contribution to the adult microglial pool. To determine if the mutations seen in the blood of CHIP carriers could also be found in the brain, we obtained 8 occipital cortex samples from autopsy of donors with CHIP, 6 of whom were cognitively normal at the time of death. The 8 CHIP carriers had mutations in DNMT3A, TET2, ASXL1, SF3B1, and GNB1 with the highest frequency in DNMT3A and TET2, which is representative of the relative proportion of these mutations in the general population. We detected the CHIP somatic variants in the microglia enriched (NeuN- c-Maf+) fraction of brain in 7 out of 8 CHIP carriers, with a VAF ranging from 0.02 to 0.28 (representing 4% to 56% of nuclei) (Figure 2), but at low levels or absent in the other fractions of brain. We then performed single-cell ATAC-sequencing on brain samples from 2 CHIP carriers and 1 control to specify the cellular population harboring CHIP mutations. This revealed that hematopoietic cells in the 3 samples formed a single myeloid cluster that had accessible chromatin at the microglia marker genes TMEM119, P2RY12, and SALL1, but not in genes specific to monocytes or dendritic cells. We further determined that the proportion of cells in this cluster bearing the CHIP mutations ranged from ~40-80% in these two samples, indicating widespread replacement of the endogenous microglial pool by mutant cells. We show here that, unexpectedly, the presence of CHIP is associated with protection from AD dementia. CHIP is also associated with lower levels of neuritic plaques and neurofibrillary tangles in those without dementia, indicating a possible modulating effect of CHIP on the underlying pathophysiology of AD. Consistent with this hypothesis, we also detect substantial infiltration of brain by marrow-derived mutant cells which adopt a microglial-like phenotype. We speculate that the mutations associated with CHIP confer circulating precursor cells with an enhanced ability to engraft in the brain, to differentiate into microglia once engrafted, and/or to clonally expand relative to unmutated cells in the brain microenvironment. These non-mutually exclusive possibilities could provide protection from AD by supplementing the phagocytic capacity of the endogenous microglial system during aging. Figure 1 Figure 1. Disclosures Jaiswal: Novartis: Consultancy, Honoraria; Foresite Labs: Consultancy; Genentech: Consultancy, Honoraria; AVRO Bio: Consultancy, Honoraria; Caylo: Current holder of stock options in a privately-held company.

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Abdelnaby, Ramy, Samar A. Amer, Jaidaa Mekky, Khaled Mohamed, Khaled Dardeer, Walid Hassan, Bana Alafandi, and Mohamed Elsayed. "Brain Chip Implant: Public’s knowledge, Attitude, and Determinants. A Multi-Country Study, 2021." Open Access Macedonian Journal of Medical Sciences 10, B (October 22, 2022): 2489–97. http://dx.doi.org/10.3889/oamjms.2022.9982.

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Background: In August 2020, a brain chip was announced as implantation in the human brain targeted to boost brain activity without significant side effects. The aim of this work was to examine the level of knowledge, awareness, and public concerns about the use of brain chip implants. Methods: An online cross-sectional survey targeted 326 adults from more than five countries in the Middle East and North Africa during the period from May 2021 to July 2021. The data was collected through a validated self-administrated questionnaire composed of five sections. The collected data were coded and analyzed using suitable tests and methods. Results: According to our results, 54.6% of the study participants mentioned that they had heard about the Brain Chip Implant; while only 6.1% stated that they knew its importance. The most common reported indication for the Brain Chip Implant was improving memory, followed by treatment of epilepsy and improving mental function. Brain Chip Implant safety seemed to be the most common public concern, as most of the participants were hesitant about using it and had concerns regarding its safety. Conclusion: Medical personnel seems to be the most concerned about the use of the brain chip implant. Safety measures, confidentiality, and security procedures, respectively, are the major issues that might limit the broad use of the brain chip implant.

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Staicu, Cristina Elena, Florin Jipa, Emanuel Axente, Mihai Radu, Beatrice Mihaela Radu, and Felix Sima. "Lab-on-a-Chip Platforms as Tools for Drug Screening in Neuropathologies Associated with Blood–Brain Barrier Alterations." Biomolecules 11, no. 6 (June 21, 2021): 916. http://dx.doi.org/10.3390/biom11060916.

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Lab-on-a-chip (LOC) and organ-on-a-chip (OOC) devices are highly versatile platforms that enable miniaturization and advanced controlled laboratory functions (i.e., microfluidics, advanced optical or electrical recordings, high-throughput screening). The manufacturing advancements of LOCs/OOCs for biomedical applications and their current limitations are briefly discussed. Multiple studies have exploited the advantages of mimicking organs or tissues on a chip. Among these, we focused our attention on the brain-on-a-chip, blood–brain barrier (BBB)-on-a-chip, and neurovascular unit (NVU)-on-a-chip applications. Mainly, we review the latest developments of brain-on-a-chip, BBB-on-a-chip, and NVU-on-a-chip devices and their use as testing platforms for high-throughput pharmacological screening. In particular, we analyze the most important contributions of these studies in the field of neurodegenerative diseases and their relevance in translational personalized medicine.

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Geddes, Linda. "Chip replaces part of rat brain." New Scientist 211, no. 2831 (September 2011): 25. http://dx.doi.org/10.1016/s0262-4079(11)62329-4.

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Lu, Donna. "Brain-inspired chip could transform AI." New Scientist 243, no. 3241 (August 2019): 12. http://dx.doi.org/10.1016/s0262-4079(19)31406-x.

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Song, Jiyoung, Seokyoung Bang, Nakwon Choi, and Hong Nam Kim. "Brain organoid-on-a-chip: A next-generation human brain avatar for recapitulating human brain physiology and pathology." Biomicrofluidics 16, no. 6 (December 2022): 061301. http://dx.doi.org/10.1063/5.0121476.

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Neurodegenerative diseases and neurodevelopmental disorders have become increasingly prevalent; however, the development of new pharmaceuticals to treat these diseases has lagged. Animal models have been extensively utilized to identify underlying mechanisms and to validate drug efficacies, but they possess inherent limitations including genetic heterogeneity with humans. To overcome these limitations, human cell-based in vitro brain models including brain-on-a-chip and brain organoids have been developed. Each technique has distinct advantages and disadvantages in terms of the mimicry of structure and microenvironment, but each technique could not fully mimic the structure and functional aspects of the brain tissue. Recently, a brain organoid-on-a-chip (BOoC) platform has emerged, which merges brain-on-a-chip and brain organoids. BOoC can potentially reflect the detailed structure of the brain tissue, vascular structure, and circulation of fluid. Hence, we summarize recent advances in BOoC as a human brain avatar and discuss future perspectives. BOoC platform can pave the way for mechanistic studies and the development of pharmaceuticals to treat brain diseases in future.

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Herreros, Pedro, Silvia Tapia-González, Laura Sánchez-Olivares, María Fe Laguna Heras, and Miguel Holgado. "Alternative Brain Slice-on-a-Chip for Organotypic Culture and Effective Fluorescence Injection Testing." International Journal of Molecular Sciences 23, no. 5 (February 25, 2022): 2549. http://dx.doi.org/10.3390/ijms23052549.

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Mouse brain slices are one of the most common models to study brain development and functioning, increasing the number of study models that integrate microfluidic systems for hippocampal slice cultures. This report presents an alternative brain slice-on-a-chip, integrating an injection system inside the chip to dispense a fluorescent dye for long-term monitoring. Hippocampal slices have been cultured inside these chips, observing fluorescence signals from living cells, maintaining the cytoarchitecture of the slices. Having fluorescence images of biological samples inside the chip demonstrates the effectiveness of the staining process using the injection method avoiding leaks or biological contamination. The technology developed in this study presents a significant improvement in the local administration of reagents within a brain slice-on-a-chip system, which could be a suitable option for organotypic cultures in a microfluidic chip acting as a highly effective bioreactor.

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Akcay, Gulden, and Regina Luttge. "Microenvironments Matter: Advances in Brain-on-Chip." Biosensors 13, no. 5 (May 16, 2023): 551. http://dx.doi.org/10.3390/bios13050551.

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To highlight the particular needs with respect to modeling the unique and complex organization of the human brain structure, we reviewed the state-of-the-art in devising brain models with engineered instructive microenvironments. To acquire a better perspective on the brain’s working mechanisms, we first summarize the importance of regional stiffness gradients in brain tissue, varying per layer and the cellular diversities of the layers. Through this, one can acquire an understanding of the essential parameters in emulating the brain in vitro. In addition to the brain’s organizational architecture, we addressed also how the mechanical properties have an impact on neuronal cell responses. In this respect, advanced in vitro platforms emerged and profoundly changed the methods of brain modeling efforts from the past, mainly focusing on animal or cell line research. The main challenges in imitating features of the brain in a dish are with regard to composition and functionality. In neurobiological research, there are now methods that aim to cope with such challenges by the self-assembly of human-derived pluripotent stem cells (hPSCs), i.e., brainoids. Alternatively, these brainoids can be used stand-alone or in conjunction with Brain-on-Chip (BoC) platform technology, 3D-printed gels, and other types of engineered guidance features. Currently, advanced in vitro methods have made a giant leap forward regarding cost-effectiveness, ease-of-use, and availability. We bring these recent developments together into one review. We believe our conclusions will give a novel perspective towards advancing instructive microenvironments for BoCs and the understanding of the brain’s cellular functions either in modeling healthy or diseased states of the brain.

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Oh, Seongwoog, and Jungsuek Oh. "Novel Heat-Mitigating Chip-on-Probe for Brain Stimulation Behavior Experiments." Sensors 20, no. 24 (December 21, 2020): 7334. http://dx.doi.org/10.3390/s20247334.

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This paper proposes a novel design for a chip-on-probe with the aim of overcoming the heat dissipation effect during brain stimulations using modulated microwave signals. The temperature of the stimulus chip during normal operation is generally 40 °C–60 °C, which is sufficient to cause unintended temperature effects during stimulation. This effect is particularly fatal in brain stimulation applications that require repeated stimulation. This paper proposes, for the first time, a topology that vertically separates the stimulus chip generating the stimulus signal and the probe delivering the signal into the brain to suppress the heat transfer while simultaneously minimizing the radio frequency (RF) transmission loss. As the proposed chip-on-probe should be attached to the head of a small animal, an auxiliary board with a heat sink was carefully designed considering the weight that does not affect the behavior experiment. When the transition structures are properly designed, a heat sink can be mounted to maximize the cooling effect, reducing the temperature by more than 13 °C in a simulation when the heat generated by the chip is transferred to the brain, while the transition from the chip to the probe experiences a loss of 1.2 dB. Finally, the effectiveness of the proposed design is demonstrated by fabricating a chip with the 0.28 μm silicon-on-insulator (SOI) complementary metal–oxide–semiconductor (CMOS) process and a probe with a RT6010 printed-circuit board (PCB), showing a temperature reduction of 49.8 °C with a maximum output power of 11 dBm. In the proposed chip-on-probe device, the temperature formed in the area in contact with the brain is measured at 31.1 °C.

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Nakada, Tsutomu. "Brain science of the mind." Social Science Information 50, no. 1 (March 2011): 25–38. http://dx.doi.org/10.1177/0539018410388837.

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The human cerebral cortex contains more than one hundred billion neurons and 1014 synapses. Even without regard to the size of the genome, it can be easily deduced that a deterministic blueprint for connectivity of such an enormous number of networks is unrealistic. Existing scientific knowledge indicates that nature utilizes principal rules instead of complete deterministic descriptions to fashion a desired structure, namely, the rules of self-organization. The brain is a complex system and self-organizes based on the Markovian process. Accordingly, brain functionality can be seen as specific patterns created by self-organizing processes based on conditions defined by genes and the environment. Three categorically different systems are now recognized based on their physiological functional unit configuration. While the oldest system is made up of deterministic connectivity, the remaining two systems, namely, cerebellum and cerebrum, utilize modifiable units, often referred to as cerebellar chip and brain chip, respectively. Classical conditioning, as in the case of Pavlov’s dog, is now recognized to be based on functionality of the cerebellum and its learning unit, the cerebellar chip, which in principle works as McCulloch-Pitts neurons. The cerebrum utilizes the concept of Kohonen’s non-linear self-organizing map in the organization of the brain chip, a system that effectively creates entropy fields. In contrast to cerebellar learning which is adaptive, cerebral learning is stochastic in nature, and follows the rule known as Pólya’s Urn.

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Zakharova, M., M. A. Palma do Carmo, M. W. van der Helm, H. Le-The, M. N. S. de Graaf, V. Orlova, A. van den Berg, A. D. van der Meer, K. Broersen, and L. I. Segerink. "Multiplexed blood–brain barrier organ-on-chip." Lab on a Chip 20, no. 17 (2020): 3132–43. http://dx.doi.org/10.1039/d0lc00399a.

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The developed multiplexed chip contains 8 channels that can be accessed individually or simultaneously with increased throughput. The visual inspection of cells in the device was improved with our fabricated 2 μm-thick porous PDMS membrane.

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Mims, Christopher. "A Chip that Thinks Like a Brain." Scientific American 305, no. 6 (November 15, 2011): 43. http://dx.doi.org/10.1038/scientificamerican1211-43.

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Zhao, Yanan, Utkan Demirci, Yun Chen, and Pu Chen. "Multiscale brain research on a microfluidic chip." Lab on a Chip 20, no. 9 (2020): 1531–43. http://dx.doi.org/10.1039/c9lc01010f.

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We report recent progress in applying innovative microfluidic chip-based neurotechnologies to promote multiscale brain research across the hierarchical organizations from the molecular, cellular, and tissue levels up to the whole organism level.

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Xu, Shihong, Yaoyao Liu, Yan Yang, Kui Zhang, Wei Liang, Zhaojie Xu, Yirong Wu, Jinping Luo, Chengyu Zhuang, and Xinxia Cai. "Recent Progress and Perspectives on Neural Chip Platforms Integrating PDMS-Based Microfluidic Devices and Microelectrode Arrays." Micromachines 14, no. 4 (March 23, 2023): 709. http://dx.doi.org/10.3390/mi14040709.

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Recent years have witnessed a spurt of progress in the application of the encoding and decoding of neural activities to drug screening, diseases diagnosis, and brain–computer interactions. To overcome the constraints of the complexity of the brain and the ethical considerations of in vivo research, neural chip platforms integrating microfluidic devices and microelectrode arrays have been raised, which can not only customize growth paths for neurons in vitro but also monitor and modulate the specialized neural networks grown on chips. Therefore, this article reviews the developmental history of chip platforms integrating microfluidic devices and microelectrode arrays. First, we review the design and application of advanced microelectrode arrays and microfluidic devices. After, we introduce the fabrication process of neural chip platforms. Finally, we highlight the recent progress on this type of chip platform as a research tool in the field of brain science and neuroscience, focusing on neuropharmacology, neurological diseases, and simplified brain models. This is a detailed and comprehensive review of neural chip platforms. This work aims to fulfill the following three goals: (1) summarize the latest design patterns and fabrication schemes of such platforms, providing a reference for the development of other new platforms; (2) generalize several important applications of chip platforms in the field of neurology, which will attract the attention of scientists in the field; and (3) propose the developmental direction of neural chip platforms integrating microfluidic devices and microelectrode arrays.

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Sood, Ankur, Anuj Kumar, Atul Dev, Vijai Kumar Gupta, and Sung Soo Han. "Advances in Hydrogel-Based Microfluidic Blood–Brain-Barrier Models in Oncology Research." Pharmaceutics 14, no. 5 (May 5, 2022): 993. http://dx.doi.org/10.3390/pharmaceutics14050993.

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The intrinsic architecture and complexity of the brain restricts the capacity of therapeutic molecules to reach their potential targets, thereby limiting therapeutic possibilities concerning neurological ailments and brain malignancy. As conventional models fail to recapitulate the complexity of the brain, progress in the field of microfluidics has facilitated the development of advanced in vitro platforms that could imitate the in vivo microenvironments and pathological features of the blood–brain barrier (BBB). It is highly desirous that developed in vitro BBB-on-chip models serve as a platform to investigate cancer metastasis of the brain along with the possibility of efficiently screening chemotherapeutic agents against brain malignancies. In order to improve the proficiency of BBB-on-chip models, hydrogels have been widely explored due to their unique physical and chemical properties, which mimic the three-dimensional (3D) micro architecture of tissues. Hydrogel-based BBB-on-chip models serves as a stage which is conducive for cell growth and allows the exchange of gases and nutrients and the removal of metabolic wastes between cells and the cell/extra cellular matrix (ECM) interface. Here, we present recent advancements in BBB-on-chip models targeting brain malignancies and examine the utility of hydrogel-based BBB models that could further strengthen the future application of microfluidic devices in oncology research.

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Shaima, Mujiba, Norun Nabi, Md Nasir Uddin Rana, Md Tanvir Islam, Estak Ahmed, Mazharul Islam Tusher, Mousumi Hasan Mukti, and Quazi Saad-Ul-Mosaher. "Elon Musk’s Neuralink Brain Chip: A Review on ‘Brain-Reading’ Device." Journal of Computer Science and Technology Studies 6, no. 1 (February 23, 2024): 200–203. http://dx.doi.org/10.32996/jcsts.2024.6.1.22.

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With its novel bidirectional communication method, Neuralink, the brain-reading gadget created by Elon Musk, is poised to transform human-machine relations. It represents a revolutionary combination of health science, neurology, and artificial intelligence. Neuralink is a potentially beneficial brain implant that consists of tiny electrodes placed behind the ear and a small chip. It can be used to treat neurological conditions and improve cognitive function. Important discussions are nevertheless sparked by ethical worries about abuse, privacy, and security. It is important to maintain a careful balance between the development of technology and moral issues, as seen by the imagined future in which people interact with computers through thinking processes. In order for Neuralink to be widely accepted and responsibly incorporated into the fabric of human cognition and connectivity, ongoing discussions about ethical standards, regulatory frameworks, and societal ramifications are important. Meanwhile, new advancements in Brain-Chip-Interfaces (BCHIs) bring the larger context into focus. By enhancing signal transmission between nerve cells and chips, these developments offer increased signal fidelity and improved spatiotemporal resolution. The potential revolutionary influence of these innovations on neuroscience and human-machine symbiosis raises important considerations about the ethical and societal consequences of these innovations.

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Hu, Zhengwei, Jing Yang, Shuo Zhang, Mengjie Li, Chunyan Zuo, Chengyuan Mao, Zhongxian Zhang, Mibo Tang, Changhe Shi, and Yuming Xu. "AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice." Neural Regeneration Research 20, no. 1 (March 1, 2024): 253–64. http://dx.doi.org/10.4103/nrr.nrr-d-23-01277.

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JOURNAL/nrgr/04.03/01300535-202501000-00033/figure1/v/2024-05-14T021156Z/r/image-tiff The E3 ubiquitin ligase, carboxyl terminus of heat shock protein 70 (Hsp70) interacting protein (CHIP), also functions as a co-chaperone and plays a crucial role in the protein quality control system. In this study, we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease. We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain. CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests, reduced amyloid-β plaques, and decreased the expression of both amyloid-β and phosphorylated tau. CHIP also alleviated the concentration of microglia and astrocytes around plaques. In APP/PS1 mice of a younger age, CHIP overexpression promoted an increase in ADAM10 expression and inhibited β-site APP cleaving enzyme 1, insulin degrading enzyme, and neprilysin expression. Levels of HSP70 and HSP40, which have functional relevance to CHIP, were also increased. Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated, which may also reflect a potential mechanism for the neuroprotective effect of CHIP. Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice. Indeed, overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

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Faezi, Sina, Rozhin Yasaei, Anomadarshi Barua, and Mohammad Abdullah Al Faruque. "Brain-Inspired Golden Chip Free Hardware Trojan Detection." IEEE Transactions on Information Forensics and Security 16 (2021): 2697–708. http://dx.doi.org/10.1109/tifs.2021.3062989.

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Stevenazzi, Lorenzo, Andrea Baschirotto, Giorgio Zanotto, Elia Arturo Vallicelli, and Marcello De Matteis. "Noise Power Minimization in CMOS Brain-Chip Interfaces." Bioengineering 9, no. 2 (January 18, 2022): 42. http://dx.doi.org/10.3390/bioengineering9020042.

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This paper presents specific noise minimization strategies to be adopted in silicon–cell interfaces. For this objective, a complete and general model for the analog processing of the signal coming from cell–silicon junctions is presented. This model will then be described at the level of the single stages and of the fundamental parameters that characterize them (bandwidth, gain and noise). Thanks to a few design equations, it will therefore be possible to simulate the behavior of a time-division multiplexed acquisition channel, including the most relevant parameters for signal processing, such as amplification (or power of the analog signal) and noise. This model has the undoubted advantage of being particularly simple to simulate and implement, while maintaining high accuracy in estimating the signal quality (i.e., the signal-to-noise ratio, SNR). Thanks to the simulation results of the model, it will be possible to set an optimal operating point for the front-end to minimize the artifacts introduced by the time-division multiplexing (TDM) scheme and to maximize the SNR at the a-to-d converter input. The proposed results provide an SNR of 12 dB at 10 µVRMS of noise power and 50 µVRMS of signal power (both evaluated at input of the analog front-end, AFE). This is particularly relevant for cell–silicon junctions because it demonstrates that it is possible to detect weak extracellular events (of the order of few µVRMS) without necessarily increasing the total amplification of the front-end (and, therefore, as a first approximation, the dissipated electrical power), while adopting a specific gain distribution through the acquisition chain.

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Dickey, Chad A., Cam Patterson, Dennis Dickson, and Leonard Petrucelli. "Brain CHIP: removing the culprits in neurodegenerative disease." Trends in Molecular Medicine 13, no. 1 (January 2007): 32–38. http://dx.doi.org/10.1016/j.molmed.2006.11.003.

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Vassanelli, Stefano. "Brain-Chip Interfaces: The Present and The Future." Procedia Computer Science 7 (2011): 61–64. http://dx.doi.org/10.1016/j.procs.2011.12.020.

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Musafargani, Sikkandhar, Sachin Mishra, Miklós Gulyás, P. Mahalakshmi, Govindaraju Archunan, Parasuraman Padmanabhan, and Balázs Gulyás. "Blood brain barrier: A tissue engineered microfluidic chip." Journal of Neuroscience Methods 331 (February 2020): 108525. http://dx.doi.org/10.1016/j.jneumeth.2019.108525.

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Flangea, Corina, Alina Serb, Eugen Sisu, and Alina D. Zamfir. "Chip-based nanoelectrospray mass spectrometry of brain gangliosides." Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1811, no. 9 (September 2011): 513–35. http://dx.doi.org/10.1016/j.bbalip.2011.06.008.

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Marshall, Michael. "Chip that mimics the brain outstrips normal computers." New Scientist 216, no. 2892 (November 2012): 21. http://dx.doi.org/10.1016/s0262-4079(12)62997-2.

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Felderer, Florian, and Peter Fromherz. "Transistor needle chip for recording in brain tissue." Applied Physics A 104, no. 1 (May 5, 2011): 1–6. http://dx.doi.org/10.1007/s00339-011-6392-2.

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Zhou, Shutong. "Blood-brain barrier on-a-chip and its application." Theoretical and Natural Science 8, no. 1 (November 13, 2023): 290–95. http://dx.doi.org/10.54254/2753-8818/8/20240433.

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In the past five years, the organ-on-a-chip technology developed quickly and provided a novel platform for in vitro modelling and experimental testing. Blood-brain barrier (BBB) is an important barrier separating the brain from the rest of the body, thereby protecting the brain from toxins. It is important to study the BBB in terms of its permeability to various molecules, not only identifying potential toxins that might harm the brain, but also to design administration routes for drugs targeting the central nervous system (CNS). This review will summarize various recent designs of the BBB chips and their pros and cons, as well as the future directions for the organ-on-chip technology.

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Forro, Csaba, Davide Caron, Gian Angotzi, Vincenzo Gallo, Luca Berdondini, Francesca Santoro, Gemma Palazzolo, and Gabriella Panuccio. "Electrophysiology Read-Out Tools for Brain-on-Chip Biotechnology." Micromachines 12, no. 2 (January 24, 2021): 124. http://dx.doi.org/10.3390/mi12020124.

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Brain-on-Chip (BoC) biotechnology is emerging as a promising tool for biomedical and pharmaceutical research applied to the neurosciences. At the convergence between lab-on-chip and cell biology, BoC couples in vitro three-dimensional brain-like systems to an engineered microfluidics platform designed to provide an in vivo-like extrinsic microenvironment with the aim of replicating tissue- or organ-level physiological functions. BoC therefore offers the advantage of an in vitro reproduction of brain structures that is more faithful to the native correlate than what is obtained with conventional cell culture techniques. As brain function ultimately results in the generation of electrical signals, electrophysiology techniques are paramount for studying brain activity in health and disease. However, as BoC is still in its infancy, the availability of combined BoC–electrophysiology platforms is still limited. Here, we summarize the available biological substrates for BoC, starting with a historical perspective. We then describe the available tools enabling BoC electrophysiology studies, detailing their fabrication process and technical features, along with their advantages and limitations. We discuss the current and future applications of BoC electrophysiology, also expanding to complementary approaches. We conclude with an evaluation of the potential translational applications and prospective technology developments.

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Park, JiSoo, Bo Kyeong Lee, Gi Seok Jeong, Jung Keun Hyun, C. Justin Lee, and Sang-Hoon Lee. "Three-dimensional brain-on-a-chip with an interstitial level of flow and its application as an in vitro model of Alzheimer's disease." Lab on a Chip 15, no. 1 (2015): 141–50. http://dx.doi.org/10.1039/c4lc00962b.

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In this paper, we developed a three-dimensional brain-on-a-chip with an interstitial level of flow. The chip contains an osmotic micropump system for providing interstitial flow and a concave microwell array for mimicking the brain's 3D cytoarchitecture.

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Miccoli, Beatrice, Dries Braeken, and Yi-Chen Ethan Li. "Brain-on-a-chip Devices for Drug Screening and Disease Modeling Applications." Current Pharmaceutical Design 24, no. 45 (April 16, 2019): 5419–36. http://dx.doi.org/10.2174/1381612825666190220161254.

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:Neurodegenerative disorders are related to the progressive functional loss of the brain, often connected to emotional and physical disability and, ultimately, to death. These disorders, strongly connected to the aging process, are becoming increasingly more relevant due to the increase of life expectancy. Current pharmaceutical treatments poorly tackle these diseases, mainly acting only on their symptomology. One of the main reasons of this is the current drug development process, which is not only expensive and time-consuming but, also, still strongly relies on animal models at the preclinical stage.:Organ-on-a-chip platforms have the potential to strongly impact and improve the drug screening process by recreating in vitro the functionality of human organs. Patient-derived neurons from different regions of the brain can be directly grown and differentiated on a brain-on-a-chip device where the disease development, progression and pharmacological treatments can be studied and monitored in real time. The model reliability is strongly improved by using human-derived cells, more relevant than animal models for pharmacological screening and disease monitoring. The selected cells will be then capable of proliferating and organizing themselves in the in vivo environment thanks to the device architecture, materials selection and bio-chemical functionalization.:In this review, we start by presenting the fundamental strategies adopted for brain-on-a-chip devices fabrication including e.g., photolithography, micromachining and 3D printing technology. Then, we discuss the state-of-theart of brain-on-a-chip platforms including their role in the study of the functional architecture of the brain e.g., blood-brain barrier, or of the most diffuse neurodegenerative diseases like Alzheimer’s and Parkinson’s. At last, the current limitations and future perspectives of this approach for the development of new drugs and neurodegenerative diseases modeling will be discussed.

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Liu, Nien-Che, Chu-Chun Liang, Yi-Chen Ethan Li, and I.-Chi Lee. "A Real-Time Sensing System for Monitoring Neural Network Degeneration in an Alzheimer’s Disease-on-a-Chip Model." Pharmaceutics 14, no. 5 (May 9, 2022): 1022. http://dx.doi.org/10.3390/pharmaceutics14051022.

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Stem cell-based in vitro models may provide potential therapeutic strategies and allow drug screening for neurodegenerative diseases, including Alzheimer’s disease (AD). Herein, we develop a neural stem cell (NSC) spheroid-based biochip that is characterized by a brain-like structure, well-defined neural differentiation, and neural network formation, representing a brain-on-a-chip. This system consisted of microelectrode arrays with a multichannel platform and allowed the real-time monitoring of network formation and degeneration by impedance analysis. The parameters of this platform for the real-time tracking of network development and organization were established based on our previous study. Subsequently, β-amyloid (Aβ) was added into the brain-on-a-chip system to generate an AD-on-a-chip model, and toxic effects on neurons and the degeneration of synapses were observed. The AD-on-a-chip model may help us to investigate the neurotoxicity of Aβ on neurons and neural networks in real time. Aβ causes neural damage and accumulates around neurites or inside neurospheroids, as observed by immunostaining and scanning electron microscopy (SEM). After incubation with Aβ, reactive oxygen species (ROS) increased, synapse function decreased, and the neurotransmitter-acetylcholine (ACh) concentration decreased were observed. Most importantly, the real-time analysis system monitored the impedance value variation in the system with Aβ incubation, providing consecutive network disconnection data that are consistent with biological data. This platform provides simple, real-time, and convenient sensing to monitor the network microenvironment. The proposed AD-on-a-chip model enhances the understanding of neurological pathology, and the development of this model provides an alternative for the study of drug discovery and cell–protein interactions in the brain.

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Ao, Zheng, Hongwei Cai, Zhuhao Wu, Sunghwa Song, Hande Karahan, Byungwook Kim, Hui-Chen Lu, Jungsu Kim, Ken Mackie, and Feng Guo. "Tubular human brain organoids to model microglia-mediated neuroinflammation." Lab on a Chip 21, no. 14 (2021): 2751–62. http://dx.doi.org/10.1039/d1lc00030f.

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Cameron, Tiffany, Tanya Bennet, Elyn Rowe, Mehwish Anwer, Cheryl Wellington, and Karen Cheung. "Review of Design Considerations for Brain-on-a-Chip Models." Micromachines 12, no. 4 (April 15, 2021): 441. http://dx.doi.org/10.3390/mi12040441.

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In recent years, the need for sophisticated human in vitro models for integrative biology has motivated the development of organ-on-a-chip platforms. Organ-on-a-chip devices are engineered to mimic the mechanical, biochemical and physiological properties of human organs; however, there are many important considerations when selecting or designing an appropriate device for investigating a specific scientific question. Building microfluidic Brain-on-a-Chip (BoC) models from the ground-up will allow for research questions to be answered more thoroughly in the brain research field, but the design of these devices requires several choices to be made throughout the design development phase. These considerations include the cell types, extracellular matrix (ECM) material(s), and perfusion/flow considerations. Choices made early in the design cycle will dictate the limitations of the device and influence the end-point results such as the permeability of the endothelial cell monolayer, and the expression of cell type-specific markers. To better understand why the engineering aspects of a microfluidic BoC need to be influenced by the desired biological environment, recent progress in microfluidic BoC technology is compared. This review focuses on perfusable blood–brain barrier (BBB) and neurovascular unit (NVU) models with discussions about the chip architecture, the ECM used, and how they relate to the in vivo human brain. With increased knowledge on how to make informed choices when selecting or designing BoC models, the scientific community will benefit from shorter development phases and platforms curated for their application.

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Cui, Baofang, and Seung-Woo Cho. "Blood-brain barrier-on-a-chip for brain disease modeling and drug testing." BMB Reports 55, no. 5 (May 31, 2022): 213–19. http://dx.doi.org/10.5483/bmbrep.2022.55.5.043.

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Bonakdar, Mohammad, Elisa M. Wasson, Yong W. Lee, and Rafael V. Davalos. "Electroporation of Brain Endothelial Cells on Chip toward Permeabilizing the Blood-Brain Barrier." Biophysical Journal 110, no. 2 (January 2016): 503–13. http://dx.doi.org/10.1016/j.bpj.2015.11.3517.

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Dauth, Stephanie, Ben M. Maoz, Sean P. Sheehy, Matthew A. Hemphill, Tara Murty, Mary Kate Macedonia, Angie M. Greer, Bogdan Budnik, and Kevin Kit Parker. "Neurons derived from different brain regions are inherently different in vitro: a novel multiregional brain-on-a-chip." Journal of Neurophysiology 117, no. 3 (March 1, 2017): 1320–41. http://dx.doi.org/10.1152/jn.00575.2016.

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Brain in vitro models are critically important to developing our understanding of basic nervous system cellular physiology, potential neurotoxic effects of chemicals, and specific cellular mechanisms of many disease states. In this study, we sought to address key shortcomings of current brain in vitro models: the scarcity of comparative data for cells originating from distinct brain regions and the lack of multiregional brain in vitro models. We demonstrated that rat neurons from different brain regions exhibit unique profiles regarding their cell composition, protein expression, metabolism, and electrical activity in vitro. In vivo, the brain is unique in its structural and functional organization, and the interactions and communication between different brain areas are essential components of proper brain function. This fact and the observation that neurons from different areas of the brain exhibit unique behaviors in vitro underline the importance of establishing multiregional brain in vitro models. Therefore, we here developed a multiregional brain-on-a-chip and observed a reduction of overall firing activity, as well as altered amounts of astrocytes and specific neuronal cell types compared with separately cultured neurons. Furthermore, this multiregional model was used to study the effects of phencyclidine, a drug known to induce schizophrenia-like symptoms in vivo, on individual brain areas separately while monitoring downstream effects on interconnected regions. Overall, this work provides a comparison of cells from different brain regions in vitro and introduces a multiregional brain-on-a-chip that enables the development of unique disease models incorporating essential in vivo features. NEW & NOTEWORTHY Due to the scarcity of comparative data for cells from different brain regions in vitro, we demonstrated that neurons isolated from distinct brain areas exhibit unique behaviors in vitro. Moreover, in vivo proper brain function is dependent on the connection and communication of several brain regions, underlining the importance of developing multiregional brain in vitro models. We introduced a novel brain-on-a-chip model, implementing essential in vivo features, such as different brain areas and their functional connections.

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Gusev, F. E., T. V. Andreeva, and E. I. Rogaev. "Methods for ChIP-seq Normalization and Their Application for Analysis of Regulatory Elements in Brain Cells." Генетика 59, no. 8 (August 1, 2023): 859–69. http://dx.doi.org/10.31857/s0016675823080088.

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Chromatin immunoprecipitation followed by sequencing (ChIP-seq) has become one of the major tools to elucidate gene expression programs. Similar to other molecular profiling methods, ChIP-seq is sensetive to several technical biases which affect downstream results, especially in cases when material quality is difficult to control, for example, frozen post-mortem human tissue. However methods for bioinformatics analysis improve every year and allow to mitigate these effects after sequencing by adjusting for both technical ChIP-seq biases and more general biological biases like post-mortem interval or cell heterogenity of the sample. Here we review a wide selection of ChIP-seq normalization methods with a focus on application in specific experimental settings, in particular when brain tissue is investigated.

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Pradip, Kalsariya. "A Survey of Brain Chip with Functionality and Benefits." INTERNATIONAL JOURNAL OF COMPUTER ENGINEERING AND SCIENCES 1, no. 2 (February 28, 2015): 5. http://dx.doi.org/10.26472/ijces.v1i2.12.

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Ndyabawe, Kenneth, and William S. Kisaalita. "Engineering microsystems to recapitulate brain physiology on a chip." Drug Discovery Today 24, no. 9 (September 2019): 1725–30. http://dx.doi.org/10.1016/j.drudis.2019.06.008.

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Hamzelou, Jessica. "Brain with a chip lets him get a grip." New Scientist 230, no. 3069 (April 2016): 10. http://dx.doi.org/10.1016/s0262-4079(16)30642-x.

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Barry, Antonia, Sabrina Samuel, Amr Moursi, Srihari Deepak, Shailendra Achawal, Chittoor Rajaraman, Lauric Feugere, et al. "Hull’s Magic Box: Keeping Brain Tumour Biopsies “Alive” in the Lab Brings Research Opportunities for New Therapies and Earlier Diagnosis of Brain Tumour." Neuro-Oncology 24, Supplement_4 (October 1, 2022): iv2. http://dx.doi.org/10.1093/neuonc/noac200.004.

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Abstract AIMS Assess/evaluate apoptosis in GBM samples maintained on a microfluidics system in response to GSK3368715 and other PRMT inhibitors, currently in clinical trials, with the ultimate goal of synergising with personalised patient care and precision medicine. Investigate the effect of treating GBM biopsies on-chip with PRMT inhibitors at the molecular level, including RNA and protein modifications. METHOD GBM biopsies are received from Hull Royal Infirmary and maintained on-chip for 8-days. They are perfused with media, at a rate of 3 μl/min, mimicking the in vivo environment and allowing real-time analysis of tumour behaviour. PRMT inhibitors, such as GSK3368715, are added to the media, in conjunction with TMZ, to determine their efficacy ex vivo using a range of techniques, such as: immunohistochemistry, cell viability assays, protein analysis and RNA-sequencing. RESULTS We show that PRMT inhibition increases apoptosis five-fold above the control, untreated GBM-on-chip samples. This is compounded by cell viability assays, which have indicated that cell viability in these post-chip tissues is reduced by 30% upon treatment with 1μM GSK3368715. Additionally, western blot analysis has indicated that PRMT inhibition with GSK3368715 appears to switch the methylation status of fused-in-sarcoma (FUS) protein in GBM biopsies. CONCLUSION These results indicate that PRMT inhibition may not only be a viable target for GBM therapy, but could also highlight a mechanism for re-sensitising MGMT-negative GBM to TMZ. This data produces an exciting argument for further research into the use of this novel inhibitor for improving prognosis for patients diagnosed with this devastating disease.

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Tunesi, Marta, Luca Izzo, Ilaria Raimondi, Diego Albani, and Carmen Giordano. "A miniaturized hydrogel-based in vitro model for dynamic culturing of human cells overexpressing beta-amyloid precursor protein." Journal of Tissue Engineering 11 (January 2020): 204173142094563. http://dx.doi.org/10.1177/2041731420945633.

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Recent findings have highlighted an interconnection between intestinal microbiota and the brain, referred to as microbiota–gut–brain axis, and suggested that alterations in microbiota composition might affect brain functioning, also in Alzheimer’s disease. To investigate microbiota–gut–brain axis biochemical pathways, in this work we developed an innovative device to be used as modular unit in an engineered multi-organ-on-a-chip platform recapitulating in vitro the main players of the microbiota–gut–brain axis, and an innovative three-dimensional model of brain cells based on collagen/hyaluronic acid or collagen/poly(ethylene glycol) semi-interpenetrating polymer networks and β-amyloid precursor protein-Swedish mutant-expressing H4 cells, to simulate the pathological scenario of Alzheimer’s disease. We set up the culturing conditions, assessed cell response, scaled down the three-dimensional models to be hosted in the organ-on-a-chip device, and cultured them both in static and in dynamic conditions. The results suggest that the device and three-dimensional models are exploitable for advanced engineered models representing brain features also in Alzheimer’s disease scenario.

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Luttge, Regina. "Editorial for the Special Issue on Microfluidic Brain-on-a-Chip." Micromachines 12, no. 9 (September 13, 2021): 1100. http://dx.doi.org/10.3390/mi12091100.

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Orii, Yasumitsu, Akihiro Horibe, Kuniaki Sueoka, Keiji Matsumoto, Toyohiro Aoki, Hirokazu Noma, Sayuri Kohara, et al. "PERSPECTIVE ON REQUIRED PACKAGING TECHNOLOGIES FOR NEUROMORPHIC DEVICES." International Symposium on Microelectronics 2015, no. 1 (October 1, 2015): 000561–66. http://dx.doi.org/10.4071/isom-2015-tha15.

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Cognitive computing has capability of machine learning, recognition and proposal. It is essential to make human life richer, more productive and more intelligent. For the realization of the cognitive computing, an efficient and scalable non-von Neumann architecture inspired by the human brain structure has been developed and a device which demonstrates the concept was also built. This device mimics the signal processing of the human brain, packing one million neuron circuits in 4,096 cores. It consumes almost 1,000 times less energy per event compared with a state-of-the-art multiprocessor. However, one million neurons only correspond to those of the bee's brain, and to mimic the brains of higher order animals, the inter-chip wiring becomes much more important, because this kind of neuromorphic device requires a large number of parallel signal lines for massive parallel signal operations. 3D chip stacking is, of course, a crucial technology in achieving the device. Technologies associated with 3D stacking such as low cost TSV formation and fine-pitch interconnection, smaller than 10μm pitch technology are required. From the reliability point of view, the optimization of solder composition is also important. Injection Molded Solder (IMS) is well fit to this fine pitch interconnection, in terms of material optimization and low cost joints. As for the interposer, the build-up organic interposer is the most attractive candidates for the cost issue, but in the most top layer, ultra-fine pitch wiring with the line and space widths smaller than 1μm should be prepared. Lots of material and process innovations are necessary for the inter-chip connection for neuromorphic devices.

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Dong, Fang, and Jun Zhang. "Inactivation of carboxyl terminus of Hsc70-interacting protein prevents hypoxia-induced pulmonary arterial smooth muscle cells proliferation by reducing intracellular Ca2+ concentration." Pulmonary Circulation 9, no. 3 (July 2019): 204589401987534. http://dx.doi.org/10.1177/2045894019875343.

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Carboxyl terminus of Hsc70-interacting protein (CHIP) is a 35-kDa cytoplasmic protein expressed in human striated muscle, brain, aortic smooth muscle, endothelial cells, and other tissues. Studies have confirmed that CHIP regulates cell growth, apoptosis, cell phenotype, metabolism, neurodegeneration, etc. However, whether CHIP is involved in pulmonary artery smooth muscle cell (PASMC) proliferation, a vital contributor to chronic hypoxia-induced pulmonary hypertension (CHPH), remains unknown. In this study, we first evaluated CHIP expression in the pulmonary arteries (PAs) of CHPH model rats. Subsequently, by silencing CHIP, we investigated the effect of CHIP on hypoxia-induced PASMC proliferation and the underlying mechanism. Our results showed that CHIP expression was upregulated in the PAs of CHPH model rats. Silencing CHIP significantly suppressed the hypoxia-triggered promotion of proliferation, [Ca2+]i, store-operated Ca2+ entry (SOCE), and some regulators of SOCE such as TRPC1 and TRPC6 in cultured PASMCs. These results indicate that CHIP likely contributes to hypoxia-induced PASMC proliferation by targeting the SOCE-[Ca2+]i pathway through the regulation of TRPC1 and TRPC6 in the PASMCs. In conclusion, the findings of the current study clarify the role of CHIP in hypoxia-induced PASMC proliferation.

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Xu, Jing, Jia-yu Wan, Song-tao Yang, Shou-feng Zhang, Na Xu, Nan Li, Ji-ping Li, Hai-ying Wang, Xue Bai, and Wen-sen Liu. "A surface plasmon resonance biosensor for direct detection of the rabies virus." Acta Veterinaria Brno 81, no. 2 (2012): 107–11. http://dx.doi.org/10.2754/avb201281020107.

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A surface plasmon resonance biosensor chip was constructed for detection of rabies virus. For the construction of the biosensor chip, N protein specific antibody and N protein specific antibody combined with G protein specific antibody of rabies virus were linked on two different flow cells on one CM5 chip, respectively. The chip was tested for the detection of rabies virus antigens using the crude extract of rabies virus from infected BHK cell strain culture. Tenfold serial dilutions of SRV9 strain virus-infected cell cultures were tested by the biosensor chip to establish the detection limit. The limit detection was approximately 70 pg/ml of nucleoprotein and glycoprotein. The biosensor chip developed in this study was employed for the detection of rabies virus in five suspect infectious specimens of brain tissue from guinea pigs; the results were compared by fluorescent antibody test. Surface plasmon resonance biosensor chip could be a useful automatic tool for prompt detection of rabies virus infection.

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Hou, Qinghong, Lina Zhu, Le Wang, Xiaoyan Liu, Feng Xiao, Yangzhouyun Xie, Wenfu Zheng, and Xingyu Jiang. "Screening on-chip fabricated nanoparticles for penetrating the blood–brain barrier." Nanoscale 14, no. 8 (2022): 3234–41. http://dx.doi.org/10.1039/d1nr05825h.

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We synthesized a series of brain-targeting drug nanocarriers on multi-channel syringe pump-integrated microfluidic chips, and evaluated their performance in penetrating the blood–brain barrier by in vitro and in vivo experiments.

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Johnson, Anissa Elice, Sagardeep Singh, Paul Lockman, Tuoen Liu, and Gabor Szalai. "Abstract 2363: Transcription factors of keratin 18 gene in MDA-MB-231Br (brain-colonizing) breast cancer cells." Cancer Research 82, no. 12_Supplement (June 15, 2022): 2363. http://dx.doi.org/10.1158/1538-7445.am2022-2363.

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Abstract Among all cancer types, breast cancer has the highest incidence rate and second highest mortality rate in females in the United States. Breast cancer patients with brain metastasis have a poor prognosis, with a median survival time of less than 1 year despite treatment. Decreasing the prevalence of brain metastasis would improve the overall prognosis of patients. We previously built a novel mouse model of breast cancer brain metastasis by intracardiac injection of the MDA-MB-231 (triple-negative breast cancer cell line) cells in mice. The brain colonizing counterpart of the parental cells primarily metastasizes to the brain, which is called the MDA-MB-231Br cell line. We have also shown that keratin 18 (an epithelial marker) plays a crucial role in the brain metastasis process as the MDA-MB-231Br cells have lower expression of the keratin 18 gene compared to their parental MDA-MBA-231 cells. Therefore, it is important to understand the transcriptional control of the keratin 18 gene, in order to fully understand the role of keratin 18 in regulating brain metastasis of breast cancer. We hypothesize that keratin 18 gene expression differs between these two cell lines due to the differential occupation of the gene by transcription factors such as Fli-1 or ETS-1. In this study, we analyzed the pattern of chromatin occupation of transcription factors ETS-1 and Fli-1 to determine whether they are responsible for the altered expression of the keratin 18 gene in MDA-MB-231Br cells.The Chromatin Immunoprecipitation (ChIP) was performed using the Pierce Magnetic ChIP Kit to analyze the presence of transcription factors Fli-1 and ETS-1 with enzymatic and mechanical shearing combined. The ChIP Kit included the positive control anti-RNA Polymerase II Antibody and GAPDH control primers. We optimized the experimental conditions including ChIP analysis for MDA-MB-231Br cells, detection of expected positive control results, and sonication settings to break apart the chromatin. We measured the ChIP mediated enrichment of the intron 1 region of the keratin 18 gene, as the DNA is hypermethylated in this region in MDA-MB-231Br cells. The primers were designed and used as follows: forward: 5′-GATCATCGAGGACCTGAGGG-3′ and reverse: 5′-GGGGAGCAGATCCTTCTTAGC-3′. Our results indicated that an ETS transcription factor occupies intron 1 of the keratin 18 gene in the MDA-MB-231Br cells, also showing that ChIP is an effective method to examine transcription factor binding. For future studies, we plan to perform similar experiments with the parental MDA-MB-231 cells. Then a quantitative PCR will be used to measure DNA binding sites of the transcription factors and determine if there is a significant difference in the level of chromatin occupation between the regular and brain-colonizing breast cancer cells. Our studies are necessary to understand the role of the keratin 18 gene in regulating tumor metastasis at the molecular level. Citation Format: Anissa Elice Johnson, Sagardeep Singh, Paul Lockman, Tuoen Liu, Gabor Szalai. Transcription factors of keratin 18 gene in MDA-MB-231Br (brain-colonizing) breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2363.

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Journal articles on the topic 'Brain on a chip'

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